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Special Issue "Natural Product Pharmacology and Medicinal Chemistry"

A special issue of Molecules (ISSN 1420-3049). This special issue belongs to the section "Natural Products Chemistry".

Deadline for manuscript submissions: 31 July 2019

Special Issue Editors

Guest Editor
Prof. Marcello Locatelli

Department of Pharmacy Build B, level 2; University "G. d'Annunzio" of Chieti-Pescara; Via dei Vestini, 31; I-66100 Chieti; Italy
Website | E-Mail
Phone: +3908713554590
Interests: Innovative (micro) extraction procedures (MEPS, FPSE, DLLME, SULLE, MAE, etc.) and hyphenated instrument configurations; Bioactive compounds (drugs, drugs associations, and natural bioactive compounds); Characterization, fingerprints, and method validation; HPLC; Mass spectrometry (MS and MS/MS).
Guest Editor
Prof. Dr. Simone Carradori

Department of Pharmacy, “G. d’Annunzio” University of Chieti-Pescara, 66100 Chieti, Italy
Website | E-Mail
Interests: medicinal chemistry; microwave-assisted extraction; natural compounds; antifungals; anti-Helicobacter pylori agents; parasiticidal compounds
Guest Editor
Dr. Andrei Mocan

Department of Pharmaceutical Botany, Iuliu Hațieganu University of Medicine and Pharmacy, 23 Ghe. Marinescu Street, Cluj-Napoca 400337, Romania
E-Mail
Interests: pharmaceutical biology (botany); valorization of traditional medicinal and edible plants and fungi; extraction optimization of bioactive compounds from plant materials; experimental design applied to extraction and process optimization; bioactivity and chemical characterization of natural products, development of new nutraceuticals based on medicinal plants and fungi, natural products as enzyme inhibitors

Special Issue Information

Dear Colleagues,

This Special Issue "Natural Product Pharmacology and Medicinal Chemistry” aims to collect and to disseminate some of the most significant and recent contributions in the interdisciplinary area of pharmacology and medicinal chemistry, namely the characterization and analysis of synthetic and natural products.

Prof. Dr. Marcello Locatelli
Prof. Dr. Simone Carradori
Dr. Andrei Mocan
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All papers will be peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Molecules is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1800 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • pharmacology
  • biological assays
  • extraction procedures
  • analysis
  • instrument configuration
  • medicinal chemistry
  • new chemical entities characterization

Published Papers (19 papers)

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Research

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Open AccessArticle
Comparative Phytochemical Profile, Antioxidant, Antimicrobial and In Vivo Anti-Inflammatory Activity of Different Extracts of Traditionally Used Romanian Ajuga genevensis L. and A. reptans L. (Lamiaceae)
Molecules 2019, 24(8), 1597; https://doi.org/10.3390/molecules24081597
Received: 19 March 2019 / Revised: 17 April 2019 / Accepted: 20 April 2019 / Published: 23 April 2019
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Abstract
Several Ajuga species are used in Romanian folk medicine for their antioxidant, antimicrobial and anti-inflammatory properties, to treat pain, fever or arthritis. Still, the active compounds responsible for these effects and their mechanism of action are scarcely known. This research was designed to [...] Read more.
Several Ajuga species are used in Romanian folk medicine for their antioxidant, antimicrobial and anti-inflammatory properties, to treat pain, fever or arthritis. Still, the active compounds responsible for these effects and their mechanism of action are scarcely known. This research was designed to investigate the phytochemical profile (e.g. iridoids, polyphenolic compounds, phytosterols), as well as the biological potential (antioxidant, antibacterial, antifungal, anti-inflammatory properties) of two selected Ajuga species collected from different regions of Romanian spontaneous flora. The main compounds identified in A. reptans aerial parts extracts were 8-O-acetylharpagide, isoquercitrin and β-sitosterol, whilst in A. genevensis were 8-O-acetylharpagide, luteolin and campesterol. The extracts were screened for their antioxidant potential using different methods (DPPH, TEAC, EPR) and the results showed a good activity, in accordance with the polyphenol content (18–26 mg GAE/g dw). The antifungal activity on the tested strains was good. The determination of few parameters linked with the inflammatory mechanism allowed the assessment of in vivo anti-inflammatory potential. Ajuga reptans and A. genevensis ethanol extracts had anti-inflammatory activity through lowering the oxidative stress, phagocytosis, PMN and total leukocytes. The best anti-oxidative and anti-inflammatory activity was observed for the Ajuga reptans 100 mg dw/mL extract when compared with diclofenac, thus the dose could be correlated with the pharmacological effect. These findings provide substantial evidence that both selected Ajuga species have the potential to be valued as sources of phytochemicals in effective anti-inflammatory herbal preparations. Full article
(This article belongs to the Special Issue Natural Product Pharmacology and Medicinal Chemistry)
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Open AccessArticle
Evaluation of Polyphenolic Compounds and Pharmacological Activities in Hairy Root Cultures of Ligularia fischeri Turcz. f. spiciformis (Nakai)
Molecules 2019, 24(8), 1586; https://doi.org/10.3390/molecules24081586
Received: 20 March 2019 / Revised: 17 April 2019 / Accepted: 17 April 2019 / Published: 22 April 2019
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Abstract
A considerable amount of bioactive compounds have been used for the biopharmaceutical engineering to help human health and nutrition. Hairy root culture (HRC) or transgenic root is a favourable alternative technique for phytochemical production. Ligularia fischeri is a significant source of pharmaceutically important [...] Read more.
A considerable amount of bioactive compounds have been used for the biopharmaceutical engineering to help human health and nutrition. Hairy root culture (HRC) or transgenic root is a favourable alternative technique for phytochemical production. Ligularia fischeri is a significant source of pharmaceutically important active compounds with an enormous range of health care applications. HRC of L. fischeri was developed using Agrobacterium rhizogenes for the production of polyphenolic compounds with antioxidant, antimicrobial, antidiabetic, anticancer and anti-inflammatory pharmaceutical activities. Hairy roots (HRs) were selected by morphological assessment, genetic and molecular analyses. The maximum accumulation of fresh mass (94.15 g/L) and dry mass (9.45 g/L) was recorded in MS liquid medium supplemented with 30 g/L sucrose at 28 days. Furthermore, HRs successfully produced numerous polyphenolic compounds, including six hydroxycinnamic acids, seven flavonols, seven hydroxybenzoic acids, vanillin, resveratrol, pyrogallol, homogentisic, and veratric acids, which were identified by UHPLC analysis. HRs produced higher total phenolic (185.65 mg/g), and flavonoid (5.25 mg/g) contents than non-transformed roots (125.55 mg/g and 3.75 mg/g). As a result of these metabolic changes, pharmaceutical activities were found higher in HRs than non-transformed roots (NTRs). The present study indicates that HRC has the potential to increase the content of beneficial polyphenolic compounds with higher potential pharmaceutical activities. To the best of our knowledge, the present study is the first report on enhancing the production of polyphenolic compounds with pharmaceutical activities from the HRCs of L. fischeri. Full article
(This article belongs to the Special Issue Natural Product Pharmacology and Medicinal Chemistry)
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Open AccessArticle
Purification of an Antifungal Peptide from Seeds of Brassica oleracea var. gongylodes and Investigation of Its Antifungal Activity and Mechanism of Action
Molecules 2019, 24(7), 1337; https://doi.org/10.3390/molecules24071337
Received: 16 March 2019 / Revised: 2 April 2019 / Accepted: 2 April 2019 / Published: 4 April 2019
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Abstract
In this study, a 8.5-kDa antifungal peptide designated as BGAP was purified from the crude extract of the seeds of Brassica oleracea var. gongylodes by employing a protocol that comprised cation exchange chromatography on SP-Sepharose, cation exchange chromatography on Mono S and gel [...] Read more.
In this study, a 8.5-kDa antifungal peptide designated as BGAP was purified from the crude extract of the seeds of Brassica oleracea var. gongylodes by employing a protocol that comprised cation exchange chromatography on SP-Sepharose, cation exchange chromatography on Mono S and gel filtration chromatography on Superdex peptide. BGAP showed the highest amino acid sequence similarity to defensin peptides by mass spectrometric analysis. BGAP showed a broad spectrum of antifungal activity with a half maximal inhibitory concentration at 17.33 μg/mL, 12.37 μg/mL, 16.81 μg/mL, and 5.60 μg/mL toward Colletotrichum higginsianum, Exserohilum turcicum, Magnaporthe oryzae and Mycosphaerella arachidicola, respectively. The antifungal activity of BGAP remained stable (i) after heat treatment at 40–100 °C for 15 min; (ii) after exposure to solutions of pH 1–3 and 11–13 for 15 min; (iii) after incubation with solutions containing K+, Ca2+, Mg2+, Mn2+ or Fe3+ ions at the concentrations of 20–150 mmol/L for 2 h; and (iv) following treatment with 10% methyl alcohol, 10% ethanol, 10% isopropanol or 10% chloroform for 2 h. Fluorescence staining experiments showed that BGAP brought about an increase in cell membrane permeability, a rise in reactive oxygen species production, a decrease in mitochondrial membrane potential, and an accumulation of chitin at the hyphal tips of Mycosphaerella arachidicola. Full article
(This article belongs to the Special Issue Natural Product Pharmacology and Medicinal Chemistry)
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Open AccessArticle
Neuroprotective Effects of an Aqueous Extract of Forsythia viridissima and Its Major Constituents on Oxaliplatin-Induced Peripheral Neuropathy
Molecules 2019, 24(6), 1177; https://doi.org/10.3390/molecules24061177
Received: 26 February 2019 / Revised: 20 March 2019 / Accepted: 22 March 2019 / Published: 25 March 2019
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Abstract
The dried fruits of Forsythia viridissima have been prescribed to relive fever, pain, vomiting, and nausea in traditional medicine. Oxaliplatin (LOHP) is used to treat advanced colorectal cancer; however, it frequently induces peripheral neuropathies. This study was done to evaluate the neuroprotective effects [...] Read more.
The dried fruits of Forsythia viridissima have been prescribed to relive fever, pain, vomiting, and nausea in traditional medicine. Oxaliplatin (LOHP) is used to treat advanced colorectal cancer; however, it frequently induces peripheral neuropathies. This study was done to evaluate the neuroprotective effects of an aqueous extract of Forsythia viridissima fruits (EFVF) and its major constituents. Chemical constituents from EFVF were characterized and quantified with the UHPLC-diode array detector method, and three major constituents were identified as arctiin, matairesinol, and arctigenin. The in vitro cytotoxicity was measured by the Ez-cytox viability assay, and the in vivo neuroprotection activity was evaluated by a von Frey test in two rodent animal models that were administered LOHP. EFVF significantly alleviated the LOHP-induced mechanical hypersensitivity in the induction model. EFVF also prevented the induction of mechanical hyperalgesia by LOHP in the pre- and co-treatment of LOHP and EFVF. Consistently, EFVF exerted protective effects against LOHP-induced neurotoxicity as well as inhibited neurite outgrowths in PC12 and dorsal root ganglion cells. Among the major components of EFVF, arctigenin and matairesinol exerted protective effects against LOHP-induced neurotoxicity. Therefore, EFVF may be useful for relieving or preventing LOHP-induced peripheral neuropathy in cancer patients undergoing chemotherapy with LOHP. Full article
(This article belongs to the Special Issue Natural Product Pharmacology and Medicinal Chemistry)
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Open AccessArticle
Flavopereirine—An Alkaloid Derived from Geissospermum vellosii—Presents Leishmanicidal Activity In Vitro
Molecules 2019, 24(4), 785; https://doi.org/10.3390/molecules24040785
Received: 24 December 2018 / Revised: 25 January 2019 / Accepted: 27 January 2019 / Published: 21 February 2019
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Abstract
Chemotherapy is limited in the treatment of leishmaniasis due to the toxic effects of drugs, low efficacy of alternative treatments, and resistance of the parasite. This work assesses the in vitro activity of flavopereirine on promastigote cultures of Leishmania amazonensis. In addition, [...] Read more.
Chemotherapy is limited in the treatment of leishmaniasis due to the toxic effects of drugs, low efficacy of alternative treatments, and resistance of the parasite. This work assesses the in vitro activity of flavopereirine on promastigote cultures of Leishmania amazonensis. In addition, an in silico evaluation of the physicochemical characteristics of this alkaloid is performed. The extract and fractions were characterized by thin-layer chromatography and HPLC-DAD, yielding an alkaloid identified by NMR. The antileishmanial activity and cytotoxicity were assayed by cell viability test (MTT). The theoretical molecular properties were calculated on the Molinspiration website. The fractionation made it possible to isolate a beta-carboline alkaloid (flavopereirine) in the alkaloid fraction. Moreover, it led to obtaining a fraction with greater antileishmanial activity, since flavopereirine is very active. Regarding the exposure time, a greater inhibitory effect of flavopereirine was observed at 24 h and 72 h (IC50 of 0.23 and 0.15 μg/mL, respectively). The extract, fractions, and flavopereirine presented low toxicity, with high selectivity for the alkaloid. Furthermore, flavopereirine showed no violation of Lipinski’s rule of five, showing even better results than the known inhibitor of oligopeptidase B, antipain, with three violations. Flavopereirine also interacted with residue Tyr-499 of oligopeptidase B during the molecular dynamics simulations, giving a few insights of a possible favorable mechanism of interaction and a possible inhibitory pathway. Flavopereirine proved to be a promising molecule for its antileishmanial activity. Full article
(This article belongs to the Special Issue Natural Product Pharmacology and Medicinal Chemistry)
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Open AccessArticle
Selective Inhibition of Human AKR1B10 by n-Humulone, Adhumulone and Cohumulone Isolated from Humulus lupulus Extract
Molecules 2018, 23(11), 3041; https://doi.org/10.3390/molecules23113041
Received: 17 October 2018 / Revised: 16 November 2018 / Accepted: 19 November 2018 / Published: 21 November 2018
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Abstract
Hop-derived compounds have been subjected to numerous biomedical studies investigating their impact on a wide range of pathologies. Isomerised bitter acids (isoadhumulone, isocohumulone and isohumulone) from hops, used in the brewing process of beer, are known to inhibit members of the aldo-keto-reductase superfamily. [...] Read more.
Hop-derived compounds have been subjected to numerous biomedical studies investigating their impact on a wide range of pathologies. Isomerised bitter acids (isoadhumulone, isocohumulone and isohumulone) from hops, used in the brewing process of beer, are known to inhibit members of the aldo-keto-reductase superfamily. Aldo-keto-reductase 1B10 (AKR1B10) is upregulated in various types of cancer and has been reported to promote carcinogenesis. Inhibition of AKR1B10 appears to be an attractive means to specifically treat RAS-dependent malignancies. However, the closely related reductases AKR1A1 and AKR1B1, which fulfil important roles in the detoxification of endogenous and xenobiotic carbonyl compounds oftentimes crossreact with inhibitors designed to target AKR1B10. Accordingly, there is an ongoing search for selective AKR1B10 inhibitors that do not interact with endogeneous AKR1A1 and AKR1B1-driven detoxification systems. In this study, unisomerised α-acids (adhumulone, cohumulone and n-humulone) were separated and tested for their inhibitory potential on AKR1A1, AKR1B1 and AKR1B10. Also AKR1B10-mediated farnesal reduction was effectively inhibited by α-acid congeners with Ki-values ranging from 16.79 ± 1.33 µM (adhumulone) to 3.94 ± 0.33 µM (n-humulone). Overall, α-acids showed a strong inhibition with selectivity (115–137 fold) for AKR1B10. The results presented herein characterise hop-derived α-acids as a promising basis for the development of novel and selective AKR1B10-inhibitors. Full article
(This article belongs to the Special Issue Natural Product Pharmacology and Medicinal Chemistry)
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Open AccessArticle
UPLC-MS/MS Method for the Determination of 14 Compounds in Rat Plasma and Its Application in a Pharmacokinetic Study of Orally Administered Xiaoyao Powder
Molecules 2018, 23(10), 2514; https://doi.org/10.3390/molecules23102514
Received: 9 September 2018 / Revised: 25 September 2018 / Accepted: 26 September 2018 / Published: 30 September 2018
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Abstract
Xiaoyao Powder (XYP), a common Chinese medicine, comprises eight traditional Chinese herbs and has been widely used clinically to treat liver damage and mental disorders. An ultra-performance liquid chromatography–tandem mass spectrometry method was developed to investigate the pharmacokinetics of 14 compounds (albiflorin, paeoniflorin, [...] Read more.
Xiaoyao Powder (XYP), a common Chinese medicine, comprises eight traditional Chinese herbs and has been widely used clinically to treat liver damage and mental disorders. An ultra-performance liquid chromatography–tandem mass spectrometry method was developed to investigate the pharmacokinetics of 14 compounds (albiflorin, paeoniflorin, ferulic acid, senkyunolide I, quercetin, isoliquiritigenin, atractylenolide III, ligustilide, atractylenolide II, liquiritin, liquiritigenin, saikosaponin c, glycyrrhizic acid, and saikosaponin a) in XYP. Naringenin was used as the internal standard. The compounds were separated using an ACQUITY UPLCTM BEH C18 column (1.7 μm, 50 × 2.1 mm) with a mobile phase consisting of acetonitrile and 0.1% formic acid in water at a flow rate of 0.3 mL/min. Detection was performed on a triple-quadrupole tandem mass spectrometer using multiple reaction monitoring and an electrospray ionization source in both positive and negative ionization modes. All calibration curves exhibited good linearity (r2 > 0.9974) over the measured ranges. The intra- and inter-day precisions were within 12%, and the accuracy ranged from 89.93% to 106.64%. Extraction recovery and matrix effect results were satisfactory. The method was successfully applied in a pharmacokinetic study of the 14 compounds in rat plasma after the oral administration of XYP. Full article
(This article belongs to the Special Issue Natural Product Pharmacology and Medicinal Chemistry)
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Open AccessArticle
Trichosanthis Pericarpium Aqueous Extract Protects H9c2 Cardiomyocytes from Hypoxia/Reoxygenation Injury by Regulating PI3K/Akt/NO Pathway
Molecules 2018, 23(10), 2409; https://doi.org/10.3390/molecules23102409
Received: 27 August 2018 / Revised: 18 September 2018 / Accepted: 18 September 2018 / Published: 20 September 2018
Cited by 1 | PDF Full-text (2854 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Trichosanthis Pericarpium (TP) is a traditional Chinese medicine for treating cardiovascular diseases. In this study, we investigated the effects of TP aqueous extract (TPAE) on hypoxia/reoxygenation (H/R) induced injury in H9c2 cardiomyocytes and explored the underlying mechanisms. H9c2 cells were cultured under the [...] Read more.
Trichosanthis Pericarpium (TP) is a traditional Chinese medicine for treating cardiovascular diseases. In this study, we investigated the effects of TP aqueous extract (TPAE) on hypoxia/reoxygenation (H/R) induced injury in H9c2 cardiomyocytes and explored the underlying mechanisms. H9c2 cells were cultured under the hypoxia condition induced by sodium hydrosulfite for 30 min and reoxygenated for 4 h. Cell viability was measured by MTT assay. The amounts of LDH, NO, eNOS, and iNOS were tested by ELISA kits. Apoptotic rate was detected by Annexin V-FITC/PI staining. QRT-PCR was performed to analyze the relative mRNA expression of Akt, Bcl-2, Bax, eNOS, and iNOS. Western blotting was used to detect the expression of key members in the PI3K/Akt pathway. Results showed that the pretreatment of TPAE remarkably enhanced cell viability and decreased apoptosis induced by H/R. Moreover, TPAE decreased the release of LDH and expression of iNOS. In addition, TPAE increased NO production and Bcl-2/Bax ratio. Furthermore, the mRNA and protein expression of p-Akt and eNOS were activated by TPAE pretreatment. On the contrary, a specific inhibitor of PI3K, LY294002 not only inhibited TPAE-induced p-Akt/eNOS upregulation but alleviated its anti-apoptotic effects. In conclusion, results indicated that TPAE protected against H/R injury in cardiomyocytes, which consequently activated the PI3K/Akt/NO signaling pathway. Full article
(This article belongs to the Special Issue Natural Product Pharmacology and Medicinal Chemistry)
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Open AccessArticle
Folic Acid Has a Protective Effect on Retinal Vascular Endothelial Cells against High Glucose
Molecules 2018, 23(9), 2326; https://doi.org/10.3390/molecules23092326
Received: 22 August 2018 / Revised: 8 September 2018 / Accepted: 10 September 2018 / Published: 12 September 2018
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Abstract
Diabetic retinopathy (DR) is a severe complication of diabetes, which seriously affects the life quality of patients. Because of the damage caused by DR, there is an urgent need to develop effective drugs. Folic acid, a water-soluble vitamin, is one of the vitamin [...] Read more.
Diabetic retinopathy (DR) is a severe complication of diabetes, which seriously affects the life quality of patients. Because of the damage caused by DR, there is an urgent need to develop effective drugs. Folic acid, a water-soluble vitamin, is one of the vitamin B complexes. Folic acid is widely found in the meat and vegetables. In the clinic, low folic acid levels in the body may have a certain correlation with DR. However, there is no relevant basic research proving a relationship between folic acid levels and DR. The purpose of this study was therefore to investigate whether folic acid has a protective effect on the retinal vascular endothelial cells against high glucose levels. Moreover, the molecular mechanism of action of folic acid was further explored. The results showed that folic acid significantly suppressed the cell viability, tube length, migrated cells and the percentage of BrdU+ cells compared with the high glucose group. Moreover, folic acid decreased the mRNA expression of TEAD1 and the protein expression of TEAD1 and YAP1. These findings indicate that folic acid can protect retinal vascular endothelial cells from high glucose-induced injury by regulating the proteins in the Hippo signaling pathway. Full article
(This article belongs to the Special Issue Natural Product Pharmacology and Medicinal Chemistry)
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Open AccessArticle
Analgesic Effect of 5-(3,4-Dihydroxyphenyl)-3-hydroxy-1-(2-hydroxyphenyl)penta-2,4-dien-1-one in Experimental Animal Models of Nociception
Molecules 2018, 23(9), 2099; https://doi.org/10.3390/molecules23092099
Received: 8 June 2018 / Revised: 5 July 2018 / Accepted: 6 July 2018 / Published: 21 August 2018
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Abstract
Curcuminoids derived from turmeric rhizome have been reported to exhibit antinociceptive, antioxidant and anti-inflammatory activities. We evaluated the peripheral and central antinociceptive activities of 5-(3,4-dihydroxyphenyl)-3-hydroxy-1-(2-hydroxyphenyl)penta-2,4-dien-1-one (DHHPD), a novel synthetic curcuminoid analogue at 0.1, 0.3, 1 and 3 mg/kg (intraperitoneal), through chemical [...] Read more.
Curcuminoids derived from turmeric rhizome have been reported to exhibit antinociceptive, antioxidant and anti-inflammatory activities. We evaluated the peripheral and central antinociceptive activities of 5-(3,4-dihydroxyphenyl)-3-hydroxy-1-(2-hydroxyphenyl)penta-2,4-dien-1-one (DHHPD), a novel synthetic curcuminoid analogue at 0.1, 0.3, 1 and 3 mg/kg (intraperitoneal), through chemical and thermal models of nociception. The effects of DHHPD on the vanilloid and glutamatergic systems were evaluated through the capsaicin- and glutamate-induced paw licking tests. Results showed that DHHPD significantly (p < 0.05) attenuated the writhing response produced by the 0.8% acetic acid injection. In addition, 1 and 3 mg/kg of DHHPD significantly (p < 0.05) reduced the licking time spent by each mouse in both phases of the 2.5% formalin test and increased the response latency of mice on the hot-plate. However, the effect produced in the latter was not reversed by naloxone, a non-selective opioid receptor antagonist. Despite this, DHHPD decreased the licking latency of mice in the capsaicin- and glutamate-induced paw licking tests in a dose response manner. In conclusion, DHHPD showed excellent peripheral and central antinociceptive activities possibly by attenuation of the synthesis and/or release of pro-inflammatory mediators in addition to modulation of the vanilloid and glutamatergic systems without an apparent effect on the opioidergic system. Full article
(This article belongs to the Special Issue Natural Product Pharmacology and Medicinal Chemistry)
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Open AccessArticle
Atriplex mollis Desf. Aerial Parts: Extraction Procedures, Secondary Metabolites and Color Analysis
Molecules 2018, 23(8), 1962; https://doi.org/10.3390/molecules23081962
Received: 26 July 2018 / Revised: 2 August 2018 / Accepted: 5 August 2018 / Published: 6 August 2018
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Abstract
A method using high-performance liquid chromatography coupled with a photodiode array detector was proposed for the rapid characterization of different phenolic constituents from the extracts of Atriplex mollis aerial parts. Atriplex species are known for their multiple biological activities, but no information is [...] Read more.
A method using high-performance liquid chromatography coupled with a photodiode array detector was proposed for the rapid characterization of different phenolic constituents from the extracts of Atriplex mollis aerial parts. Atriplex species are known for their multiple biological activities, but no information is available in the literature about A. mollis. With the aim to firstly characterize the main secondary metabolites of this plant, so as to orient better the biological evaluation, we applied three different extraction procedures and compared the chromatographic results. Microwave-assisted extraction gave the best yield and recovery of important compounds such as gallic acid, catechin, chlorogenic acid, p-OH benzoic acid, rutin, sinapinic acid, t-ferulic acid, naringenin and benzoic acid. These constituents belong to three important chemical classes: phenolic acids, flavonoids and monoterpenes. Color evaluation and analysis of chlorophylls (a and b) and carotenoids complete the preliminary profile of this plant. From these analyses, Atriplex mollis is a source of bioactive compounds (especially rutin, t-ferulic acid and gallic acid) and could be recommended as a plant of phyto-pharmaceutical relevance, opening new perspectives on this salt-tolerant plant. Full article
(This article belongs to the Special Issue Natural Product Pharmacology and Medicinal Chemistry)
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Open AccessArticle
Decomposing the Mechanism of Qishen Granules in the Treatment of Heart Failure by a Quantitative Pathway Analysis Method
Molecules 2018, 23(7), 1829; https://doi.org/10.3390/molecules23071829
Received: 24 June 2018 / Revised: 17 July 2018 / Accepted: 18 July 2018 / Published: 23 July 2018
Cited by 1 | PDF Full-text (3083 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Qishen granules (QSG) have beneficial therapeutic effects for heart failure, but the effects of decomposed recipes, including Wenyang Yiqi Huoxue (WYH) and Qingre Jiedu (QJ), are not clear. In this study, the efficacy of WYH and QJ on heart failure is evaluated by [...] Read more.
Qishen granules (QSG) have beneficial therapeutic effects for heart failure, but the effects of decomposed recipes, including Wenyang Yiqi Huoxue (WYH) and Qingre Jiedu (QJ), are not clear. In this study, the efficacy of WYH and QJ on heart failure is evaluated by using transverse aortic constriction (TAC) induced mice and the significantly changed genes in heart tissues were screened with a DNA array. Furthermore, a new quantitative pathway analysis tool is developed to evaluate the differences of pathways in different groups and to identify the pharmacological contributions of the decomposed recipes. Finally, the related genes in the significantly changed pathways are verified by a real-time polymerase chain reaction and a Western blot. Our data show that both QJ and WYH improve the left ventricular ejection fraction, which explain their contributions to protect against heart failure. In the energy metabolism, QJ achieves the therapeutic effects of QSG through nicotinamide nucleotide transhydrogenase (Nnt)-mediated mechanisms. In ventricular remodeling and inflammation reactions, QJ and WYH undertake the therapeutic effects through 5′-nucleotidase ecto (Nt5e)-mediated mechanisms. Together, QJ and WYH constitute the therapeutic effects of QSG and play important roles in myocardial energy metabolism and inflammation, which can exert therapeutic effects for heart failure. Full article
(This article belongs to the Special Issue Natural Product Pharmacology and Medicinal Chemistry)
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Open AccessArticle
Innovative Natural Ingredients-Based Multiple Emulsions: The Effect on Human Skin Moisture, Sebum Content, Pore Size and Pigmentation
Molecules 2018, 23(6), 1428; https://doi.org/10.3390/molecules23061428
Received: 17 May 2018 / Revised: 7 June 2018 / Accepted: 11 June 2018 / Published: 12 June 2018
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Abstract
The increased interest in natural cosmetics has resulted in a higher market demand for preservative-free products based on herbal ingredients. An innovative W/O/W type emulsions containing herbal extracts were prepared directly; its cation form was induced by an ethanolic rosemary extract and stabilized [...] Read more.
The increased interest in natural cosmetics has resulted in a higher market demand for preservative-free products based on herbal ingredients. An innovative W/O/W type emulsions containing herbal extracts were prepared directly; its cation form was induced by an ethanolic rosemary extract and stabilized using weak herbal gels. Due to the wide phytochemical composition of herbal extracts and the presence of alcohol in the emulsion system, which can cause skin irritation, sensitization or dryness when applied topically, the safety of the investigated drug delivery system is necessary. The aim of our study was to estimate the potential of W/O/W emulsions based on natural ingredients for skin irritation and phototoxicity using reconstructed 3D epidermis models in vitro and to evaluate in vivo its effect on human skin moisture, sebum content and pigmentation by biomedical examination using a dermatoscopic camera and corneometer. According to the results obtained after in vitro cell viability test the investigated emulsion was neither irritant nor phototoxic to human skin keratinocytes. W/O/W emulsion did not cause skin dryness in vivo, despite the fact that it contained ethanol. We can conclude that the emulsion is safe for use as a leave-on product due to the positive effect on human skin characteristics or as a semisolid pharmaceutical base where active compounds could be encapsulated. Full article
(This article belongs to the Special Issue Natural Product Pharmacology and Medicinal Chemistry)
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Open AccessArticle
Piplartine Analogues and Cytotoxic Evaluation against Glioblastoma
Molecules 2018, 23(6), 1382; https://doi.org/10.3390/molecules23061382
Received: 27 April 2018 / Revised: 14 May 2018 / Accepted: 14 May 2018 / Published: 8 June 2018
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Abstract
Piplartine (1) is an alkamide extracted from plants of the genus Piper which shows several pharmacological properties, including antitumor activity. To improve this activity, a series of analogues based on 1 have been synthesized by esterification and amidation using the 3,4,5-trimethoxycinnamic [...] Read more.
Piplartine (1) is an alkamide extracted from plants of the genus Piper which shows several pharmacological properties, including antitumor activity. To improve this activity, a series of analogues based on 1 have been synthesized by esterification and amidation using the 3,4,5-trimethoxycinnamic acid-like starting material. During the study, the moieties 3-(3,4,5-trimethoxyphenyl)acrylate and 3-(3,4,5-trimethoxyphenyl)acrylamide were maintained on esters and amides respectively. Meanwhile, functional changes were exploited, and it was revealed that the presence of two aromatic rings in the side-chain was important to improve the cytotoxic activity against the U87MG cell line, such as the compound (E)-benzhydryl 3-(3,4,5-trimethoxyphenyl)acrylate (10), an ester that exhibited strong cytotoxicity and a similar level of potency to that of paclitaxel, a positive control. Compound 10 had a marked concentration-dependent inhibitory effect on the viability of the U87MG cell line with apoptotic and oxidative processes, showing good potential for altering main molecular pathways to prevent tumor development. Moreover, it has strong bioavailability with non-genotoxic and non-cytotoxic properties on human blood cells. In conclusion, the findings of the present study demonstrated that compound 10 is a promising agent that may find applications combatting diseases associated with oxidative stress and as a prototype for the development of novel drugs used in the treatment of glioblastoma. Full article
(This article belongs to the Special Issue Natural Product Pharmacology and Medicinal Chemistry)
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Open AccessArticle
Synthesis, Antiviral and Cytotoxic Activity of Novel Terpenyl Hybrid Molecules Prepared by Click Chemistry
Molecules 2018, 23(6), 1343; https://doi.org/10.3390/molecules23061343
Received: 17 May 2018 / Revised: 1 June 2018 / Accepted: 1 June 2018 / Published: 3 June 2018
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Abstract
Naturally occurring terpenes were combined by click reactions to generate sixteen hybrid molecules. The diterpene imbricatolic acid (IA) containing an azide group was used as starting compound for the synthesis of all the derivatives. The alkyne group in the terpenes cyperenoic acid, dehydroabietinol, [...] Read more.
Naturally occurring terpenes were combined by click reactions to generate sixteen hybrid molecules. The diterpene imbricatolic acid (IA) containing an azide group was used as starting compound for the synthesis of all the derivatives. The alkyne group in the terpenes cyperenoic acid, dehydroabietinol, carnosic acid γ-lactone, ferruginol, oleanolic acid and aleuritolic acid was obtained by esterification using appropriate alcohols or acids. The hybrid compounds were prepared by combining the IA azide function with the different terpene-alkynes under click chemistry conditions. The cytotoxic activity of the terpene hybrids 116 was assessed against Vero cells and tumour cell lines (HEP-2, C6 and Raw 264.7). Compounds 1, 2, 3 and 7 showed cytotoxic activity against the tested cell lines. The antiviral activity of the compounds was evaluated against HSV-1 KOS, Field and B2006 strain. For the pairs of hybrid compounds formed between IA-diterpene (compounds 38, except for compound 7), a moderate activity was observed against the three HSV-1 strains with an interesting selectivity index (SI ≥10, SI = CC50/CE50) for some compounds. Full article
(This article belongs to the Special Issue Natural Product Pharmacology and Medicinal Chemistry)
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Open AccessReview
Ethnomedicinal, Phytochemical and Pharmacological Investigations of Perilla frutescens (L.) Britt.
Molecules 2019, 24(1), 102; https://doi.org/10.3390/molecules24010102
Received: 14 October 2018 / Revised: 28 November 2018 / Accepted: 2 December 2018 / Published: 28 December 2018
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Abstract
Perilla frutescens (L.) Britt. (PF) is an annual herbal medicinal, aromatic, functional food, and ornamental plant that belongs to the mint family, Lamiaceae. The origin of perilla traces back to East Asian countries (China, Japan, Korea, Taiwan, Vietnam, and India), where it has [...] Read more.
Perilla frutescens (L.) Britt. (PF) is an annual herbal medicinal, aromatic, functional food, and ornamental plant that belongs to the mint family, Lamiaceae. The origin of perilla traces back to East Asian countries (China, Japan, Korea, Taiwan, Vietnam, and India), where it has been used as a valuable source of culinary and traditional medicinal uses. The leaves, seeds, and stems of P. frutescens are used for various therapeutic applications in folk medicine. In the absence of a comprehensive review regarding all aspects of perilla, this review aims to present an overview pertaining to the botanical drug, ethnobotany, phytochemistry, and biological activity. It was found that the taxonomic classification of perilla species is quite confused, and the number of species is vague. Perilla has traditionally been prescribed to treat depression-related disease, anxiety, asthma, chest stuffiness, vomiting, coughs, colds, flus, phlegm, tumors, allergies, intoxication, fever, headache, stuffy nose, constipation, abdominal pain, and indigestion, and acts as an analgesic, anti-abortive agent, and a sedative. Until now, 271 natural molecules have been identified in perilla organs including phenolic acids, flavonoids, essential oils, triterpenes, carotenoids, phytosterols, fatty acids, tocopherols, and policosanols. In addition to solvent extracts, these individual compounds (rosmarinic acid, perillaldehyde, luteolin, apigenin, tormentic acid, and isoegomaketone) have attracted researchers’ interest for its pharmacological properties. Perilla showed various biological activities such as antioxidant, antimicrobial, anti-allergic, antidepressant, anti-inflammatory, anticancer, and neuroprotection effects. Although the results are promising in preclinical studies (in vitro and in vivo), clinical studies are insufficient; therefore, further study needs to be done to validate its therapeutic effects and to ensure its safety and efficacy. Full article
(This article belongs to the Special Issue Natural Product Pharmacology and Medicinal Chemistry)
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Open AccessReview
Tagetes spp. Essential Oils and Other Extracts: Chemical Characterization and Biological Activity
Molecules 2018, 23(11), 2847; https://doi.org/10.3390/molecules23112847
Received: 12 July 2018 / Revised: 19 October 2018 / Accepted: 28 October 2018 / Published: 1 November 2018
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Abstract
Tagetes (marigold) is native to America, and its cultivation currently extends to other countries in Africa, Asia, and Europe. Many species of this genus, such as T. minuta, T. erecta, T. patula, and T. tenuifolia, are cultivated as ornamental [...] Read more.
Tagetes (marigold) is native to America, and its cultivation currently extends to other countries in Africa, Asia, and Europe. Many species of this genus, such as T. minuta, T. erecta, T. patula, and T. tenuifolia, are cultivated as ornamental plants and studied for their medicinal properties on the basis of their use in folk medicine. Different parts of the Tagetes species are used as remedies to treat various health problems, including dental, stomach, intestinal, emotional, and nervous disorders, as well as muscular pain, across the world. Furthermore, these plants are studied in the field of agriculture for their fungicidal, bactericidal, and insecticidal activities. The phytochemical composition of the extracts of different Tagetes species parts are reported in this work. These compounds exhibit antioxidant, antiinflammatory, and enzyme inhibitory properties. Cultivation and the factors affecting the chemical composition of Tagetes species are also covered. In the current work, available literature on Tagetes species in traditional medicine, their application as a food preservative, and their antimicrobial activities are reviewed. Full article
(This article belongs to the Special Issue Natural Product Pharmacology and Medicinal Chemistry)
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Open AccessReview
Phytochemical Constituents and Biological Activities of Melicope lunu-ankenda
Molecules 2018, 23(10), 2708; https://doi.org/10.3390/molecules23102708
Received: 20 September 2018 / Revised: 17 October 2018 / Accepted: 18 October 2018 / Published: 20 October 2018
Cited by 1 | PDF Full-text (7639 KB) | HTML Full-text | XML Full-text
Abstract
Natural products, either pure compounds or standardized plant extracts, have provided opportunities for the discovery of new drugs. Nowadays, most of the world’s population still relies on traditional medicines for healthcare purposes. Plants, in particular, are always used as traditional medicine, as they [...] Read more.
Natural products, either pure compounds or standardized plant extracts, have provided opportunities for the discovery of new drugs. Nowadays, most of the world’s population still relies on traditional medicines for healthcare purposes. Plants, in particular, are always used as traditional medicine, as they contain a diverse number of phytochemicals that can be used for the treatment of diseases. The multicomponent feature in the plants is considered a positive phytotherapeutic hallmark. Hence, ethnopharmacognosy has been the focus for finding alternative treatments for diseases. Melicope lunu-ankenda, also known as Euodia lunu-ankenda, is widely distributed in tropical regions of Asia. Different parts of M. lunu-ankenda have been used for treatment of hypertension, menstrual disorder, diabetes, and fever, and as an emmenagogue and tonic. It has also been consumed as salad and as a condiment for food flavorings. The justification of use of M. lunu-ankenda in folk medicines is supported by its reported biological activities, including its cytotoxic, antibacterial, antioxidant, analgesic, antidiabetic, and anti-inflammatory activities. This review summarizes the phytochemical compounds isolated from various parts of M. lunu-ankenda, such as root and leaves, and also its biological activities, which could make the species a new therapeutic agent for some diseases, including diabetes, in the future. Full article
(This article belongs to the Special Issue Natural Product Pharmacology and Medicinal Chemistry)
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Open AccessReview
Ethnobotany, Phytochemistry and Pharmacological Effects of Plants in Genus Cynanchum Linn. (Asclepiadaceae)
Molecules 2018, 23(5), 1194; https://doi.org/10.3390/molecules23051194
Received: 28 April 2018 / Revised: 11 May 2018 / Accepted: 14 May 2018 / Published: 16 May 2018
Cited by 3 | PDF Full-text (2665 KB) | HTML Full-text | XML Full-text
Abstract
Genus Cynanchum L. belongs to the family Asclepiadaceae, which comprise more than 200 species distributed worldwide. In Chinese medical practice, numerous drugs (such as tablets and powders) containing different parts of plants of this genus are used to treat snake bites, bruises, osteoblasts, [...] Read more.
Genus Cynanchum L. belongs to the family Asclepiadaceae, which comprise more than 200 species distributed worldwide. In Chinese medical practice, numerous drugs (such as tablets and powders) containing different parts of plants of this genus are used to treat snake bites, bruises, osteoblasts, rheumatoid arthritis and tumors. A search for original articles published on the cynanchum genus was performed by using several resources, including Flora of China Official Website and various scientific databases, such as PubMed, SciFinder, the Web of Science, Science Direct, and China Knowledge Resource Integrated (CNKI). Advances in the botanical, ethnomedicinal, phytochemical, and pharmacological studies of this genus are reviewed in this paper. Results showed that more than 440 compounds, including C21 steroids, steroidal saponins, alkaloids, flavonoids and terpene, have been isolated and identified from Cynanchum plants up to now. In vivo and in vitro studies have shown that plants possess an array of biological activities, including anti-tumor, neuroprotective and anti-fungal effects. Popular traditional prescription of Cynanchum sp. was also summed up in this paper. However, many Cynanchum species have received little or no attention. Moreover, few reports on the clinical use and toxic effects of Cynanchum sp. are available. Further attention should be focused on the study of these species to gather information on their respective toxicology data and relevant quality-control measures and clinical value of the crude extracts, active compounds, and bioactive metabolites from this genus. Further research on Cynanchum sp. should be conducted, and bioactivity-guided isolation strategies should be emphasized. In addition, systematic studies of the chemical composition of plants should be enhanced. Full article
(This article belongs to the Special Issue Natural Product Pharmacology and Medicinal Chemistry)
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