DOCSLIB.ORG

Silychristin Derivatives Conjugated with Coniferylalcohols from Silymarin and Their Pancreatic Α-Amylase Inhibitory Title Activity

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Silychristin Derivatives Conjugated with Coniferylalcohols from Silymarin and Their Pancreatic Α-Amylase Inhibitory Title Activity Silychristin derivatives conjugated with coniferylalcohols from silymarin and their pancreatic α-amylase inhibitory Title activity Author(s) Kato, Eisuke; Kushibiki, Natsuka; Satoh, Hiroshi; Kawabata, Jun Natural Product Research, 34(6), 759-765 Citation https://doi.org/10.1080/14786419.2018.1499639 Issue Date 2020-03-18 Doc URL http://hdl.handle.net/2115/80605 This is an Accepted Manuscript of an article published by Taylor & Francis in Natural Product Research on Rights Mar.18.2020, available online: http://www.tandfonline.com/10.1080/14786419.2018.1499639. Type article (author version) File Information EK_NatProdRes_milk_thistle_w_supplement.pdf Instructions for use Hokkaido University Collection of Scholarly and Academic Papers : HUSCAP *Post-print manuscript This document is the unedited Author's version of a Submitted Work that was subsequently accepted for publication in “Natural Product Research” published by Taylor & Francis after peer review. To access the final edited and published work see https://doi.org/10.1080/14786419.2018.1499639 Graphical abstract 1 RESEARCH ARTICLE Silychristin derivatives conjugated with coniferylalcohols from silymarin and their pancreatic α-amylase inhibitory activity Eisuke Katoa*, Natsuka Kushibikib, Hiroshi Satohc and Jun Kawabataa aDivision of Fundamental AgriScience and Research, Research Faculty of Agriculture, Hokkaido University, Kita-ku, Sapporo, Hokkaido 060-8589, Japan bDivision of Applied Bioscience, Graduate School of Agriculture, Hokkaido University, Kita-ku, Sapporo, Hokkaido 060-8589, Japan cNissei Bio Co. Ltd., Eniwa, Hokkaido, 061-1374, Japan *Corresponding author. Eisuke Kato, 1Division of Fundamental AgriScience and Research, Research Faculty of Agriculture, Hokkaido University, Kita-ku, Sapporo, Hokkaido 060-8589, Japan; Tel/Fax: +81 11 706 2496; e-mail: [email protected] 2 Abstract Silymarin is a mixture of flavonolignans extracted from the fruit of Silybum marianum (milk thistle). The latter is used as a medicinal plant to treat liver and gallbladder disorders. Recently, silymarin has been investigated for its effects against diabetes mellitus, and shown to reduce serum levels of glucose in model animals and in clinical trials. This effect can be explained mainly by the protective effect of silymarin against pancreatic beta-cells, but the involvement of other mechanisms is possible. We demonstrated the α-amylase inhibitory activity of silymarin and investigated the components responsible for this effect. Two major flavonolignans, silibinin and silychristin, did not show inhibition against α-amylase, but two novel silychristin derivatives conjugated with dehydrodiconiferyl alcohol were isolated as the mildly inhibiting components of silymarin. Further analyses indicated the presence of various silychristin derivatives in silymarin that may act synergistically to show α-amylase inhibitory activity. Keywords: silymarin; milk thistle; α-amylase; diabetes mellitus 3 1. Introduction Silymarin is a mixture of flavonoids extracted from the fruits of Silybum marianum (milk thistle). The latter was used by physicians in ancient Greece as a medicinal plant to treat disorders of the liver and gallbladder, as well as to protect liver against chemical and environmental toxins (Kren & Walterova 2005; Rainone 2005). Silymarin is the active component of milk thistle, and its effects against hepatic diseases and non-alcoholic fatty liver disease have been shown in several studies (Federico et al. 2017). Recent studies of silymarin have also reported its neuroprotective (Borah et al. 2013), renoprotective (Shahbazi et al. 2012), immunomodulative (Esmaeil et al. 2017), and cardioprotective effects (Razavi & Karimi 2016), thereby making it an interesting material for research. Recently, silymarin has garnered attention for use against diabetes mellitus (DM) (Kazazis et al. 2014; Voroneanu et al. 2016; Stolf et al. 2017). DM is a metabolic disorder that causes an increase in the glucose level in blood. DM incidence has been increasing rapidly worldwide in recent years. A high amount of glucose in blood vessels leads to an increased risk of various complications. Therefore, the prevention and treatment of DM has been studied widely. The effect of silymarin has been shown in several in vivo experiments against model animals and in clinical trials. Silymarin treatment to streptozotocin- or alloxan-induced DM in rats reduces serum levels of glucose and protects the pancreas (Soto et al. 2010; Amniattalab et al. 2016). Similar treatment with silymarin to partially 4 pancreatectomized rats also reduces serum levels of glucose compared with control, increases the insulin level, and induces the neogenesis of pancreatic beta-cells (C. Soto et al. 2014; Claudia Soto et al. 2014). Moreover, a trial of silymarin in DM patients reduced the levels of fasting blood glucose and glycated hemoglobin (Huseini et al. 2006). These positive effects of silymarin against DM could be attributed to its antioxidant and protective effects on pancreatic beta-cells. However, other effects may also contribute to the anti-DM property of silymarin, and the mechanism of action of silymarin is not completely explored. Digestion of carbohydrates by glycosidases in the gastrointestinal tract is a target of anti-DM medications. Inhibition of α-amylase and α-glucosidase delays the digestion and absorption of carbohydrates, which reduces the rapid increase in the glucose level in blood after food consumption. These digestive enzymes are also studied as common targets of medicinal plants with anti-DM properties (Governa et al. 2018). Here, we investigated if silymarin can modulate α-amylase activity and explored its active constituents. Silymarin showed inhibitory activity against α-amylase. However, silibinin (1) and silychristin (2), the major flavonolignans in silymarin (Csupor et al. 2016), were not shown to be α-amylase inhibitors. Investigation of the active components in silymarin led to the isolation of three novel silychristin derivatives (4–6) and mariamide B (3). 2. Results and Discussion Silymarin showed inhibitory activity against pancreatic α-amylase in a 5 dose-dependent manner at 0.1–5 mg/mL (Figure S1). To ascertain if the major flavonolignans contained in silymarin contribute to α-amylase inhibitory activity, silibinin (1, commercial, Sigma-Aldrich Co.) and silychristin (2, isolated, Cheng et al. 2013) were tested for their activity. However, silibinin (1) showed no inhibitory activity at <1.0 mg/mL, and nor did silychristin (2). Thus, activity-guided separation was undertaken to elucidate the component in silymarin with α-amylase inhibitory activity. Silymarin was partitioned between solvents (water, 1-butanol, ethyl acetate). The ethyl-acetate layer was separated twice by silica-gel column chromatography to obtain the active fraction (AF). However, further separation of the AF by the reverse-phase column resulted in dispersed activity within broad range of fractions. This finding suggested that several compounds contribute to the α-amylase inhibitory activity of silymarin. Next, we focused on analyzing the AF to explore the type of compound that contributes to α-amylase inhibition. The fractions obtained after reverse-phase column chromatography were analyzed by high-performance liquid chromatography (HPLC) and the major peaks were collected. The peaks were analyzed by nuclear magnetic resonance (NMR) and mass spectroscopy (MS) to elucidate their structures and these compounds were numbered 3–6 (Figure 1). Compound 3 was obtained as a mixture which appeared as two peaks upon HPLC. These two peaks converted readily to each other and a single peak could not be 6 obtained, so they were analyzed as a mixture to elucidate their structures. Proton (1H)-NMR suggested that the mixtures were cis/trans stereoisomers resulting from isomerization of an alkene moiety (trans isomer: 7.45/6.44 ppm, J = 15.5 Hz; cis isomer: 6.64/5.85 ppm, J = 12.7 Hz). Additional NMR procedures (13C, correlated spectroscopy (COSY), heteronuclear multiple quantum coherence (HSQC) and heteronuclear multiple bond correlation (HMBC), Figure S4-S6) and comparison with the reported value (Choudhary et al. 2008; Qin et al. 2017) of predicted structures revealed compound 3 to be the mixture of mariamide B and its trans-isomer. Compound 4 was analyzed by high resolution (HR)-electrospray ionization + (ESI)-MS to reveal the molecular formula C35H32O13 (found m/z 683.17583 [M+Na] , + 1 C35H32O13Na requires 683.17351). H-NMR showed a similar spectrum to that of silychristin (2) but with additional signals indicating condensation of coniferyl alcohol. The predicted structure with the determined molecular formula did not correspond to any of the structures reported previously, thereby suggesting a novel compound. Careful analyses of compound 4 with 13C-NMR, COSY, HSQC, and HMBC showed its structure (Table S1, Figure S7-S10)., which was named coniferylsilychristin (4) Compounds 5 and 6 were analyzed by HR-ESI-MS to reveal the molecular + formula C45H42O15 (compound 5: found m/z 845.24252 [M+Na] ; compound 6: found + + 1 m/z 845.24139 [M+Na] ; C45H42O15Na requires 845.24159). H-NMR of compounds 5 and 6 showed a similar spectrum to that of silychristin (2) but with additional signals suggesting the conjugation of dehydrodiconiferyl alcohol, and compounds 5 and 6 were presumed to be novel compounds. Analyses of compounds 5 and 6 by 13C-NMR, COSY, HSQC, and HMBC revealed their structures (Table S2,S3, Figure S11-S18), which were 7 named
Load more

Recommended publications
  • Single Laboratory Validation of a Quantitative Core Shell-Based LC
    Single Laboratory Validation of a Quantitative Core Shell-Based LC Separation for the Evaluation of Silymarin Variability and Associated Antioxidant Activity of Pakistani Ecotypes of Milk Thistle (Silybum Marianum L.) Samantha Drouet, Bilal Haider Abbasi, Annie Falguieres, Waqar Ahmad, S. Sumaira, Clothilde Ferroud, Joël Doussot, Jean Vanier, Christophe Hano To cite this version: Samantha Drouet, Bilal Haider Abbasi, Annie Falguieres, Waqar Ahmad, S. Sumaira, et al.. Single Laboratory Validation of a Quantitative Core Shell-Based LC Separation for the Evaluation of Sily- marin Variability and Associated Antioxidant Activity of Pakistani Ecotypes of Milk Thistle (Silybum Marianum L.). Molecules, MDPI, 2018, 23 (4), pp.904. 10.3390/molecules23040904. hal-02538464 HAL Id: hal-02538464 https://hal.archives-ouvertes.fr/hal-02538464 Submitted on 9 Apr 2020 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. Distributed under a Creative Commons Attribution| 4.0 International License molecules Article Single Laboratory Validation of a Quantitative Core Shell-Based
    [Show full text]
  • Addis Ababa University College of Health Sciences
    ADDIS ABABA UNIVERSITY COLLEGE OF HEALTH SCIENCES SCHOOL OF MEDICINE DEPARTMENT OF BIOCHEMISTRY Hepatoprotective Effect of Silymarin on Fructose Induced Nonalcoholic Fatty Liver Disease in Male Albino Wistar Rats. By: Tewodros Mengesha (BSc.) A Thesis Submitted To School of Graduate Studies, College of Health Sciences, Addis Ababa University In Partial Fulfillment of The Requirement For The Degree of Master of Sciences In Medical Biochemistry. June, 2016 Addis Ababa, Ethiopia Hepatoprotective Effect of Silymarin on Fructose Induced Nonalcoholic Fatty Liver Disease in Male Albino Wistar Rats. Advisors 1. N. Gnana Sekeheram, PhD Department of Biochemistry, School of Medicine Addis Ababa University, Addis Ababa, Ethiopia. 2. Mahilet Arayasilasie, MD, Pathologist Head, Department of Pathology, School of Medicine Addis Ababa University, Addis Ababa, Ethiopia. Addis Ababa University School of Graduate Studies This is to clarify that thesis prepared by Tewodros Mengesha entitled “Hepatoprotective Effect of Silymarin on Fructose Induced Nonalcoholic Fatty Liver Disease in Male Albino Wistar Rats” is submitted in partial fulfillment of the Requirement for the Degree of Master of Sciences in Medical Biochemistry complies with the regulations of the university and meets the accepted standards with respect to the originality and quality. Signed by the examining committee: Examiner Signature Date Advisor Signature Date Advisor Signature Date Advisor Signature Date Chair of Department or Graduate Program Coordinator Abstract Background: Nonalcoholic fatty liver disease is one of the most common causes of chronic liver disease in the Western world, and it‟s likely to parallel the increasing prevalence of type 2 diabetes, obesity, and other components of metabolic syndrome. There is also growing evidence in both animal models and human studies suggesting that high dietary intake of fructose is an important nutritional factor in the development of metabolic syndrome and its associated complications of NAFLD.
    [Show full text]
  • Bioconversion of Callus-Produced Precursors to Silymarin Derivatives in Silybum Marianum Leaves for the Production of Bioactive Compounds
    International Journal of Molecular Sciences Article Bioconversion of Callus-Produced Precursors to Silymarin Derivatives in Silybum marianum Leaves for the Production of Bioactive Compounds Dina Gad 1,2,* , Hamed El-Shora 3, Daniele Fraternale 4 , Elisa Maricchiolo 4, Andrea Pompa 4,* and Karl-Josef Dietz 2 1 Botany and Microbiology Department, Faculty of Science, Menoufia University, Shebin EL-Koum 32511, Egypt 2 Biochemistry and Physiology of Plants, Faculty of Biology W5, Bielefeld University, 33501 Bielefeld, Germany; [email protected] 3 Botany Department, Faculty of Science, Mansoura University, Mansoura 35511, Egypt; [email protected] 4 Department of Biomolecular Sciences, University of Urbino “Carlo Bo” Via Donato Bramante, 28, 61029 Urbino, Italy; [email protected] (D.F.); [email protected] (E.M.) * Correspondence: [email protected]fia.edu.eg (D.G.); [email protected] (A.P.) Abstract: The present study aimed to investigate the enzymatic potential of Silybum marianum leaves to bioconvert phenolic acids produced in S. marianum callus into silymarin derivatives as chemopreventive agent. Here we demonstrate that despite the fact that leaves of S. marianum did not accumulate silymarin themselves, expanding leaves had the full capacity to convert di- caffeoylquinic acid to silymarin complex. This was proven by HPLC separations coupled with Citation: Gad, D.; El-Shora, H.; electrospray ionization mass spectrometry (ESI-MS) analysis. Soaking the leaf discs with S. marianum Fraternale, D.; Maricchiolo, E.; callus extract for different times revealed that silymarin derivatives had been formed at high yield Pompa, A.; Dietz, K.-J. Bioconversion after 16 h. Bioconverted products displayed the same retention time and the same mass spectra (MS of Callus-Produced Precursors to or MS/MS) as standard silymarin.
    [Show full text]
  • Skin Aging Handbook
    SKIN AGING HANDBOOK An Integrated Approach to Biochemistry and Product Development Edited by Nava Dayan Norwich, NY, USA Copyright © 2008 by William Andrew Inc. No part of this book may be reproduced or utilized in any form or by any means, electronic or me- chanical, including photocopying, recording, or by any information storage and retrieval system, without permission in writing from the Publisher. ISBN: 978-0-8155-1584-5 Library of Congress Cataloging-in-Publication Data Skin aging handbook : an integrated approach to biochemistry and product development / edited by Nava Dayan. p. ; cm. -- (Personal care and cosmetic technology) Includes bibliographical references and index. ISBN 978-0-8155-1584-5 (alk. paper) 1. Skin--Aging. 2. Cosmetics. 3. Dermatologic agents. 4. Cosmetic industry. 5. Dermatologic agents industry. I. Dayan, Nava. II. Series. [DNLM: 1. Skin Physiology--drug effects. 2. Aging--drug effects. 3. Chemistry, Pharmaceutical. 4. Cosmetics--economics. 5. Cosmetics--pharmacology. 6. Cosmetics--therapeutic use. WR 102 S62715 2008] QP88.5.S553 2008 612.7’9--dc22 2008009757 Printed in the United States of America This book is printed on acid-free paper. 10 9 8 7 6 5 4 3 2 1 Published by: William Andrew Inc. 13 Eaton Avenue Norwich, NY 13815 1-800-932-7045 www.williamandrew.com Cover Design by Russell Richardson ENVIRONMENTALLY FRIENDLY This book has been printed digitally because this process does not use any plates, ink, chemicals, or press solutions that are harmful to the environment. The paper used in this book has a 30% recycled content. NOTICE To the best of our knowledge the information in this publication is accurate; however the Publisher does not assume any responsibility or liability for the accuracy or completeness of, or consequences arising from, such information.
    [Show full text]
  • Silybin, a Major Bioactive Component of Milk Thistle (Silybum Marianum L
    molecules Review Silybin, a Major Bioactive Component of Milk Thistle (Silybum marianum L. Gaernt.)—Chemistry, Bioavailability, and Metabolism Michal Bijak Department of General Biochemistry, Faculty of Biology and Environmental Protection, University of Lodz, Pomorska 141/143, 90-236 Lodz, Poland; [email protected]; Tel./Fax: +48-42-635-4336 Received: 10 October 2017; Accepted: 8 November 2017; Published: 10 November 2017 Abstract: Milk thistle (Silybum marianum) is a medicinal plant that has been used for thousands of years as a remedy for a variety of ailments. The main component of S. marianum fruit extract (silymarin) is a flavonolignan called silybin, which is not only the major silymarin element but is also the most active ingredient of this extract, which has been confirmed in various studies. This compound belongs to the flavonoid group known as flavonolignans. Silybin’s structure consists in two main units. The first is based on a taxifolin, the second a phenyllpropanoid unit, which in this case is conyferil alcohol. These two units are linked together into one structure by an oxeran ring. Since the 1970s, silybin has been regarded in official medicine as a substance with hepatoprotective properties. There is a large body of research that demonstrates silybin’s many other healthy properties, but there are still a lack of papers focused on its molecular structure, chemistry, metabolism, and novel form of administration. Therefore, the aim of this paper is a literature review presenting and systematizing our knowledge of the silybin molecule, with particular emphasis on its structure, chemistry, bioavailability, and metabolism. Keywords: silybin; silymarin; chemistry; bioavailability 1.
    [Show full text]
  • Mechanistic Study of the Biomimetic Synthesis of Flavonolignan Diastereoisomers in Milk Thistle
    Mechanistic Study of the Biomimetic Synthesis of Flavonolignan Diastereoisomers in Milk Thistle By: Hanan S. Althagafy, Maria Elena Meza-Aviña, Nicholas H. Oberlies, Mitchell P. Croatt Althagafy, H.S.; Meza-Aviña, M.E.; Oberlies, N.H.; Croatt, M.P. Mechanistic Study of the Biomimetic Synthesis of Flavonolignan Diastereoisomers in Milk Thistle. The Journal of Organic Chemistry, 2013, 78, 7594-7600. This document is the unedited author's version of a Submitted Work that was subsequently accepted for publication in The Journal of Organic Chemistry, copyright © American Chemical Society after peer review. To access the final edited and published work, see http://dx.doi.org/10.1021/jo4011377. Abstract: The mechanism for the biomimetic synthesis of flavonolignan diastereoisomers in milk thistle is proposed to proceed by single-electron oxidation of coniferyl alcohol, subsequent reaction with one of the oxygen atoms of taxifolin’s catechol moiety, and finally, further oxidation to form four of the major components of silymarin: silybin A, silybin B, isosilybin A, and isosilybin B. This mechanism is significantly different from a previously proposed process that involves the coupling of two independently formed radicals. Graphical Abstract: Keywords: Organic chemistry | Milk thistle | flavonolignan diastereoisomers | silymarin | silybin Article: Introduction Milk thistle [Silybum marianum (L.) Gaertn. (Asteraceae)] has been used as a medicinal herb since antiquity. As outlined in several reviews, modern pharmacological studies typically focus on the hepatoprotective properties(1-3) (as milk thistle is the top herbal supplement for hepatitis C patients(2)), the prostate cancer chemopreventive properties(4-6) (where promising results have been observed, especially for isosilybin B(7-10)), or both.
    [Show full text]
  • Antifungal Activity Against Botryosphaeriaceae Fungi of the Hydro-Methanolic Extract of Silybum Marianum Capitula Conjugated with Stevioside
    plants Article Antifungal Activity against Botryosphaeriaceae Fungi of the Hydro-Methanolic Extract of Silybum marianum Capitula Conjugated with Stevioside Natalia Langa-Lomba 1,2, Laura Buzón-Durán 3, Eva Sánchez-Hernández 3 , Pablo Martín-Ramos 1,* , José Casanova-Gascón 1 , Jesús Martín-Gil 3 and Vicente González-García 2 1 Instituto Universitario de Investigación en Ciencias Ambientales de Aragón (IUCA), EPS, Universidad de Zaragoza, Carretera de Cuarte, s/n, 22071 Huesca, Spain; [email protected] (N.L.-L.); [email protected] (J.C.-G.) 2 Plant Protection Unit, Agrifood Research and Technology Centre of Aragón, Instituto Agroalimentario de Aragón—IA2 (CITA-Universidad de Zaragoza), Avda. Montañana 930, 50059 Zaragoza, Spain; [email protected] 3 Agriculture and Forestry Engineering Department, ETSIIAA, Universidad de Valladolid, Avenida de Madrid 44, 34004 Palencia, Spain; [email protected] (L.B.-D.); [email protected] (E.S.-H.); [email protected] (J.M.-G.) * Correspondence: [email protected] Abstract: Silybum marianum (L.) Gaertn, viz. milk thistle, has been the focus of research efforts in the past few years, albeit almost exclusively restricted to the medicinal properties of its fruits (achenes). Citation: Langa-Lomba, N.; Buzón- Given that other milk thistle plant organs and tissues have been scarcely investigated for the pres- Durán, L.; Sánchez-Hernández, E.; ence of bioactive compounds, in this study, we present a phytochemical analysis of the extracts of Martín-Ramos, P.; Casanova-Gascón, S. marianum capitula during the flowering phenological stage (stage 67). Gas chromatography–mass J.; Martín-Gil, J.; González-García, V. spectroscopy results evidenced the presence of high contents of coniferyl alcohol (47.4%), and sec- Antifungal Activity against ondarily of ferulic acid ester, opening a new valorization strategy of this plant based on the former Botryosphaeriaceae Fungi of the Hydro-Methanolic Extract of high-added-value component.
    [Show full text]
  • Regioselective Alcoholysis of Silychristin Acetates Catalyzed by Lipases ‡
    Int. J. Mol. Sci. 2015, 16, 11983-11995; doi:10.3390/ijms160611983 OPEN ACCESS International Journal of Molecular Sciences ISSN 1422-0067 www.mdpi.com/journal/ijms Article Regioselective Alcoholysis of Silychristin Acetates Catalyzed ‡ by Lipases Eva Vavříková 1,†, Paolo Gavezzotti 2,†, Kateřina Purchartová 1, Kateřina Fuksová 1, David Biedermann 1, Marek Kuzma 1, Sergio Riva 2,* and Vladimír Křen 1,* 1 Laboratory of Biotransformation, Institute of Microbiology, Academy of Sciences of the Czech Republic, Vídeňská 1083, CZ 142 20 Prague, Czech Republic; E-Mails: [email protected] (E.V.); [email protected] (K.P.); [email protected] (K.F.); [email protected] (D.B.); [email protected] (M.K.) 2 Istituto di Chimica del Riconoscimento Molecolare, Consiglio Nazionale delle Ricerche, Via Mario Bianco 9, I 20131 Milano, Italy; E-Mail: [email protected] † These authors contributed equally to this work. ‡ This paper is dedicated to the memory of the late Prof. Bruno Danieli, Professor of Organic Chemistry, Università degli Studi di Milano, 20122 Milano, Italy. * Authors to whom correspondence should be addressed; E-Mails: [email protected] (V.K.); [email protected] (S.R.); Tel.: +420-296-442-510 (V.K.). Academic Editor: Ritva Tikkanen Received: 27 April 2015 / Accepted: 19 May 2015 / Published: 26 May 2015 Abstract: A panel of lipases was screened for the selective acetylation and alcoholysis of silychristin and silychristin peracetate, respectively. Acetylation at primary alcoholic group (C-22) of silychristin was accomplished by lipase PS (Pseudomonas cepacia) immobilized on diatomite using vinyl acetate as an acetyl donor, whereas selective deacetylation of 22-O-acetyl silychristin was accomplished by Novozym 435 in methyl tert-butyl ether/ n-butanol.
    [Show full text]
  • Silymarin and Cancer: a Dual Strategy in Both in Chemoprevention and Chemosensitivity
    molecules Review Silymarin and Cancer: A Dual Strategy in Both in Chemoprevention and Chemosensitivity Dominique Delmas 1,2,3,*, Jianbo Xiao 4 , Anne Vejux 1,5 and Virginie Aires 1,2 1 Université de Bourgogne Franche-Comté, F-21000 Dijon, France; [email protected] (A.V.); [email protected] (V.A.) 2 INSERM Research Center U1231—Cancer and Adaptive Immune Response Team, Dijon, Bioactive Molecules and Health research group, F-21000 Dijon, France 3 Centre anticancéreux Georges François Leclerc Center, F-21000 Dijon, France 4 International Research Center for Food Nutrition and Safety, Jiangsu University, Zhenjiang 212013, China; [email protected] 5 Laboratoire Bio-PeroxIL“Biochemistry of the Peroxisome, Inflammation and Lipid Metabolism”—EA 7270, UFR Sciences Vie Terre Environnement (SVTE), 6 Bd Gabriel, F-21000 Dijon, France * Correspondence: [email protected]; Tel.: +33-380-39-32-26 Academic Editor: Saverio Bettuzzi Received: 11 March 2020; Accepted: 21 April 2020; Published: 25 April 2020 Abstract: Silymarin extracted from milk thistle consisting of flavonolignan silybin has shown chemopreventive and chemosensitizing activity against various cancers. The present review summarizes the current knowledge on the potential targets of silymarin against various cancers. Silymarin may play on the system of xenobiotics, metabolizing enzymes (phase I and phase II) to protect normal cells against various toxic molecules or to protect against deleterious effects of chemotherapeutic agents on normal cells. Furthermore,
    [Show full text]
  • Chemistry of Silybin
    Natural Product Reports Chemistry of silybin Journal: Natural Product Reports Manuscript ID: NP-REV-11-2013-070122.R1 Article Type: Review Article Date Submitted by the Author: 30-Apr-2014 Complete List of Authors: Biedermann, David; Inst. of Microbiology, Vavříková, Eva; Inst. of Microbiology, Cvak, Ladislav; Teva Pharmaceuticals, R&D Kren, Vladimir; Inst. of Microbiology, Page 1 of 24 Natural Product Reports Journal Name RSC Publishing ARTICLE Chemistry of silybin a a b a,* Cite this: DOI: 10.1039/x0xx00000x D. Biedermann, E. Vavříková, L. Cvak and V. Křen Silybin, a secondary metabolite isolated from the seeds of the blessed milk thistle ( Silybum marianum ) was discovered as the first member of a new family of natural compounds called flavonolignans in 1959. Received 00th 2013, Accepted 00th 2013 Over the years it has received the research attention of many organic chemists. This research has resulted in a number of semisynthetic derivatives prepared in an effort to modulate and better target DOI: 10.1039/x0xx00000x the biological activities of silybin or to improve its physical properties, such as solubility. A fundamental www.rsc.org/ breakthrough in silybin chemistry was the determination of the absolute configurations of silybin A and silybin B, and the development of the methods for their separation. This review covers articles dealing with silybin chemistry and also summarizes all the derivatives prepared. Covering: 1959-2013. 1 Introduction 5.10 Chemoenzymatic glycosidations 1.1 Flavonoids and flavonolignans 5.11 Other chemoenzymatic
    [Show full text]
  • A Quest for Staunch Effects of Flavonoids
    Arabian Journal of Chemistry (2012) xxx, xxx–xxx King Saud University Arabian Journal of Chemistry www.ksu.edu.sa www.sciencedirect.com REVIEW A quest for staunch effects of flavonoids: Utopian protection against hepatic ailments Anju Dhiman a,*, Arun Nanda a, Sayeed Ahmad b a Department of Pharmaceutical Sciences, Maharshi Dayanand University, Rohtak 124001, Haryana, India b Bioactive Natural Product Laboratory, Department of Pharmacognosy & Phytochemistry, Faculty of Pharmacy, Jamia Hamdard, New Delhi 110062, India Received 2 September 2011; accepted 15 May 2012 KEYWORDS Abstract The role of flavonoids as the major red, blue and purple pigments in plants has gained Antioxidant; these secondary products a great deal of attention over the years. Flavonoids are polyphenols Flavonoids; and occur as aglycones, glycosides and methylated derivatives. Flavonoids are the main compo- Hepatoprotection; nents of a healthy diet containing fruits and vegetables and are concentrated especially in tea, apples Phenolic compounds and onions. Till date, more than 6000 flavonoids have been discovered, out of which 500 are found in free state. They are abundant in polygonaceae, rutaceae, leguminosae, umbelliferae and compos- itae. Flavonoids are powerful antioxidants. In addition to their role in nutrition, flavonoids possess many types of pharmacological activities, including anti-inflammatory, antioxidative, hepatoprotec- tive, vasorelaxant, antiviral and anticarcinogenic effects. The present review is focused on flavo- noids derived from natural products that have shown a wise way to get a true and potentially rich source of drug candidates against liver ailments. The present review initially highlights the cur- rent status of flavonoids and their pharmaceutical significance, role of flavonoids in hepatoprotec- tion, therapeutic options available in herbal medicines and in later section, summarizes flavonoids as lead molecules, which have shown significant hepatoprotective activities.
    [Show full text]
  • Silybum Marianum (L.) Gaertn.
    Journal of Medicinal Plants A Review on Pharmacological, Cultivation and Biotechnology Aspects of Milk Thistle (Silybum marianum (L.) Gaertn.) Qavami N (Ph.D. Student), Naghdi Badi H (Ph.D.), Labbafi MR (Ph.D.), Mehrafarin A (Ph.D.)* Cultivation & Development Department of Medicinal Plants Research Center, Institute of Medicinal Plants, ACECR, Karaj, Iran * Corresponding author: Medicinal Plants Research Center, Institute of Medicinal Plants, Iranian Academic Center for Education, Culture and Research (ACECR), P.O.Box: 33651/66571, Karaj, Iran Tel: +98-26-34764010-9, Fax: +98-26-34764021 Email: [email protected] Received: 4 May 2013 Accepted: 9 July 2013 Abstract Milk thistle (Silybum marianum (L.) Gaertn.) is one of the valuable medicinal plants which used in the treatment of liver disorders. The major active constituents in this plant are flavonolignans, collectively known as silymarin which is a mixture of three isomer silybin, silydianin and silycristin. Its therapeutic properties are due to the presence of silymarin. The seeds contain the highest amount of silymarin, but the other plant parts have less amount of this compound. The silymarin content in fruits depends on milk thistle variety and geographic and climatic condition. In this review, we summarized the accomplished investigations on aspects of medicinal, cultivation, biology and biotechnology of milk thistle. Keywords: Silybum marianum, Silymarin, Silybin, Flavonolignan, Cultivation and Medicinal Downloaded from jmp.ir at 0:10 +0330 on Saturday September 25th 2021 properties 19 Volume 12, No. 47, Summer 2013 A Review on Pharmaco. … Introduction of the fruit for treatment of liver diseases was Milk thistle (Silybum marianum (L.) revitalized by the German physician Gaetrn) has been used since the time of ancient Rademacher [1, 7, 9, 10].
    [Show full text]