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Special Issue "The Potential Use of Herbal Medicinal Products in Chronic Disorders"

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

Deadline for manuscript submissions: 30 June 2019

Special Issue Editor

Guest Editor
Prof. Dr. Chingfeng Weng

Department of Life Science and Institute of Biotechnology, National Dong Hwa University, Hualien, Taiwan
Website | E-Mail
Phone: 886-3-8903649
Interests: molecular physiology; herbal medicine; translational medicine; endocrinology

Special Issue Information

Dear Colleagues,

Recently, many conventional drugs have been hampered by a lack of effectiveness, antibiotic resistance, high side effects and burdens. This has to be overcome by new strategies and therapeutic alternatives. Natural products are considered to be an important source for new anticancer, antidiabetic, neurodegenerative diseases, antimicrobials, pathogenic fungi, viruses, and parasites. For the past few dacades, herbal medicinal products have proven their efficacy at curing or attenuating symptoms of many chronic diseases, such as metabolic disorder (diabetes, hypercholesterolemia, hyperlipidemia, steatosis), auto-immune diseases (lupus, rhumatoid arthritis), inflammation diseases (inflammatory bowel disease, colitis), and degenerative diseases (arthritis, Parkinson’s disease, Alzeheimer’s disease). These herbal medicinal products, including pure compounds, extracts, and decoctions, ameliorate disease progression through many characteristics, such as inflammatory modulators, insulin sensitizers, and homeostatic keepers. This Special Issue hopes to comprehensively highlight the newest discoveries in herbal medicinal products for treating or attenuating symptoms of chronic diseases, especially herbal medicinal products as adjuvants for current treatments, side effect attenuators, or synergy toward current medicines. Additionally, studies that debate herbal–herbal interactions and herbal–drug are welcome.

Prof. Dr. Chingfeng Weng
Guest Editor

Manuscript Submission Information

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Keywords

  • herbal medicine
  • chronic diseases
  • adjuvant
  • herbal-herbal interaction
  • alternative medicine

Published Papers (10 papers)

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Research

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Open AccessArticle
Characterizing the Neuroprotective Effects of S/B Remedy (Scutellaria baicalensis Georgi and Bupleurum scorzonerifolfium Willd) in Spinal Cord Injury
Molecules 2019, 24(10), 1885; https://doi.org/10.3390/molecules24101885
Received: 4 April 2019 / Revised: 10 May 2019 / Accepted: 14 May 2019 / Published: 16 May 2019
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Abstract
The main causes of dysfunction after a spinal cord injury (SCI) include primary and secondary injuries that occur during the first minutes, hours, to days after injury. This treatable secondary cascade provides a window of opportunity for delivering therapeutic interventions. An S/B remedy [...] Read more.
The main causes of dysfunction after a spinal cord injury (SCI) include primary and secondary injuries that occur during the first minutes, hours, to days after injury. This treatable secondary cascade provides a window of opportunity for delivering therapeutic interventions. An S/B remedy (Scutellaria baicalensis Georgi and Bupleurum scorzonerifolfium Willd) has anti-inflammatory, cytoprotective, and anticarcinogenic effects in liver or neurodegenerative diseases. The present work examined the effect of S/B on injured spinal cord neurons in cultures and in vivo. S/B effectively reduced peroxide toxicity and lipopolysaccharide stimulation in both spinal cord neuron/glial and microglial cultures with the involvement of PKC and HSP70. The effect of S/B was further conducted in contusive SCI rats. Intraperitoneal injections of S/B to SCI rats preserved spinal cord tissues and effectively attenuated microglial activation. Consistently, S/B treatment significantly improved hindlimb functions of SCI rats. In the acute stage of injury, S/B treatment markedly reduced the levels of ED1 expression and lactate and had a tendency to decrease lipid peroxidation. Taken together, we demonstrated long-term hindlimb restoration alongside histological improvements with systemic S/B remedy treatment in a clinically relevant model of contusive SCI. Our findings highlight the potential of an S/B remedy for acute therapeutic intervention after SCI. Full article
(This article belongs to the Special Issue The Potential Use of Herbal Medicinal Products in Chronic Disorders)
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Open AccessCommunication
Plantago asiatica Seed Extracts Alleviated Blood Pressure in Phase I–Spontaneous Hypertension Rats
Molecules 2019, 24(9), 1734; https://doi.org/10.3390/molecules24091734
Received: 2 April 2019 / Revised: 24 April 2019 / Accepted: 30 April 2019 / Published: 4 May 2019
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Abstract
Arterial pressure of each new breeding spontaneous Phase-1 hypertension (P1-HT) rat was recorded for 5 min by intravascular femoral artery catheter that served as a reference value prior to treatment. In the acute antihypertensive test, 0.36 g/kg Bwt of Plantago asiatica seed extract [...] Read more.
Arterial pressure of each new breeding spontaneous Phase-1 hypertension (P1-HT) rat was recorded for 5 min by intravascular femoral artery catheter that served as a reference value prior to treatment. In the acute antihypertensive test, 0.36 g/kg Bwt of Plantago asiatica seed extract (PSE) was administered, via gavage feeding, to P1-HT rats, and the arterial pressures were continuously recorded for 1 h. The acute antihypertensive effects of PSE on P1-HT rats appeared within 15 min after PSE administration and lasted over 1 h with systolic pressure decreased 31.5 mmHg and diastolic pressure decreased 18.5 mmHg. The systolic pressure decreased 28 mmHg and diastolic pressure decreased 16 mmHg in P1-HT rats when simultaneously compared with verapamil hydrochloride (reference drug), whereas there were no significant differences in the pretreated reference values of acute PSE treatment and the untreated control. In the chronic test, P1-HT rats received 0.36 g/kg Bwt day of PSE or equal volume of water for 4 weeks via oral gavage, and the lower blood pressure tendencies of chronic PSE treatment were also found when compared with the controls. The antihypertensive values of PSE were also confirmed in spontaneously hypertensive rats (SHRs). Oral administration with PSE can effectively moderate blood pressure within an hour, while taking PSE daily can control the severity of hypertension, suggesting PSE is a potentially antihypertensive herb. Full article
(This article belongs to the Special Issue The Potential Use of Herbal Medicinal Products in Chronic Disorders)
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Open AccessArticle
Inhibition of Amyloid Beta Aggregation and Deposition of Cistanche tubulosa Aqueous Extract
Molecules 2019, 24(4), 687; https://doi.org/10.3390/molecules24040687
Received: 17 January 2019 / Revised: 13 February 2019 / Accepted: 13 February 2019 / Published: 14 February 2019
Cited by 1 | PDF Full-text (2859 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Cistanche tubulosa aqueous extract (CTE) is already used as a botanical prescription drug for treating dementia in China. Our previous studies reported that phenylethanoid glycosides of CTE have anti-Alzheimer’s disease (AD) activity by inhibiting amyloid β peptide (Aβ) aggregation and deposition. However, recent [...] Read more.
Cistanche tubulosa aqueous extract (CTE) is already used as a botanical prescription drug for treating dementia in China. Our previous studies reported that phenylethanoid glycosides of CTE have anti-Alzheimer’s disease (AD) activity by inhibiting amyloid β peptide (Aβ) aggregation and deposition. However, recent studies considered that the phenylethanoid glycosides may be metabolized by intestinal bacteria, because all analysis results showed that the bioavailability of phenylethanoid glycosides is extremely low. In this study we demonstrate how iron chelation plays a crucial role in the Aβ aggregation and deposition inhibition mechanism of phenylethanoid glycosides of CTE. In addition, we further proved phenylethanoid glycosides (13) could reach brain. Active CTE component and action mechanism confirmation will be a great help for product quality control and bioavailability studies in the future. At the same time, we provide a new analysis method useful in determining phenylethanoid glycosides (13) in plants, foods, blood, and tissues for chemical fingerprint and pharmacokinetic research. Full article
(This article belongs to the Special Issue The Potential Use of Herbal Medicinal Products in Chronic Disorders)
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Open AccessArticle
New Anti-inflammatory Flavonol Glycosides from Lindera akoensis Hayata
Molecules 2019, 24(3), 563; https://doi.org/10.3390/molecules24030563
Received: 31 December 2018 / Revised: 31 January 2019 / Accepted: 1 February 2019 / Published: 4 February 2019
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Abstract
Inflammation is related to many diseases. Lindera akoensis Hayata was often used in folk
therapy in Taiwan for inflammation. In this study, three new flavonol acyl glycosides, namely
kaempferol-3-O--D-4”,6”-di-(E)-p-coumaroylglucoside (1), 3”-(E)-p-coumaroylafzelin (2) and 40-Omethyl-
2”,4”-di-(E)-p-coumaroylquercitrin (3), and [...] Read more.
Inflammation is related to many diseases. Lindera akoensis Hayata was often used in folk
therapy in Taiwan for inflammation. In this study, three new flavonol acyl glycosides, namely
kaempferol-3-O--D-4”,6”-di-(E)-p-coumaroylglucoside (1), 3”-(E)-p-coumaroylafzelin (2) and 40-Omethyl-
2”,4”-di-(E)-p-coumaroylquercitrin (3), and three components, 3-dodecyl-4-hydroxy-
5-methyldihydrofuran-2-one (4), 2-acetoxyclovan-9-ol (5), (1,4,6)-trihydroxyeudesmane
(6) that were isolated from the natural product for the first time were obtained along with 25 known
compounds from L. akoensis. Their structures were determined by comprehensive spectroscopic
analyses (1D and 2D NMR, EI-, ESI- and HRESI-MS). The ability of 1 to decrease the LPS-stimulated
production of nitrite in RAW264.7 cell was evaluated, showing an IC50 value of 36.3 ± 3.2 μM.
This result supports the value of L. akoensis as a traditional medicine resource. Full article
(This article belongs to the Special Issue The Potential Use of Herbal Medicinal Products in Chronic Disorders)
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Open AccessArticle
The Cholesterol-Modulating Effect of Methanol Extract of Pigeon Pea (Cajanus cajan (L.) Millsp.) Leaves on Regulating LDLR and PCSK9 Expression in HepG2 Cells
Molecules 2019, 24(3), 493; https://doi.org/10.3390/molecules24030493
Received: 8 January 2019 / Revised: 22 January 2019 / Accepted: 29 January 2019 / Published: 30 January 2019
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Abstract
Pigeon pea (Cajanus cajan (L.) Millsp.) is a legume crop consumed as an indigenous vegetable in the human diet and a traditional medicinal plant with therapeutic properties. The current study highlights the cholesterol-modulating effect and underlying mechanisms of the methanol extract of [...] Read more.
Pigeon pea (Cajanus cajan (L.) Millsp.) is a legume crop consumed as an indigenous vegetable in the human diet and a traditional medicinal plant with therapeutic properties. The current study highlights the cholesterol-modulating effect and underlying mechanisms of the methanol extract of Cajanus cajan L. leaves (MECC) in HepG2 cells. We found that MECC increased the LDLR expression, the cell-surface LDLR levels and the LDL uptake activity in HepG2 cells. We further demonstrated that MECC suppressed the proprotein convertase subtilisin/kexin type 9 (PCSK9) mRNA and protein expression, but not affected the expression of other cholesterol or lipid metabolism-related genes including inducible degrader of LDLR (IDOL), HMG-CoA reductase (HMGCR), fatty acid synthase (FASN), acetyl-CoA carboxylase (ACC1), and liver X receptor-α (LXR-α) in HepG2 cells. Furthermore, we demonstrated that MECC down-regulated the PCSK9 gene expression through reducing the amount of nuclear hepatocyte nuclear factor-1α (HNF-1α), a major transcriptional regulator for activation of PCSK9 promoter, but not that of nuclear sterol-responsive element binding protein-2 (SREBP-2) in HepG2 cells. Finally, we identified the cajaninstilbene acid, a main bioactive stilbene component in MECC, which significantly modulated the LDLR and PCSK9 expression in HepG2 cells. Our current data suggest that the cajaninstilbene acid may contribute to the hypocholesterolemic activity of Cajanus cajan L. leaves. Our findings support that the extract of Cajanus cajan L. leaves may serve as a cholesterol-lowering agent. Full article
(This article belongs to the Special Issue The Potential Use of Herbal Medicinal Products in Chronic Disorders)
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Graphical abstract

Open AccessArticle
Preparation of Herbal Formulation for Inflammatory Bowel Disease Based on In Vitro Screening and In Vivo Evaluation in a Mouse Model of Experimental Colitis
Molecules 2019, 24(3), 464; https://doi.org/10.3390/molecules24030464
Received: 31 December 2018 / Revised: 19 January 2019 / Accepted: 25 January 2019 / Published: 28 January 2019
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Abstract
Many medicinal plants have been used traditionally in East Asia for the treatment of gastrointestinal disease and inflammation. The aim of this study was to evaluate the anti-inflammatory activity of 350 extracts (175 water extracts and 175 ethanol extracts) from 71 single plants, [...] Read more.
Many medicinal plants have been used traditionally in East Asia for the treatment of gastrointestinal disease and inflammation. The aim of this study was to evaluate the anti-inflammatory activity of 350 extracts (175 water extracts and 175 ethanol extracts) from 71 single plants, 97 mixtures of two plants, and seven formulations based on traditional medicine, to find herbal formulations to treat inflammatory bowel disease (IBD). In the in vitro screening, nitric oxide (NO), tumor necrosis factor (TNF)-α, and interleukin (IL)-6 levels were determined in LPS-treated RAW264.7 cells and the TNF-α induced monocyte-epithelial cell adhesion assay was used for the evaluation of the anti-inflammatory activity of the compounds. Dextran sulfate sodium (DSS)-induced colitis model and 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis model were used to evaluate the therapeutic effect against IBD of the samples selected from the in vitro screening. KM1608, composed of Zingiber officinale, Terminalia chebula and Aucklandia lappa, was prepared based on the screening experiments. The oral administration of KM1608 significantly attenuated the severity of colitis symptoms, such as weight loss, diarrhea, and rectal bleeding, in TNBS-induced colitis. In addition, inflammatory mediators, such as myeloperoxidase, TNF-α, and IL-6 levels decreased in the lysate of colon tissues treated with KM1608. Collectively, KM1608 ameliorated colitis through the regulation of inflammatory responses within the colon, which indicated that KM1608 had potential for the treatment of IBD. Full article
(This article belongs to the Special Issue The Potential Use of Herbal Medicinal Products in Chronic Disorders)
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Open AccessArticle
Protective Effect of Phenolic Compounds Isolated from Mugwort (Artemisia argyi) against Contrast-Induced Apoptosis in Kidney Epithelium Cell Line LLC-PK1
Molecules 2019, 24(1), 195; https://doi.org/10.3390/molecules24010195
Received: 26 November 2018 / Revised: 3 January 2019 / Accepted: 3 January 2019 / Published: 7 January 2019
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Abstract
We investigated whether 14 phenolic compounds isolated from Artemisia argyi could prevent the apoptotic damage caused by iodixanol, an iodinated contrast agent, on LLC-PK1 cells. Iodixanol was used to induce cytotoxicity in LLC-PK1 cells. Apoptotic cell death was observed as the fluorescence intensity [...] Read more.
We investigated whether 14 phenolic compounds isolated from Artemisia argyi could prevent the apoptotic damage caused by iodixanol, an iodinated contrast agent, on LLC-PK1 cells. Iodixanol was used to induce cytotoxicity in LLC-PK1 cells. Apoptotic cell death was observed as the fluorescence intensity emitted by annexin V and Hoechst 33342 stains. Western blotting was used to detect specific proteins. Seven phenolic compounds protected against iodixanol-induced LLC-PK1 cell death in a concentration-dependent manner. Among them, methyl caffeate exerted the strongest protective effect, and co-treatment with 50 and 100 μM methyl caffeate decreased intracellular reactive oxygen species elevated by 25 mg/mL iodixanol. In addition, the treatment of LLC-PK1 cells with iodixanol resulted in an increase in apoptotic cell death, which decreased by co-treatment with methyl caffeate. Iodixanol caused a cytotoxicity-related increase in the phosphorylation of extracellular-signal-regulated kinase, c-Jun N-terminal kinase, and P38; and a similar increase in the expression levels of kidney injury molecule-1 and cleaved caspase-3. However, the up-regulation of these proteins was reversed by co-treatment with methyl caffeate. These findings suggest that phenolic compounds isolated from A. argyi play an important role in protecting kidney epithelium cells against apoptotic damage caused by iodixanol. Full article
(This article belongs to the Special Issue The Potential Use of Herbal Medicinal Products in Chronic Disorders)
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Open AccessArticle
Comparative Bioavailability of Two Diosmin Formulations after Oral Administration to Healthy Volunteers
Molecules 2018, 23(9), 2174; https://doi.org/10.3390/molecules23092174
Received: 26 July 2018 / Revised: 24 August 2018 / Accepted: 25 August 2018 / Published: 29 August 2018
Cited by 1 | PDF Full-text (665 KB) | HTML Full-text | XML Full-text
Abstract
Diosmin is a flavonoid commonly found in citrus fruits, largely used as adjuvant treatment for circulatory disorders, including chronic venous insufficiency (CVI) and hemorrhoids. Following oral administration, diosmin is not directly absorbed but must first be hydrolyzed into its aglycone, diosmetin, which is [...] Read more.
Diosmin is a flavonoid commonly found in citrus fruits, largely used as adjuvant treatment for circulatory disorders, including chronic venous insufficiency (CVI) and hemorrhoids. Following oral administration, diosmin is not directly absorbed but must first be hydrolyzed into its aglycone, diosmetin, which is then absorbed into the systemic circulation. The aim of the current cross-over clinical study was to assess the pharmacokinetic profile of µSmin® Plus, a micronized diosmin flavonoid complex standardized in diosmin and formulated with a buffering agent (tested formulation). The study compared this to unformulated micronized diosmin (reference), in 16 healthy volunteers. Plasma samples were analyzed by HPLC-MS and plasma diosmetin concentration was measured after deconjugation with β-glucuronidase. For the tested formulation area under the curve (AUC0-t), and maximum plasma and time concentration (Cmax; tmax) were found to be 298.4 ± 163.7, 50.3 ± 22.6 and 2.2 ± 2.9, respectively. AUC0-t and Cmax of the reference were 31.9 ± 100.4 and 2.4 ± 1.9, respectively. The tested formulation showed higher plasmatic concentrations of diosmetin in comparison to those obtained after the administration of unformulated micronized diosmin. The relative bioavailability was 9.4 greater for the tested formulation than in micronized diosmin. In conclusion, our data indicate that µSmin® Plus was rapidly and well absorbed into systemic circulation and may therefore be ideally suitable to deliver diosmin in human interventional trials. Full article
(This article belongs to the Special Issue The Potential Use of Herbal Medicinal Products in Chronic Disorders)
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Review

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Open AccessReview
A Systems-Level Analysis of Mechanisms of Platycodon grandiflorum Based on A Network Pharmacological Approach
Molecules 2018, 23(11), 2841; https://doi.org/10.3390/molecules23112841
Received: 27 September 2018 / Revised: 23 October 2018 / Accepted: 29 October 2018 / Published: 1 November 2018
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Abstract
Platycodon grandiflorum (PG) is widely used in Asia for its various beneficial effects. Although many studies were conducted to understand the molecular mechanisms of PG, it is still unclear how the combinations of multiple ingredients work together to exert its therapeutic effects. The [...] Read more.
Platycodon grandiflorum (PG) is widely used in Asia for its various beneficial effects. Although many studies were conducted to understand the molecular mechanisms of PG, it is still unclear how the combinations of multiple ingredients work together to exert its therapeutic effects. The aim of the present study was to provide a comprehensive review of the systems-level mechanisms of PG by adopting network pharmacological analysis. We constructed a compound–target–disease network for PG using experimentally validated and machine-leaning-based prediction results. Each target of the network was analyzed based on previously known pharmacological activities of PG. Gene ontology analysis revealed that the majority of targets were related to cellular and metabolic processes, responses to stimuli, and biological regulation. In pathway enrichment analyses of targets, the terms related to cancer showed the most significant enrichment and formed distinct clusters. Degree matrix analysis for target–disease associations of PG suggested the therapeutic potential of PG in various cancers including hepatocellular carcinoma, gastric cancer, prostate cancer, small-cell lung cancer, and renal cell carcinoma. We expect that network pharmacological approaches will provide an understanding of the systems-level mechanisms of medicinal herbs and further develop their therapeutic potentials. Full article
(This article belongs to the Special Issue The Potential Use of Herbal Medicinal Products in Chronic Disorders)
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Open AccessReview
Neuroprotective Role of Phytochemicals
Molecules 2018, 23(10), 2485; https://doi.org/10.3390/molecules23102485
Received: 13 September 2018 / Revised: 25 September 2018 / Accepted: 26 September 2018 / Published: 27 September 2018
Cited by 4 | PDF Full-text (1939 KB) | HTML Full-text | XML Full-text
Abstract
Neurodegenerative diseases are normally distinguished as disorders with loss of neurons. Various compounds are being tested to treat neurodegenerative diseases (NDs) but they possess solitary symptomatic advantages with numerous side effects. Accumulative studies have been conducted to validate the benefit of phytochemicals to [...] Read more.
Neurodegenerative diseases are normally distinguished as disorders with loss of neurons. Various compounds are being tested to treat neurodegenerative diseases (NDs) but they possess solitary symptomatic advantages with numerous side effects. Accumulative studies have been conducted to validate the benefit of phytochemicals to treat neurodegenerative diseases including Alzheimer’s disease (AD) and Parkinson’s disease (PD). In this present review we explored the potential efficacy of phytochemicals such as epigallocatechin-3-galate, berberin, curcumin, resveratrol, quercetin and limonoids against the most common NDs, including Alzheimer’s disease (AD) and Parkinson’s disease (PD). The beneficial potentials of these phytochemicals have been demonstrated by evidence-based but more extensive investigation needs to be conducted for reducing the progression of AD and PD. Full article
(This article belongs to the Special Issue The Potential Use of Herbal Medicinal Products in Chronic Disorders)
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