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Study on the Mechanism of Medicinal Plants on Diseases
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Study on the Mechanism of Medicinal Plants on Diseases

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

Deadline for manuscript submissions: closed (31 July 2021) | Viewed by 43366

Special Issue Editors

Dr. Young-won Chin

E-Mail Website
Guest Editor
College of Pharmacy, Seoul National University, Seoul 08826, Republic of Korea
Interests: anti-inflammatory natural products; metabolic disease modulatory natural products
Dr. Young Hee Choi

E-Mail Website
Guest Editor
College of Pharmacy and Integrated Research Institute for Drug Development, Dongguk University_Seoul, 32 Dongguk-lo, Ilsandong-gu, Goyang-si, Gyonggi-do 10326, Korea
Interests: Metformin; pharmacokinetics; metabolism; metabolite ID
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Hojun Kim

E-Mail Website
Guest Editor
College of Korean Medicine, Dongguk University, Gyeonggi-do 10326, Korea
Interests: herbal medicine; precision medicine; gut microbiome; metabolic disease

Special Issue Information

Dear Colleagues,

Medicinal plants have been used as traditional medicines, modern botanical drugs, and dietary supplements for the treatment or prevention of a variety of diseases and human health benefits.

Many plant extracts have been studied and documented, but still many others have not been reported. Thus, a Special Issue on the mechanism of medicinal plants on diseases is timely. This Special Issue aims to publish new pharmacological or biological research articles and comprehensive reviews in plant extract products with mechanistic interventions on diseases.

We cordially invite authors to contribute original articles and reviews that disclose new mechanisms of plant extract products to expand their use for the benefit of human health.

Prof. Young Hee Choi
Prof. Young-won Chin
Prof. Hojun Kim
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 submissions that pass pre-check are 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 2700 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

  • In vitro or in vivo studies of plant extracts
  • In vitro or in vivo studies of traditional medicines
  • Mechanism of plant extracts on specific diseases or biological events in vitro or in vivo
  • Clinical studies of plant extract products
  • Chronic or acute diseases

Published Papers (15 papers)

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Research

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11 pages, 2579 KiB  
Article
Schisandrin C Affects Glucose-Stimulated Insulin Secretion in Pancreatic β-Cells and Glucose Uptake in Skeletal Muscle Cells
by Dahae Lee, Young-Mi Kim, Hyun Woo Kim, You-Kyoung Choi, Bang Ju Park, Sang Hoon Joo and Ki Sung Kang
Molecules 2021, 26(21), 6509; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules26216509 - 28 Oct 2021
Cited by 4 | Viewed by 2435
Abstract
The aim of our study was to investigate the effect of three lignans (schisandrol A, schisandrol B, and schisandrin C) on insulin secretion in rat INS-1 pancreatic β-cells and glucose uptake in mouse C2C12 skeletal muscle cells. Schisandrol A and schisandrin C enhanced [...] Read more.
The aim of our study was to investigate the effect of three lignans (schisandrol A, schisandrol B, and schisandrin C) on insulin secretion in rat INS-1 pancreatic β-cells and glucose uptake in mouse C2C12 skeletal muscle cells. Schisandrol A and schisandrin C enhanced insulin secretion in response to high glucose levels with no toxic effects on INS-1 cells. The effect of schisandrin C was superior to that of gliclazide (positive control), a drug commonly used to treat type 2 diabetes (T2D). In addition, western blot analysis showed that the expression of associated proteins, including peroxisome proliferator-activated receptor γ (PPARγ), pancreatic and duodenal homeobox 1 (PDX-1), phosphatidylinositol 3-kinase (PI3K), Akt, and insulin receptor substrate-2 (IRS-2), was increased in INS-1 cells after treatment with schisandrin C. In addition, insulin secretion effect of schisandrin C were enhanced by the Bay K 8644 (L-type Ca2+ channel agonist) and glibenclamide (K+ channel blocker), were abolished by the nifedipine (L-type Ca2+ channel blocker) and diazoxide (K+ channel activator). Moreover, schisandrin C enhanced glucose uptake with no toxic effects on C2C12 cells. Western blot analysis showed that the expression of associated proteins, including insulin receptor substrate-1 (IRS-1), AMP-activated protein kinase (AMPK), PI3K, Akt, glucose transporter type 4 (GLUT-4), was increased in C2C12 cells after treatment with schisandrin C. Schisandrin C may improve hyperglycemia by enhancing insulin secretion in pancreatic β-cells and improving glucose uptake into skeletal muscle cells. Our findings may provide evidence that schisandrin C may be beneficial in devising novel anti-T2D strategies. Full article
(This article belongs to the Special Issue Study on the Mechanism of Medicinal Plants on Diseases)
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12 pages, 24872 KiB  
Article
The Enhancing Immune Response and Anti-Inflammatory Effects of Caulerpa lentillifera Extract in RAW 264.7 Cells
by Sittikorn Yoojam, Atcharaporn Ontawong, Narissara Lailerd, Kriangsak Mengamphan and Doungporn Amornlerdpison
Molecules 2021, 26(19), 5734; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules26195734 - 22 Sep 2021
Cited by 4 | Viewed by 2657
Abstract
Background: Caulerpa lentillifera (CL) is a green seaweed, and its edible part represents added value as a functional ingredient. CL was dried and extracted for the determination of its active compounds and the evaluation of its biological activities. The major constituents of CL [...] Read more.
Background: Caulerpa lentillifera (CL) is a green seaweed, and its edible part represents added value as a functional ingredient. CL was dried and extracted for the determination of its active compounds and the evaluation of its biological activities. The major constituents of CL extract (CLE), including tannic acid, catechin, rutin, and isoquercetin, exhibited beneficial effects, such as antioxidant activity, anti-diabetic activity, immunomodulatory effects, and anti-cancer activities in in vitro and in vivo models. Whether CLE has an anti-inflammatory effect and immune response remains unclear. Methods: This study examined the effect of CLE on the inflammatory status and immune response of lipopolysaccharide (LPS)-stimulated RAW 264.7 cells and the mechanisms involved therein. RAW264.7 cells were treated with different concentrations of CLE (0.1–1000 µg/mL) with or without LPS (1 µg/mL) for 24 h. Expression and production of the inflammatory cytokines, enzymes, and mediators were evaluated. Results: CLE suppressed expression and production of the pro-inflammatory cytokines IL-6 and TNF-α. Moreover, CLE inhibited expression and secretion of the inflammatory enzyme COX-2 and the mediators PGE2 and NO. CLE also reduced DNA damage. Furthermore, CLE stimulated the immune response by modulating the cell cycle regulators p27, p53, cyclin D2, and cyclin E2. Conclusions: CLE inhibits inflammatory responses in LPS-activated macrophages by downregulating inflammatory cytokines and mediators. Furthermore, CLE has an immunomodulatory effect by modulating cell cycle regulators. Full article
(This article belongs to the Special Issue Study on the Mechanism of Medicinal Plants on Diseases)
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15 pages, 763 KiB  
Article
Effect of Water Extract of Mangosteen Pericarp on Donepezil Pharmacokinetics in Mice
by Mingoo Bae, Seung Yon Han, Eun-Sun Kim, Byung Hoon You, Young-Mi Kim, Jungsook Cho, Young-Won Chin and Young Hee Choi
Molecules 2021, 26(17), 5246; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules26175246 - 30 Aug 2021
Cited by 5 | Viewed by 2560
Abstract
The pharmacokinetic (PK) change in a drug by co-administered herbal products can alter the efficacy and toxicity. In the circumstances that herb–drug combinations have been increasingly attempted to alleviate Alzheimer’s disease (AD), the PK evaluation of herb–drug interaction (HDI) is necessary. The change [...] Read more.
The pharmacokinetic (PK) change in a drug by co-administered herbal products can alter the efficacy and toxicity. In the circumstances that herb–drug combinations have been increasingly attempted to alleviate Alzheimer’s disease (AD), the PK evaluation of herb–drug interaction (HDI) is necessary. The change in systemic exposure as well as target tissue distribution of the drug have been issued in HDIs. Recently, the memory-enhancing effects of water extract of mangosteen pericarp (WMP) has been reported, suggesting a potential for the combination of WMP and donepezil (DNP) for AD treatment. Thus, it was evaluated how WMP affects the PK change of donepezil, including systemic exposure and tissue distribution in mice after simultaneous oral administration of DNP with WMP. Firstly, co-treatment of WMP and donepezil showed a stronger inhibitory effect (by 23.0%) on the neurotoxicity induced by Aβ(25–35) in SH-SY5Y neuroblastoma cells than donepezil alone, suggesting that the combination of WMP and donepezil may be more effective in moderating neurotoxicity than donepezil alone. In PK interaction, WMP increased donepezil concentration in the brain at 4 h (by 63.6%) after administration without affecting systemic exposure of donepezil. Taken together, our results suggest that WMP might be used in combination with DNP as a therapy for AD. Full article
(This article belongs to the Special Issue Study on the Mechanism of Medicinal Plants on Diseases)
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8 pages, 1419 KiB  
Article
Psychological and Antibacterial Effects of Footbath Using the Lindera umbellata Essential Oil
by Maiko Kitajima, Marika Miura, Naoki Nanashima, Toshiko Tomisawa, Shizuka Takamagi, Miyuki Fujioka, Naoya In and Tomohiro Osanai
Molecules 2021, 26(17), 5128; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules26175128 - 24 Aug 2021
Cited by 4 | Viewed by 2080
Abstract
Lindera umbellata (Lu) essential oil primarily contains linalool and has relaxation properties. We investigated the psychological and antibacterial effects of footbath with Lu essential oil. The participants included 20 women without medical history and received two intervention plans: footbath without any [...] Read more.
Lindera umbellata (Lu) essential oil primarily contains linalool and has relaxation properties. We investigated the psychological and antibacterial effects of footbath with Lu essential oil. The participants included 20 women without medical history and received two intervention plans: footbath without any essential oil and footbath using Lu essential oil. Next, questionnaires regarding impressions and mood states were provided for them to answer. In addition, their autonomic nervous system activity was measured, and the aerobic viable of count on the feet was determined. The high-frequency value reflecting the parasympathetic nervous system activity significantly increased after footbath using Lu essential oil. In the questionnaire about the mood states, the subscale scores of tension–anxiety, depression, fatigue, and confusion after intervention were lower than those before intervention regardless of the use of the essential oil. Conversely, the anger–hostility score decreased only in the group using Lu essential oil. Furthermore, the decrease in aerobic viable count after intervention was not significantly different between the two groups. Footbath using Lu essential oil increased the parasympathetic nervous system activity and relieved anger. Taken together, we suggest that footbath using Lu essential oil has a relaxation effect. Full article
(This article belongs to the Special Issue Study on the Mechanism of Medicinal Plants on Diseases)
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11 pages, 1781 KiB  
Article
Quercetin-3-O-glucuronide in the Ethanol Extract of Lotus Leaf (Nelumbo nucifera) Enhances Sleep Quantity and Quality in a Rodent Model via a GABAergic Mechanism
by Singeun Kim, Ki-Bae Hong, Kyungae Jo and Hyung Joo Suh
Molecules 2021, 26(10), 3023; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules26103023 - 19 May 2021
Cited by 16 | Viewed by 3621
Abstract
Current pharmacological treatments for insomnia carry several and long-term side effects. Therefore, natural products without side effects are warranted. In this study, the sleep-promoting activity of the lotus leaf (Nelumbo nucifera) extract was assessed using ICR mice and Sprague Dawley rats. [...] Read more.
Current pharmacological treatments for insomnia carry several and long-term side effects. Therefore, natural products without side effects are warranted. In this study, the sleep-promoting activity of the lotus leaf (Nelumbo nucifera) extract was assessed using ICR mice and Sprague Dawley rats. A pentobarbital-induced sleep test and electroencephalogram analysis were conducted to measure sleep latency time, duration, and sleep architecture. The action mechanism of the extract was evaluated through ligand binding experiments. A high dose (300 mg/kg) of the ethanolic lotus leaf extract significantly increased sleep duration compared to the normal group (p < 0.01). Administration of low (150 mg/kg) and high doses (300 mg/kg) of the extract significantly increased sleep quality, especially the relative power of theta waves (p < 0.05), compared to the normal group. Furthermore, caffeine and lotus leaf extract administration significantly recovered caffeine-induced sleep disruption (p < 0.001), and the sleep quality was similar to that of the normal group. Additionally, ligand binding assay using [3H]-flumazenil revealed that quercetin-3-O-glucuronide contained in the lotus leaf extract (77.27 μg/mg of extract) enhanced sleep by binding to GABAA receptors. Collectively, these results indicated that the lotus leaf extract, particularly quercetin-3-O-glucuronide, exhibits sleep quantity- and quality-enhancing activity via the GABAergic pathway. Full article
(This article belongs to the Special Issue Study on the Mechanism of Medicinal Plants on Diseases)
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23 pages, 6370 KiB  
Article
Neuroprotective Effect and Antioxidant Potency of Fermented Cultured Wild Ginseng Root Extracts of Panax ginseng C.A. Meyer in Mice
by Chul-Joong Kim, Hyeon-Yeol Ryu, Somin Lee, Han-Joo Lee, Yoon-Soek Chun, Jong-Kyu Kim, Chang-Yeon Yu, Bimal Kumar Ghimire and Jae-Geun Lee
Molecules 2021, 26(10), 3001; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules26103001 - 18 May 2021
Cited by 12 | Viewed by 2788
Abstract
Wild ginseng has better pharmacological effects than cultivated ginseng. However, its industrialization is limited by the inability to grow wild ginseng on a large scale. Herein, we demonstrate how to optimize ginseng production through cultivation, and how to enhance the concentrations of specific [...] Read more.
Wild ginseng has better pharmacological effects than cultivated ginseng. However, its industrialization is limited by the inability to grow wild ginseng on a large scale. Herein, we demonstrate how to optimize ginseng production through cultivation, and how to enhance the concentrations of specific ginsenosides through fermentation. In the study, we also evaluated the ability of fermented cultured wild ginseng root extract (HLJG0701-β) to inhibit acetylcholinesterase (AChE), as well as its neuroprotective effects and antioxidant activity. In invitro tests, HLJG0701-β inhibited AChE activity and exerted neuroprotective and antioxidant effects (showing increased catalyst activity but decreased reactive oxygen species concentration). In invivo tests, after HLJG0701-β was orally administered at doses of 0, 125, 250, and 500 mg/kg in an animal model of memory impairment, behavioral evaluation (Morris water maze test and Y-maze task test) was performed. The levels of AChE, acetylcholine (ACh), blood catalase (CAT), and malondialdehyde (MDA) in brain tissues were measured. The results showed that HLJG0701-β produced the best results at a dose of 250 mg/kg or more. The neuroprotective mechanism of HLJG0701-β was determined to involve the inhibition of AChE activity and a decrease in oxidative stress. In summary, both invitro and invivo tests confirmed that HJG0701-β administration can lead to memory improvement. Full article
(This article belongs to the Special Issue Study on the Mechanism of Medicinal Plants on Diseases)
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11 pages, 14326 KiB  
Article
Wikstroemiaganpi Extract Improved Atopic Dermatitis-Like Skin Lesions via Suppression of Interleukin-4 in 2,4-Dinitrochlorobenzene-Induced SKH-1 Hairless Mice
by Jonghwan Jegal, No-June Park, Beom-Geun Jo, Tae-Young Kim, Sim-Kyu Bong, Sangho Choi, Jin-Hyub Paik, Jung-Won Kim, Su-Nam Kim and Min Hye Yang
Molecules 2021, 26(7), 2016; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules26072016 - 01 Apr 2021
Cited by 5 | Viewed by 2332
Abstract
Plants of the genus Wikstroemia are used in Chinese traditional medicine to treat inflammatory diseases, such as arthritis, bronchitis, and pneumonia. The present study was designed to determine whether Wikstroemia ganpi (Siebold and Zucc.) Maxim. offers a potential means of treating 2,4-dinitrochlorobenzene (DNCB)-induced [...] Read more.
Plants of the genus Wikstroemia are used in Chinese traditional medicine to treat inflammatory diseases, such as arthritis, bronchitis, and pneumonia. The present study was designed to determine whether Wikstroemia ganpi (Siebold and Zucc.) Maxim. offers a potential means of treating 2,4-dinitrochlorobenzene (DNCB)-induced atopic dermatitis (AD) in mice. Symptoms such as redness, edema, and keratinization in AD mice induced by DNCB were alleviated by the co-application of an ethanolic extract of W. ganpi for 2 weeks. The severity of skin barrier function damage was evaluated by measuring TEWL (transepidermal water loss). TEWLs of DNCB sensitized mouse dorsal skin were reduced by the application of a W. ganpi ethanolic extract, and skin hydration was increased. In addition, the infiltration of inflammatory cells into the dermis was significantly reduced, as were blood levels of IgE and IL-4, which play an important role in the expression of AD. The results of this experiment suggest that W. ganpi is a potential therapeutic agent for AD. Full article
(This article belongs to the Special Issue Study on the Mechanism of Medicinal Plants on Diseases)
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15 pages, 8857 KiB  
Article
Antidiabetic and Renoprotective Effects of Coffea arabica Pulp Aqueous Extract through Preserving Organic Cation Transport System Mediated Oxidative Stress Pathway in Experimental Type 2 Diabetic Rats
by Oranit Boonphang, Atcharaporn Ontawong, Tipthida Pasachan, Manussabhorn Phatsara, Acharaporn Duangjai, Doungporn Amornlerdpison, Metee Jinakote and Chutima Srimaroeng
Molecules 2021, 26(7), 1907; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules26071907 - 28 Mar 2021
Cited by 15 | Viewed by 2697
Abstract
Coffea arabica pulp (CP) is a by-product of coffee processing. CP contains polyphenols that have exhibited beneficial effects, including antioxidant and lipid-lowering effects, as well as enhanced insulin sensitivity, in in vitro and in vivo models. How polyphenols, as found in CP aqueous [...] Read more.
Coffea arabica pulp (CP) is a by-product of coffee processing. CP contains polyphenols that have exhibited beneficial effects, including antioxidant and lipid-lowering effects, as well as enhanced insulin sensitivity, in in vitro and in vivo models. How polyphenols, as found in CP aqueous extract (CPE), affect type 2 diabetes (T2D) has not been investigated. Thus, the present study examined the potential antidiabetic, antioxidant, and renoprotective effects of CPE-rich polyphenols, using an experimental model of T2D in rats induced by a high-fat diet and a single low dose of streptozotocin. The T2D rats received either 1000 mg/kg body weight (BW) of CPE, 30 mg/kg BW of metformin (Met), or a combination treatment (CPE + Met) for 3 months. Plasma parameters, kidney morphology and function, and renal organic transport were determined. Significant hyperglycemia, hypertriglyceridemia, insulin resistance, increased renal lipid content and lipid peroxidation, and morphological kidney changes related to T2D were restored by both CPE and CPE + Met treatments. Additionally, the renal uptake of organic cation, 3H-1-methyl-4-phenylpyridinium (MPP+), was reduced in T2D, while transport was restored by CPE and CPE + Met, through an up-regulation of antioxidant genes and protein kinase Cα deactivation. Thus, CPE has antidiabetic and antioxidant effects that potentially ameliorate kidney function in T2D by preserving renal organic cation transport through an oxidative stress pathway. Full article
(This article belongs to the Special Issue Study on the Mechanism of Medicinal Plants on Diseases)
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21 pages, 1594 KiB  
Article
An In Vitro Study of the Effect of Viburnum opulus Extracts on Key Processes in the Development of Staphylococcal Infections
by Urszula Wójcik-Bojek, Joanna Rywaniak, Przemysław Bernat, Anna Podsędek, Dominika Kajszczak and Beata Sadowska
Molecules 2021, 26(6), 1758; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules26061758 - 21 Mar 2021
Cited by 10 | Viewed by 2767
Abstract
Staphylococcus aureus is still one of the leading causes of both hospital- and community-acquired infections. Due to the very high percentage of drug-resistant strains, the participation of drug-tolerant biofilms in pathological changes, and thus the limited number of effective antibiotics, there is an [...] Read more.
Staphylococcus aureus is still one of the leading causes of both hospital- and community-acquired infections. Due to the very high percentage of drug-resistant strains, the participation of drug-tolerant biofilms in pathological changes, and thus the limited number of effective antibiotics, there is an urgent need to search for alternative methods of prevention or treatment for S. aureus infections. In the present study, biochemically characterized (HPLC/UPLC–QTOF–MS) acetonic, ethanolic, and water extracts from fruits and bark of Viburnum opulus L. were tested in vitro as diet additives that potentially prevent staphylococcal infections. The impacts of V. opulus extracts on sortase A (SrtA) activity (Fluorimetric Assay), staphylococcal protein A (SpA) expression (FITC-labelled specific antibodies), the lipid composition of bacterial cell membranes (LC-MS/MS, GC/MS), and biofilm formation (LIVE/DEAD BacLight) were assessed. The cytotoxicity of V. opulus extracts to the human fibroblast line HFF-1 was also tested (MTT reduction). V. opulus extracts strongly inhibited SrtA activity and SpA expression, caused modifications of S. aureus cell membrane, limited biofilm formation by staphylococci, and were non-cytotoxic. Therefore, they have pro-health potential. Nevertheless, their usefulness as diet supplements that are beneficial for the prevention of staphylococcal infections should be confirmed in animal models in the future. Full article
(This article belongs to the Special Issue Study on the Mechanism of Medicinal Plants on Diseases)
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20 pages, 5331 KiB  
Article
Two Key Amino Acids Variant of α-l-arabinofuranosidase from Bacillus subtilis Str. 168 with Altered Activity for Selective Conversion Ginsenoside Rc to Rd
by Ru Zhang, Shi Quan Tan, Bian Ling Zhang, Zi Yu Guo, Liang Yu Tian, Pei Weng and Zhi Yong Luo
Molecules 2021, 26(6), 1733; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules26061733 - 19 Mar 2021
Cited by 11 | Viewed by 2107
Abstract
α-l-arabinofuranosidase is a subfamily of glycosidases involved in the hydrolysis of l-arabinofuranosidic bonds, especially in those of the terminal non-reducing arabinofuranosyl residues of glycosides, from which efficient glycoside hydrolases can be screened for the transformation of ginsenosides. In this study, [...] Read more.
α-l-arabinofuranosidase is a subfamily of glycosidases involved in the hydrolysis of l-arabinofuranosidic bonds, especially in those of the terminal non-reducing arabinofuranosyl residues of glycosides, from which efficient glycoside hydrolases can be screened for the transformation of ginsenosides. In this study, the ginsenoside Rc-hydrolyzing α-l-arabinofuranosidase gene, BsAbfA, was cloned from Bacilus subtilis, and its codons were optimized for efficient expression in E. coli BL21 (DE3). The recombinant protein BsAbfA fused with an N-terminal His-tag was overexpressed and purified, and then subjected to enzymatic characterization. Site-directed mutagenesis of BsAbfA was performed to verify the catalytic site, and the molecular mechanism of BsAbfA catalyzing ginsenoside Rc was analyzed by molecular docking, using the homology model of sequence alignment with other β-glycosidases. The results show that the purified BsAbfA had a specific activity of 32.6 U/mg. Under optimal conditions (pH 5, 40 °C), the kinetic parameters Km of BsAbfA for pNP-α-Araf and ginsenoside Rc were 0.6 mM and 0.4 mM, while the Kcat/Km were 181.5 s−1 mM−1 and 197.8 s−1 mM−1, respectively. More than 90% of ginsenoside Rc could be transformed by 12 U/mL purified BsAbfA at 40 °C and pH 5 in 24 h. The results of molecular docking and site-directed mutagenesis suggested that the E173 and E292 variants for BsAbfA are important in recognizing ginsenoside Rc effectively, and to make it enter the active pocket to hydrolyze the outer arabinofuranosyl moieties at C20 position. These remarkable properties and the catalytic mechanism of BsAbfA provide a good alternative for the effective biotransformation of the major ginsenoside Rc into Rd. Full article
(This article belongs to the Special Issue Study on the Mechanism of Medicinal Plants on Diseases)
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18 pages, 23103 KiB  
Article
Betulinic Acid Restricts Human Bladder Cancer Cell Proliferation In Vitro by Inducing Caspase-Dependent Cell Death and Cell Cycle Arrest, and Decreasing Metastatic Potential
by So Young Kim, Hyun Hwangbo, Min Yeong Kim, Seon Yeong Ji, Da Hye Kim, Hyesook Lee, Gi-Young Kim, Sung-Kwon Moon, Sun-Hee Leem, Seok Joong Yun, Wun-Jae Kim, JaeHun Cheong, Cheol Park and Yung Hyun Choi
Molecules 2021, 26(5), 1381; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules26051381 - 04 Mar 2021
Cited by 17 | Viewed by 2504
Abstract
Betulinic acid (BA) is a naturally occurring pentacyclic triterpenoid and generally found in the bark of birch trees (Betula sp.). Although several studies have been reported that BA has diverse biological activities, including anti-tumor effects, the underlying anti-cancer mechanism in bladder cancer [...] Read more.
Betulinic acid (BA) is a naturally occurring pentacyclic triterpenoid and generally found in the bark of birch trees (Betula sp.). Although several studies have been reported that BA has diverse biological activities, including anti-tumor effects, the underlying anti-cancer mechanism in bladder cancer cells is still lacking. Therefore, this study aims to investigate the anti-proliferative effect of BA in human bladder cancer cell lines T-24, UMUC-3, and 5637, and identify the underlying mechanism. Our results showed that BA induced cell death in bladder cancer cells and that are accompanied by apoptosis, necrosis, and cell cycle arrest. Furthermore, BA decreased the expression of cell cycle regulators, such as cyclin B1, cyclin A, cyclin-dependent kinase (Cdk) 2, cell division cycle (Cdc) 2, and Cdc25c. In addition, BA-induced apoptosis was associated with mitochondrial dysfunction that is caused by loss of mitochondrial membrane potential, which led to the activation of mitochondrial-mediated intrinsic pathway. BA up-regulated the expression of Bcl-2-accociated X protein (Bax) and cleaved poly-ADP ribose polymerase (PARP), and subsequently activated caspase-3, -8, and -9. However, pre-treatment of pan-caspase inhibitor markedly suppressed BA-induced apoptosis. Meanwhile, BA did not affect the levels of intracellular reactive oxygen species (ROS), indicating BA-mediated apoptosis was ROS-independent. Furthermore, we found that BA suppressed the wound healing and invasion ability, and decreased the expression of Snail and Slug in T24 and 5637 cells, and matrix metalloproteinase (MMP)-9 in UMUC-3 cells. Taken together, this is the first study showing that BA suppresses the proliferation of human bladder cancer cells, which is due to induction of apoptosis, necrosis, and cell cycle arrest, and decrease of migration and invasion. Furthermore, BA-induced apoptosis is regulated by caspase-dependent and ROS-independent pathways, and these results provide the underlying anti-proliferative molecular mechanism of BA in human bladder cancer cells. Full article
(This article belongs to the Special Issue Study on the Mechanism of Medicinal Plants on Diseases)
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17 pages, 5999 KiB  
Article
16-Hydroxycleroda-3,13-Dien-15,16-Olide Induces Apoptosis in Human Bladder Cancer Cells through Cell Cycle Arrest, Mitochondria ROS Overproduction, and Inactivation of EGFR-Related Signalling Pathways
by Yu-Chi Chen, Po-Yu Wang, Bu-Miin Huang, Yu-Jen Chen, Wei-Chang Lee and Yung-Chia Chen
Molecules 2020, 25(17), 3958; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules25173958 - 30 Aug 2020
Cited by 10 | Viewed by 2594
Abstract
A clerodane diterpene compound 16-hydroxycleroda-3,13-dien-15,16-olide (CD) is considered a therapeutic agent with pharmacological activities. The present study investigated the mechanisms of CD-induced apoptosis in T24 human bladder cancer cells. CD inhibited cell proliferation in a concentration and time-dependent manner. CD-induced overproduction of reactive [...] Read more.
A clerodane diterpene compound 16-hydroxycleroda-3,13-dien-15,16-olide (CD) is considered a therapeutic agent with pharmacological activities. The present study investigated the mechanisms of CD-induced apoptosis in T24 human bladder cancer cells. CD inhibited cell proliferation in a concentration and time-dependent manner. CD-induced overproduction of reactive oxygen species and reduced mitochondrial membrane potential, associated with reduced expression of Bcl-2 and increased levels of cytosolic cytochrome c, cleaved PARP-1 and caspase-3. In addition, CD treatment led to cell cycle arrest at the G0/G1 phase and inhibited expression of cyclin D1 and cyclin-dependent kinases 2 and 4 and led to increased levels of p21, p27Kip1 and p53. All of these events were accompanied with a reduction of pEGFR, pMEK1/2, pERK1/2, pAkt, pmTOR, pP70S6K1, HIF-1α, c-Myc and VEGF. RNAseq-based analysis revealed that CD-induced cell death was characterised by an increased expression of stress and apoptotic-related genes as well as inhibition of the cell cycle-related genes. In summary, CD induces apoptosis in T24 bladder cancer cells through targeting multiple intracellular signaling pathways as a result of oxidative stress and cell cycle arrest. Full article
(This article belongs to the Special Issue Study on the Mechanism of Medicinal Plants on Diseases)
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12 pages, 2964 KiB  
Article
Standardized Extract of Atractylodis Rhizoma Alba and Fructus Schisandrae Ameliorates Coughing and Increases Expectoration of Phlegm
by Hee-Sung Chae, Sun Young Kim, Pisey Pel, Jungmoo Huh, Sun-Woo Joo, Yun Young Lim, Shin Jung Park, Jong Lae Lim and Young-Won Chin
Molecules 2020, 25(13), 3064; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules25133064 - 04 Jul 2020
Cited by 6 | Viewed by 2984
Abstract
Cough and phlegm frequently occur in respiratory diseases like upper respiratory tract infections, acute bronchitis, and chronic obstructive pulmonary diseases. To relieve these symptoms and diseases, various ingredients are being used despite the debates on their clinical efficacy. We aimed to investigate the [...] Read more.
Cough and phlegm frequently occur in respiratory diseases like upper respiratory tract infections, acute bronchitis, and chronic obstructive pulmonary diseases. To relieve these symptoms and diseases, various ingredients are being used despite the debates on their clinical efficacy. We aimed to investigate the effects of the extract CKD-497, composed of Atractylodis Rhizoma Alba and Fructus Schisandrae, in relieving cough and facilitating expectoration of phlegm. CKD-497 was found to inhibit inflammatory mediators such as interleukin-8 (IL-8) and tumor necrosis factor α (TNF-α) in lipopolysaccharide (LPS)-treated mouse macrophages and transient receptor potential cation channel 1 (TRPV-1)-overexpressed human bronchial epithelial cells stimulated by capsaicin. CKD-497 decreased the viscosity of the mucin solution. During in vivo experiments, CKD-497 reduced coughing numbers and increased expectoration of phlegm via mucociliary clearance enhancement. Collectively, these data suggest that CKD-497 possesses potential for cough and phlegm expectoration treatment. Full article
(This article belongs to the Special Issue Study on the Mechanism of Medicinal Plants on Diseases)
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16 pages, 5666 KiB  
Article
Antimetastatic Effects of Sesamin on Human Head and Neck Squamous Cell Carcinoma through Regulation of Matrix Metalloproteinase-2
by Jian-Ming Chen, Pei-Yin Chen, Chia-Chieh Lin, Ming-Chang Hsieh and Jen-Tsun Lin
Molecules 2020, 25(9), 2248; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules25092248 - 10 May 2020
Cited by 13 | Viewed by 2764
Abstract
Background: Sesamin is a lignin present in sesame oil from the bark of Zanthoxylum spp. Sesamin reportedly has anticarcinogenic potential and exerts anti-inflammatory effects on several tumors. Hypothesis/Purpose: However, the effect of sesamin on metastatic progression in human head and neck squamous carcinoma [...] Read more.
Background: Sesamin is a lignin present in sesame oil from the bark of Zanthoxylum spp. Sesamin reportedly has anticarcinogenic potential and exerts anti-inflammatory effects on several tumors. Hypothesis/Purpose: However, the effect of sesamin on metastatic progression in human head and neck squamous carcinoma (HNSCC) remains unknown in vitro and in vivo; hence, we investigated the effect of sesamin on HNSCC cells in vitro. Methods and Results: Sesamin-treated human oral cancer cell lines FaDu, HSC-3, and Ca9-22 were subjected to a wound-healing assay. Furthermore, Western blotting was performed to assess the effect of sesamin on the expression levels of matrix metalloproteinase (MMP)-2 and proteins of the MAPK signaling pathway, including p-ERK1/2, P-p38, and p-JNK1/2. In addition, we investigated the association between MMP-2 expression and the MAPK pathway in sesamin-treated oral cancer cells. Sesamin inhibited cell migration and invasion in FaDu, Ca9-22, and HSC-3 cells and suppressed MMP-2 at noncytotoxic concentrations (0 to 40 μM). Furthermore, sesamin significantly reduced p38 MAPK and JNK phosphorylation in a dose-dependent manner in FaDu and HSC-3 cells. Conclusions: These results indicate that sesamin suppresses the migration and invasion of HNSCC cells by regulating MMP-2 and is thus a potential antimetastatic agent for treating HNSCC. Full article
(This article belongs to the Special Issue Study on the Mechanism of Medicinal Plants on Diseases)
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Review

Jump to: Research

18 pages, 396 KiB  
Review
Application of Light-Emitting Diodes for Improving the Nutritional Quality and Bioactive Compound Levels of Some Crops and Medicinal Plants
by Woo-Suk Jung, Ill-Min Chung, Myeong Ha Hwang, Seung-Hyun Kim, Chang Yeon Yu and Bimal Kumar Ghimire
Molecules 2021, 26(5), 1477; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules26051477 - 09 Mar 2021
Cited by 33 | Viewed by 5074
Abstract
Light is a key factor that affects phytochemical synthesis and accumulation in plants. Due to limitations of the environment or cultivated land, there is an urgent need to develop indoor cultivation systems to obtain higher yields with increased phytochemical concentrations using convenient light [...] Read more.
Light is a key factor that affects phytochemical synthesis and accumulation in plants. Due to limitations of the environment or cultivated land, there is an urgent need to develop indoor cultivation systems to obtain higher yields with increased phytochemical concentrations using convenient light sources. Light-emitting diodes (LEDs) have several advantages, including consumption of lesser power, longer half-life, higher efficacy, and wider variation in the spectral wavelength than traditional light sources; therefore, these devices are preferred for in vitro culture and indoor plant growth. Moreover, LED irradiation of seedlings enhances plant biomass, nutrient and secondary metabolite levels, and antioxidant properties. Specifically, red and blue LED irradiation exerts strong effects on photosynthesis, stomatal functioning, phototropism, photomorphogenesis, and photosynthetic pigment levels. Additionally, ex vitro plantlet development and acclimatization can be enhanced by regulating the spectral properties of LEDs. Applying an appropriate LED spectral wavelength significantly increases antioxidant enzyme activity in plants, thereby enhancing the cell defense system and providing protection from oxidative damage. Since different plant species respond differently to lighting in the cultivation environment, it is necessary to evaluate specific wavebands before large-scale LED application for controlled in vitro plant growth. This review focuses on the most recent advances and applications of LEDs for in vitro culture organogenesis. The mechanisms underlying the production of different phytochemicals, including phenolics, flavonoids, carotenoids, anthocyanins, and antioxidant enzymes, have also been discussed. Full article
(This article belongs to the Special Issue Study on the Mechanism of Medicinal Plants on Diseases)
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