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Topical Collection "Herbal Medicine Research"

A topical collection in Molecules (ISSN 1420-3049). This collection belongs to the section "Medicinal Chemistry".

Editors

Collection Editor
Prof. Dr. Christopher W.K. Lam

State Key Laboratory of Quality Research in Chinese Medicine, Macau Institute for Applied Research in Medicine and Health, Macau University of Science and Technology, Macau, China
Website | E-Mail
Interests: allergy and clinical immunology; nephrology; diabetology; toxicology; clinical biochemistry; laboratory medicine; Chinese medicine
Collection Editor
Prof. Dr. Thomas Efferth

Department of Pharmaceutical Biology, Institute of Pharmacy and Biochemistry, University of Mainz, Staudinger Weg, 555128 Mainz, Germany
E-Mail
Fax: +49 6131 3923752
Interests: cancer; pharmacogenomics; molecular docking and virtual drug screening; molecular pharmacology; natural products; phytotherapy

Topical Collection Information

Dear Colleagues,

Herbal medicine is practiced widely in different cultures of the world because it is usually affordable, locally accessible, and generally efficacious. Government statistics (2011) in Hong Kong, China showed that about 27% of all primary healthcare consultations were provided by Chinese medicine (CM) practitioners, while 90% of cancer patients used both CM and western medicine. An ongoing survey initiated by the State Council of the People’s Republic of China from 1988 found 11,146 registered herbal Chinese medicines that were currently in use in the last 5-year cycle. These together with herbal medicines of other territories constitute a wealth of natural botanical resources of traditional and newer drugs or more often, prototype compounds for candidate drugs. Herbal medicine research encompasses old and modern disciplines of plant biology, medicinal chemistry and biochemistry, cell and molecular biology, pharmcogenomics, proteomics, and metabolomics. It utilizes traditional and rapidly advancing analytical methods and instrumentation such as gas or liquid chromatography coupled with tandem mass spectrometry, nuclear magnetic resonance and electron-spin resonance, and gene and protein arrays for fractionation, purification, chemical and genetic fingerprinting, derivatization, modification, synthesis, and clinical trials of herbal medicines starting from cell-line to animal and patient studies. Such multidisciplinary efforts will continue to foster novel therapeutic applications of herbal medicines, such as accelerating apoptosis of pro-inflammatory cells in autoimmune diseases, inducing autophagy for anti-aging and oncosuppression, and overcoming resistance of cancer cells to cytotoxic chemotherapy.

This collection of Molecules on “Herbal Medicine Research” welcomes submission of previously unpublished manuscripts from original work on all the above aspects. We plan to receive submissions from 1 August 2015 to 31 January 2016.

With kind regards and best wishes,

Prof. Dr. Christopher W.K. Lam
Prof. Dr. Thomas Efferth
Collection Editor

Manuscript Submission Information

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Keywords

  • herbal medicines
  • analytical chemistry
  • medicinal chemistry
  • pharmacology and pharamacogenomics
  • proteomics and metabolomics
  • drug synthesis and modification
  • clinical trials

Published Papers (76 papers)

2017

Jump to: 2016, 2015

Open AccessArticle Hippeastrum reticulatum (Amaryllidaceae): Alkaloid Profiling, Biological Activities and Molecular Docking
Molecules 2017, 22(12), 2191; doi:10.3390/molecules22122191
Received: 24 October 2017 / Revised: 5 December 2017 / Accepted: 7 December 2017 / Published: 9 December 2017
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Abstract
The Amaryllidaceae family has proven to be a rich source of active compounds, which are characterized by unique skeleton arrangements and a broad spectrum of biological activities. The aim of this work was to perform the first detailed study of the alkaloid constituents
[...] Read more.
The Amaryllidaceae family has proven to be a rich source of active compounds, which are characterized by unique skeleton arrangements and a broad spectrum of biological activities. The aim of this work was to perform the first detailed study of the alkaloid constituents of Hippeastrum reticulatum (Amaryllidaceae) and to determine the anti-parasitological and cholinesterase (AChE and BuChE) inhibitory activities of the epimers (6α-hydroxymaritidine and 6β-hydroxymaritidine). Twelve alkaloids were identified in H. reticulatum: eight known alkaloids by GC-MS and four unknown (6α-hydroxymaritidine, 6β-hydroxymaritidine, reticulinine and isoreticulinine) by NMR. The epimer mixture (6α-hydroxymaritidine and 6β-hydroxymaritidine) showed low activity against all protozoan parasites tested and weak AChE-inhibitory activity. Finally, a molecular docking analysis of AChE and BuChE proteins showed that isoreticulinine may be classified as a potential inhibitory molecule since it can be stabilized in the active site through hydrogen bonds, π-π stacking and hydrophobic interactions. Full article
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Open AccessReview Review of Ethnomedicinal Uses, Phytochemistry and Pharmacological Properties of Euclea natalensis A.DC.
Molecules 2017, 22(12), 2128; doi:10.3390/molecules22122128
Received: 1 November 2017 / Revised: 17 November 2017 / Accepted: 30 November 2017 / Published: 2 December 2017
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Abstract
Euclea natalensis is traditionally used as herbal medicine for several human diseases and ailments in tropical Africa. This study reviews information on ethnomedicinal uses, botany, phytochemical constituents, pharmacology and toxicity of E. natalensis. Results of this study are based on literature search
[...] Read more.
Euclea natalensis is traditionally used as herbal medicine for several human diseases and ailments in tropical Africa. This study reviews information on ethnomedicinal uses, botany, phytochemical constituents, pharmacology and toxicity of E. natalensis. Results of this study are based on literature search from several sources including electronic databases, books, book chapters, websites, theses and conference proceedings. This study showed that E. natalensis is used as traditional medicine in 57.1% of the countries where it is indigenous. Euclea natalensis has a high degree of consensus on abdominal pains, antidote for snake bites, diabetes, diarrhoea, malaria, roundworms, stomach problems, toothache, venereal diseases and wounds. Several ethnopharmacological studies have shown that crude extracts and chemical compounds from E. natalensis demonstrated many biological activities both in vitro and in vivo, which included antibacterial, antidiabetic, antifungal, antimycobacterial, antiviral, antioxidant, antiplasmodial, larvicidal, antischistosomal, molluscicidal, dentin permeability and hepatoprotective activities. Future studies should focus on the mechanism of biological activities of both crude extracts and chemical compounds from the species, as well as structure–function relationships of bioactive constituents of the species. Full article
Open AccessArticle Modulation of Cytochrome P450, P-glycoprotein and Pregnane X Receptor by Selected Antimalarial Herbs—Implication for Herb-Drug Interaction
Molecules 2017, 22(12), 2049; doi:10.3390/molecules22122049
Received: 30 October 2017 / Accepted: 20 November 2017 / Published: 23 November 2017
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Abstract
Seven medicinal plants popularly used for treating malaria in West Africa were selected to assess herb-drug interaction potential through a series of in vitro methods. Fluorescent cytochrome P450 (CYP) assays were conducted using the recombinant CYP enzymes for CYP1A2, CYP2A6, CYP2B6, CYP2C9, CYP2C19,
[...] Read more.
Seven medicinal plants popularly used for treating malaria in West Africa were selected to assess herb-drug interaction potential through a series of in vitro methods. Fluorescent cytochrome P450 (CYP) assays were conducted using the recombinant CYP enzymes for CYP1A2, CYP2A6, CYP2B6, CYP2C9, CYP2C19, CYP2D6 and CYP3A4 to assess the effect of the methanolic extracts on the metabolic activity of CYPs. Secondly, the inhibitory effect of the extracts was evaluated on P-glycoproteins (P-gp) using calcein-AM, a fluorescent substrate, in MDCK-II and hMDR1-MDCK-II cells. The inhibition of P-gp activity was determined as a reflection of increase in calcein-AM uptake. Additionally, the enzyme induction potential of the extracts was assessed through the modulation of PXR activity in HepG2 cells transiently transfected with pSG5-PXR and PCR5 plasmid DNA. Significant inhibition of CYP activity (IC50 < 10 µg/mL) was observed with the following herbs: A. muricata [CYP2C9, 3A4 and CYP2D6]; M. indica [CYP2C9]; M. charantia [CYP2C9 and CYP2C19]; P. amarus [CYP2C19, CYP2C9 and CYP3A4]; T. diversifolia [CYP2C19 and CYP3A4]. Extracts of four herbs (P. amarus, M. charantia, T. diversifolia and A. muricata) exhibited significant inhibition of P-gp with IC50 values (µg/mL) of 17 ± 1, 16 ± 0.4, 26 ± 1, and 24 ± 1, respectively. In addition, four herbs (A. mexicana, M. charantia, P. amarus and T. diversifolia) showed a >two-fold increase in induction in PXR activity. These findings suggest that these herbs may be capable of eliciting herb-drug interactions if consumed in high quantities with concomitant use of conventional therapies. Full article
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Open AccessCommunication Preparative Separation and Purification of Four Glycosides from Gentianae radix by High-Speed Counter-Current Chromatography and Comparison of Their Anti-NO Production Effects
Molecules 2017, 22(11), 2002; doi:10.3390/molecules22112002
Received: 3 November 2017 / Revised: 16 November 2017 / Accepted: 16 November 2017 / Published: 17 November 2017
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Abstract
Secoiridoid and iridoid glycosides are the main active components of Gentianae radix. In this work, one iridoid and three secoiridoid glycosides from Gentianae radix have been purified by high-speed counter-current chromatography in two runs using different solvent systems. Ethyl acetate–n-butanol–water
[...] Read more.
Secoiridoid and iridoid glycosides are the main active components of Gentianae radix. In this work, one iridoid and three secoiridoid glycosides from Gentianae radix have been purified by high-speed counter-current chromatography in two runs using different solvent systems. Ethyl acetate–n-butanol–water (2:1:3, v/v/v) was the optimum solvent system to purify ca. 4.36 mg of loganic acid, 3.05 mg of swertiamarin, and 35.66 mg of gentiopicroside with 98.1%, 97.2% and 98.6% purities, respectively, while 31.15 mg of trifloroside with 98.9% purity was separated using hexane–ethyl acetate–methanol–water (1:3:1:3, v/v/v/v). The structures of the glycosides were identified by mass spectrometry and NMR. After separation, the anti-nitric oxide production effects of the compounds on lipopolysaccharide-induced BV-2 murine microglial cells were also evaluated. All of the compounds inhibited the production of nitric oxide in lipopolysaccharide-induced BV-2 cells with high cell viabilities in a concentration-dependent manner, which demonstrated that were able to be used as a nitric oxide inhibitor. Full article
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Open AccessArticle Sulforaphane Alters β-Naphthoflavone-Induced Changes in Activity and Expression of Drug-Metabolizing Enzymes in Rat Hepatocytes
Molecules 2017, 22(11), 1983; doi:10.3390/molecules22111983
Received: 24 October 2017 / Accepted: 14 November 2017 / Published: 16 November 2017
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Abstract
Sulforaphane (SFN), an isothiocyanate found in cruciferous vegetables, exerts many beneficial effects on human health such as antioxidant, anti-inflammatory, and anticancer effects. The effect of SFN alone on drug-metabolizing enzymes (DMEs) has been investigated in numerous in vitro and in vivo models, but
[...] Read more.
Sulforaphane (SFN), an isothiocyanate found in cruciferous vegetables, exerts many beneficial effects on human health such as antioxidant, anti-inflammatory, and anticancer effects. The effect of SFN alone on drug-metabolizing enzymes (DMEs) has been investigated in numerous in vitro and in vivo models, but little is known about the effect of SFN in combination with cytochrome P450 (CYP) inducer. The aim of our study was to evaluate the effect of SFN on the activity and gene expression of selected DMEs in primary cultures of rat hepatocytes treated or non-treated with β-naphthoflavone (BNF), the model CYP1A inducer. In our study, SFN alone did not significantly alter the activity and expression of the studied DMEs, except for the glutathione S-transferase (GSTA1) mRNA level, which was significantly enhanced. Co-treatment of hepatocytes with SFN and BNF led to a substantial increase in sulfotransferase, aldoketoreductase 1C, carbonylreductase 1 and NAD(P)H:quinone oxidoreductase 1 activity and a marked decrease in cytochrome P450 (CYP) Cyp1a1, Cyp2b and Cyp3a4 expression in comparison to the treatment with BNF alone. Sulforaphane is able to modulate the activity and/or expression of DMEs, thus shifting the balance of carcinogen metabolism toward deactivation, which could represent an important mechanism of its chemopreventive activity. Full article
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Open AccessArticle An Optimized and Sensitive Pharmacokinetic Quantitative Method of Investigating Gastrodin, Parishin, and Parishin B, C and E in Beagle Dog Plasma using LC-MS/MS after Intragastric Administration of Tall Gastrodia Capsules
Molecules 2017, 22(11), 1938; doi:10.3390/molecules22111938
Received: 10 October 2017 / Revised: 6 November 2017 / Accepted: 7 November 2017 / Published: 10 November 2017
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Abstract
Gastrodia elata Blume, called Tianma in China, has been widely used to treat headaches, convulsions and epilepsy for thousands of years. In the present study, a series of optimizations were employed to develop a rapid, sensitive, and reliable high-performance liquid chromatography-triple quadrupole mass
[...] Read more.
Gastrodia elata Blume, called Tianma in China, has been widely used to treat headaches, convulsions and epilepsy for thousands of years. In the present study, a series of optimizations were employed to develop a rapid, sensitive, and reliable high-performance liquid chromatography-triple quadrupole mass spectrometry method, which was then used for the simultaneous determination of gastrodin, parishin, parishin B, parishin C and parishin E in beagle dog plasma after intragastric administration of tall Gastrodia capsules (Tianma brand). The chromatographic separation was achieved on a C18 column with gradient elution by using a mixture of 0.4% formic acid aqueous solution and acetonitrile as the mobile phase at a flow rate of 0.15 mL/min. A tandem mass spectrometric detection was conducted using multiple-reaction monitoring (MRM) via electrospray ionization (ESI) source in negative ionization mode. Samples were pre-treated by a single-step protein precipitation with methanol, and bergenin was used as internal standard (IS). Under the optimized conditions, the lower limit of quantification (LLOQ) was 0.10 ng/mL for gastrodin, 0.40 ng/mL for parishin B, 0.02 ng/mL for parishin E and 0.20 ng/mL for parishin and parishin C, all of which previously were the highest levels of sensitivity. The methods were optimized for selectivity, calibration curves, accuracy and precision. Extraction recoveries, matrix effects and stability were within acceptable ranges. Pharmacokinetic parameters of the tested substances were also quantitatively determined. Finally, a possible metabolic pathway was induced based on correlations obtained from quantitative and qualitative data analysis in vivo. Full article
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Open AccessArticle Ginger and Propolis Exert Neuroprotective Effects against Monosodium Glutamate-Induced Neurotoxicity in Rats
Molecules 2017, 22(11), 1928; doi:10.3390/molecules22111928
Received: 23 October 2017 / Revised: 30 October 2017 / Accepted: 1 November 2017 / Published: 8 November 2017
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Abstract
Central nervous system cytotoxicity is linked to neurodegenerative disorders. The objective of the study was to investigate whether monosodium glutamate (MSG) neurotoxicity can be reversed by natural products, such as ginger or propolis, in male rats. Four different groups of Wistar rats were
[...] Read more.
Central nervous system cytotoxicity is linked to neurodegenerative disorders. The objective of the study was to investigate whether monosodium glutamate (MSG) neurotoxicity can be reversed by natural products, such as ginger or propolis, in male rats. Four different groups of Wistar rats were utilized in the study. Group A served as a normal control, whereas group B was orally administered with MSG (100 mg/kg body weight, via oral gavage). Two additional groups, C and D, were given MSG as group B along with oral dose (500 mg/kg body weight) of either ginger or propolis (600 mg/kg body weight) once a day for two months. At the end, the rats were sacrificed, and the brain tissue was excised and levels of neurotransmitters, ß-amyloid, and DNA oxidative marker 8-OHdG were estimated in the brain homogenates. Further, formalin-fixed and paraffin-embedded brain sections were used for histopathological evaluation. The results showed that MSG increased lipid peroxidation, nitric oxide, neurotransmitters, and 8-OHdG as well as registered an accumulation of ß-amyloid peptides compared to normal control rats. Moreover, significant depletions of glutathione, superoxide dismutase, and catalase as well as histopathological alterations in the brain tissue of MSG-treated rats were noticed in comparison with the normal control. In contrast, treatment with ginger greatly attenuated the neurotoxic effects of MSG through suppression of 8-OHdG and β-amyloid accumulation as well as alteration of neurotransmitter levels. Further improvements were also noticed based on histological alterations and reduction of neurodegeneration in the brain tissue. A modest inhibition of the neurodegenerative markers was observed by propolis. The study clearly indicates a neuroprotective effect of ginger and propolis against MSG-induced neurodegenerative disorders and these beneficial effects could be attributed to the polyphenolic compounds present in these natural products. Full article
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Open AccessArticle Enhanced Agronomic Traits and Medicinal Constituents of Autotetraploids in Anoectochilus formosanus Hayata, a Top-Grade Medicinal Orchid
Molecules 2017, 22(11), 1907; doi:10.3390/molecules22111907
Received: 13 September 2017 / Revised: 29 October 2017 / Accepted: 30 October 2017 / Published: 7 November 2017
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Abstract
This study developed an efficient and reliable system for inducing polyploidy in Anoectochilus formosanus Hayata, a top-grade medicinal orchid. The resulting tetraploid gave a significant enhancement on various agronomic traits, including dry weight, fresh weight, shoot length, root length, leaf width, the size
[...] Read more.
This study developed an efficient and reliable system for inducing polyploidy in Anoectochilus formosanus Hayata, a top-grade medicinal orchid. The resulting tetraploid gave a significant enhancement on various agronomic traits, including dry weight, fresh weight, shoot length, root length, leaf width, the size of stoma, and number of chloroplasts per stoma. A reduction of the ratio of length to width was observed in stomata and leaves of the tetraploid, and consequently, an alteration of organ shape was found. The major bioactive compounds, total flavonoid and gastrodin, were determined by the aluminum chloride colorimetric method and ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS), respectively. The tetraploid produced significantly higher contents of total flavonoid and gastrodin in the leaf, the stem, and the whole plant when compared with the diploid. The resulting tetraploids in this study are proposed to be suitable raw materials in the pharmaceutical industry for enhancing productivity and reducing cost. Full article
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Open AccessArticle Anti-HIV Activity of Ocimum labiatum Extract and Isolated Pheophytin-a
Molecules 2017, 22(11), 1763; doi:10.3390/molecules22111763
Received: 10 September 2017 / Accepted: 16 October 2017 / Published: 6 November 2017
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Abstract
Ocimum plants are traditionally used to manage HIV/AIDS in various African countries. The effects of Ocimum labiatum extract on HIV-1 protease (PR) and reverse transcriptase (RT) is presented here along with characterization of an identified bioactive compound, achieved through 1H- and 13
[...] Read more.
Ocimum plants are traditionally used to manage HIV/AIDS in various African countries. The effects of Ocimum labiatum extract on HIV-1 protease (PR) and reverse transcriptase (RT) is presented here along with characterization of an identified bioactive compound, achieved through 1H- and 13C-NMR. The extract’s effect on HIV-1 replication was assessed by HIV-1 p24 antigen capture. Cytotoxicity of samples was evaluated using tetrazolium dyes and real-time cell electronic sensing (RT-CES). Ocimum labiatum inhibited HIV-1 PR with an IC50 value of 49.8 ± 0.4 μg/mL and presented weak inhibition (21%) against HIV-1 RT. The extract also reduced HIV-1 replication in U1 cells at a non-cytotoxic concentration (25 μg/mL). The CC50 value of the extract in U1 cells was 42.0 ± 0.13 μg/mL. The HIV-1 PR inhibiting fraction was purified using prep-HPLC and yielded a chlorophyll derivative, pheophytin-a (phy-a). Phy-a inhibited HIV-1 PR with an IC50 value of 44.4 ± 1.5 μg/mL (51 ± 1.7 μM). The low cytotoxicity of phy-a in TZM-bl cells was detected by RT-CES and the CC50 value in U1 cells was 51.3 ± 1.0 μg/mL (58.9 ± 1.2 μM). This study provides the first in vitro evidence of anti-HIV activity of O. labiatum and isolated phy-a, supporting further investigation of O. labiatum for lead compounds against HIV-1. Full article
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Open AccessArticle Marrubium vulgare L. Leave Extract: Phytochemical Composition, Antioxidant and Wound Healing Properties
Molecules 2017, 22(11), 1851; doi:10.3390/molecules22111851
Received: 6 September 2017 / Revised: 13 October 2017 / Accepted: 26 October 2017 / Published: 28 October 2017
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Abstract
Several factors contribute in wound generation, e.g., accidental traumas or surgery, and in certain cases, this dermal injury may have a devastating outcome. When skin damage occurs, the human body puts in place a sophisticated choreography, which involves numerous repairing processes to restore
[...] Read more.
Several factors contribute in wound generation, e.g., accidental traumas or surgery, and in certain cases, this dermal injury may have a devastating outcome. When skin damage occurs, the human body puts in place a sophisticated choreography, which involves numerous repairing processes to restore physiological conditions. Nevertheless, natural healing mechanisms are ineffective towards chronic or non-healing wounds and thus, therapeutic strategies may represent the only beneficial alternative to counteract these tissue insults. Over the years, numerous studies showed the great potential of plants in promoting wound healing, by virtue of their high contents in antioxidant species. These compounds trigger a molecular cascade that collimate into the promotion of reparative processes. In this article, we report on the potential effect on wound healing of Marrubium vulgare L., a medicinal plant well known for several pharmaceutical activities. To this aim, the methanolic extract was prepared and subjected to a phytochemical investigation, quantifying the amount of marrubiin via NMR and drawing the phytochemical fingerprint via high performance liquid chromatography—ultra violet/photodiode-array detection-electrospray/mass (HPLC-UV/PAD-ESI/MS) analysis. Lastly, the antioxidant properties and wound healing potential have been evaluated. Full article
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Open AccessArticle Simultaneous Determination of Seven Anthraquinone Aglycones of Crude and Processed Semen Cassiae Extracts in Rat Plasma by UPLC–MS/MS and Its Application to a Comparative Pharmacokinetic Study
Molecules 2017, 22(11), 1803; doi:10.3390/molecules22111803
Received: 28 September 2017 / Revised: 17 October 2017 / Accepted: 22 October 2017 / Published: 28 October 2017
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Abstract
Semen cassiae is the ripe seed of Cassia obtusifolia L. or Cassia tora L. of the family Leguminosae. In traditional Chinese medicine, the two forms of Semen cassiae are raw Semen cassiae (R-SC) and parched Semen cassiae (P-SC). To clarify the processing mechanism
[...] Read more.
Semen cassiae is the ripe seed of Cassia obtusifolia L. or Cassia tora L. of the family Leguminosae. In traditional Chinese medicine, the two forms of Semen cassiae are raw Semen cassiae (R-SC) and parched Semen cassiae (P-SC). To clarify the processing mechanism of Semen cassiae, the pharmacokinetics of R-SC and P-SC extracts were examined. A simple, rapid, sensitive ultra-high-performance liquid chromatography–tandem mass spectroscopy (UPLC-MS/MS) method was developed and validated for the simultaneous determination of seven anthraquinone aglycones of Semen cassiae (aurantio-obtusin, obtusifolin, questin, 2-hydroxyemodin-1-methyl-ether, rhein, emodin, 1,2,7-trimethoxyl-6,8-dihydroxy-3-methylanthraquinone) to compare the pharmacokinetics of raw and parched Semen cassiae in rat plasma. Compared with the R-SC group, Cmax and AUC0-12 tended to be higher in the P-SC group. In particular, Cmax values for aurantio-obtusin, obtusifolin, questin, 2-hydroxyemodin-1-methyl-ether and rhein were significantly higher in the P-SC group (p < 0.05). Meanwhile, Tmax and MRT0-12 tended to be lower in the P-SC group. Specifically, Tmax for aurantio-obtusin and 2-hydroxyemodin-1-methyl-ether and MRT0-12 for obtusifolin and rhein were significantly higher in the P-SC group (p < 0.05). Full article
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Open AccessArticle Spectrum-Effect Relationships between Fingerprints of Caulophyllum robustum Maxim and Inhabited Pro-Inflammation Cytokine Effects
Molecules 2017, 22(11), 1826; doi:10.3390/molecules22111826
Received: 2 September 2017 / Revised: 21 October 2017 / Accepted: 22 October 2017 / Published: 26 October 2017
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Abstract
Caulophyllum robustum Maxim (CRM) is a Chinese folk medicine with significant effect on treatment of rheumatoid arthritis (RA). This study was designed to explore the spectrum-effect relationships between high-performance liquid chromatography (HPLC) fingerprints and the anti-inflammatory effects of CRM. Seventeen common peaks were
[...] Read more.
Caulophyllum robustum Maxim (CRM) is a Chinese folk medicine with significant effect on treatment of rheumatoid arthritis (RA). This study was designed to explore the spectrum-effect relationships between high-performance liquid chromatography (HPLC) fingerprints and the anti-inflammatory effects of CRM. Seventeen common peaks were detected by fingerprint similarity evaluation software. Among them, 15 peaks were identified by Liquid Chromatography-Mass Spectrometry (LC-MS). Pharmacodynamics experiments were conducted in collagen-induced arthritis (CIA) mice to obtain the anti-inflammatory effects of different batches of CRM with four pro-inflammation cytokines (TNF-α, IL-β, IL-6, and IL-17) as indicators. These cytokines were suppressed at different levels according to the different batches of CRM treatment. The spectrum-effect relationships between chemical fingerprints and the pro-inflammation effects of CRM were established by multiple linear regression (MLR) and gray relational analysis (GRA). The spectrum-effect relationships revealed that the alkaloids (N-methylcytisine, magnoflorine), saponins (leiyemudanoside C, leiyemudanoside D, leiyemudanoside G, leiyemudanoside B, cauloside H, leonticin D, cauloside G, cauloside D, cauloside B, cauloside C, and cauloside A), sapogenins (oleanolic acid), β-sitosterols, and unknown compounds (X3, X17) together showed anti-inflammatory efficacy. The results also showed that the correlation between saponins and inflammatory factors was significantly closer than that of alkaloids, and saponins linked with less sugar may have higher inhibition effect on pro-inflammatory cytokines in CIA mice. This work provided a general model of the combination of HPLC and anti-inflammatory effects to study the spectrum-effect relationships of CRM, which can be used to discover the active substance and to control the quality of this treatment. Full article
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Open AccessArticle Hepatotoxicity Induced by Sophora flavescens and Hepatic Accumulation of Kurarinone, a Major Hepatotoxic Constituent of Sophora flavescens in Rats
Molecules 2017, 22(11), 1809; doi:10.3390/molecules22111809
Received: 20 September 2017 / Accepted: 23 October 2017 / Published: 25 October 2017
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Abstract
Our previous study showed that kurarinone was the main hepatotoxic ingredient of Sophora flavescens, accumulating in the liver. This study characterized the mechanism of Sophora flavescens extract (ESF) hepatotoxicity and hepatic accumulation of kurarinone. ESF impaired hepatic function and caused fat accumulation
[...] Read more.
Our previous study showed that kurarinone was the main hepatotoxic ingredient of Sophora flavescens, accumulating in the liver. This study characterized the mechanism of Sophora flavescens extract (ESF) hepatotoxicity and hepatic accumulation of kurarinone. ESF impaired hepatic function and caused fat accumulation in the liver after oral administration (1.25 and 2.5 g/kg for 14 days in rats). Serum metabolomics evaluation based on high-resolution mass spectrometry was conducted and real-time PCR was used to determine the expression levels of CPT-1, CPT-2, PPAR-α, and LCAD genes. Effects of kurarinone on triglyceride levels were evaluated in HL-7702 cells. Tissue distribution of kurarinone and kurarinone glucuronides was analyzed in rats receiving ESF (2.5 g/kg). Active uptake of kurarinone and kurarinone glucuronides was studied in OAT2-, OATP1B1-, OATP2B1-, and OATP1B3-transfected HEK293 cells. Our results revealed that after oral administration of ESF in rats, kurarinone glucuronides were actively transported into hepatocytes by OATP1B3 and hydrolyzed into kurarinone, which inhibited fatty acid β-oxidation through the reduction of l-carnitine and the inhibition of PPAR-α pathway, ultimately leading to lipid accumulation and liver injury. These findings contribute to understanding hepatotoxicity of kurarinone after oral administration of ESF. Full article
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Open AccessArticle Triterpenoids from Ocimum labiatum Activates Latent HIV-1 Expression In Vitro: Potential for Use in Adjuvant Therapy
Molecules 2017, 22(10), 1703; doi:10.3390/molecules22101703
Received: 9 September 2017 / Revised: 4 October 2017 / Accepted: 9 October 2017 / Published: 13 October 2017
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Abstract
Latent HIV reservoirs in infected individuals prevent current treatment from eradicating infection. Treatment strategies against latency involve adjuvants for viral reactivation which exposes viral particles to antiretroviral drugs. In this study, the effect of novel triterpenoids isolated from Ocimum labiatum on HIV-1 expression
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Latent HIV reservoirs in infected individuals prevent current treatment from eradicating infection. Treatment strategies against latency involve adjuvants for viral reactivation which exposes viral particles to antiretroviral drugs. In this study, the effect of novel triterpenoids isolated from Ocimum labiatum on HIV-1 expression was measured through HIV-1 p24 antigen capture in the U1 latency model of HIV-1 infection and in peripheral blood mononuclear cells (PBMCs) of infected patients on combination antiretroviral therapy (cART). The mechanism of viral reactivation was determined through the compound’s effect on cytokine production, histone deacetylase (HDAC) inhibition, and protein kinase C (PKC) activation. Cytotoxicity of the triterpenoids was determined using a tetrazolium dye and flow cytometry. The isolated triterpene isomers, 3-hydroxy-4,6a,6b,11,12,14b-hexamethyl-1,2,3,4,6,6a,6b,7,8,8a,9,10,11,12,12a,14,14a,14b-octadecahydropicene-4,8a-dicarboxylic acid (HHODC), significantly (p < 0.05) induced HIV-1 expression in a dose-dependent manner in U1 cells at non-cytotoxic concentrations. HHODC also induced viral expression in PBMCs of HIV-1 infected patients on cART. In addition, the compound up-regulated the production of interleukin (IL)-2, IL-6, tumour necrosis factor (TNF)-α, and interferon (IFN)-γ but had no effect on HDAC and PKC activity, suggesting cytokine upregulation as being involved in latency activation. The observed in vitro reactivation of HIV-1 introduces the adjuvant potential of HHODC for the first time here. Full article
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Open AccessReview Chemical and Biological Research on Herbal Medicines Rich in Xanthones
Molecules 2017, 22(10), 1698; doi:10.3390/molecules22101698
Received: 11 September 2017 / Accepted: 9 October 2017 / Published: 11 October 2017
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Abstract
Xanthones, as some of the most active components and widely distributed in various herb medicines, have drawn more and more attention in recent years. So far, 168 species of herbal plants belong to 58 genera, 24 families have been reported to contain xanthones.
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Xanthones, as some of the most active components and widely distributed in various herb medicines, have drawn more and more attention in recent years. So far, 168 species of herbal plants belong to 58 genera, 24 families have been reported to contain xanthones. Among them, Calophyllum, Cratoxylum, Cudrania, Garcinia, Gentiana, Hypericum and Swertia genera are plant resources with great development prospect. This paper summarizes the plant resources, bioactivity and the structure-activity relationships (SARs) of xanthones from references published over the last few decades, which may be useful for new drug research and development on xanthones. Full article
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Open AccessArticle Influence of Plant Growth Retardants on Quality of Codonopsis Radix
Molecules 2017, 22(10), 1655; doi:10.3390/molecules22101655
Received: 8 September 2017 / Revised: 28 September 2017 / Accepted: 1 October 2017 / Published: 9 October 2017
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Abstract
Plant growth retardant (PGR) refers to organics that can inhibit the cell division of plant stem tip sub-apical meristem cells or primordial meristem cell. They are widely used in the cultivation of rhizomatous functional plants; such as Codonopsis Radix, that is a famous
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Plant growth retardant (PGR) refers to organics that can inhibit the cell division of plant stem tip sub-apical meristem cells or primordial meristem cell. They are widely used in the cultivation of rhizomatous functional plants; such as Codonopsis Radix, that is a famous Chinese traditional herb. However, it is still unclear whether PGR affects the medicinal quality of C. Radix. In the present study, amino acid analyses, targeted and non-targeted analyses by ultra-performance liquid chromatography combined with time-of-flight mass spectrometry (UPLC-TOF-MS) and gas chromatography-MS were used to analyze and compare the composition of untreated C. Radix and C. Radix treated with PGR. The contents of two key bioactive compounds, lobetyolin and atractylenolide III, were not affected by PGR treatment. The amounts of polysaccharides and some internal volatiles were significantly decreased by PGR treatment; while the free amino acids content was generally increased. Fifteen metabolites whose abundance were affected by PGR treatment were identified by UPLC-TOF-MS. Five of the up-regulated compounds have been reported to show immune activity, which might contribute to the healing efficacy (“buqi”) of C. Radix. The results of this study showed that treatment of C. Radix with PGR during cultivation has economic benefits and affected some main bioactive compounds in C. Radix. Full article
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Open AccessArticle Intestinal Absorption of Triterpenoids and Flavonoids from Glycyrrhizae radix et rhizoma in the Human Caco-2 Monolayer Cell Model
Molecules 2017, 22(10), 1627; doi:10.3390/molecules22101627
Received: 12 September 2017 / Revised: 23 September 2017 / Accepted: 27 September 2017 / Published: 29 September 2017
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Abstract
Glycyrrhizae radix et rhizoma has been used as a traditional Chinese medicine for the treatment of various diseases. Triterpenoids and flavonoids from the plant have many beneficial effects and their chemical structures are modified in the gastrointestinal tract after oral administration. However, absorption
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Glycyrrhizae radix et rhizoma has been used as a traditional Chinese medicine for the treatment of various diseases. Triterpenoids and flavonoids from the plant have many beneficial effects and their chemical structures are modified in the gastrointestinal tract after oral administration. However, absorption of these triterpenoids and flavonoids still needs to be defined. Here, the uptake and transepithelial transport of the selected major triterpenoids, glycyrrhizin (1), glycyrrhetic acid-3-O-mono-β-d-glucuronide (2), and glycyrrhetinic acid (3); and the selected major flavonoids, licochalcone A (4), licochalcone B (5), licochalcone C (6), echinatin (7), isoliquiritin apioside (8), liquiritigenin (9), liquiritin apioside (10) isolated from Glycyrrhizae radix et rhizoma, were investigated in the human intestinal epithelium-like Caco-2 cell monolayer model. Compounds 3, 57, and 9 were designated as well-absorbed compounds, 2 and 4 were designated as moderately absorbed ones, and 1, 8, and 10 were assigned for the poorly absorbed ones. The absorption mechanism of well and moderately absorbed compound was mainly passive diffusion to pass through the human intestinal Caco-2 cell monolayer. These findings provided useful information for predicting their oral bioavailability and the clinical application. Full article
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Open AccessArticle Diuretic Activity of Compatible Triterpene Components of Alismatis rhizoma
Molecules 2017, 22(9), 1459; doi:10.3390/molecules22091459
Received: 15 August 2017 / Revised: 31 August 2017 / Accepted: 31 August 2017 / Published: 6 September 2017
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Abstract
Alismatis rhizoma (AR), the dried rhizoma of Alisma orientale Juzepzuk (Alismataceae), is a traditional Chinese medicine. AR is an important part of many prescriptions and is commonly used as a diuretic agent in Asia. This study aimed to evaluate the diuretic effects of
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Alismatis rhizoma (AR), the dried rhizoma of Alisma orientale Juzepzuk (Alismataceae), is a traditional Chinese medicine. AR is an important part of many prescriptions and is commonly used as a diuretic agent in Asia. This study aimed to evaluate the diuretic effects of total triterpene extract (TTE) and triterpene component compatibility (TCC, the mixture of alisol B 23-acetate, alisol B, alisol A 24-acetate, alisol A, and alisol C 23-acetate) of AR in saline-loaded rats. The optimal diuretic TCC of AR was optimized using a uniform design. Different doses (5, 20, and 40 mg/kg) of TTE and TCC groups (N1–N8) were orally administered to rats. Urinary excretion rate, pH, and electrolyte excretion were measured in the urine of saline-loaded rats. Results showed that TTE doses increased urine volume and electrolyte excretion compared with the control group. All uniformly designed groups of TCC also increased urine excretion. In addition, optimal diuretic TCC was calculated (alisol B 23-acetate: alisol B: alisol A 24-acetate: alisol A: alisol C 23-acetate 7.2:0.6:2.8:3.0:6.4) and further validated by saline-loaded rats. This study demonstrated that TTE presented a notable diuretic effect by increasing Na+, K+, and Cl displacements. The most suitable TTC compatible proportion of alisol B 23-acetate: alisol B: alisol A 24-acetate: alisol A: alisol C 23-acetate for diuretic activity was validated, and triterpenes were the material basis for the diuretic activity of AR. Full article
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Open AccessArticle Identification of a Quality Marker (Q-Marker) of Danhong Injection by the Zebrafish Thrombosis Model
Molecules 2017, 22(9), 1443; doi:10.3390/molecules22091443
Received: 1 August 2017 / Revised: 24 August 2017 / Accepted: 25 August 2017 / Published: 31 August 2017
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Abstract
Quality-marker (Q-marker) is an emerging concept to ensure the quality and batch-to-batch consistency of Chinese medicine (CM). However, significant difficulties remain in the identification of Q-markers due to the unclear relationship between complex chemical compositions and the pharmacological efficacy of CM. In the
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Quality-marker (Q-marker) is an emerging concept to ensure the quality and batch-to-batch consistency of Chinese medicine (CM). However, significant difficulties remain in the identification of Q-markers due to the unclear relationship between complex chemical compositions and the pharmacological efficacy of CM. In the present study, we proposed a novel strategy to identify the potential Q-marker of danhong injection (DHI) by an in vivo zebrafish thrombosis model. The anti-thrombotic effects of DHI and its major constituents were evaluated by the zebrafish model of arachidonic acid (AA)-induced thrombosis. The results indicated that DHI can attenuate tail venous thrombus and recover the decrease of heart red blood cell (RBC) intensity in a dose-dependent manner. The result that DHI prevented the formulation of thrombosis in zebrafish was also validated in the zebrafish thrombosis model with green fluorescence protein (GFP)-labeled hemoglobin. The major components of DHI, namely danshen (DS) and honghua (HH), as well as the major chemical constituents of DHI, also exerted anti-thrombotic effects, among which rosmarinic acid (RA) and p-coumaric acid (pCA) showed moderate anti-thrombotic effects. This is the first time that pCA from HH has been found as an active compound exerting an anti-thrombotic effect in a dose-dependent manner, whose IC50 value is approximately 147 μg/mL. By analyzing 10 batches of normal DHI samples and five abnormal samples by high-performance liquid chromatography (HPLC), we found the contents of pCA and RA can be positively correlated to the anti-thrombotic effect of DHI, suggesting that pCA and RA could be potential Q-markers of DHI to ensure batch-to-batch consistency. Our findings illustrated that discovering major active compounds from CM by in vivo pharmacological models can be a useful approach to identifying Q-markers of CM, and in vivo pharmacological models can be a potential tool to evaluate batch-to-batch consistency of CMs. Full article
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Open AccessArticle Alkaloid Constituents of the Amaryllidaceae Plant Amaryllis belladonna L
Molecules 2017, 22(9), 1437; doi:10.3390/molecules22091437
Received: 19 July 2017 / Accepted: 26 August 2017 / Published: 31 August 2017
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Abstract
The plant family Amaryllidaceae is well-known for its unique alkaloid constituents, which exhibit a wide range of biological activities. Its representative, Amaryllis belladonna, has a geographical distribution covering mainly southern Africa, where it has significant usage in the traditional medicine of the
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The plant family Amaryllidaceae is well-known for its unique alkaloid constituents, which exhibit a wide range of biological activities. Its representative, Amaryllis belladonna, has a geographical distribution covering mainly southern Africa, where it has significant usage in the traditional medicine of the native people. In this study, A. belladonna samples collected in Brazil were examined for alkaloid content. Alkaloid profiles of A. belladonna bulbs were generated by a combination of chromatographic, spectroscopic and spectrometric methods, including GC–MS and 2D NMR. In vitro screening against four different parasitic protozoa (Trypanosoma cruzi, T. brucei rhodesiense, Leishmania donovani and Plasmodium falciparum) was carried out using the A. belladonna crude methanol extract, as well as three of its alkaloid isolates. Twenty-six different Amaryllidaceae alkaloids were identified in the A. belladonna bulb samples, and three of them were isolated. Evidence for their respective biosynthetic pathways was afforded via their mass-spectral fragmentation data. Improved data for 1-O-acetylcaranine was provided by 2D NMR experiments, together with new 1H-NMR data for buphanamine. The crude extract and 3-O-acetylhamayne exhibited good antiprotozoal activity in vitro, although both with a high cytotoxic index. Full article
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Open AccessArticle Anti-Anxiety Effect of (−)-Syringaresnol-4-O-β-d-apiofuranosyl-(1→2)-β-d-glucopyranoside from Albizzia julibrissin Durazz (Leguminosae)
Molecules 2017, 22(8), 1331; doi:10.3390/molecules22081331
Received: 4 July 2017 / Revised: 4 August 2017 / Accepted: 10 August 2017 / Published: 11 August 2017
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Abstract
Albizzia julibrissin Durazz, a Chinese Medicine, is commonly used for its anti-anxiety effects. (−)-syringaresnol-4-O-β-d-apiofuranosyl-(1→2)-β-d-glucopyranoside (SAG) is the main ingredient of Albizzia julibrissin Durazz. The present study investigated the anxiolytic effect and potential mechanisms on the HPA axis
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Albizzia julibrissin Durazz, a Chinese Medicine, is commonly used for its anti-anxiety effects. (−)-syringaresnol-4-O-β-d-apiofuranosyl-(1→2)-β-d-glucopyranoside (SAG) is the main ingredient of Albizzia julibrissin Durazz. The present study investigated the anxiolytic effect and potential mechanisms on the HPA axis and monoaminergic systems of SAG on acute restraint-stressed rats. The anxiolytic effect of SAG was examined through an open field test and an elevated plus maze test. The concentration of CRF, ACTH, and CORT in plasma was examined by an enzyme-linked immune sorbent assay (ELISA) kit while neurotransmitters in the cerebral cortex and hippocampus of the brain were examined by High Performance Liquid Chromatography (HPLC). We show that repeated treatment with SAG (3.6 mg/kg, p.o.) significantly increased the number and time spent on the central entries in the open-field test when compared to the vehicle/stressed group. In the elevated plus maze test, 3.6 mg/kg SAG could increase the percentage of entries into and time spent on the open arms of the elevated plus maze. In addition, the concentration of CRF, ACTH, and CORT in plasma and neurotransmitters (NE, 5-HT, DA and their metabolites 5-HIAA, DOPAC, and HVA) in the cerebral cortex and hippocampus of the brain were decreased after SAG treatment, as compared to the repeated acute restraint-stressed rats. These results suggest that SAG is a potential anti-anxiety drug candidate. Full article
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Open AccessArticle Time- and NADPH-Dependent Inhibition on CYP3A by Gomisin A and the Pharmacokinetic Interactions between Gomisin A and Cyclophosphamide in Rats
Molecules 2017, 22(8), 1298; doi:10.3390/molecules22081298
Received: 4 July 2017 / Accepted: 3 August 2017 / Published: 8 August 2017
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Abstract
The traditional Chinese medicine Schisandra chinensis has remarkable protective effects against chemical-induced toxicity. Cyclophosphamide (CTX), in spite advances in chemotherapy and immunosuppressive regimes, is prone to cause severe toxicity due to its chloroacetaldehyde (CAA) metabolite produced by CYP3A. Our previous study identified that
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The traditional Chinese medicine Schisandra chinensis has remarkable protective effects against chemical-induced toxicity. Cyclophosphamide (CTX), in spite advances in chemotherapy and immunosuppressive regimes, is prone to cause severe toxicity due to its chloroacetaldehyde (CAA) metabolite produced by CYP3A. Our previous study identified that S. chinensis extract (SCE) co-administration potently decreased CAA production and attenuated liver, kidney and brain injuries in CTX-treated rats. Gomisin A (Gom A) is proved to be one of the most abundant bioactive lignans in S. chinensis with a significant CYP3A inhibitory effect. To find out whether and how Gom A participated in the chemoprevention of SCE against CTX toxicity, the Gom A-caused CYP3A inhibition in vitro as well as the pharmacokinetic interactions between Gom A and CTX in vivo were examined in this study. Using human liver microsomes, a reversible inhibition assay revealed that Gom A was a competitive inhibitor with a KI value of 1.10 µM, and the time- and NADPH-dependent CYP3A inhibition of Gom A was observed in a time-dependent inhibition assay (KI = 0.35 µM, kinact = 1.96 min−1). Hepatic CYP3A mRNA expression experienced a significant increase in our rat model with Gom A administration. This explained why CAA production decreased in the 0.5 h- and 6 h-pretreatment rat groups while it increased in the 24 h- and 72 h-pretreatment groups, indicating a bidirectional effect of Gom A on CYP3A-mediated CTX metabolism. The present study suggested that Gom A participates like SCE in the pharmacokinetic intervention of CTX by blocking CYP3A-mediated metabolism and reducing CAA production, and thus plays an important role in the chemopreventive activity of S. chinensis against CTX toxicity, in addition to the previously recognized protective effects. Also, the combined use of S. chinensis preparation or other drugs containing Gom A as the main component with CTX needed to be addressed for better clinical intervention. Full article
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Open AccessArticle A Novel and Practical Chromatographic “Fingerprint-ROC-SVM” Strategy Applied to Quality Analysis of Traditional Chinese Medicine Injections: Using KuDieZi Injection as a Case Study
Molecules 2017, 22(7), 1237; doi:10.3390/molecules22071237
Received: 9 July 2017 / Revised: 21 July 2017 / Accepted: 22 July 2017 / Published: 23 July 2017
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Abstract
Fingerprinting is widely and commonly used in the quality control of traditional Chinese medicine (TCM) injections. However, current studies informed that the fingerprint similarity evaluation was less sensitive and easily generated false positive results. For this reason, a novel and practical chromatographic “Fingerprint-ROC-SVM”
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Fingerprinting is widely and commonly used in the quality control of traditional Chinese medicine (TCM) injections. However, current studies informed that the fingerprint similarity evaluation was less sensitive and easily generated false positive results. For this reason, a novel and practical chromatographic “Fingerprint-ROC-SVM” strategy was established by using KuDieZi (KDZ) injection as a case study in the present article. Firstly, the chromatographic fingerprints of KDZ injection were obtained by UPLC and the common characteristic peaks were identified with UPLC/Q-TOF-MS under the same chromatographic conditions. Then, the receiver operating characteristic (ROC) curve was used to optimize common characteristic peaks by the AUCs value greater than 0.7. Finally, a support vector machine (SVM) model, with the accuracy of 97.06%, was established by the optimized characteristic peaks and applied to monitor the quality of KDZ injection. As a result, the established model could sensitively and accurately distinguish the qualified products (QPs) with the unqualified products (UPs), high-temperature processed samples (HTPs) and high-illumination processed samples (HIPs) of KDZ injection, and the prediction accuracy was 100.00%, 93.75% and 100.00%, respectively. Furthermore, through the comparison with other chemometrics methods, the superiority of the novel analytical strategy was more prominent. It indicated that the novel and practical chromatographic “Fingerprint-ROC-SVM” strategy could be further applied to facilitate the development of the quality analysis of TCM injections. Full article
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Open AccessArticle Spectrum Effect Relationship and Component Knock-Out in Angelica Dahurica Radix by High Performance Liquid Chromatography-Q Exactive Hybrid Quadrupole-Orbitrap Mass Spectrometer
Molecules 2017, 22(7), 1231; doi:10.3390/molecules22071231
Received: 2 July 2017 / Revised: 18 July 2017 / Accepted: 19 July 2017 / Published: 21 July 2017
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Abstract
Different extracts of Angelica dahuricae were available for whitening or treating vitiligo clinically. They showed inhibitory or activating effects on tyrosinase, a rate-limiting enzyme of melanogenesis. This study aimed to identify active compounds on tyrosinase in water extract of Angelica dahurica Radix. We
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Different extracts of Angelica dahuricae were available for whitening or treating vitiligo clinically. They showed inhibitory or activating effects on tyrosinase, a rate-limiting enzyme of melanogenesis. This study aimed to identify active compounds on tyrosinase in water extract of Angelica dahurica Radix. We applied spectrum-effect relationship and component knock-out methods to make it clear. HPLC was used to obtain the specific chromatograms. The effects on tyrosinase activity were examined by measuring the oxidation rate of levodopa in vitro. Partial least squares method was used to examine the spectrum-effect relationships. The knocked-out samples were prepared by HPLC method, and the identification of knocked-out compounds was conducted by the high performance liquid chromatography-four stage rod-electrostatic field orbit trap high resolution mass spectrometry. Results showed that S6, S14, S18, S21, S35, S36, S37, S40, and S41 were positively correlated to inhibitory activity of Angelica dahuricae on tyrosinase whereas S9, S11, S8, S12, S22, and S30 were negatively correlated. When the concentration of each sample was 1 g·mL−1, equal to the amount of raw medicinal herbs, oxypeucedanin hydrate, imperatorin, cnidilin, and isoimperatorin had inhibitory effects on tyrosinase activity whereas byakangelicin and bergapten had activating effects. Full article
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Open AccessArticle Evaluation of the Cardiotoxicity of Evodiamine In Vitro and In Vivo
Molecules 2017, 22(6), 943; doi:10.3390/molecules22060943
Received: 19 May 2017 / Revised: 1 June 2017 / Accepted: 2 June 2017 / Published: 9 June 2017
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Abstract
Evodiamine is a bioactive alkaloid that is specified as a biomarker for the quality assessment of Evodia rutaecarpa (E. rutaecarpa) and for traditional Chinese medicines containing this plant. We previously reported that quantitative structure–activity modeling indicated that evodiamine may cause cardiotoxicity.
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Evodiamine is a bioactive alkaloid that is specified as a biomarker for the quality assessment of Evodia rutaecarpa (E. rutaecarpa) and for traditional Chinese medicines containing this plant. We previously reported that quantitative structure–activity modeling indicated that evodiamine may cause cardiotoxicity. However, previous investigations have indicated that evodiamine has beneficial effects in patients with cardiovascular diseases and there are no previous in vitro or in vivo reports of evodiamine-induced cardiotoxicity. The present study investigated the effects of evodiamine on primary cultured neonatal rat cardiomyocytes in vitro, and on zebrafish in vivo. Cell viability was reduced in vitro, where evodiamine had a 24 h 50% inhibitory concentration of 28.44 µg/mL. Cells exposed to evodiamine also showed increased lactate dehydrogenase release and maleic dialdehyde levels, and reduced superoxide dismutase activity. In vivo, evodiamine had a 10% lethal concentration of 354 ng/mL and induced cardiac malfunction, as evidenced by changes in heart rate and circulation, and pericardial malformations. This study indicated that evodiamine could cause cardiovascular side effects involving oxidative stress. These findings suggest that cardiac function should be monitored in patients receiving preparations containing evodiamine. Full article
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Open AccessArticle A UPLC-MS/MS Method for Simultaneous Determination of Free and Total Forms of a Phenolic Acid and Two Flavonoids in Rat Plasma and Its Application to Comparative Pharmacokinetic Studies of Polygonum capitatum Extract in Rats
Molecules 2017, 22(3), 353; doi:10.3390/molecules22030353
Received: 1 February 2017 / Revised: 22 February 2017 / Accepted: 23 February 2017 / Published: 25 February 2017
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Abstract
The principal active constituents of Polygonum capitatum are phenolic acids and flavonoids, such as gallic acid, quercitrin, and quercetin. The aim of this study was to develop and validate a method to determine the three constituents and the corresponding conjugated metabolites of Polygonum
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The principal active constituents of Polygonum capitatum are phenolic acids and flavonoids, such as gallic acid, quercitrin, and quercetin. The aim of this study was to develop and validate a method to determine the three constituents and the corresponding conjugated metabolites of Polygonum capitatum in vivo and to conduct pharmacokinetic studies on the herb, a well-known Miao medicinal plant in China. Gallic acid, quercitrin, and quercetin were analysed by ultra-performance liquid chromatography-electrospray ionization-tandem mass spectrometry (UPLC-ESI-MS/MS). Protein precipitation in plasma samples was performed using methanol. For the determination of total forms of analytes, an additional process of hydrolysis was conducted using β-glucuronidase and sulphatase. The analytes were separated on a BEH C18 column (50 mm × 2.1 mm; i.d., 1.7 μm) and quantified by multiple reaction monitoring (MRM) mode. The linear regression showed high linearity over a 729-fold dynamic range for the three analytes. The relative standard deviations of intra- and inter-day measurements were less than 9.5%, and the method was accurate to within −11.1% to 12.5%. The extraction recoveries for gallic acid, quercitrin, and quercetin were 94.3%–98.8%, 88.9%–98.8%, and 95.7%–98.5%, respectively. All samples were stable under short- and long-term storage conditions. The validated method was successfully applied to a comparative pharmacokinetic study of gallic acid, quercitrin, and quercetin in their free and total forms in rat plasma. The study revealed significantly higher exposure of the constituents in total forms for gallic acid and quercetin, while quercitrin was detected mainly in its corresponding free form in vivo. The established method was rapid and sensitive for the simultaneous quantification of free and total forms of multiple constituents of Polygonum capitatum extract in plasma. Full article
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Open AccessArticle Comprehensive Quantitative Analysis of 32 Chemical Ingredients of a Chinese Patented Drug Sanhuang Tablet
Molecules 2017, 22(1), 111; doi:10.3390/molecules22010111
Received: 14 November 2016 / Revised: 24 December 2016 / Accepted: 5 January 2017 / Published: 12 January 2017
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Abstract
Sanhuang Tablet (SHT) is a Chinese patented drug commonly used for the treatment of inflammations of the respiratory tract, gastrointestinal tract, and skin. It contains a special medicinal composition including the single compound berberine hydrochloride, extracts of Scutellariae Radix and Rhei Radix et
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Sanhuang Tablet (SHT) is a Chinese patented drug commonly used for the treatment of inflammations of the respiratory tract, gastrointestinal tract, and skin. It contains a special medicinal composition including the single compound berberine hydrochloride, extracts of Scutellariae Radix and Rhei Radix et Rhizoma, as well as the powder of Rhei Radix et Rhizoma. Despite advances in analytical techniques, quantitative evaluation of a Chinese patented drug like SHT remains a challenge due to the complexity of its chemical profile. In this study, ultra-high performance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry (UHPLC-Q-TOF-MS) was used to simultaneously quantify 29 non-sugar small molecule components of SHT (11 flavonoids, two isoflavonoids, one flavanone, five anthraquinones, two dianthranones, five alkaloids, two organic acids and one stilbene). Three major saccharide components, namely fructose, glucose, and sucrose, were also quantitatively determined using high performance liquid chromatography-charged aerosol detector (HPLC-CAD) on an Asahipak NH2P-50 4E amino column. The established methods were validated in terms of linearity, sensitivity, precision, accuracy, and stability, and then successfully applied to analyze 27 batches of commercial SHT products. A total of up to 57.61% (w/w) of SHT could be quantified, in which the contents of the determined non-saccharide small molecules varied from 5.91% to 16.83% (w/w) and three saccharides accounted for 4.41% to 48.05% (w/w). The results showed that the quality of the commercial products was inconsistent, and only four of those met Chinese Pharmacopoeia criteria. Full article
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Open AccessArticle Radix isatidis Polysaccharides Inhibit Influenza a Virus and Influenza A Virus-Induced Inflammation via Suppression of Host TLR3 Signaling In Vitro
Molecules 2017, 22(1), 116; doi:10.3390/molecules22010116
Received: 28 November 2016 / Revised: 8 January 2017 / Accepted: 9 January 2017 / Published: 11 January 2017
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Abstract
Influenza remains one of the major epidemic diseases worldwide, and rapid virus replication and collateral lung tissue damage caused by excessive pro-inflammatory host immune cell responses lead to high mortality rates. Thus, novel therapeutic agents that control influenza A virus (IAV) propagation and
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Influenza remains one of the major epidemic diseases worldwide, and rapid virus replication and collateral lung tissue damage caused by excessive pro-inflammatory host immune cell responses lead to high mortality rates. Thus, novel therapeutic agents that control influenza A virus (IAV) propagation and attenuate excessive pro-inflammatory responses are needed. Polysaccharide extract from Radix isatidis, a traditional Chinese herbal medicine, exerted potent anti-IAV activity against human seasonal influenza viruses (H1N1 and H3N2) and avian influenza viruses (H6N2 and H9N2) in vitro. The polysaccharides also significantly reduced the expression of pro-inflammatory cytokines (IL-6) and chemokines (IP-10, MIG, and CCL-5) stimulated by A/PR/8/34 (H1N1) at a range of doses (7.5 mg/mL, 15 mg/mL, and 30 mg/mL); however, they were only effective against progeny virus at a high dose. Similar activity was detected against inflammation induced by avian influenza virus H9N2. The polysaccharides strongly inhibited the protein expression of TLR-3 induced by PR8, suggesting that they impair the upregulation of pro-inflammatory factors induced by IAV by inhibiting activation of the TLR-3 signaling pathway. The polysaccharide extract from Radix isatidis root therefore has the potential to be used as an adjunct to antiviral therapy for the treatment of IAV infection. Full article
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2016

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Open AccessReview A Review of the Botany, Phytochemistry, Pharmacology and Toxicology of Rubiae Radix et Rhizoma
Molecules 2016, 21(12), 1747; doi:10.3390/molecules21121747
Received: 22 October 2016 / Revised: 2 December 2016 / Accepted: 15 December 2016 / Published: 20 December 2016
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Abstract
Rubia cordifolia Linn (Rubiaceae) is a climbing perennial herbal plant, which is widely distributed in China and India. Its root and rhizome, Rubiae Radix et Rhizoma (called Qiancao in China and Indian madder in India), is a well known phytomedicine used for hematemesis,
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Rubia cordifolia Linn (Rubiaceae) is a climbing perennial herbal plant, which is widely distributed in China and India. Its root and rhizome, Rubiae Radix et Rhizoma (called Qiancao in China and Indian madder in India), is a well known phytomedicine used for hematemesis, epistaxis, flooding, spotting, traumatic bleeding, amenorrhea caused by obstruction, joint impediment pain, swelling and pain caused by injuries from falls. In addition, it is a kind of pigment utilized as a food additive and a dye for wool or fiber. This review mainly concentrates on studies of the botany, phytochemistry, pharmacology and toxicology of this Traditional Chinese Medicine. The phytochemical evidences indicated that over a hundred chemical components have been found and isolated from the medicine, such as anthraquinones, naphthoquinones, triterpenoids, cyclic hexapeptides and others. These components are considered responsible for the various bioactivities of the herbal drug, including anti-oxidation, anti-inflammation, immunomodulation, antitumor, effects on coagulation-fibrinolysis system, neuroprotection and other effects. Additionally, based on these existing results, we also propose some interesting future research directions. Consequently, this review should help us to more comprehensively understand and to more fully utilize the herbal medicine Rubiae Radix et Rhizoma. Full article
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Open AccessArticle Using Light Microscopy and Liquid Chromatography Tandem Mass Spectrometry for Qualitative and Quantitative Control of a Combined Three-Herb Formulation in Different Preparations
Molecules 2016, 21(12), 1673; doi:10.3390/molecules21121673
Received: 10 November 2016 / Revised: 1 December 2016 / Accepted: 1 December 2016 / Published: 6 December 2016
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Abstract
Artemisia capillaries Thunb, Gardenia jasminoides Ellis, and Rheum officinale Baill have been combined to treat jaundice for thousands of years. Studies have revealed that these herbs induce anti-hepatic fibrosis and anti-hepatic apoptosis and alleviate hepatic oxidative stress. This study aims to determine the
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Artemisia capillaries Thunb, Gardenia jasminoides Ellis, and Rheum officinale Baill have been combined to treat jaundice for thousands of years. Studies have revealed that these herbs induce anti-hepatic fibrosis and anti-hepatic apoptosis and alleviate hepatic oxidative stress. This study aims to determine the quality and quantity of an herbal formulation (Chinese name: Yin-Chen-Hao-Tang) using physical and chemical examinations. Physical examination of Yin-Chen-Hao-Tang in pharmaceutical herbal products, raw fiber powders, and decoction preparations was performed using Congo red and iodine-potassium staining. A sensitive and validated method employing ultra-high-performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) was developed to simultaneously quantify the bioactive compounds scoparone, geniposide, and rhein in the Yin-Chen-Hao-Tang formulation in different preparations. Physical examination indicated that cellulose fibers with irregular round shapes were present in the pharmaceutical herbal products. The developed UHPLC-MS/MS method showed good linearity and was well validated. The quantification results revealed that the decoction preparations had the highest amounts of geniposide and rhein. Scoparone appeared in pharmaceutical herbal products from two manufacturers. This experiment provides a qualitative and quantitative method using physical and chemical examinations to test different preparations of herbal products. The results provide a reference for clinical herbal product preparations and further pharmacokinetic research. Full article
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Open AccessArticle Evaluation and Comparison of the Inhibition Effect of Astragaloside IV and Aglycone Cycloastragenol on Various UDP-Glucuronosyltransferase (UGT) Isoforms
Molecules 2016, 21(12), 1616; doi:10.3390/molecules21121616
Received: 8 October 2016 / Revised: 8 November 2016 / Accepted: 22 November 2016 / Published: 29 November 2016
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Abstract
As one of the main active ingredients from Radix Astragali (RA), orally dosed astragaloside IV (AST) is easily transformed to sapogenin-cycloastragenol (CAG) by deglycosylation in the gastrointestinal tract. Because the potential adverse effects of AST and CAG remain unclear, the present study in
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As one of the main active ingredients from Radix Astragali (RA), orally dosed astragaloside IV (AST) is easily transformed to sapogenin-cycloastragenol (CAG) by deglycosylation in the gastrointestinal tract. Because the potential adverse effects of AST and CAG remain unclear, the present study in this article was carried out to investigate the inhibition effects of AST and CAG on UDP-glucuronosyltransferases (UGTs) to explore potential clinical toxicity. An in vitro UGTs incubation mixture was employed to study the inhibition of AST and CAG towards UGT isoforms. Concentrations of 100 μM for each compound were used to initially screen the inhibitory efficiency. Deglycosylation of AST to CAG could strongly increase the inhibitory effects towards almost all of the tested UGT isoforms, with an IC50 of 0.84 μM and 11.28 μM for UGT1A8 and UGT2B7, respectively. Ulteriorly, the inhibition type and kinetics of CAG towards UGT1A8 and UGT2B7 were evaluated depending on the initial screening results. Data fitting using Dixon and Lineweaver–Burk plots demonstrated that CAG competitively inhibited UGT1A8 and noncompetitively inhibited UGT2B7. From the second plot drawn with the slopes from the Lineweaver–Burk plot versus the concentrations of CAG, the inhibition constant (Ki) was calculated to be 0.034 μM and 20.98 μM for the inhibition of UGT1A8 and UGT2B7, respectively. Based on the [I]/Ki standard ([I]/Ki < 0.1, low possibility; 1 > [I]/Ki > 0.1, medium possibility; [I]/Ki > 1, high possibility), it was successfully predicted here that an in vivo herb–drug interaction between AST/CAG and drugs mainly undergoing UGT1A8- or UGT2B7-catalyzed metabolism might occur when the plasma concentration of CAG is above 0.034 μM and 20.98 μM, respectively. Full article
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Open AccessArticle Piper sarmentosum Effects on 11β-Hydroxysteroid Dehydrogenase Type 1 Enzyme in Serum and Bone in Rat Model of Glucocorticoid-Induced Osteoporosis
Molecules 2016, 21(11), 1523; doi:10.3390/molecules21111523
Received: 29 August 2016 / Revised: 4 November 2016 / Accepted: 9 November 2016 / Published: 15 November 2016
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Abstract
Glucocorticoid-induced osteoporosis is one of the common causes of secondary osteoporosis. Piper sarmentosum (Ps) extract possesses antioxidant and anti-inflammatory activities. In this study, we determined the correlation between the effects of Ps leaf water extract with the regulation of 11β-hydroxysteroid dehydrogenase
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Glucocorticoid-induced osteoporosis is one of the common causes of secondary osteoporosis. Piper sarmentosum (Ps) extract possesses antioxidant and anti-inflammatory activities. In this study, we determined the correlation between the effects of Ps leaf water extract with the regulation of 11β-hydroxysteroid dehydrogenase (HSD) type 1 enzyme activity in serum and bone of glucocorticoid-induced osteoporotic rats. Twenty-four Sprague-Dawley rats were grouped into following: G1: sham-operated group administered with intramuscular vehicle olive oil and vehicle normal saline orally; G2: adrenalectomized (adrx) control group given intramuscular dexamethasone (120 μg/kg/day) and vehicle normal saline orally; G3: adrx group given intramuscular dexamethasone (120 μg/kg/day) and water extract of Piper sarmentosum (125 mg/kg/day) orally. After two months, the femur and serum were taken for ELISA analysis. Results showed that Ps leaf water extract significantly reduced the femur corticosterone concentration (p < 0.05). This suggests that Ps leaf water extract was able to prevent bone loss due to long-term glucocorticoid therapy by acting locally on the bone cells by increasing the dehydrogenase action of 11β-HSD type 1. Thus, Ps may have the potential to be used as an alternative medicine against osteoporosis and osteoporotic fracture in patients on long-term glucocorticoid treatment. Full article
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Open AccessArticle A High Content Screening Assay to Identify Compounds with Anti-Epithelial-Mesenchymal Transition Effects from the Chinese Herbal Medicine Tong-Mai-Yang-Xin-Wan
Molecules 2016, 21(10), 1340; doi:10.3390/molecules21101340
Received: 17 August 2016 / Revised: 29 September 2016 / Accepted: 6 October 2016 / Published: 10 October 2016
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Abstract
Chronic kidney disease (CKD) is a worldwide health problem with growing prevalence in developing countries. Renal tubular epithelial-mesenchymal transition (EMT) is a critical step and key factor in the development of this condition. Renal tubulointerstitial fibrosis is a basic pathological change at the
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Chronic kidney disease (CKD) is a worldwide health problem with growing prevalence in developing countries. Renal tubular epithelial-mesenchymal transition (EMT) is a critical step and key factor in the development of this condition. Renal tubulointerstitial fibrosis is a basic pathological change at the later stages of the disease. Therefore, blocking the development of EMT could be a critical factor in curing CKD. We have established a cell-based high-content screening (HCS) method to identify inhibitors of EMT in human proximal tubular epithelial (HK-2) cells by automatic acquisition and processing of dual-fluorescent labeled images. With the aid of chromatographic separation and mass spectrometry, we achieved the rapid and reliable screening of active compounds from the Chinese herbal medicine Tong-Mai-Yang-Xin-Wan (TMYX) for treating EMT. Five fractions were found to exert anti-EMT activity and were further identified by liquid chromatography coupled with tandem mass spectrometry. Glycyrrhizic acid, glyasperin A, and licorisoflavan A were found to inhibit EMT. The proposed approach was successfully applied to screen active compounds from TMYX on TGF-β1-stimulated HK-2 cells and may offer a new means for identifying lead compounds for treating EMT from registered Chinese herbal medicines. Full article
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Open AccessArticle Effects of Sanguis Draconis on Perforator Flap Survival in Rats
Molecules 2016, 21(10), 1262; doi:10.3390/molecules21101262
Received: 20 July 2016 / Revised: 14 September 2016 / Accepted: 19 September 2016 / Published: 26 September 2016
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Abstract
Sanguis draconis, a resin known to improve blood circulation, relieve pain, stimulate tissue regeneration, and heal wounds, is widely used in clinical practice. In this study, we prepared an ethanol extract of sanguis draconis (EESD) containing 75.08 mg/g of dracorhodin. The experiment was
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Sanguis draconis, a resin known to improve blood circulation, relieve pain, stimulate tissue regeneration, and heal wounds, is widely used in clinical practice. In this study, we prepared an ethanol extract of sanguis draconis (EESD) containing 75.08 mg/g of dracorhodin. The experiment was carried out on 20 rats that were divided into two groups, a control group (n = 10) and an EESD group (n = 10). All the rats underwent a perforator flap surgery, after which post-operative abdominal compressions of EESD were given to the EESD group for seven days, while the control group received saline. Flap survival percentages were determined after seven days, and were found to be significantly higher in the EESD group than in the control group. Results of laser Doppler flowmetry (LDF) showed that perforator flaps in the EESD group had higher perfusion values than those of the control group. The flap tissues were stained with hematoxylin and eosin, followed by immunohistochemical evaluation. Superoxide dismutase (SOD) expression and micro-vessel development markedly increased in the EESD group, while malondialdehyde (MDA) levels decreased. This is the first study to investigate the effect of sanguis draconis on perforator flap survival. Our results demonstrate that sanguis draconis can improve perforator flap survival in rats by promoting microvessel regeneration and blood perfusion. Full article
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Open AccessArticle Effects of Dihydrophaseic Acid 3′-O-β-d-Glucopyranoside Isolated from Lycii radicis Cortex on Osteoblast Differentiation
Molecules 2016, 21(9), 1260; doi:10.3390/molecules21091260
Received: 14 August 2016 / Revised: 16 September 2016 / Accepted: 17 September 2016 / Published: 21 September 2016
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Abstract
Our previous study showed that ethanol extract of Lycii radicis cortex (LRC) prevented the loss of bone mineral density in ovariectomized mice by promoting the differentiation of osteoblast linage cells. Here, we performed fractionation and isolation of the bioactive compound(s) responsible for the
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Our previous study showed that ethanol extract of Lycii radicis cortex (LRC) prevented the loss of bone mineral density in ovariectomized mice by promoting the differentiation of osteoblast linage cells. Here, we performed fractionation and isolation of the bioactive compound(s) responsible for the bone formation–enhancing effect of LRC extract. A known sesquiterpene glucoside, (1′R,3′S,5′R,8′S,2Z,4E)-dihydrophaseic acid 3′-O-β-d-glucopyranoside (abbreviated as DPA3G), was isolated from LRC extract and identified as a candidate constituent. We investigated the effects of DPA3G on osteoblast and osteoclast differentiation, which play fundamental roles in bone formation and bone resorption, respectively, during bone remodeling. The DPA3G fraction treatment in mesenchymal stem cell line C3H10T1/2 and preosteoblast cell line MC3T3-E1 significantly enhanced cell proliferation and alkaline phosphatase activity in both cell lines compared to the untreated control cells. Furthermore, DPA3G significantly increased mineralized nodule formation and the mRNA expression of osteoblastogenesis markers, Alpl, Runx2, and Bglap, in MC3T3-E1 cells. The DPA3G treatment, however, did not influence osteoclast differentiation in primary-cultured monocytes of mouse bone marrow. Because osteoblastic and osteoclastic precursor cells coexist in vivo, we tested the DPA3G effects under the co-culture condition of MC3T3-E1 cells and monocytes. Remarkably, DPA3G enhanced not only osteoblast differentiation of MC3T3-El cells but also osteoclast differentiation of monocytes, indicating that DPA3G plays a role in the maintenance of the normal bone remodeling balance. Our results suggest that DPA3G may be a good candidate for the treatment of osteoporosis. Full article
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Open AccessArticle Effect of Phyllanthus amarus Extract on 5-Fluorouracil-Induced Perturbations in Ribonucleotide and Deoxyribonucleotide Pools in HepG2 Cell Line
Molecules 2016, 21(9), 1254; doi:10.3390/molecules21091254
Received: 16 August 2016 / Revised: 14 September 2016 / Accepted: 14 September 2016 / Published: 20 September 2016
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Abstract
The aim of this study was to investigate the antitumor activities of Phyllanthus amarus (PHA) and its potential of herb–drug interactions with 5-Fluorouracil (5-FU). Cell viability, ribonucleotides (RNs) and deoxyribonucleotides (dRNs) levels, cell cycle distribution, and expression of thymidylate synthase (TS) and ribonucleotide
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The aim of this study was to investigate the antitumor activities of Phyllanthus amarus (PHA) and its potential of herb–drug interactions with 5-Fluorouracil (5-FU). Cell viability, ribonucleotides (RNs) and deoxyribonucleotides (dRNs) levels, cell cycle distribution, and expression of thymidylate synthase (TS) and ribonucleotide reductase (RR) proteins were measured with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, high performance liquid chromatography tandem mass spectrometry (HPLC/MS/MS) method, flow cytometry and Western blot analysis, respectively. Our standardized PHA extract showed toxicity to HepG2 cells at high concentrations after 72 h exposure and induced G2/M cell cycle arrest. Combined use of 5-FU with PHA resulted in significant decreases in ATP, CTP, GTP, UTP and dTTP levels, while AMP, CMP, GMP and dUMP levels increased significantly compared with use of 5-FU alone. Further, PHA could increase the role of cell cycle arrest at S phase induced by 5-FU. Although PHA alone had no direct impact on TS and RR, PHA could change the levels of RNs and dRNs when combined with 5-FU. This may be due to cell cycle arrest or regulation of key enzyme steps in intracellular RNs and dRNs metabolism. Full article
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Open AccessArticle Chemical Composition, Antioxidant, and Antibacterial Activity of Wood Vinegar from Litchi chinensis
Molecules 2016, 21(9), 1150; doi:10.3390/molecules21091150
Received: 12 July 2016 / Revised: 16 August 2016 / Accepted: 24 August 2016 / Published: 30 August 2016
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Abstract
The antioxidant and antibacterial activities of wood vinegar from Litchi chinensis, and its components have been studied. The chemical compositions of wood vinegar were analyzed by gas chromatography-mass spectrometry (GC-MS). A total of 17 chemical compounds were identified, representing 83.96% of the
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The antioxidant and antibacterial activities of wood vinegar from Litchi chinensis, and its components have been studied. The chemical compositions of wood vinegar were analyzed by gas chromatography-mass spectrometry (GC-MS). A total of 17 chemical compounds were identified, representing 83.96% of the compositions in the wood vinegar. Three major components, included 2,6-dimethoxyphenol (syringol, 29.54%), 2-methoxyphenol (guaiacol, 12.36%), and 3,5-dimethoxy-4-hydroxytoluene (11.07%), were found in the wood vinegar. Antioxidant activities of the acids were investigated from the aspects of 1,1-Diphyl-2-picrylhydrazyl (DPPH) free radicals scavenging capacity, superoxide anion radical scavenging capacity, and reducing power. The pyroligneous acid exhibited high antioxidant activity which was comparable to the reference standards (vitamin C and butylated hydroxyl toluene) at the same dose with IC50 values of 36.5 ppm calculated by the DPPH radical scavenging assay, 38.38 g Trolox equivalent/100 g DW by the trolox equivalent antioxidant capacity (TEAC) assay, and 67.9 by the reducing power analysis. Antibacterial activity was evaluated using the disc diffusion and microdilution methods against a group of clinically antibiotic resistant isolates. The major components exhibited broad spectrum inhibition against all the bacterial strains with a range of disc inhibition zoon between 15–19 mm. The minimum inhibition concentration and minimum bactericide concentration against the test strains was ranging in 0.95–3.80 μL/100 μL and 1.90–3.80 μL/100 μL, respectively. Most of the antibiotic resistant strains were more susceptible to the wood vinegar than the non-antibiotic resistant strain except the strain of ornithine resistant Staphylococcus aureus. Based on the chemical profile, it was considered that the strongest antioxidant and antibacterial activity of Litchi chinensis wood vinegar was due to its highly phenolic compositions. This study revealed that the Litchi chinensis wood vinegar is valuable to develop as alternative food antioxidant and antibiotics. Full article
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Open AccessArticle Comprehensive Quantitative Analysis of SQ Injection Using Multiple Chromatographic Technologies
Molecules 2016, 21(8), 1092; doi:10.3390/molecules21081092
Received: 21 July 2016 / Revised: 11 August 2016 / Accepted: 15 August 2016 / Published: 19 August 2016
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Abstract
Quality control of Chinese medicine injections remains a challenge due to our poor knowledge of their complex chemical profile. This study aims to investigate the chemical composition of one of the best-selling injections, Shenqi Fuzheng (SQ) injection (SQI), via a full component quantitative
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Quality control of Chinese medicine injections remains a challenge due to our poor knowledge of their complex chemical profile. This study aims to investigate the chemical composition of one of the best-selling injections, Shenqi Fuzheng (SQ) injection (SQI), via a full component quantitative analysis. A total of 15 representative small molecular components of SQI were simultaneously determined using ultra-high performance liquid chromatography (UHPLC) coupled with quadrupole tandem time-of-flight mass spectrometry (Q-TOF-MS); saccharide composition of SQI was also quantitatively determined by high performance liquid chromatography (HPLC) with evaporative light scattering detector (ELSD) on an amino column before and after acid hydrolysis. The existence of polysaccharides was also examined on a gel permeation chromatography column. The method was well validated in terms of linearity, sensitivity, precision, accuracy and stability, and was successfully applied to analyze 13 SQI samples. The results demonstrate that up to 94.69% (w/w) of this injection product are quantitatively determined, in which small molecules and monosaccharide/sucrose account for 0.18%–0.21%, and 53.49%–58.2%, respectively. The quantitative information contributes to accumulating scientific evidence to better understand the therapy efficacy and safety of complex Chinese medicine injections. Full article
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Open AccessArticle Variations in Essential Oil Yield, Composition, and Antioxidant Activity of Different Plant Organs from Blumea balsamifera (L.) DC. at Different Growth Times
Molecules 2016, 21(8), 1024; doi:10.3390/molecules21081024
Received: 14 June 2016 / Revised: 28 July 2016 / Accepted: 1 August 2016 / Published: 5 August 2016
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Abstract
Blumea balsamifera, also named Ainaxiang, is widely used as an ancient medicinal herb in tropical and subtropical Asia. It is rich in essential oils. In this work the essential oils of B. balsamifera from different plant organs and in different months were
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Blumea balsamifera, also named Ainaxiang, is widely used as an ancient medicinal herb in tropical and subtropical Asia. It is rich in essential oils. In this work the essential oils of B. balsamifera from different plant organs and in different months were extracted, and then analyzed by gas chromatography-mass spectrometry. The results showed that essential oil yield of young leaves was the highest (0.65 mL/100 g), followed by mature leaves (0.57 mL/100 g), and the oil yield was higher in October (0.47 mL/100 g) than other months. A total of 44 compounds were identified, representing 92.64%–96.71% of the oil. Eighteen common chemical components were found among the six plant organs, representing >80% of the oil constituents. l-borneol was the main ingredient in leaves, and its content was the highest in senescent leaves and in December. In the essential oils of young shoots and young stems, the main component was dimethoxydurene. Antioxidant activity was also determined using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) and β-carotene bleaching (BCB) assays. The results indicated that the β-carotene bleaching activity was far stronger than the DPPH radical-scavenging capacity, and the young leaves and young shoots showed stronger antioxidant activity. Dimethoxydurene, β-caryophyllene, and α-caryophyllene play a positive role in good antioxidant activity, while β-eudesmol, phytol, and tetradecanal play a negative role. The antioxidant activity revealed in this study might help in developing this promising bioresource for use in the medicinal and cosmetic industries. Full article
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Open AccessArticle Siegesbeckia orientalis Extract Inhibits TGFβ1-Induced Migration and Invasion of Endometrial Cancer Cells
Molecules 2016, 21(8), 1021; doi:10.3390/molecules21081021
Received: 12 July 2016 / Revised: 1 August 2016 / Accepted: 3 August 2016 / Published: 5 August 2016
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Abstract
Type II endometrial carcinoma typically exhibits aggressive metastasis and results in a poor prognosis. Siegesbeckia orientalis Linne is a traditional Chinese medicinal herb with several medicinal benefits, including the cytotoxicity against various cancers. This study investigates the inhibitory effects of S. orientalis ethanol
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Type II endometrial carcinoma typically exhibits aggressive metastasis and results in a poor prognosis. Siegesbeckia orientalis Linne is a traditional Chinese medicinal herb with several medicinal benefits, including the cytotoxicity against various cancers. This study investigates the inhibitory effects of S. orientalis ethanol extract (SOE) on the migration and invasion of endometrial cancer cells, which were stimulated by transforming growth factor β (TGFβ). The inhibitory effects were evaluated by determining wound healing and performing the Boyden chamber assay. This study reveals that SOE can inhibit TGFβ1-induced cell wound healing, cell migration, and cell invasion in a dose-dependent manner in RL95-2 and HEC-1A endometrial cancer cells. SOE also reversed the TGFβ1-induced epithelial-mesenchymal transition, including the loss of the cell-cell junction and the lamellipodia-like structures. Western blot analysis revealed that SOE inhibited the phosphorylation of ERK1/2, JNK1/2, and Akt, as well as the expression of MMP-9, MMP-2, and u-PA in RL95-2 cells dose-dependently. The results of this investigation suggest that SOE is a potential anti-metastatic agent against human endometrial tumors. Full article
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Open AccessReview Precision or Personalized Medicine for Cancer Chemotherapy: Is there a Role for Herbal Medicine
Molecules 2016, 21(7), 889; doi:10.3390/molecules21070889
Received: 23 March 2016 / Revised: 26 June 2016 / Accepted: 1 July 2016 / Published: 7 July 2016
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Abstract
Although over 100 chemotherapeutic agents are currently available for the treatment of cancer patients, the overall long term clinical benefit is disappointing due to the lack of effectiveness or severe side effects from these agents. In order to improve the therapeutic outcome, a
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Although over 100 chemotherapeutic agents are currently available for the treatment of cancer patients, the overall long term clinical benefit is disappointing due to the lack of effectiveness or severe side effects from these agents. In order to improve the therapeutic outcome, a new approach called precision medicine or personalized medicine has been proposed and initiated by the U.S. National Institutes of Health. However, the limited availability of effective medications and the high cost are still the major barriers for many cancer patients. Thus alternative approaches such as herbal medicines could be a feasible and less costly option. Unfortunately, scientific evidence for the efficacy of a majority of herbal medicines is still lacking and their development to meet FDA approval or other regulatory agencies is a big challenge. However, herbal medicines may be able to play an important role in precision medicine or personalized medicine. This review will focus on the existing and future technologies that could speed the development of herbal products for treatment of resistant cancer in individual patients. Specifically, it will concentrate on reviewing the phenotypic (activity based) rather than genotypic (mechanism based) approach to develop herbal medicine useful for personalized cancer chemotherapy. Full article
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Open AccessReview The Hedyotis diffusa Willd. (Rubiaceae): A Review on Phytochemistry, Pharmacology, Quality Control and Pharmacokinetics
Molecules 2016, 21(6), 710; doi:10.3390/molecules21060710
Received: 26 April 2016 / Revised: 22 May 2016 / Accepted: 24 May 2016 / Published: 30 May 2016
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Abstract
Hedyotis diffusa Willd (H. diffusa) is a well-known Chinese medicine with a variety of activities, especially its anti-cancer effect in the clinic. Up to now, 171 compounds have been reported from H. diffusa, including 32 iridoids, 26 flavonoids, 24 anthraquinones,
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Hedyotis diffusa Willd (H. diffusa) is a well-known Chinese medicine with a variety of activities, especially its anti-cancer effect in the clinic. Up to now, 171 compounds have been reported from H. diffusa, including 32 iridoids, 26 flavonoids, 24 anthraquinones, 26 phenolics and their derivatives, 50 volatile oils and 13 miscellaneous compounds. In vitro and in vivo studies show these phytochemicals and plant extracts to exhibit a range of pharmacological activities of anti-cancer, antioxidant, anti-inflammatory, anti-fibroblast, immunomodulatory and neuroprotective effects. Although a series of methods have been established for the quality control of H. diffusa, a feasible and reliable approach is still needed in consideration of its botanical origin, collecting time and bioactive effects. Meanwhile, more pharmacokinetics researches are needed to illustrate the characteristics of H. diffusa in vivo. The present review aims to provide up-to-date and comprehensive information on the phytochemistry, pharmacology, quality control and pharmacokinetic characteristics of H. diffusa for its clinical use and further development. Full article
Open AccessArticle Purification, Characterization and Biological Activity of Polysaccharides from Dendrobium officinale
Molecules 2016, 21(6), 701; doi:10.3390/molecules21060701
Received: 22 March 2016 / Revised: 24 May 2016 / Accepted: 25 May 2016 / Published: 30 May 2016
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Abstract
Polysaccharide (DOPA) from the stem of D. officinale, as well as two fractions (DOPA-1 and DOPA-2) of it, were isolated and purified by DEAE cellulose-52 and Sephacryl S-300 chromatography, and their structural characteristics and bioactivities were investigated. The average molecular weights of
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Polysaccharide (DOPA) from the stem of D. officinale, as well as two fractions (DOPA-1 and DOPA-2) of it, were isolated and purified by DEAE cellulose-52 and Sephacryl S-300 chromatography, and their structural characteristics and bioactivities were investigated. The average molecular weights of DOPA-1 and DOPA-2 were 394 kDa and 362 kDa, respectively. They were mainly composed of d-mannose, d-glucose, and had a backbone consisting of 1,4-linked β-d-Manp and 1,4-linked β-d-Glcp with O-acetyl groups. Bioactivity studies indicated that both DOPA and its purified fractions (DOPA-1 and DOPA-2) could activate splenocytes and macrophages. The D. officinale polysaccharides had stimulatory effects on splenocytes, T-lymphocytes and B-lymphocytes, promoting the cell viability and NO production of RAW 264.7 macrophages. Furthermore, DOPA, DOPA-1 and DOPA-2 were found to protect RAW 264.7 macrophages against hydrogen peroxide (H2O2)-induced oxidative injury by promoting cell viability, suppressing apoptosis and ameliorating oxidative lesions. These results suggested that D. officinale polysaccharides possessed antioxidant activity and mild immunostimulatory activity. Full article
Open AccessReview The Traditional Medicine and Modern Medicine from Natural Products
Molecules 2016, 21(5), 559; doi:10.3390/molecules21050559
Received: 19 March 2016 / Revised: 24 April 2016 / Accepted: 25 April 2016 / Published: 29 April 2016
Cited by 26 | PDF Full-text (2929 KB) | HTML Full-text | XML Full-text
Abstract
Natural products and traditional medicines are of great importance. Such forms of medicine as traditional Chinese medicine, Ayurveda, Kampo, traditional Korean medicine, and Unani have been practiced in some areas of the world and have blossomed into orderly-regulated systems of medicine. This study
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Natural products and traditional medicines are of great importance. Such forms of medicine as traditional Chinese medicine, Ayurveda, Kampo, traditional Korean medicine, and Unani have been practiced in some areas of the world and have blossomed into orderly-regulated systems of medicine. This study aims to review the literature on the relationship among natural products, traditional medicines, and modern medicine, and to explore the possible concepts and methodologies from natural products and traditional medicines to further develop drug discovery. The unique characteristics of theory, application, current role or status, and modern research of eight kinds of traditional medicine systems are summarized in this study. Although only a tiny fraction of the existing plant species have been scientifically researched for bioactivities since 1805, when the first pharmacologically-active compound morphine was isolated from opium, natural products and traditional medicines have already made fruitful contributions for modern medicine. When used to develop new drugs, natural products and traditional medicines have their incomparable advantages, such as abundant clinical experiences, and their unique diversity of chemical structures and biological activities. Full article
Open AccessArticle Anti-Inflammatory Activities of Pentaherbs Formula, Berberine, Gallic Acid and Chlorogenic Acid in Atopic Dermatitis-Like Skin Inflammation
Molecules 2016, 21(4), 519; doi:10.3390/molecules21040519
Received: 28 December 2015 / Revised: 14 April 2016 / Accepted: 15 April 2016 / Published: 20 April 2016
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Abstract
Atopic dermatitis (AD) is a common allergic skin disease, characterized by dryness, itchiness, thickening and inflammation of the skin. Infiltration of eosinophils into the dermal layer and presence of edema are typical characteristics in the skin biopsy of AD patients. Previous in vitro
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Atopic dermatitis (AD) is a common allergic skin disease, characterized by dryness, itchiness, thickening and inflammation of the skin. Infiltration of eosinophils into the dermal layer and presence of edema are typical characteristics in the skin biopsy of AD patients. Previous in vitro and clinical studies showed that the Pentaherbs formula (PHF) consisting of five traditional Chinese herbal medicines, Flos Lonicerae, Herba Menthae, Cortex Phellodendri, Cortex Moutan and Rhizoma Atractylodis at w/w ratio of 2:1:2:2:2 exhibited therapeutic potential in treating AD. In this study, an in vivo murine model with oxazolone (OXA)-mediated dermatitis was used to elucidate the efficacy of PHF. Active ingredients of PHF water extract were also identified and quantified, and their in vitro anti-inflammatory activities on pruritogenic cytokine IL-31- and alarmin IL-33-activated human eosinophils and dermal fibroblasts were evaluated. Ear swelling, epidermis thickening and eosinophils infiltration in epidermal and dermal layers, and the release of serum IL-12 of the murine OXA-mediated dermatitis were significantly reduced upon oral or topical treatment with PHF (all p < 0.05). Gallic acid, chlorogenic acid and berberine contents (w/w) in PHF were found to be 0.479%, 1.201% and 0.022%, respectively. Gallic acid and chlorogenic acid could suppress the release of pro-inflammatory cytokine IL-6 and chemokine CCL7 and CXCL8, respectively, in IL-31- and IL-33-treated eosinophils-dermal fibroblasts co-culture; while berberine could suppress the release of IL-6, CXCL8, CCL2 and CCL7 in the eosinophil culture and eosinophils-dermal fibroblasts co-culture (all p < 0.05). These findings suggest that PHF can ameliorate allergic inflammation and attenuate the activation of eosinophils. Full article
Open AccessArticle Contact and Repellent Activities of the Essential Oil from Juniperus formosana against Two Stored Product Insects
Molecules 2016, 21(4), 504; doi:10.3390/molecules21040504
Received: 23 January 2016 / Revised: 8 April 2016 / Accepted: 12 April 2016 / Published: 16 April 2016
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Abstract
The chemical composition of the essential oil from Juniperus formosana leaves and its contact and repellent activities against Tribolium castaneum and Liposcelis bostrychophila adults were investigated. The essential oil of J. formosana leaves was obtained by hydrodistillation and analyzed by GC-MS. A total
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The chemical composition of the essential oil from Juniperus formosana leaves and its contact and repellent activities against Tribolium castaneum and Liposcelis bostrychophila adults were investigated. The essential oil of J. formosana leaves was obtained by hydrodistillation and analyzed by GC-MS. A total of 28 components were identified and the main compounds in the essential oil were α-pinene (21.66%), 4-terpineol (11.25%), limonene (11.00%) and β-phellandrene (6.63%). The constituents α-pinene, 4-terpineol and d-limonene were isolated from the essential oil. It was found that the essential oil exhibited contact activity against T. castaneum and L. bostrychophila adults (LD50 = 29.14 μg/adult and 81.50 µg/cm2, respectively). The compound 4-terpineol exhibited the strongest contact activity (LD50 = 7.65 μg/adult). In addition, data showed that at 78.63 nL/cm2, the essential oil and the three isolated compounds strongly repelled T. castaneum adults. The compounds α-pinene and d-limonene reached the same level (Class V) of repellency as DEET (p = 0.396 and 0.664) against L. bostrychophila at 63.17 nL/cm2 after 2 h treatment. The results indicate that the essential oil and the isolated compounds have potential to be developed into natural insecticides and repellents to control insects in stored products. Full article
Open AccessArticle Pharmacogenomics of Scopoletin in Tumor Cells
Molecules 2016, 21(4), 496; doi:10.3390/molecules21040496
Received: 10 February 2016 / Revised: 1 April 2016 / Accepted: 7 April 2016 / Published: 15 April 2016
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Abstract
Drug resistance and the severe side effects of chemotherapy necessitate the development of novel anticancer drugs. Natural products are a valuable source for drug development. Scopoletin is a coumarin compound, which can be found in several Artemisia species and other plant genera. Microarray-based
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Drug resistance and the severe side effects of chemotherapy necessitate the development of novel anticancer drugs. Natural products are a valuable source for drug development. Scopoletin is a coumarin compound, which can be found in several Artemisia species and other plant genera. Microarray-based RNA expression profiling of the NCI cell line panel showed that cellular response of scopoletin did not correlate to the expression of ATP-binding cassette (ABC) transporters as classical drug resistance mechanisms (ABCB1, ABCB5, ABCC1, ABCG2). This was also true for the expression of the oncogene EGFR and the mutational status of the tumor suppressor gene, TP53. However, mutations in the RAS oncogenes and the slow proliferative activity in terms of cell doubling times significantly correlated with scopoletin resistance. COMPARE and hierarchical cluster analyses of transcriptome-wide mRNA expression resulted in a set of 40 genes, which all harbored binding motifs in their promoter sequences for the transcription factor, NF-κB, which is known to be associated with drug resistance. RAS mutations, slow proliferative activity, and NF-κB may hamper its effectiveness. By in silico molecular docking studies, we found that scopoletin bound to NF-κB and its regulator IκB. Scopoletin activated NF-κB in a SEAP-driven NF-κB reporter cell line, indicating that NF-κB might be a resistance factor for scopoletin. In conclusion, scopoletin might serve as lead compound for drug development because of its favorable activity against tumor cells with ABC-transporter expression, although NF-κB activation may be considered as resistance factor for this compound. Further investigations are warranted to explore the full therapeutic potential of this natural product. Full article
Open AccessArticle Distinguishing Astragalus mongholicus and Its Planting Soil Samples from Different Regions by ICP-AES
Molecules 2016, 21(4), 482; doi:10.3390/molecules21040482
Received: 25 February 2016 / Revised: 1 April 2016 / Accepted: 7 April 2016 / Published: 12 April 2016
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Abstract
Daodi herb” enjoys a good reputation for its quality and clinical effects. As one of the most popular daodi herbs, Astragalus membranaceus (Fisch.) Bge var. mongholicus (Bge.) Hsiao (A. membranaceus) is popularly used for its anti-oxidant, anti-inflammatory and immune-enhancing properties.
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Daodi herb” enjoys a good reputation for its quality and clinical effects. As one of the most popular daodi herbs, Astragalus membranaceus (Fisch.) Bge var. mongholicus (Bge.) Hsiao (A. membranaceus) is popularly used for its anti-oxidant, anti-inflammatory and immune-enhancing properties. In this study, we used inductively coupled plasma atomic emission spectrometry (ICP-AES) technique to investigate the inorganic elements contents in A. mongholicu and its soil samples from daodi area (Shanxi) and non-daodi areas (Inner Mongolia and Gansu). A total of 21 inorganic elements (Pb, Cd, As, Hg, Cu, P, K, Zn, Mn, Ca, Mg, Fe, Se, B, Al, Na, Cr, Ni, Ba, Ti and Sr) were simultaneously determined. Principal component analysis (PCA) was performed to differentiate A. mongholicu and soil samples from the three main producing areas. It was found that the inorganic element characteristics as well as the uptake and accumulation behavior of the three kinds of samples were significantly different. The high contents of Fe, B, Al, Na, Cr and Ni could be used as a standard in the elements fingerprint to identify daodi and non-daodi A. Mongholicus. As the main effective compounds were closely related to the pharmacodynamics activities, the inter-relationships between selected elements and components could reflect that the quality of A. Mongholicus from Shanxi were superior to others to a certain degree. This finding highlighted the usefulness of ICP-AES elemental analysis and evidenced that the inorganic element profile can be employed to evaluate the genuineness of A. mongholicus. Full article
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Open AccessArticle Wild Bitter Melon Leaf Extract Inhibits Porphyromonas gingivalis-Induced Inflammation: Identification of Active Compounds through Bioassay-Guided Isolation
Molecules 2016, 21(4), 454; doi:10.3390/molecules21040454
Received: 28 February 2016 / Revised: 29 March 2016 / Accepted: 30 March 2016 / Published: 6 April 2016
Cited by 2 | PDF Full-text (1821 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Porphyromonas gingivalis has been identified as one of the major periodontal pathogens. Activity-directed fractionation and purification processes were employed to identify the anti-inflammatory active compounds using heat-killed P. gingivalis-stimulated human monocytic THP-1 cells in vitro. Five major fractions were collected from
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Porphyromonas gingivalis has been identified as one of the major periodontal pathogens. Activity-directed fractionation and purification processes were employed to identify the anti-inflammatory active compounds using heat-killed P. gingivalis-stimulated human monocytic THP-1 cells in vitro. Five major fractions were collected from the ethanol/ethyl acetate extract of wild bitter melon (Momordica charantia Linn. var. abbreviata Ser.) leaves and evaluated for their anti-inflammatory activity against P. gingivalis. Among the test fractions, Fraction 5 effectively decreased heat-killed P. gingivalis-induced interleukin (IL)-8 and was subjected to separation and purification by using chromatographic techniques. Two cucurbitane triterpenoids were isolated from the active fraction and identified as 5β,19-epoxycucurbita-6,23-diene-3β,19,25-triol (1) and 3β,7β,25-trihydroxycucurbita-5,23-dien-19-al (2) by comparing spectral data. Treatments of both compounds in vitro potently suppressed P. gingivalis-induced IL-8, IL-6, and IL-1β levels and the activation of mitogen-activated protein kinase (MAPK) in THP-1 cells. Both compounds effectively inhibited the mRNA levels of IL-6, tumor necrosis factor (TNF)-α, and cyclooxygenase (COX)-2 in P. gingivalis-stimulated gingival tissue of mice. These findings imply that 5β,19-epoxycucurbita-6,23-diene-3β,19,25-triol and 3β,7β,25-trihydroxycucurbita-5,23-dien-19-al could be used for the development of novel therapeutic approaches against P. gingivalis infections. Full article
Open AccessArticle Identification of Oxygenated Fatty Acid as a Side Chain of Lipo-Alkaloids in Aconitum carmichaelii by UHPLC-Q-TOF-MS and a Database
Molecules 2016, 21(4), 437; doi:10.3390/molecules21040437
Received: 18 February 2016 / Revised: 24 March 2016 / Accepted: 28 March 2016 / Published: 31 March 2016
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Abstract
Lipo-alkaloid is a kind of C19-norditerpenoid alkaloid usually found in Aconitum species. Structurally, they contain an aconitane skeleton and one or two fatty acid moieties of 3–25 carbon chains with 1–6 unsaturated degrees. Analysis of the lipo-alkaloids in roots of Aconitum carmichaelii resulted
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Lipo-alkaloid is a kind of C19-norditerpenoid alkaloid usually found in Aconitum species. Structurally, they contain an aconitane skeleton and one or two fatty acid moieties of 3–25 carbon chains with 1–6 unsaturated degrees. Analysis of the lipo-alkaloids in roots of Aconitum carmichaelii resulted in the isolation of six known pure lipo-alkaloids (A1–A6) and a lipo-alkaloid mixture (A7). The mixture shared the same aconitane skeleton of 14-benzoylmesaconine, but their side chains were determined to be 9-hydroxy-octadecadienoic acid, 13-hydroxy-octadecadienoic acid and 10-hydroxy-octadecadienoic acid, respectively, by MS/MS analysis after alkaline hydrolysis. To our knowledge, this is the first time of the reporting of the oxygenated fatty acids as the side chains in naturally-occurring lipo-alkaloids. In order to identify more lipo-alkaloids, a compound database was established based on various combinations between the aconitane skeleton and the fatty acid chain, and then, the identification of lipo-alkaloids was conducted using the database, UHPLC-Q-TOF-MS and MS/MS. Finally, 148 lipo-alkaloids were identified from A. carmichaelii after intensive MS/MS analysis, including 93 potential new compounds and 38 compounds with oxygenated fatty acid moieties. Full article
Open AccessReview Plectranthus amboinicus (Lour.) Spreng: Botanical, Phytochemical, Pharmacological and Nutritional Significance
Molecules 2016, 21(4), 369; doi:10.3390/molecules21040369
Received: 30 January 2016 / Revised: 2 March 2016 / Accepted: 8 March 2016 / Published: 30 March 2016
Cited by 8 | PDF Full-text (802 KB) | HTML Full-text | XML Full-text
Abstract
Plectranthus amboinicus (Lour.) Spreng. is a perennial herb belonging to the family Lamiaceae which occurs naturally throughout the tropics and warm regions of Africa, Asia and Australia. This herb has therapeutic and nutritional properties attributed to its natural phytochemical compounds which are highly
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Plectranthus amboinicus (Lour.) Spreng. is a perennial herb belonging to the family Lamiaceae which occurs naturally throughout the tropics and warm regions of Africa, Asia and Australia. This herb has therapeutic and nutritional properties attributed to its natural phytochemical compounds which are highly valued in the pharmaceutical industry. Besides, it has horticultural properties due to its aromatic nature and essential oil producing capability. It is widely used in folk medicine to treat conditions like cold, asthma, constipation, headache, cough, fever and skin diseases. The leaves of the plant are often eaten raw or used as flavoring agents, or incorporated as ingredients in the preparation of traditional food. The literature survey revealed the occurrence 76 volatiles and 30 non-volatile compounds belonging to different classes of phytochemicals such as monoterpenoids, diterpenoids, triterpenoids, sesquiterpenoids, phenolics, flavonoids, esters, alcohols and aldehydes. Studies have cited numerous pharmacological properties including antimicrobial, antiinflammatory, antitumor, wound healing, anti-epileptic, larvicidal, antioxidant and analgesic activities. Also, it has been found to be effective against respiratory, cardiovascular, oral, skin, digestive and urinary diseases. Yet, scientific validation of many other traditional uses would be appreciated, mainly to discover and authenticate novel bioactive compounds from this herb. This review article provides comprehensive information on the botany, phytochemistry, pharmacology and nutritional importance of P. amboinicus essential oil and its various solvent extracts. This article allows researchers to further explore the further potential of this multi-utility herb for various biomedical applications. Full article
Open AccessReview Sinigrin and Its Therapeutic Benefits
Molecules 2016, 21(4), 416; doi:10.3390/molecules21040416
Received: 30 January 2016 / Revised: 7 March 2016 / Accepted: 22 March 2016 / Published: 29 March 2016
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Abstract
Sinigrin (allyl-glucosinolate or 2-propenyl-glucosinolate) is a natural aliphatic glucosinolate present in plants of the Brassicaceae family, such as broccoli and brussels sprouts, and the seeds of Brassica nigra (mustard seeds) which contain high amounts of sinigrin. Since ancient times, mustard has been used
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Sinigrin (allyl-glucosinolate or 2-propenyl-glucosinolate) is a natural aliphatic glucosinolate present in plants of the Brassicaceae family, such as broccoli and brussels sprouts, and the seeds of Brassica nigra (mustard seeds) which contain high amounts of sinigrin. Since ancient times, mustard has been used by mankind for its culinary, as well as medicinal, properties. It has been systematically described and evaluated in the classical Ayurvedic texts. Studies conducted on the pharmacological activities of sinigrin have revealed anti-cancer, antibacterial, antifungal, antioxidant, anti-inflammatory, wound healing properties and biofumigation. This current review will bring concise information about the known therapeutic activities of sinigrin. However, the information on known biological activities is very limited and, hence, further studies still need to be conducted and its molecular mechanisms also need to be explored. This review on the therapeutic benefits of sinigrin can summarize current knowledge about this unique phytocompounds. Full article
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Open AccessArticle Compound Library Screening Identified Cardiac Glycoside Digitoxin as an Effective Growth Inhibitor of Gefitinib-Resistant Non-Small Cell Lung Cancer via Downregulation of α-Tubulin and Inhibition of Microtubule Formation
Molecules 2016, 21(3), 374; doi:10.3390/molecules21030374
Received: 5 January 2016 / Revised: 14 March 2016 / Accepted: 15 March 2016 / Published: 18 March 2016
Cited by 8 | PDF Full-text (2964 KB) | HTML Full-text | XML Full-text
Abstract
Non-small-cell lung cancer (NSCLC) dominates over 85% of all lung cancer cases. Epidermal growth factor receptor (EGFR) activating mutation is a common situation in NSCLC. In the clinic, molecular-targeting with Gefitinib as a tyrosine kinase inhibitor (TKI) for EGFR downstream signaling is initially
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Non-small-cell lung cancer (NSCLC) dominates over 85% of all lung cancer cases. Epidermal growth factor receptor (EGFR) activating mutation is a common situation in NSCLC. In the clinic, molecular-targeting with Gefitinib as a tyrosine kinase inhibitor (TKI) for EGFR downstream signaling is initially effective. However, drug resistance frequently happens due to additional mutation on EGFR, such as substitution from threonine to methionine at amino acid position 790 (T790M). In this study, we screened a traditional Chinese medicine (TCM) compound library consisting of 800 single compounds in TKI-resistance NSCLC H1975 cells, which contains substitutions from leucine to arginine at amino acid 858 (L858R) and T790M mutation on EGFR. Attractively, among these compounds there are 24 compounds CC50 of which was less than 2.5 μM were identified. We have further investigated the mechanism of the most effective one, Digitoxin. It showed a significantly cytotoxic effect in H1975 cells by causing G2 phase arrest, also remarkably activated 5′ adenosine monophosphate-activated protein kinase (AMPK). Moreover, we first proved that Digitoxin suppressed microtubule formation through decreasing α-tubulin. Therefore, it confirmed that Digitoxin effectively depressed the growth of TKI-resistance NSCLC H1975 cells by inhibiting microtubule polymerization and inducing cell cycle arrest. Full article
Open AccessReview New Potential Pharmacological Functions of Chinese Herbal Medicines via Regulation of Autophagy
Molecules 2016, 21(3), 359; doi:10.3390/molecules21030359
Received: 20 January 2016 / Revised: 29 February 2016 / Accepted: 9 March 2016 / Published: 17 March 2016
Cited by 11 | PDF Full-text (2240 KB) | HTML Full-text | XML Full-text
Abstract
Autophagy is a universal catabolic cellular process for quality control of cytoplasm and maintenance of cellular homeostasis upon nutrient deprivation and environmental stimulus. It involves the lysosomal degradation of cellular components such as misfolded proteins or damaged organelles. Defects in autophagy are implicated
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Autophagy is a universal catabolic cellular process for quality control of cytoplasm and maintenance of cellular homeostasis upon nutrient deprivation and environmental stimulus. It involves the lysosomal degradation of cellular components such as misfolded proteins or damaged organelles. Defects in autophagy are implicated in the pathogenesis of diseases including cancers, myopathy, neurodegenerations, infections and cardiovascular diseases. In the recent decade, traditional drugs with new clinical applications are not only commonly found in Western medicines, but also highlighted in Chinese herbal medicines (CHM). For instance, pharmacological studies have revealed that active components or fractions from Chaihu (Radix bupleuri), Hu Zhang (Rhizoma polygoni cuspidati), Donglingcao (Rabdosia rubesens), Hou po (Cortex magnoliae officinalis) and Chuan xiong (Rhizoma chuanxiong) modulate cancers, neurodegeneration and cardiovascular disease via autophagy. These findings shed light on the potential new applications and formulation of CHM decoctions via regulation of autophagy. This article reviews the roles of autophagy in the pharmacological actions of CHM and discusses their new potential clinical applications in various human diseases. Full article
Open AccessReview Role of Intestinal Microbiota in Baicalin-Induced Drug Interaction and Its Pharmacokinetics
Molecules 2016, 21(3), 337; doi:10.3390/molecules21030337
Received: 10 February 2016 / Revised: 2 March 2016 / Accepted: 7 March 2016 / Published: 10 March 2016
Cited by 8 | PDF Full-text (396 KB) | HTML Full-text | XML Full-text
Abstract
Since many glycoside compounds in natural products are hydrolyzed by intestinal microbiota when administered orally, it is of interest to know whether their pharmacological effects are derived from the glycoside itself or from the aglycone form in vivo. An interesting example is
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Since many glycoside compounds in natural products are hydrolyzed by intestinal microbiota when administered orally, it is of interest to know whether their pharmacological effects are derived from the glycoside itself or from the aglycone form in vivo. An interesting example is baicalin versus baicalein, the aglycone of baicalin, which is contained in some herbs from Labiatae including Scutellaria baicalensis Georgi and Scutellaria lateriflora Linne. The herbs have been extensively used for treatment of inflammatory diseases in Asia. Although there have been numerous reports regarding the pharmacological effects of baicalin and baicalein in vivo and in vitro, some reports indicated that the glycoside form would hardly be absorbed in the intestine and that it should be hydrolyzed to baicalein in advance for absorption. Therefore, the role of metabolism by intestinal microbiota should also be considered in the metabolism of baicalin. In addition, baicalin contains a glucuronide moiety in its structure, by which baicalin and baicalein show complex pharmacokinetic behaviors, due to the interconversion between them by phase II enzymes in the body. Recently, concerns about drug interaction with baicalin and/or baicalein have been raised, because of the co-administration of Scutellaria species with certain drugs. Herein, we reviewed the role of intestinal microbiota in pharmacokinetic characteristics of baicalin and baicalein, with regards to their pharmacological and toxicological effects. Full article
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Open AccessReview Review on a Traditional Herbal Medicine, Eurycoma longifolia Jack (Tongkat Ali): Its Traditional Uses, Chemistry, Evidence-Based Pharmacology and Toxicology
Molecules 2016, 21(3), 331; doi:10.3390/molecules21030331
Received: 28 January 2016 / Revised: 2 March 2016 / Accepted: 3 March 2016 / Published: 10 March 2016
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Abstract
Eurycoma longifolia Jack (known as tongkat ali), a popular traditional herbal medicine, is a flowering plant of the family Simaroubaceae, native to Indonesia, Malaysia, Vietnam and also Cambodia, Myanmar, Laos and Thailand. E. longifolia, is one of the well-known folk medicines for
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Eurycoma longifolia Jack (known as tongkat ali), a popular traditional herbal medicine, is a flowering plant of the family Simaroubaceae, native to Indonesia, Malaysia, Vietnam and also Cambodia, Myanmar, Laos and Thailand. E. longifolia, is one of the well-known folk medicines for aphrodisiac effects as well as intermittent fever (malaria) in Asia. Decoctions of E. longifolia leaves are used for washing itches, while its fruits are used in curing dysentery. Its bark is mostly used as a vermifuge, while the taproots are used to treat high blood pressure, and the root bark is used for the treatment of diarrhea and fever. Mostly, the roots extract of E. longifolia are used as folk medicine for sexual dysfunction, aging, malaria, cancer, diabetes, anxiety, aches, constipation, exercise recovery, fever, increased energy, increased strength, leukemia, osteoporosis, stress, syphilis and glandular swelling. The roots are also used as an aphrodisiac, antibiotic, appetite stimulant and health supplement. The plant is reported to be rich in various classes of bioactive compounds such as quassinoids, canthin-6-one alkaloids, β-carboline alkaloids, triterpene tirucallane type, squalene derivatives and biphenyl neolignan, eurycolactone, laurycolactone, and eurycomalactone, and bioactive steroids. Among these phytoconstituents, quassinoids account for a major portion of the E. longifolia root phytochemicals. An acute toxicity study has found that the oral Lethal Dose 50 (LD50) of the alcoholic extract of E. longifolia in mice is between 1500–2000 mg/kg, while the oral LD50 of the aqueous extract form is more than 3000 mg/kg. Liver and renal function tests showed no adverse changes at normal daily dose and chronic use of E. longifolia. Based on established literature on health benefits of E. longifolia, it is important to focus attention on its more active constituents and the constituents’ identification, determination, further development and most importantly, the standardization. Besides the available data, more evidence is required regarding its therapeutic efficacy and safety, so it can be considered a rich herbal source of new drug candidates. It is very important to conserve this valuable medicinal plant for the health benefit of future generations. Full article
Open AccessArticle Isolation, Purification and Quantification of Ginsenoside F5 and F3 Isomeric Compounds from Crude Extracts of Flower Buds of Panax ginseng
Molecules 2016, 21(3), 315; doi:10.3390/molecules21030315
Received: 26 December 2015 / Revised: 24 February 2016 / Accepted: 3 March 2016 / Published: 9 March 2016
Cited by 2 | PDF Full-text (1885 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
In this paper, the isolation, purification and quantification of ginsenoside F5 and F3 isomeric compounds from crude extracts of flower buds of Panax ginseng (CEFBPG) was investigated by reversed-phase high-performance liquid chromatography (RP-HPLC) for the first time. The satisfied separation at
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In this paper, the isolation, purification and quantification of ginsenoside F5 and F3 isomeric compounds from crude extracts of flower buds of Panax ginseng (CEFBPG) was investigated by reversed-phase high-performance liquid chromatography (RP-HPLC) for the first time. The satisfied separation at analytical scale was achieved using a Zorbax Eclipse XDB C-18 column with a ternary mobile phase of acetonitrile–water–phosphoric acid (28:71:1) at a flow rate of 1.0 mL/min within 40 min. UV detection was set at 203 nm. Ginsenoside F5 and F3 was 4.21 mg and 5.13 mg in 1 g flower buds of P. ginseng (FBPG), respectively. The preparation of ginsenoside F5 and F3 at semi-preparative scale was performed by using a Daisogel C-18 column and gradient elution system of acetonitrile–water (32:68 → 28:72) at a flow rate of 10 mL/min with a sample load of 20–30 mg, and yielded ginsenosides in purity of more than 96%. Their structures were characterized by NMR and high resolution electrospray ionization mass spectrometry (HRESIMS). All the method validations showed acceptable limits. The results indicate a new source to obtain ginsenoside F5 and F3, and show that the method developed here appears to be reliable for simultaneously preparing them from CEFBPG. Full article
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Open AccessReview Natural Products from Chinese Medicines with Potential Benefits to Bone Health
Molecules 2016, 21(3), 239; doi:10.3390/molecules21030239
Received: 9 December 2015 / Revised: 3 February 2016 / Accepted: 12 February 2016 / Published: 27 February 2016
Cited by 6 | PDF Full-text (6441 KB) | HTML Full-text | XML Full-text
Abstract
Osteoporosis is a progressive, systemic bone disorder characterized by loss of bone mass and microstructure, leading to reduced bone strength and increased risk of fracture. It is often associated with reduced quality of life and other medical complications. The disease is common in
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Osteoporosis is a progressive, systemic bone disorder characterized by loss of bone mass and microstructure, leading to reduced bone strength and increased risk of fracture. It is often associated with reduced quality of life and other medical complications. The disease is common in the aging population, particularly among postmenopausal women and patients who receive long-term steroidal therapy. Given the rapid growth of the aging population, increasing life expectancy, the prevalence of bone loss, and financial burden to the healthcare system and individuals, demand for new therapeutic agents and nutritional supplements for the management and promotion of bone health is pressing. With the advent of global interest in complementary and alternative medicine and natural products, Chinese medicine serves as a viable source to offer benefits for the improvement and maintenance of bone health. This review summarizes the scientific information obtained from recent literatures on the chemical ingredients of Chinese medicinal plants that have been reported to possess osteoprotective and related properties in cell-based and/or animal models. Some of these natural products (or their derivatives) may become promising leads for development into dietary supplements or therapeutic drugs. Full article
Open AccessArticle Antibacterial and Synergistic Activity of Pentacyclic Triterpenoids Isolated from Alstonia scholaris
Molecules 2016, 21(2), 139; doi:10.3390/molecules21020139
Received: 24 December 2015 / Revised: 12 January 2016 / Accepted: 21 January 2016 / Published: 25 January 2016
Cited by 7 | PDF Full-text (662 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
(1) Background: Alstonia scholaris (Apocynaceae) is an important medicinal plant that has been historically used in “Dai” ethnopharmacy to treat infectious diseases in China. Although various pharmacological activities have been reported, the antimicrobial constitutes of A. scholaris have not yet been identified. The
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(1) Background: Alstonia scholaris (Apocynaceae) is an important medicinal plant that has been historically used in “Dai” ethnopharmacy to treat infectious diseases in China. Although various pharmacological activities have been reported, the antimicrobial constitutes of A. scholaris have not yet been identified. The objective of this study is to evaluate the antibacterial constitutes from the leaf extract of A. scholaris and to assess the synergistic effects of isolated compounds with antibiotics against bacterial pathogens.; (2) Methods: The chemical constitutes isolated from the leaf extract of A. scholaris were structurally identified by NMR. The antibacterial and synergistic effect of compounds was assessed by calculating the minimal inhibitory concentration (MIC), checkerboard dilution test, and time-kill assay.; (3) Results: Six pentacyclic triterpenoids were structurally identified as (1) lupeol, (2) betulin, (3) 3-hydroxy-11-ursen-28,13-olide, (4) betulinic acid, (5) oleanolic acid and (6) ursolic acid. Both oleanolic and ursolic acid showed antibacterial activity but were limited to Gram-positive bacteria. Ursolic acid showed a synergistic effect with ampicillin and tetracycline against both Bacillus cereus and S. aureus.; (4) Conclusion: These findings reflect that pentacyclic triterpenoids are the antibacterial chemicals in A. scholaris. The ability of ursolic acid to enhance the activity of antibiotics can constitute a valuable group of therapeutic agents in the future. Full article
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Open AccessArticle The Protective Effects of Alisol A 24-Acetate from Alisma canaliculatum on Ovariectomy Induced Bone Loss in Vivo
Molecules 2016, 21(1), 74; doi:10.3390/molecules21010074
Received: 2 December 2015 / Revised: 7 January 2016 / Accepted: 7 January 2016 / Published: 9 January 2016
Cited by 4 | PDF Full-text (4250 KB) | HTML Full-text | XML Full-text
Abstract
Alisma canaliculatum is a herb commonly used in traditional Korean medicine, and has been shown in scientific studies to have antitumor, diuretic hepatoprotective, and antibacterial effects. Recently, the anti-osteoclastogenesis of alisol A 24-acetate from Alisma canaliculatum was investigated in vitro. However, the
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Alisma canaliculatum is a herb commonly used in traditional Korean medicine, and has been shown in scientific studies to have antitumor, diuretic hepatoprotective, and antibacterial effects. Recently, the anti-osteoclastogenesis of alisol A 24-acetate from Alisma canaliculatum was investigated in vitro. However, the influence of alisol A 24-acetate on osteoporosis in animals has not been investigated. The present study was undertaken to investigate the anti-osteoporotic effect of alisol A 24-acetate on bone mass in ovariectomized (OVX) mice and to identify the mechanism responsible for its effects. OVX mice were treated daily with 0.5 or 2 μg/g of alisol A 24-acetate for a period of six weeks. It was found that these administrations significantly suppressed osteoporosis in OVX mice and improved bone morphometric parameters. The serum estradiol, bone alkaline phosphatase levels, regulatory T/Th17 cell numbers were significantly increased by alisol A 24-acetate as compared with untreated OVX mice. In addition, TRAP activity was inhibited by alisol A 24-acetate in OVX mice. These results suggest alisol A 24-acetate effectively prevents bone loss in OVX mice, and that it can be considered a potential therapeutic for the treatment of postmenopausal osteoporosis. Full article

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Open AccessArticle Mechanism of Breast Cancer Preventive Action of Pomegranate: Disruption of Estrogen Receptor and Wnt/β-Catenin Signaling Pathways
Molecules 2015, 20(12), 22315-22328; doi:10.3390/molecules201219853
Received: 10 November 2015 / Revised: 2 December 2015 / Accepted: 8 December 2015 / Published: 12 December 2015
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Abstract
A pomegranate emulsion (PE), containing various bioactive phytochemicals, has recently been found to exert substantial chemopreventive effect against 7,12-dimethylbenz(a)anthracene (DMBA)-induced mammary tumorigenesis in rats via antiproliferative and proapoptotic actions. Nevertheless, the underlying mechanisms of action are not completely understood. The present
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A pomegranate emulsion (PE), containing various bioactive phytochemicals, has recently been found to exert substantial chemopreventive effect against 7,12-dimethylbenz(a)anthracene (DMBA)-induced mammary tumorigenesis in rats via antiproliferative and proapoptotic actions. Nevertheless, the underlying mechanisms of action are not completely understood. The present study was designed to investigate the effects of PE treatment on intratumor expression of estrogen receptor (ER)-α, ER-β,β-catenin and cyclin D1 during DMBA rat mammary carcinogenesis. Mammary tumor sections were harvested from a chemopreventive study in which PE (0.2, 1.0 and 5.0 g/kg) exhibited inhibition of mammary tumorigenesis in a dose-response manner. The expressions of ER-α, ER-β, β-catenin and cyclin D1 were analyzed by immunohistochemical techniques. PE downregulated the expression of intratumor ER-α and ER-β and lowered ER-α:ER-β ratio. PE also decreased the expression, cytoplasmic accumulation, and nuclear translocation of β-catenin, an essential transcriptional cofactor for Wnt signaling. Moreover, PE suppressed the expression of cell growth regulatory protein cyclin D1, which is a downstream target for both ER and Wnt signaling. Our current results in conjunction with our previous findings indicate that concurrent disruption of ER and Wnt/β-catenin signaling pathways possibly contributes to antiproliferative and proapoptotic effects involved in PE-mediated chemoprevention of DMBA-inflicted rat mammary tumorigenesis. Full article
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Open AccessArticle Herb-Drug Pharmacokinetic Interactions: Transport and Metabolism of Indinavir in the Presence of Selected Herbal Products
Molecules 2015, 20(12), 22113-22127; doi:10.3390/molecules201219838
Received: 19 October 2015 / Revised: 2 December 2015 / Accepted: 7 December 2015 / Published: 10 December 2015
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Abstract
Patients receiving anti-retroviral drug treatment are sometimes simultaneously taking herbal remedies, which may result in pharmacokinetic herb-drug interactions. This study aimed to determine if pharmacokinetic interactions exist between selected commercially available herbal products (i.e., Linctagon Forte®, Viral Choice®
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Patients receiving anti-retroviral drug treatment are sometimes simultaneously taking herbal remedies, which may result in pharmacokinetic herb-drug interactions. This study aimed to determine if pharmacokinetic interactions exist between selected commercially available herbal products (i.e., Linctagon Forte®, Viral Choice® and Canova®) and indinavir in terms of in vitro transport and metabolism. Bi-directional transport of indinavir was evaluated across Caco-2 cell monolayers in the presence and absence of the selected herbal products and verapamil (positive control). Metabolism of indinavir was determined in LS180 cells in the presence and absence of the selected herbal products as well as ketoconazole (positive control). The secretory transport of indinavir increased in a concentration dependent way in the presence of Linctagon Forte® and Viral Choice® when compared to that of indinavir alone. Canova® only slightly affected the efflux of indinavir compared to that of the control group. There was a pronounced inhibition of the metabolism of indinavir in LS180 cells over the entire concentration range for all the herbal products investigated in this study. These in vitro pharmacokinetic interactions indicate the selected herbal products may affect indinavir’s bioavailability, but the clinical significance needs to be confirmed with in vivo studies before final conclusions can be made. Full article
Open AccessArticle Safety Evaluation, in Vitro and in Vivo Antioxidant Activity of the Flavonoid-Rich Extract from Maydis stigma
Molecules 2015, 20(12), 22102-22112; doi:10.3390/molecules201219835
Received: 29 October 2015 / Revised: 4 December 2015 / Accepted: 7 December 2015 / Published: 10 December 2015
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Abstract
This study aimed to assess the acute toxicity and safety of flavonoid-rich extract from Maydis stigma (FMS) in mice. The in vitro antioxidant activity of FMS was determined by 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2,2′-azinobis-(3-ethyl-benzthiazoline-6-sulphonate) (ABTS) scavenging assays. Furthermore, the in vivo antioxidant of FMS
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This study aimed to assess the acute toxicity and safety of flavonoid-rich extract from Maydis stigma (FMS) in mice. The in vitro antioxidant activity of FMS was determined by 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2,2′-azinobis-(3-ethyl-benzthiazoline-6-sulphonate) (ABTS) scavenging assays. Furthermore, the in vivo antioxidant of FMS against ethanol-induced oxidative damage in mice was determined by analysis of the serum total superoxide dismutase (T-SOD) activity, malondialdehyde (MDA) content, liver tissue glutathione (GSH) content, and protein carbonyl (PC) content in liver tissue. The oral administration of FMS at doses of 30 g/kg did not cause death in mice, and there were no significant biologically adverse effects in mice. These results indicated that the median lethal dose (LD50) is higher than this dose. The IC50 values of FMS for the DPPH and ABTS scavenging activity were 50.73 and 0.23 mg/mL, respectively. Meanwhile, FMS could significantly enhance T-SOD activity, reduce MDA content in the serum, increase GSH content, and decrease PC content in the liver tissue at the tested doses (25, 50, 100, 200 mg/kg·day). These results indicate that FMS can be generally regarded as safe and used potentially as a bioactive source of natural antioxidants. Full article
Open AccessArticle Bioactive Constituents from the Aerial Parts of Lippia triphylla
Molecules 2015, 20(12), 21946-21959; doi:10.3390/molecules201219814
Received: 27 September 2015 / Revised: 27 November 2015 / Accepted: 4 December 2015 / Published: 8 December 2015
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Abstract
Five new compounds, lippianosides A (1), B (2), C (3), D (4), and E (5), along with 26 (631) known ones were obtained from the 95% EtOH extract of
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Five new compounds, lippianosides A (1), B (2), C (3), D (4), and E (5), along with 26 (631) known ones were obtained from the 95% EtOH extract of Lippia triphylla (L. triphylla) aerial parts collected from Rwanda, Africa. Among the known compounds, 11 and 1730 were isolated from the Lippia genus for the first time. In addition, 12, 13, and 16 were firstly obtained from this species. The structures of them were elucidated by chemical and spectroscopic methods. The antioxidant and triglyceride accumulation inhibition effects of the 31 compounds were examined in L6 cells and HepG2 cells, respectively. Full article
Open AccessArticle Chemical Compositions and Insecticidal Activities of Alpinia kwangsiensis Essential Oil against Lasioderma serricorne
Molecules 2015, 20(12), 21939-21945; doi:10.3390/molecules201219818
Received: 16 November 2015 / Revised: 28 November 2015 / Accepted: 1 December 2015 / Published: 8 December 2015
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Abstract
The essential oil obtained by hydrodistillation from Alpinia kwangsiensis rhizomes was investigated by GC-MS. A total of 31 components representing 92.45% of the oil were identified and the main compounds in the oil were found to be camphor (17.59%), eucalyptol (15.16%), β-pinene (11.15%)
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The essential oil obtained by hydrodistillation from Alpinia kwangsiensis rhizomes was investigated by GC-MS. A total of 31 components representing 92.45% of the oil were identified and the main compounds in the oil were found to be camphor (17.59%), eucalyptol (15.16%), β-pinene (11.15%) and α-pinene (10.50%). These four compounds were subsequently isolated and the essential oil and four isolated compounds exhibited potent insecticidal activity against Lasioderma serricorne adults. During the assay, it was shown that the essential oil exhibited both potential contact (LD50 = of 24.59 μg/adult) and fumigant (LC50 = of 9.91 mg/L air) toxicity against Lasioderma serricorne. The study revealed that the insecticidal activity of the essential oil can be attributed to the synergistic effects of its diverse major components, which indicates that oil of Alpinia kwangsiensis and its isolated compounds have potential to be developed into natural insecticides to control insects in stored grains and traditional Chinese medicinal materials. Full article
Open AccessArticle Analysis of Chemical Constituents in Wuzi-Yanzong-Wan by UPLC-ESI-LTQ-Orbitrap-MS
Molecules 2015, 20(12), 21373-21404; doi:10.3390/molecules201219765
Received: 21 October 2015 / Revised: 20 November 2015 / Accepted: 23 November 2015 / Published: 1 December 2015
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Abstract
Wuzi-Yanzong-Wan (WZYZW), a classical traditional Chinese medicine (TCM) prescription containing Fructus Lych, Semen Cuscutae (fried), Fructus Rubi, Fructus Schisandrae chinensis (steamed) and Semen Plantaginis (fried with salt), is widely used to treat impotence, sterility, spermatorrhea, premature ejaculation, lumbago and post-micturation dribble.
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Wuzi-Yanzong-Wan (WZYZW), a classical traditional Chinese medicine (TCM) prescription containing Fructus Lych, Semen Cuscutae (fried), Fructus Rubi, Fructus Schisandrae chinensis (steamed) and Semen Plantaginis (fried with salt), is widely used to treat impotence, sterility, spermatorrhea, premature ejaculation, lumbago and post-micturation dribble. However, the chemical profile of WZYZW has not been established yet. In this work, a rapid and sensitive method for systematically screening and identifying the chemical constituents of WZYZW in both positive and negative ion modes using Ultra-Performance LC coupled with ESI-linear ion trap-Orbitrap tandem mass spectrometry (UPLC-ESI-LTQ-Orbitrap-MS) has been developed. Based on the chromatographic and spectrometric data, and referring to the literature, we could tentatively identify 106 compounds, including organic acids, flavonoids, phenylpropanoids, alkaloids and terpenoids. Fourteen ingredients from Fructus Lych were identified, while 10 ingredients were from Semen Cuscutae (fried), 33 ingredients were from Fructus Rubi, 37 ingredients were from Fructus Schisandrae chinensis (steamed), and 20 ingredients were from Semen Plantaginis (fried with salt). The results may provide essential data for further quality control, pharmacological research and clinical evaluation of WZYZW. Furthermore, this study indicates the developed approach based on UPLC-ESI-LTQ-Orbitrap-MS is suitable for characterizing the chemical profiles of TCM prescriptions. This is the first report to provide a comprehensive analysis of the chemical constituents of WZYZW. Full article
Open AccessArticle Role of the Red Ginseng in Defense against the Environmental Heat Stress in Sprague Dawley Rats
Molecules 2015, 20(11), 20240-20253; doi:10.3390/molecules201119692
Received: 18 September 2015 / Revised: 3 November 2015 / Accepted: 5 November 2015 / Published: 10 November 2015
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Abstract
Global temperature change causes heat stress related disorders in humans. A constituent of red ginseng has been known the beneficial effect on the resistance to many diseases. However, the mechanism of red ginseng (RG) against heat stress still remains unclear. To determine the
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Global temperature change causes heat stress related disorders in humans. A constituent of red ginseng has been known the beneficial effect on the resistance to many diseases. However, the mechanism of red ginseng (RG) against heat stress still remains unclear. To determine the effect of RG on heat stress, we examined the effect of the RG on the gene expression profiles in rats subjected to environmental heat stress. We evaluated the transcripts associated with hepatic lipid accumulation and oxidative stress in rats subjected to heat stress. We also analyzed the reactive oxygen species (ROS) contents. Our results suggested RG inhibited heat stress mediated altering mRNA expressions include HSPA1, DEAF1, HMGCR, and FMO1. We also determined RG attenuated fat accumulation in the liver by altering C/EBPβ expression. RG promoted to repress the heat stress mediated hepatic cell death by inhibiting of Bcl-2 expression in rats subjected to heat stress. Moreover, RG administered group during heat stress dramatically decreased the malondialdehyde (MDA) contents and ROS associated genes compared with the control group. Thus, we suggest that RG might influence inhibitory effect on environmental heat stress induced abnormal conditions in humans. Full article
Open AccessArticle Bitter Gentian Teas: Nutritional and Phytochemical Profiles, Polysaccharide Characterisation and Bioactivity
Molecules 2015, 20(11), 20014-20030; doi:10.3390/molecules201119674
Received: 15 October 2015 / Revised: 29 October 2015 / Accepted: 30 October 2015 / Published: 5 November 2015
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Abstract
As a result of the wide distribution of herbal teas the data on nutritional characterisation, chemical profile and biological activity of these products are required. The decoctions of Gentiana algida, G. decumbens, G. macrophylla and G. triflora herb teas were nutritionally
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As a result of the wide distribution of herbal teas the data on nutritional characterisation, chemical profile and biological activity of these products are required. The decoctions of Gentiana algida, G. decumbens, G. macrophylla and G. triflora herb teas were nutritionally characterized with respect to their macronutrients, demonstrating the predominance of polysaccharides and low lipid content. Gentian decoctions were also submitted to a microcolumn RP-HPLC-UV analysis of phytochemicals demonstrating a high content of iridoids (177.18–641.04 μg/mL) and flavonoids (89.15–405.71 μg/mL). Additionally, mangiferin was detected in samples of G. triflora tea (19.89 μg/mL). Five free sugars (fructose, glucose, sucrose, gentiobiose, gentianose) were identified in all gentian teas studied, as well as six organic acids (malic, citric, tartaric, oxalic, succinic, quinic). Pectic polysaccharides with a high content of rhamnogalacturonans and arabinogalactans were also identified and characterized in gentian decoctions for the first time. Gentian tea decoctions and their specific compounds (gentiopicroside, loganic acid-6′-O-β-d-glucoside, isoorientin, isoorientin-4′-O-β-d-glucoside, mangiferin, water-soluble polysaccharides) showed a promising antimicrobial, anti-inflammatory and antioxidant potentials. Evidences obtained indicate the prospective use of gentian herb teas as food products and medicines. Full article
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Open AccessArticle Iridoids and Flavonoids of Four Siberian Gentians: Chemical Profile and Gastric Stimulatory Effect
Molecules 2015, 20(10), 19172-19188; doi:10.3390/molecules201019172
Received: 28 August 2015 / Revised: 15 October 2015 / Accepted: 16 October 2015 / Published: 21 October 2015
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Abstract
Some Gentiana species have been used by the nomadic people of Siberia as bitter teas or appetizers to eliminate digestive disorders (dyspepsia, heartburn, nausea, etc.). We studied the most frequently used gentians: Gentiana algida, G. decumbens, G. macrophylla and G. triflora
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Some Gentiana species have been used by the nomadic people of Siberia as bitter teas or appetizers to eliminate digestive disorders (dyspepsia, heartburn, nausea, etc.). We studied the most frequently used gentians: Gentiana algida, G. decumbens, G. macrophylla and G. triflora. The aim of the present study was to evaluate the phytochemical features and gastrostimulatnt activity of these four gentian herbs. Five iridoids, seven flavones and mangiferin were detected in gentian herbs after analysis by microcolumn-RP-HPLC-UV-ESI-MS. A componential phytochemical profile of the G. decumbens herb is presented for the first time, as well as information about distinct phytochemicals found in gentian herbs. HPLC quantification of the specific compounds of gentian herbs demonstrated the high content of iridoids (24.73–73.53 mg/g) and flavonoids (12.92–78.14 mg/g). The results of biological activity evaluation of four gentian decoctions demonstrated their good ability to stimulate acid-, enzyme- and mucin-forming functions of the stomach attributed to mostly by iridoids and flavonoids. In general, it can be claimed that the gentian decoctions can be used as effective and safe appetizers and are also a good source of biologically active agents. Full article
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Open AccessArticle Selected Phytochemicals and Culinary Plant Extracts Inhibit Fructose Uptake in Caco-2 Cells
Molecules 2015, 20(9), 17393-17404; doi:10.3390/molecules200917393
Received: 31 July 2015 / Revised: 1 September 2015 / Accepted: 15 September 2015 / Published: 18 September 2015
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Abstract
This study compared the ability of nine culinary plant extracts containing a wide array of phytochemicals to inhibit fructose uptake and then explored the involvement of intestinal fructose transporters and phytochemicals for selected samples. The chemical signature was characterized by high performance liquid
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This study compared the ability of nine culinary plant extracts containing a wide array of phytochemicals to inhibit fructose uptake and then explored the involvement of intestinal fructose transporters and phytochemicals for selected samples. The chemical signature was characterized by high performance liquid chromatography with mass spectrometry. Inhibition of [14C]-fructose uptake was tested by using human intestinal Caco-2 cells. Then, the relative contribution of the two apical-facing intestinal fructose transporters, GLUT2 and GLUT5, and the signature components for fructose uptake inhibition was confirmed in naive, phloretin-treated and forskolin-treated Caco-2 cells. HPLC/MS analysis of the chemical signature revealed that guava leaf contained quercetin and catechin, and turmeric contained curcumin, bisdemethoxycurcumin and dimethoxycurcumin. Similar inhibition of fructose uptake (by ~50%) was observed with guava leaf and turmeric in Caco-2 cells, but with a higher contribution of GLUT2 for turmeric and that of GLUT5 for guava leaf. The data suggested that, in turmeric, demethoxycurcumin specifically contributed to GLUT2-mediated fructose uptake inhibition, and curcumin did the same to GLUT5-mediated fructose uptake inhibition, but GLUT2 inhibition was more potent. By contrast, in guava leaf, catechin specifically contributed to GLUT5-mediated fructose uptake inhibition, and quercetin affected both GLUT5- and GLUT2-mediated fructose uptake inhibition, resulting in the higher contribution of GLUT5. These results suggest that demethoxycurcumin is an important contributor to GLUT2-mediated fructose uptake inhibition for turmeric extract, and catechin is the same to GLUT5-mediated fructose uptake inhibition for guava leaf extract. Quercetin, curcumin and bisdemethoxycurcumin contributed to both GLUT5- and GLUT2-mediated fructose uptake inhibition, but the contribution to GLUT5 inhibition was higher than the contribution to GLUT2 inhibition. Full article
Open AccessArticle Effect of Amaranthus on Advanced Glycation End-Products Induced Cytotoxicity and Proinflammatory Cytokine Gene Expression in SH-SY5Y Cells
Molecules 2015, 20(9), 17288-17308; doi:10.3390/molecules200917288
Received: 30 July 2015 / Revised: 11 September 2015 / Accepted: 11 September 2015 / Published: 18 September 2015
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Abstract
Amaranthus plants, or spinach, are used extensively as a vegetable and are known to possess medicinal properties. Neuroinflammation and oxidative stress play a major role in the pathogenesis of many neurodegenerative diseases, such as Alzheimer’s disease and Parkinson’s disease. Advanced glycation end-products (AGEs)
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Amaranthus plants, or spinach, are used extensively as a vegetable and are known to possess medicinal properties. Neuroinflammation and oxidative stress play a major role in the pathogenesis of many neurodegenerative diseases, such as Alzheimer’s disease and Parkinson’s disease. Advanced glycation end-products (AGEs) cause cell toxicity in the human neuronal cell line, SH-SY5Y, through an increase in oxidative stress, as shown by reducing cell viability and increasing cell toxicity in a dose-dependent manner. We found that preincubation of SH-SY5Y cells with either petroleum ether, dichloromethane or methanol extracts of A. lividus and A. tricolor dose-dependently attenuated the neuron toxicity caused by AGEs treatment. Moreover, the results showed that A. lividus and A. tricolor extracts significantly downregulated the gene expression of the pro-inflammatory cytokines, TNF-α, IL-1 and IL-6 genes in AGEs-induced cells. We concluded that A. lividus and A. tricolor extracts not only have a neuroprotective effect against AGEs toxicity, but also have anti-inflammatory activity by reducing pro-inflammatory cytokine gene expression. This suggests that Amaranthus may be useful for treating chronic inflammation associated with neurodegenerative disorders. Full article
Open AccessArticle Identification of Cultured and Natural Astragalus Root Based on Monosaccharide Mapping
Molecules 2015, 20(9), 16466-16490; doi:10.3390/molecules200916466
Received: 9 August 2015 / Revised: 1 September 2015 / Accepted: 3 September 2015 / Published: 11 September 2015
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Abstract
As the main substances responsible for immunomodulatory activity, saccharides can be used as quality indicators for Astragalus root (RA). Saccharide content is commonly determined by ultraviolet spectroscopy, which lacks species specificity and has not been applied in the Chinese Pharmacopoeia. Monosaccharide mapping based
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As the main substances responsible for immunomodulatory activity, saccharides can be used as quality indicators for Astragalus root (RA). Saccharide content is commonly determined by ultraviolet spectroscopy, which lacks species specificity and has not been applied in the Chinese Pharmacopoeia. Monosaccharide mapping based on trifluoroacetic acid (TFA) hydrolysis can be used for quantitative analysis of saccharide compositions. In addition, species specificity can be evaluated by analysis of the mapping characteristics. In this study, monosaccharide mapping of soluble saccharides in the cytoplasm and polysaccharides in the cell wall of 24 batches of RA samples with different growth patterns were obtained based on TFA hydrolysis followed by gas chromatography-mass spectrometry. Results indicated that the mapping and the molar ratios of saccharide compositions of the cultured and natural RA samples were different for both cytoplasm and cell wall. For example, the molar ratio of mannose and arabinose was more than 3.5:1 in cytoplasm in cultured RA, whereas the ratio was less than 3.5:1 in natural RA. This research not only lays a foundation for screening indicators for RA, but also provided new ways of evaluating the quality of Chinese medicinal materials in which saccharides are the main bioactive substances. Full article
Open AccessArticle Gallic Acid Is the Major Active Component of Cortex Moutan in Inhibiting Immune Maturation of Human Monocyte-Derived Dendritic Cells
Molecules 2015, 20(9), 16388-16403; doi:10.3390/molecules200916388
Received: 5 August 2015 / Revised: 1 September 2015 / Accepted: 1 September 2015 / Published: 10 September 2015
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Abstract
Atopic dermatitis (AD) is a widely prevalent and chronically relapsing inflammatory skin disease. Penta Herbs Formula (PHF) is efficacious in improving the quality of life and reducing topical corticosteroid used in children with AD and one of the active herbs it contains is
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Atopic dermatitis (AD) is a widely prevalent and chronically relapsing inflammatory skin disease. Penta Herbs Formula (PHF) is efficacious in improving the quality of life and reducing topical corticosteroid used in children with AD and one of the active herbs it contains is Cortex Moutan. Recent studies showed that altered functions of dendritic cells (DC) were observed in atopic individuals, suggesting that DC might play a major role in the generation and maintenance of inflammation by their production of pro-inflammatory cytokines. Hence, the aims of the present study were to identify the major active component(s) of Cortex Moutan, which might inhibit DC functions and to investigate their possible interactions with conventional corticosteroid on inhibiting the development of DC from monocytes. Monocyte-derived dendritic cells (moDC) culture model coupled with the high-speed counter-current chromatography (HSCCC), high pressure liquid chromatography (HPLC) and Liquid Chromatography-Mass Spectrometry (LCMS) analyses were used. Gallic acid was the major active component from Cortex Moutan which could dose dependently inhibit interleukin (IL)-12 p40 and the functional cluster of differentiation (CD) surface markers CD40, CD80, CD83 and CD86 expression from cytokine cocktail-activated moDC. Gallic acid could also lower the concentration of hydrocortisone required to inhibit the activation of DC. Full article
Open AccessArticle Chemical Composition, Antioxidative and Anticancer Activities of the Essential Oil: Curcumae RhizomaSparganii Rhizoma, a Traditional Herb Pair
Molecules 2015, 20(9), 15781-15796; doi:10.3390/molecules200915781
Received: 3 August 2015 / Revised: 20 August 2015 / Accepted: 25 August 2015 / Published: 28 August 2015
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Abstract
As a classical herb pair in clinics of traditional Chinese medicine, Curcumae RhizomaSparganii Rhizoma (HP CR–SR) is used for activating blood circulation to remove blood stasis. The essential components in HP CR–SR and its single herbs were comparatively analyzed using gas
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As a classical herb pair in clinics of traditional Chinese medicine, Curcumae RhizomaSparganii Rhizoma (HP CR–SR) is used for activating blood circulation to remove blood stasis. The essential components in HP CR–SR and its single herbs were comparatively analyzed using gas chromatography-mass spectrometry data. 66, 22, and 54 components in volatile oils of Curcumae Rhizoma, Sparganii Rhizoma, and HP CR–SR were identified, and total contents accounted for 75.416%, 91.857%, and 79.553% respectively. The thirty-eight components were found in HP CR–SR, and not detected in single herbs Curcumae Rhizoma and Sparganii Rhizoma. The highest radical trapping action was seen by an essential oil of HP CR–SR (IC50 = 0.59 ± 0.04 mg/mL). Furthermore, the HP CR–SR essential oil showed more remarkable cytotoxicity on tumor cell lines than that of the single herbs Curcumae Rhizoma and Sparganii Rhizoma in a dose-dependent manner: IC50 values showing 32.32 ± 5.31 μg/mL (HeLa), 34.76 ± 1.82 μg/mL (BGC823), 74.84 ± 1.66 μg/mL (MCF-7), 66.12 ± 11.23 μg/mL (SKOV3), and 708.24 ± 943.91 μg/mL (A549), respectively. In summary, the essential oil of HP CR–SR is different from any one of Curcumae Rhizoma and Sparganii Rhizoma, nor simply their superposition, and HP CR–SR oil presented more remarkable anticancer and antioxidant activities compared with Curcumae Rhizoma and Sparganii Rhizoma oils. Full article
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Open AccessArticle Chemical Composition and Bioactivities of the Essential Oil from Etlingera yunnanensis against Two Stored Product Insects
Molecules 2015, 20(9), 15735-15747; doi:10.3390/molecules200915735
Received: 14 July 2015 / Revised: 8 August 2015 / Accepted: 21 August 2015 / Published: 28 August 2015
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Abstract
The chemical composition of the essential oil of Etlingera yunnanensis rhizomes and its contact and repellent activities against Tribolium castaneum (Herbst) and Liposcelis bostrychophila (Badonnel) were investigated. The essential oil obtained from E. yunnanensis rhizomes with hydrodistillation was performed by gas chromatography-flame
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The chemical composition of the essential oil of Etlingera yunnanensis rhizomes and its contact and repellent activities against Tribolium castaneum (Herbst) and Liposcelis bostrychophila (Badonnel) were investigated. The essential oil obtained from E. yunnanensis rhizomes with hydrodistillation was performed by gas chromatography-flame ionization detection and gas chromatography-mass spectrometry. The main components of the essential oil were identified to be estragole (65.2%), β-caryophyllene (6.4%), 1,8-cineole (6.4%), limonene (5.2%), and α-pinene (2.4%). It was found that the essential oil of E. yunnanensis rhizomes possessed contact toxicity against T. castaneum and L. bostrychophila (LD50 = 23.33 μg/adult and LD50 = 47.38 μg/cm2, respectively). Estragole, 1,8-cineole, and limonene exhibited stronger contact toxicity (LD50 values of 20.41, 18.86, and 13.40 μg/adult, respectively) than β-caryophyllene (LD50 = 41.72 μg/adult) against T. castaneum adults. Estragole possessed stronger contact toxicity (LD50 = 30.22 µg/cm2) than β-caryophyllene, 1,8-cineole, and limonene (LD50 values of 74.11, 321.20, and 239.62 μg/adult, respectively) against L. bostrychophila adults. Repellency of the crude oil was also evaluated. The essential oil and constituents possessed strong repellent activity against T. castaneum adults. The four individual constituents showed weaker repellent activity than the essential oil against L. bostrychophila adults. The results indicated that the essential oil of E. yunnanensis rhizomes and the individual constituents had the potential to be developed as a natural insecticide and repellent for the control of T. castaneum and L. bostrychophila. Full article
Open AccessArticle The Influence of Sesquiterpenes from Myrica rubra on the Antiproliferative and Pro-Oxidative Effects of Doxorubicin and Its Accumulation in Cancer Cells
Molecules 2015, 20(8), 15343-15358; doi:10.3390/molecules200815343
Received: 9 July 2015 / Revised: 6 August 2015 / Accepted: 13 August 2015 / Published: 21 August 2015
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Abstract
The sesquiterpenes β-caryophyllene, β-caryophyllene oxide (CAO), α-humulene (HUM), trans-nerolidol (NER), and valencene (VAL) are substantial components of the essential oil from Myrica rubra leaves which has exhibited significant antiproliferative effects in several intestinal cancer cell lines, with CaCo-2 cells being the most
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The sesquiterpenes β-caryophyllene, β-caryophyllene oxide (CAO), α-humulene (HUM), trans-nerolidol (NER), and valencene (VAL) are substantial components of the essential oil from Myrica rubra leaves which has exhibited significant antiproliferative effects in several intestinal cancer cell lines, with CaCo-2 cells being the most sensitive. The present study was designed to evaluate the effects of these sesquiterpenes on the efficacy and toxicity of the anticancer drug doxorubicin (DOX) in CaCo-2 cancer cells and in primary culture of rat hepatocytes. Our results showed that HUM, NER, VAL and CAO inhibited proliferation of CaCo-2 cancer cells but they did not affect the viability of hepatocytes. CAO, NER and VAL synergistically potentiated the efficacy of DOX in cancer cells killing. All sesquiterpenes exhibited the ability to selectively increase DOX accumulation in cancer cells and did not affect DOX concentration in hepatocytes. Additionally, CAO and VAL were able to increase the pro-oxidative effect of DOX in CaCo-2 cells. Moreover, CAO mildly ameliorated DOX toxicity in hepatocytes. Based on all results, CAO seems to be the most promising compound for further testing. Full article
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