Download PDF
Planta Med 2017; 83(01/02): 97-103
DOI: 10.1055/s-0042-113135
Biological and Pharmacological Activity
Original Papers
Georg Thieme Verlag KG Stuttgart · New York

Protective Effect of Silybum marianum and Silibinin on Endothelial Cells Submitted to High Glucose Concentration

Olga M. Palomino
1   Faculty of Pharmacy, Universidad Complutense de Madrid, Madrid, Spain
,
Neire M. Gouveia
2   Institute of Genetics and Biochemistry, Federal University of Uberlandia, Uberlandia, Minas Gerais, Brazil
,
Sonia Ramos
3   Department of Metabolism and Nutrition, Institute of Science and Food Technology and Nutrition (ICTAN – CSIC), Madrid, Spain
,
M. Angeles Martín
3   Department of Metabolism and Nutrition, Institute of Science and Food Technology and Nutrition (ICTAN – CSIC), Madrid, Spain
4   Spanish Biomedical Research Centre in Diabetes and Associated Metabolic Disorders (CIBERDEM), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
,
Luis Goya
3   Department of Metabolism and Nutrition, Institute of Science and Food Technology and Nutrition (ICTAN – CSIC), Madrid, Spain
› Author Affiliations
Further Information

Publication History

received 17 December 2015
revised 04 July 2016

accepted 14 July 2016

Publication Date:
15 August 2016 (online)

    Permissions and Reprints

Abstract

Silybum marianum Gaertn. (Milk thistle) has been used since ancient times for the relief of liver diseases characterized by intense oxidative stress such as inflammatory liver disease and cirrhosis. As oxidative stress by hyperglycemia is involved in micro- and macrovascular complications of type 2 diabetes, our aim was to assess the protective effect of milk thistle seed extract against oxidative stress induced by a high glucose concentration on endothelial cells (EA.hy926 cells). High-performance liquid chromatographic analysis shows flavonolignans silychristin and silibinin A and B as major components. No cell toxicity was observed for concentrations up to 100 µg/mL of milk thistle extract for 24 h. Concentrations of 5–25 µg/mL of the extract were used to assess the protective effect on EA.hy926 cells treated with 30 mM glucose for 24 h. Oxidative damage by 30 mM glucose was shown as a significant decrease in reduced glutathione and a significant increase in protein carbonyls and antioxidant enzyme activities. S. marianum extract recovered reduced glutathione and balanced the elevated carbonyls and enzyme activity. Silibinin alone also recovered reduced glutathione and antioxidant enzymes. S. marianum protects endothelial cell against oxidative damage by modulating antioxidant enzyme activity, reduced glutathione, and protein carbonyl levels.

Key words

Silybum marianum - Asteraceae - Flavonolignans - endothelial cells - oxidative damage - plant antioxidants
 

  • References

  • 1 Favero G, Paganelli C, Buffoli B, Rodella LF, Rezzani R. Endothelium and its alterations in cardiovascular diseases: life style intervention. Biomed Res Int 2014; 2014: 801896
    PubMedGoogle Scholar
  • 2 Polovina MM, Potpara TS. Endothelial dysfunction in metabolic and vascular disorders. Postgrad Med 2014; 126: 38-53
    CrossrefPubMedGoogle Scholar
  • 3 Paneni F, Beckman JA, Creager MA, Cosentino F. Diabetes and vascular disease: pathophysiology, clinical consequences and medical therapy: part I. Eur Heart J 2013; 34: 2436-2443
    Google Scholar
  • 4 Ríos JL, Francini F, Schinella GR. Natural products for the treatment of type 2 diabetes mellitus. Planta Med 2015; 81: 975-994
    Article in Thieme ConnectPubMedGoogle Scholar
  • 5 González J, Valls N, Brito R, Rodrigo R. Essential hypertension and oxidative stress: New insights. World J Cardiol 2014; 6: 353-366
    CrossrefPubMedGoogle Scholar
  • 6 Song P, Zou MH. Redox regulation of endothelial cell fate. Cell Mol Life Sci 2014; 71: 3219-3239
    CrossrefPubMedGoogle Scholar
  • 7 Abenavoli L, Capasso R, Milic N, Capasso F. Milk thistle in liver diseases: past, present, future. Phytother Res 2010; 24: 1423-1432
    CrossrefPubMedGoogle Scholar
  • 8 Kim Y, Kim E, Lee E, Lee ED, Kim JH, Jang SW, Kim YG, Kwon JW, Kim WB, Lee MG. Comparative bioavailability of silibinin in healthy male volunteers. Int J Clin Pharmacol Ther 2003; 41: 593-596
    CrossrefPubMedGoogle Scholar
  • 9 Sweetman S. Martindale: the complete Drug Reference. 36th ed. London: Pharmaceutical Press; 2009: 1452
    Google Scholar
  • 10 Saller R, Melzer J, Reichling J, Brignoli R, Meier R. An updated systematic review of the pharmacology of silymarin. Forsch Komplementmed 2007; 14: 70-80
    CrossrefPubMedGoogle Scholar
  • 11 Kwon DY, Suk JY, Kim SJ, Kim YS, Choi DW, Kim YC. Alterations in sulfur amino acid metabolism in mice treated with silymarin: a novel mechanism of its action involved in enhancement of the antioxidant defense in liver. Planta Med 2013; 79: 997-1002
    Google Scholar
  • 12 Lee D, Liu Y. Molecular structure and stereochemistry of silybin A, silybin B, isosilybin A, and isosilybin B, isolated from Silybum marianum (Milk Thistle). J Nat Prod 2003; 66: 1171-1174
    CrossrefPubMedGoogle Scholar
  • 13 Quercia V, Pierini N, Incarnato G, Terracciano M, Papetti P. Identification and assay by HPLC of the flavonoid components of Silybum marianum in medicinal specialities. Fitoterapia 1980; 51: 83-88
    PubMedGoogle Scholar
  • 14 Demirci B, Dost T, Gokalp F, Birincioglu M. Silymarin improves vascular function of aged ovariectomized rats. Phytother Res 2014; 28: 868-872
    CrossrefPubMedGoogle Scholar
  • 15 Halliwell B. Cell culture, oxidative stress, and antioxidants: avoiding pitfalls. Biomed J 2014; 37: 99-105
    PubMedGoogle Scholar
  • 16 Shaker E, Mahmoud H, Mnaa S. Silymarin, the antioxidant component of Silybum marianum extracts prevents liver damage. Food Chem Toxicol 2010; 48: 803-806
    CrossrefPubMedGoogle Scholar
  • 17 Ferruzzi MG, Lobo JK, Janle EM, Cooper B, Simon JE, Wu QL, Welch C, Ho L, Weaver C, Pasinetti GM. Bioavailability of gallic acid and catechins from grape seed polyphenol extract is improved by repeated dosing in rats: implications for treatment in Alzheimerʼs disease. J Alzheimers Dis 2009; 18: 113-124
    CrossrefPubMedGoogle Scholar
  • 18 Rodríguez-Ramiro I, Ramos S, Bravo L, Goya L, Martin MA. Procyanidin B2 and a cocoa polyphenolic extract inhibit acrylamide-induced apoptosis in human Caco-2 cells by preventing oxidative stress and activation of JNK pathway. J Nutr Biochem 2011; 22: 1186-1194
    CrossrefPubMedGoogle Scholar
  • 19 Rodríguez-Ramiro I, Martín MA, Ramos S, Bravo L, Goya L. Comparative effects of dietary flavanols on antioxidant defences and their response to oxidant-induced stress in Caco2 cells. Eur J Nutr 2011; 50: 313-322
    CrossrefPubMedGoogle Scholar
  • 20 Martín MA, Fernández-Millán E, Ramos S, Bravo L, Goya L. Cocoa flavonoid epicatechin protects pancreatic beta cell viability and function against oxidative stress. Mol Nutr Food Res 2014; 58: 447-456
    CrossrefPubMedGoogle Scholar
  • 21 Ezhilarasan D, Karthikeyan S. Silibinin alleviates N-nitrosodimethylamine-induced glutathione dysregulation and hepatotoxicity in rats. Chin J Nat Med 2016; 14: 40-47
    PubMedGoogle Scholar
  • 22 León-González A, Mateos R, Ramos S, Martín MA, Sarriá B, Martín-Cordero C, López-Lázaro M, Bravo L, Goya L. Chemo-protective activity and characterization of phenolic extracts from Corema album . Food Res Int 2012; 49: 728-738
    CrossrefPubMedGoogle Scholar
  • 23 Baeza G, Amigo-Benavent M, Sarriá B, Goya L, Mateos R, Bravo L. Green coffee hydroxycinnamic acids but not caffeine protect human HepG2 cells against oxidative stress. Food Res Int 2014; 62: 1038-1046
    CrossrefPubMedGoogle Scholar
  • 24 Martín MA, Ramos S, Mateos R, Marais J, Bravo L, Khoo C, Goya L. Chemical characterization and chemo-protective activity of cranberry phenolic extracts in a model cell culture. Response of the antioxidant defences and regulation of signaling pathways. Food Res Int 2015; 71: 68-82
    CrossrefPubMedGoogle Scholar
  • 25 Ramos S, Rodríguez-Ramiro I, Martín MA, Goya L, Bravo L. Dietary flavanols exert different effects on antioxidant defences and apoptosis in Caco-2 and SW480 colon cancer cells. Toxicol In Vitro 2011; 25: 1771-1781
    CrossrefPubMedGoogle Scholar
  • 26 Cordero-Herrera I, Martín MA, Goya L, Ramos S. Cocoa flavonoids protect hepatic cells against high glucose-induced oxidative stress: relevance of MAPKs. Mol Nutr Food Res 2015; 59: 597-609
    CrossrefPubMedGoogle Scholar
  • 27 Cordero-Herrera I, Martín MA, Goya L, Ramos S. Cocoa intake ameliorates hepatic oxidative stress in young Zucker diabetic fatty rats. Food Res Int 2015; 69: 194-201
    CrossrefPubMedGoogle Scholar
  • 28 EDQM. European Pharmacopoeia. Silybum marianum. 7th edn. Strasbourg, France: EDQM Eds.; 2008: 1860
    Google Scholar
  • 29 Bouis D, Hospers GA, Meijer C, Molema G, Mulder NH. Endothelium in vitro: a review of human vascular endothelial cell lines for blood vessel-related research. Angiogenesis 2001; 4: 91-102
    CrossrefPubMedGoogle Scholar
  • 30 Granado-Serrano AB, Martín MA, Izquierdo-Pulido M, Goya L, Bravo L, Ramos S. Molecular mechanisms of (−)-epicatechin and chlorogenic acid on the regulation of the apoptotic and survival/proliferation pathways in a human hepatoma cell line. J Agric Food Chem 2007; 55: 2020-2027
    CrossrefPubMedGoogle Scholar
  • 31 Granado-Serrano AB, Martín MA, Bravo L, Goya L, Ramos S. A diet rich in cocoa attenuates N-nitrosodiethylamine-induced liver injury in rats. Food Chem Toxicol 2009; 47: 2499-2506
    CrossrefPubMedGoogle Scholar