Pharmacology of silybum marianum and its active constituents. Therapeutic activity – part 1
Pharmacology of silybum marianum and its active constituents. Therapeutic activity – part 1
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Title: | Pharmacology of silybum marianum and its active constituents. Therapeutic activity – part 1 |
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Article_Title: | Pharmacology of silybum marianum and its active constituents. Therapeutic activity – part 1 |
Authors: | Luminita Pilat1, Ciprian Mihali2, Hildegard Herman2, Cristina Popescu2, Violeta Turcus3, Aurel Ardelean3, Ardelean Gavril3, Teodora Mariasiu1, Calin Popa1, Anca Hermenean1,2* |
Affiliation: | 1“Vasile Goldis” Western University of Arad, Faculty of Medicine, Pharmacy and Dentistry, Arad, Romania 2“Vasile Goldis” Western University of Arad, Institute of Life Sciences, Arad, Romania 3“Vasile Goldis” Western University of Arad, Faculty of Natural Sciences, Arad, Romania |
Abstract: | In the last years a lot of effort has been made in demonstrating the role of plant extracts in medicine. The usage of herbal drugs for the treatment of several diseases has increased all over the world. The global popularity of herbal supplements and the promise they hold in treating various disease states has caused an unprecedented interest in understanding the molecular basis of the biological activity of traditional remedies. The herbal drugs are believed to be harmless without causing adverse reactions, as they are obtained from nature and are easily available. There are about 600 commercial herbal formulations available only for liver disease, which are claimed to have hepatoprotective effects. As the need for effective, affordable health promotion and treatment increases, especially in the growing ageing population, there is a need for rigorous scientific examination of herbal medicines. This article reviews on published reports pertaining to milk thistle’s benefits. |
Keywords: | Silymarin, disease, pharmacokinetics, regeneration, herbal medicine |
References: | Al-Anati L, Essid E, Reinehr R, Petzinger E, Silibinin protects OTA-mediated TNF-a release from perfused rat livers and isolated rat Kupffer cells. Mol.Nutr.Res., 53, 460-466, 2009. Avizeh R, Najafzadeh H, Razijalali M, Shirali S, Evaluation of prophylactic and therapeutic effects of silymarin and N-acetylcysteine in acetaminopheninduced hepatotoxicity in cats. J.Vet.Pharmacol. Therap., 33, 95-99, 2009. Basiglio C, Pozzi EJS, Mottino AD, Roma MG, Differential effects of silymarin and its active component silibinin on plasma membrane stability and hepatocellular lysis. Chemico-Biological Interactions, 179, 297-303, 2009. Brandon-Warner E, Sugg JA, Schrum LW, Mckillop LH, Silibinin inhibits ethanol metabolism and ethanoldependent cell proliferation in an vitro model of hepatocellular carcinoma. Cancer Letters, 291, 120- 129, 2010. Carpino G, Morini S, Gianinni Corradini S et al, Alpha_SMA expression in hepatic stellate cells and quantitative analysis of liver fibrosis in cirrhosis and in recurrent chronic hepatitis after liver transplantation, Dig.Liver Dis., 37, 349-356, 2005. Chang HR, Chen PN, Yang SF, Sun YS, Wu SW, Hung TW, Lian JD, Chu SC, Hsieh YS, Silibinin inhibits the invasion and migration of renal carcinoma 786-o cells in vitro, inhibits the growth of xenografts in vivo and enhances chemosensitivity to 5-fluorouracil and paclitaxel. Molecular Carcinogenesis, 50, 812–823, 2011. Chen CH, Huang TS, Wongc CH, Hong CL, Tsai YH, Liang CC, Lu FJ, Chang WH, Synergistic anticancer effect of baicalein and silymarin on human hepatoma HepG2 Cells. Food and Chemical Toxicology, 47, 638–644, 2009. Cho YK, Yun JW, Park JH, Kim HJ, Park DII, Sohn CII, Jeon WK, Kim BI, Jin W, Kwon YH, Shin MK, Yoo TM, Kang JH, Park CS, Sohn CI, Jeon WK, Kim BI, Jin W, Kwon YH, Shin MK, Yoo TM, Kang JH, Park CS, Deleterious effects of silymarin on the expression of genes controlling endothelial nitric oxide synthase activity in carbon tetrachloridetreated rat livers. Life Sciences, 85, 281-290, 2009. Colombo V, Lupi M, Falcetta F, Forestieri D, D’Incalci M, Ubezio P, Chemotherapeutic activity of silymarin combined with doxorubicin or paclitaxel in sensitive and multidrug-resistant colon cancer cells. Cancer Chemother Pharmacol, 67, 369–379, 2011. Colturato CP, Constantin RP, Maeda Jr. AS, Constantin RP, Yamamoto NS, Bracht A, Ishii-Iwamoto EL, Constantin J, Chemico-Biological Interactions, 195, 119–132, 2012. Crocenzi FA et al, Silibinin [Milk thistle] prevents cholestasis-associated retrieval of the bile salt export pump, Bsep, in isolated rat hepatocyte couplets: possible involvement of camp. Biochem Pharmacol., 69(7), 1113-20, 2005. Crocenzi FA, Sanchez-Pozzi EJ, Pellegrino JM, et al. Beneficial effects of silymarin on estrogen-induced cholestasis in the rat: A study in in vivo and in isolated hepatocyte couplets. Hepatology, 34, 329– 339, 2001. Das S, Roy P, Auddy RG, Mukherjee A, Silymarin nanoparticle prevents paracetamol-induced hepatotoxicity, International Journal of Nanomedicine, 6, 1291–1301, 2011. De La Puerta R, Martinez E, Bravo L. Effect of silymarin on different acute inflammation models and on leukocyte migration. J Pharm Pharmacol, 48, 968- 970, 1996. Deep G, Agarwal R, Antimetstatic efficacy of silibinin: molecular mechanisms and therapeutic potential against cancer. Cancer Metastasis Rev, 29, 447-463, 2010. Deep G, Oberlies NH, Kroll DJ, Agarwal R, Identifying the differential effects of silymarin constituents on cell growth and cell cycle regulatory molecules in human prostate cancer cells. Int. J. Cancer:, 123, 41–50, 2008. Dehmlow C, Erhard J, de Groot H. Inhibition of Kupffer cell functions as an explanation for the hepatoprotective properties of silibinin. Hepatology, 23, 749-754, 1996. Dehmlow C, Inhibition of Kupffer cell functions as an explanation for the hepatoprotective properties of silibinin. Hepatology, Apr; 23 (4): 749-54, 1996. Doehmer J, Weiss G, Weiss GP, Mc Gregor GP, Appel K, Assessment of a dry extract from milk thistle (Silybum marianum) for interference with human liver cytochrome P450 activities. Toxicology in vitro, 25, 21-27, 2011. Duan WJ, Li QS, Xia MY, Tashiro SI, Onodera S, Ikejima T, Silibinin activated p53 and induced autophagic death in human fibrosarcoma ht1080 cells via reactive oxygen species-p38 and c-jun n-terminal kinase pathways. Biol. Pharm. Bull., 34(1), 47—53, 2011. Erlejman AG, Verstraeten SV, Fraga CG, Oteiza PI, The interaction of flavonoids with membranes: potential determinant of flavonoid antioxidant effects. Free Radic.Res, 38, 1311-1320, 2004 Esmaily H, Hosseini-Tabatabaei A, Rahimian R, Khorasani R, Baeeri M, Barazesh-Morgani A, Yasa N, Khademi Y, Abdollahi M, On the benefits of silymarin in murine colitits by improving balance of destructive cytokines and reduction of toxic stress in the bowel cells. Centr.Eur.J.Bio., 4(2), 204-213, 2009. Esmaily H, Vaziri-Bami A, Miroliaee AE, Baeeri M, Abdollahi M, The correlation between NH-kb inhibition and disease activity by coadministration of silibinin and ursodeoxycholic acid in experimental colitis. Fundamental&Clinical Pharmacology, 25, 723-733, 2010. Fantozzi R, Brunelleschi S, Rubino A, et al. FMLPactivated neutrophils evoke histamine release from mast cells. Agents Actions, 18:155-158, 1986. Flaig TW, Glode M, Gustafson D, van Bokhoven A, Tao Y, Wilson S, Su LJ, Li Y, Harrison G, Agarwal R, Crawford ED, Lucia MS, Pollak M, A study of high-dose oral silybin-phytosome followed by prostatectomy in patients with localized prostate cancer. The Prostate 70, 848-855, 2010 Girish C, Koner BC, Jayanthi S, Rao KR, Rajesh B, Pradhan SC, Hepatoprotective activity of picroliv, cucurmin and ellagic acid compared to silymarin on paracetamol induced liver toxicity in mice. Fundamental&Clinical Pharmacology, 23, 735-745, 2009. Gopalakrishnan R., Sundaram J.,Sattu K.,Pandi A.,Thiruvengadam D., (2009) Silymarin attenuated mast cell recruitment thereby decreased the expressions of matrix metalloproteinases-2 and 9 in rat liver carcinogenesis, Invest New Drugs, 27, 233–240. Haddad Y, Vallerand D, Brault A, Haddad PS, Antioxidant and hepatoprotective effects of silibinin in a rat model of nonalcoholic steatohepatitis. Evid. Based. Complement. Alternat. Med. (Epub ahead of print), 2011. Hui J.J., Park J.-W., Lee J.S., Lee S.-R., Jang B.-C., Suh S.- I., Suh M.-H., Baek W.-K., (2009) Silibinin inhibits expression of HIF-1α through suppression of protein translation in prostate cancer cells, Biomedichal and Biophysical Research Communications 390, 71-76. Jain A, Yadav A, Bozhkov AI, Padalko VI, Flora SJS, Therapeutic efficacy of sylimarin and naringenin in reducing arsenic-induced hepatic damage in young rats. Ecotoxicology and Environmental Safety, 74, 607-614, 2011. Jeong JC, Shin WY, Kim TH, Kwon CH, Kim JH, Kim YK, Kim KH, Silibinin induces apoptosis via calpain-dependent AIF nuclear translocation in U87MG human glioma cell death. Journal of Experimental & Clinical Cancer Research, 30, 44, 1-8, 2011. Jiang YY, Huang H, Wang H, Wu D, Yang R, Tashiro S, Onodera S, Ikejima T, Interruption of mitochondrial complex IV activity and cytochrome c expression activated O2-mediated cell survival in silibinintreated human melanoma A375-S2 cells via IGF- 1R–PI3K–Akt and IGF-1R–PLC γ–PKC pathways. European Journal of Pharmacology, 668, 78–87, 2011 Jiang YY, Wang H, Wang J, Tashiro SI, Onodera S, Ikejima T, The Protective Effect of Silibinin Against Mitomycin C–Induced Intrinsic Apoptosis in Human Melanoma A375-S2 Cells. J. Pharmacol. Sci., 111, 137–146, 2009. Kauntz H, Bousserouel S, Gosse F, Raul F, Silibinin triggers apoptotic signaling pathways and autophagic survival response in human colon adenocarcinoma cells and their derived metastatic cells. Apoptosis, 16, 1042–1053, 2011. Kim KW, Choi CH, Kim TH, Kwon CH, Woo JS, Kim YK, Silibinin inhibits glioma cell proliferation via ca2+/ros/mapk dependent mechanism in vitro and glioma tumor growth in vivo. Neurochem Res, 34, 1479–1490, 2009. Kim S, Kim SH, Hur SM, Lee SK, Kim WW, Kim JS, Kim JH, Choe JH, Nam SJ, Lee JE, Yang JH, Silibinin prevents TPA-induced MMP-9 expression by down-regulation of COX-2 in human breast cancer cells. Journal of Ethnopharmacology, 126, 252–257, 2009. Koch HP, Silymarin [Silybum marianum]: potent inhibitor of cyclic AMP phosphodiesterase. Methods Find Exp Clin Pharmacol. Aug;7(8), 409-13, 1985. Kropacova K, Misurova E, Hakova H, Protective and therapeutic effect of silymarin on the development of latent liver damage. Radiats Biol Radioecol, 38, 411-415, 1998. Lieber CS, Leo MA, Cao Q, Ren C, DeCarli LM, Silymarin retards the progression of alcohol-induced hepatic fibrosis in baboons. J. Clin. Gastroenterol., 37, 336–339, 2003. Machicao F, Sonnenbichler J, Mechanism of the stimulation of RNA synthesis in rat liver nuclei by silybin, Hoppe Seylers Z.Physiol.Chem, 358, 141- 147, 1997. Mateen S, Tyagi A, Agarwal C, Singh RP, Agarwal R, Silibinin inhibits human nonsmall cell lung cancer cell growth through cell-cycle arrest by modulating expression and function of key cell-cycle regulators. Molecular Carcinogenesis, 49(3), 247–258, 2010. Mcpartland JM, Viral hepatitis treated with Phyllanthus amarus and milk thistle (Silybum marianum): A case report. Complementary Medicine International, March/April, 40- 42, 1996. Mohamed O, Salam EA, Saleem AA, Shafee N, Hepatoprotective effects of the nitric oxide donor isosorbide-5-mononitrate alone and in combination with the natural hepatoprotectant, silymarin on carbon tetrachloride-induced hepatic injury in rats. Inflammopharmacol, 18, 87-94, 2010. Nassuato G, Iemmolo RM, Strazzabosco M, Lirussi F, Deana R, Francesconi MA, Muraca M, Passera D, Fragosso A, Orlando R, Csomós G, Okolicsányi L, Effect of Silibinin on biliary composition. Experimental and clinical study. J. 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M., Agarwal R., (2010) Silibinin Prevents Lung Tumorigenesis in Wild-Type but not in iNOS-/- Mice: Potential of Real-Time Micro-CT in Lung Cancer Chemoprevention Studies, Clinical Cancer Research, March 1, 753-761. Rho JK, Choi YJ, Jeon BS, Choi SJ, Cheon GJ, Woo SK, Kim HR, Kim CH, Choi CM, Lee JC, Combined treatment with silibinin and epidermal growth factor receptor tyrosine kinase inhibitors overcomes drug resistance caused by t790m mutation. Molecular Cancer Therapeutics, March 1, 3233- 3243, 2012. Sangeetha N., Aranganathan S., Panneerselvam J., Shanthi P., Rama G., Nalini N., (2010) Oral supplementation of silibinin prevents colon carcinogenesis in a long term preclinical model, European Journal of Pharmacology 643, 93–100. Schriewer H, Weinhold F, The influence of silybin from Silybum marianum (L.) Gaertn. On in vitro phosphatidyl choline biosynthesis in rat livers. Arzneimittelforschung, 29, 791–792, 1979. Schumann J, Prockl J, Kiemer AK, Vollmar AM, Silibinin protects mice from T cell-dependent liver injury. J. Hepatol., 39, 333-340, 2003. Shafik AN, Khodeir MM, Gouda NA, Mahmoud ME, Improved antifibrotic effect of a combination of verapamil and silymarin in rat –induced liver fibrosis. Arab Journal of Gastroenterology, 12, 143– 149, 2011. Shaker ME, Shiha GE, Ibrahim TM, Comparison of early treatment with low doses of nilotinib, imatinib and a clinically relevant dose of silymarin in thioacetamide–induced liver fibrosis. European Journal of Pharmacology, 670, 593-600, 2011. Sonnenbichler J, Goldberg M, Hane I, et al., Stimulating effects of silibinin on the DNA-synthesis in partially hepatectomized rat livers: non-response in hepatoma and other malignant cell lines. Biochem Pharmacol, 35, 538-541, 1986. Sonnenbichler J, Zetl I, Biochemical effects of the flavolignane silibinin on RNA, protein and DNA synthesis in rat livers. In: Cody V, Middleton E, and Harbourne JB, ed. Plant Flavonoids in Biology and Medicine: Bio- chemical, Pharmacological, and Structure- Activity relationships. New York: Alan R. List, Inc.; 319-331, 1986. Sonnenbichler J, Zetl I. Stimulating influence of a flavonolignan derivative on proliferation, RNA syn- thesis and protein synthesis in liver cells. In: Okolocsanyi L, Csomos G, Crepaldi G, eds. Assessment and Management of Hepatobiliary Disease. Berlin: Springer-Verlag, 265-272, 1987. Soria EA., Eynard AR, Bongiovanni GA, Cytoprotective effects of silymarin on epithelial cells against arsenic-induced apoptosis in contrast with quercetin cytotoxicity, Life Sciences, 87, 309–315, 2010. Tanamly MD, Tadros F, Labeeb S, Makld H, Shehata M, Mikhail N, Abdel-Hamid M, Abu-Baki L, Medhat A, Magder LS, Afdhal NH, Strickland GT, Randomised, double-blinded trial evaluating silymarin [Silybum marianum] for chronic hepatitis C in an Egyptian village: study description and 12-month results. Dig Liver Dis., Nov, 36(11), 752- 9, 2004. 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Correspondence: | Anca Hermenean, “Vasile Goldis” Western University of Arad, Institute of Life Sciences, no. 86 Liviu Rebreanu St., 310414, Arad, Romania, Tel. +40257212111, Fax. +40257212111, email: biologie@uvvg.ro |
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Article Title: | Pharmacology of silybum marianum and its active constituents. Therapeutic activity – part 1 |
Authors: | Luminita Pilat1, Ciprian Mihali2, Hildegard Herman2, Cristina Popescu2, Violeta Turcus3, Aurel Ardelean3, Ardelean Gavril3, Teodora Mariasiu1, Calin Popa1, Anca Hermenean1,2* |
Affiliation: | 1“Vasile Goldis” Western University of Arad, Faculty of Medicine, Pharmacy and Dentistry, Arad, Romania 2“Vasile Goldis” Western University of Arad, Institute of Life Sciences, Arad, Romania 3“Vasile Goldis” Western University of Arad, Faculty of Natural Sciences, Arad, Romania |
Abstract: | In the last years a lot of effort has been made in demonstrating the role of plant extracts in medicine. The usage of herbal drugs for the treatment of several diseases has increased all over the world. The global popularity of herbal supplements and the promise they hold in treating various disease states has caused an unprecedented interest in understanding the molecular basis of the biological activity of traditional remedies. The herbal drugs are believed to be harmless without causing adverse reactions, as they are obtained from nature and are easily available. There are about 600 commercial herbal formulations available only for liver disease, which are claimed to have hepatoprotective effects. As the need for effective, affordable health promotion and treatment increases, especially in the growing ageing population, there is a need for rigorous scientific examination of herbal medicines. This article reviews on published reports pertaining to milk thistle’s benefits. |
Keywords: | Silymarin, disease, pharmacokinetics, regeneration, herbal medicine |
References: | Al-Anati L, Essid E, Reinehr R, Petzinger E, Silibinin protects OTA-mediated TNF-a release from perfused rat livers and isolated rat Kupffer cells. Mol.Nutr.Res., 53, 460-466, 2009. Avizeh R, Najafzadeh H, Razijalali M, Shirali S, Evaluation of prophylactic and therapeutic effects of silymarin and N-acetylcysteine in acetaminopheninduced hepatotoxicity in cats. J.Vet.Pharmacol. Therap., 33, 95-99, 2009. Basiglio C, Pozzi EJS, Mottino AD, Roma MG, Differential effects of silymarin and its active component silibinin on plasma membrane stability and hepatocellular lysis. Chemico-Biological Interactions, 179, 297-303, 2009. Brandon-Warner E, Sugg JA, Schrum LW, Mckillop LH, Silibinin inhibits ethanol metabolism and ethanoldependent cell proliferation in an vitro model of hepatocellular carcinoma. Cancer Letters, 291, 120- 129, 2010. Carpino G, Morini S, Gianinni Corradini S et al, Alpha_SMA expression in hepatic stellate cells and quantitative analysis of liver fibrosis in cirrhosis and in recurrent chronic hepatitis after liver transplantation, Dig.Liver Dis., 37, 349-356, 2005. Chang HR, Chen PN, Yang SF, Sun YS, Wu SW, Hung TW, Lian JD, Chu SC, Hsieh YS, Silibinin inhibits the invasion and migration of renal carcinoma 786-o cells in vitro, inhibits the growth of xenografts in vivo and enhances chemosensitivity to 5-fluorouracil and paclitaxel. Molecular Carcinogenesis, 50, 812–823, 2011. Chen CH, Huang TS, Wongc CH, Hong CL, Tsai YH, Liang CC, Lu FJ, Chang WH, Synergistic anticancer effect of baicalein and silymarin on human hepatoma HepG2 Cells. Food and Chemical Toxicology, 47, 638–644, 2009. Cho YK, Yun JW, Park JH, Kim HJ, Park DII, Sohn CII, Jeon WK, Kim BI, Jin W, Kwon YH, Shin MK, Yoo TM, Kang JH, Park CS, Sohn CI, Jeon WK, Kim BI, Jin W, Kwon YH, Shin MK, Yoo TM, Kang JH, Park CS, Deleterious effects of silymarin on the expression of genes controlling endothelial nitric oxide synthase activity in carbon tetrachloridetreated rat livers. Life Sciences, 85, 281-290, 2009. Colombo V, Lupi M, Falcetta F, Forestieri D, D’Incalci M, Ubezio P, Chemotherapeutic activity of silymarin combined with doxorubicin or paclitaxel in sensitive and multidrug-resistant colon cancer cells. Cancer Chemother Pharmacol, 67, 369–379, 2011. Colturato CP, Constantin RP, Maeda Jr. AS, Constantin RP, Yamamoto NS, Bracht A, Ishii-Iwamoto EL, Constantin J, Chemico-Biological Interactions, 195, 119–132, 2012. Crocenzi FA et al, Silibinin [Milk thistle] prevents cholestasis-associated retrieval of the bile salt export pump, Bsep, in isolated rat hepatocyte couplets: possible involvement of camp. Biochem Pharmacol., 69(7), 1113-20, 2005. Crocenzi FA, Sanchez-Pozzi EJ, Pellegrino JM, et al. Beneficial effects of silymarin on estrogen-induced cholestasis in the rat: A study in in vivo and in isolated hepatocyte couplets. Hepatology, 34, 329– 339, 2001. Das S, Roy P, Auddy RG, Mukherjee A, Silymarin nanoparticle prevents paracetamol-induced hepatotoxicity, International Journal of Nanomedicine, 6, 1291–1301, 2011. De La Puerta R, Martinez E, Bravo L. Effect of silymarin on different acute inflammation models and on leukocyte migration. J Pharm Pharmacol, 48, 968- 970, 1996. Deep G, Agarwal R, Antimetstatic efficacy of silibinin: molecular mechanisms and therapeutic potential against cancer. Cancer Metastasis Rev, 29, 447-463, 2010. Deep G, Oberlies NH, Kroll DJ, Agarwal R, Identifying the differential effects of silymarin constituents on cell growth and cell cycle regulatory molecules in human prostate cancer cells. Int. J. Cancer:, 123, 41–50, 2008. Dehmlow C, Erhard J, de Groot H. Inhibition of Kupffer cell functions as an explanation for the hepatoprotective properties of silibinin. Hepatology, 23, 749-754, 1996. Dehmlow C, Inhibition of Kupffer cell functions as an explanation for the hepatoprotective properties of silibinin. Hepatology, Apr; 23 (4): 749-54, 1996. Doehmer J, Weiss G, Weiss GP, Mc Gregor GP, Appel K, Assessment of a dry extract from milk thistle (Silybum marianum) for interference with human liver cytochrome P450 activities. Toxicology in vitro, 25, 21-27, 2011. Duan WJ, Li QS, Xia MY, Tashiro SI, Onodera S, Ikejima T, Silibinin activated p53 and induced autophagic death in human fibrosarcoma ht1080 cells via reactive oxygen species-p38 and c-jun n-terminal kinase pathways. Biol. Pharm. Bull., 34(1), 47—53, 2011. Erlejman AG, Verstraeten SV, Fraga CG, Oteiza PI, The interaction of flavonoids with membranes: potential determinant of flavonoid antioxidant effects. Free Radic.Res, 38, 1311-1320, 2004 Esmaily H, Hosseini-Tabatabaei A, Rahimian R, Khorasani R, Baeeri M, Barazesh-Morgani A, Yasa N, Khademi Y, Abdollahi M, On the benefits of silymarin in murine colitits by improving balance of destructive cytokines and reduction of toxic stress in the bowel cells. Centr.Eur.J.Bio., 4(2), 204-213, 2009. Esmaily H, Vaziri-Bami A, Miroliaee AE, Baeeri M, Abdollahi M, The correlation between NH-kb inhibition and disease activity by coadministration of silibinin and ursodeoxycholic acid in experimental colitis. Fundamental&Clinical Pharmacology, 25, 723-733, 2010. Fantozzi R, Brunelleschi S, Rubino A, et al. FMLPactivated neutrophils evoke histamine release from mast cells. Agents Actions, 18:155-158, 1986. Flaig TW, Glode M, Gustafson D, van Bokhoven A, Tao Y, Wilson S, Su LJ, Li Y, Harrison G, Agarwal R, Crawford ED, Lucia MS, Pollak M, A study of high-dose oral silybin-phytosome followed by prostatectomy in patients with localized prostate cancer. The Prostate 70, 848-855, 2010 Girish C, Koner BC, Jayanthi S, Rao KR, Rajesh B, Pradhan SC, Hepatoprotective activity of picroliv, cucurmin and ellagic acid compared to silymarin on paracetamol induced liver toxicity in mice. Fundamental&Clinical Pharmacology, 23, 735-745, 2009. Gopalakrishnan R., Sundaram J.,Sattu K.,Pandi A.,Thiruvengadam D., (2009) Silymarin attenuated mast cell recruitment thereby decreased the expressions of matrix metalloproteinases-2 and 9 in rat liver carcinogenesis, Invest New Drugs, 27, 233–240. Haddad Y, Vallerand D, Brault A, Haddad PS, Antioxidant and hepatoprotective effects of silibinin in a rat model of nonalcoholic steatohepatitis. Evid. Based. Complement. Alternat. Med. (Epub ahead of print), 2011. Hui J.J., Park J.-W., Lee J.S., Lee S.-R., Jang B.-C., Suh S.- I., Suh M.-H., Baek W.-K., (2009) Silibinin inhibits expression of HIF-1α through suppression of protein translation in prostate cancer cells, Biomedichal and Biophysical Research Communications 390, 71-76. Jain A, Yadav A, Bozhkov AI, Padalko VI, Flora SJS, Therapeutic efficacy of sylimarin and naringenin in reducing arsenic-induced hepatic damage in young rats. Ecotoxicology and Environmental Safety, 74, 607-614, 2011. Jeong JC, Shin WY, Kim TH, Kwon CH, Kim JH, Kim YK, Kim KH, Silibinin induces apoptosis via calpain-dependent AIF nuclear translocation in U87MG human glioma cell death. Journal of Experimental & Clinical Cancer Research, 30, 44, 1-8, 2011. 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*Correspondence: | Anca Hermenean, “Vasile Goldis” Western University of Arad, Institute of Life Sciences, no. 86 Liviu Rebreanu St., 310414, Arad, Romania, Tel. +40257212111, Fax. +40257212111, email: biologie@uvvg.ro |