Hepatoprotektif bir ajan: Silymarin

Silymarin, Asteraceae familyasına ait devedikeni olarak da adlandırılan Silybum marinum bitkisinin tohumlarından elde edilir. Silymarin siroz, toksik kimyasallar ve alkole bağlı yağ infiltrasyonu ve hepatit gibi çeşitli karaciğer hastalıklarında yaygın olarak kullanılan karaciğer koruyucu bir ajandır. Silymarinin etki mekanizması hala tam olarak anlaşılamamıştır. Bununla birlikte hepatoprotektif etkileri; lipit peroksidasyonunu baskılaması, reaktif oksijen türlerinin oluşumunu azaltması ve serbest radikalleri temizlemesi aracılığıyla gerçekleşen antioksidan etkilerine atfedilebilir. Silymarinin antienflamatuar, antiapoptotik, antikarsinojenik, antiviral, antifibrotik ve antianjiojenik özellikleri bildirilmiştir. Bu derleme silymarinin tedavi edici yönleri ve farmakolojik özellikleri ile ilgili özet bir bakış açısı sunmaktadır.

A hepatoprotectif agent: Silymarin

A hepatoprotectif agent: Silymarin Silymarin is a purified extract from the seeds of Silybum marinum L. (Asteraceae) also called milk thistle. Silymarin is widely used as a hepatoprotectant in the treatment of various liver disorders including hepatitis, cirrhosis and fatty acid infiltration due to alcohol and toxic chemicals. Mechanism of action of silymarin is still poorly understood. However, hepatoprotection can be attributed to its antioxidant effects which are mediated by scavenging of free radicals, decreasing formation of reactive oxygen species and inhibition of fatty acid peroxidation. Anti-inflammatory, antiapoptotic, anticarcinogenic, antiviral, anti-fibrotic and anti-angiogenic properties of silymarin have also been documented. This review presents a brief overview of the pharmacological features and therapeutic aspects of silymarin.

PDF

___

1. Ding T, Tian S, Zhang Z, et al. Determination of active component in silymarin by RP-LC and LC/MS. J. Pharmacol. Biomed. Anal 2001; 26: 155-61.
2. Parveen R, Baboota S, Ali J, Ahuja A, Vasudev SS, Ahmad S. Effects of silymarin nanoemulsion against carbon tetrachloride-induced hepatic damage. Arch Pharm Res 2011; 34: 767-74.
3. Demartini G, Esposti D. Pharmacology of Silymarin. Clin Drug Invest 2002; 22: 51-65.
4. Fuchs EC, Weyhenmeyer R, Weiner OH. Effects of silibinin and of a synthetic analogue on isolated rat hepatic stellate cells and myofibroblasts. Arzneimittelforschung 1997; 47: 1383-7.
5. Campose R, Garrido A, Guerra R. Velenzuela A. Silybin dihemisuccinate protects against glutathione depletionand lipid perioxidation induced by acetaminophen on rat liver. 1989; 55: 417-419.
6. Kren V, Walterova D. Silybin and Silymarin-new effects and applications. Biomed Papers 2005;149: 29-41.
7. Morazzoni P, Montalbetti A, Malandrino S. Comparative pharmacokinetics of silipide and silymarin in rats. Eur J Drug Metab Pharmacokinet 1993; 18: 289-97.
8. Mennicke W. What is known about the metabolism and pharmacokinetics of silymarin. In: Braatz R, Schneider CC (Editors). Symposium on the pharmacodynamic of silymarin. Munich, Berlin,Vienna: Urban & Schwarzenberg. 1976; 98- 102.
9. Pepping J. Milk thistle: Silybum marianum. Am. J. Health Syst Pharm 1999; 56: 1195-7.
10. Dixit N, Baboota S, Kohli K, Ahmad S, Ali J. Silymarin: A review of and bioavailability enhancement approaches, Indian J Phanrmacol 2007; 39: 172-179.
11. Zi X, Agarwal R. Silibinin decreases prostate-specific antigen with cell growth inhibition via G1 arrest, leading to differentiation of prostate carcinoma cells:implications for prostate cancer intervention. Proc Natl Acad Sci 1999; 96: 7490-5.
12. Kang JS, Jeon YJ, Park SK, Yang KH, Kim HM. Protection against lipopolysaccharide-induced sepsis and inhibition of interleukin-1 and prostaglandin E2 synthesis by silymarin. Biochem Pharmacol 2004; 67: 175- 81.
13. Miguez MP, Anundi I, Sainz-Pardo LA. Hepatoprotective mechanism of silymarin: no evidence for involvement of cytochrome P450 2E1. Chem Biol Interact 1994; 91: 51-63.
14. Nencini C, Giorgi G, Michelli L. Protective effect of silymarin on oxidative stress in rat brain. Phytomedicine 2007; 14: 129- 35
15. Skottova N, Kreeman V. Silymarin as a potential hypocholesterolaemic drug. Physiol 1998; 47: 1-7.
16. Fraschini F, Demartini G, Esposti D. Pharmacology of silymarin. Clinical Drug Investigation 2002; 22: 51-65.
17. Dvorák Z, Kosina P, Walterová D, Simánek V, Bachleda P, Ulrichová J. Primary cultures of human hepatocytes as a tool in cytotoxicity studies: cell protection against model toxins by flavonolignans obtained from Silybum marianum. Toxicol Lett 2003; 137: 201-12.
18. Srivastava S, Srivastava AK, Srivastava S, Patnaik GK, Dhawan BN. Effect of picroliv and silymarin on liver regeneration in rats. Indian Journal of Pharmacology 1994; 26: 19-22.
19. Soto C, Recoba R, Barron H, Alvarez C, Favari L. Silymarin increases antioxidant enzymes in alloxan-induced diabetes in rat pancreas. Comp Biochem Physiol 2003; 136: 205-12.
20. Tager M, Dietzmann J, Thiel U, Neumann Kh, Ansorge S. Restoration of the cellular thiol status of peritoneal macrophages from CAPD patients by the flavonoids silibinin and silymarin. Free Rad Res 2000; 34: 137-51.
21. Yang SH, Lin JK, Chen WS, Chiu JH. Anti-angiogenic effect of silymarin on colon cancer LoVo cell line. J Surg Res 2003; 113: 133-8.
22. Raschini F, Demartini G, Esposti D. Pharmacology of Silymarin. Clin Drug Invest 2002; 22: 51-65.
23. Sobodova A, Walterova D, Psotova J. Influence of silymarin and its flavonolignans on H2O2- induced oxidative stress in human keratinocytes and mouse fibroblasts. Burns 2006; 32: 973-9.
24. Vaid M, Singh T, Prasad R, Katiyar SK. Silymarin inhibits melanoma cell growth both in vitro and in vivo by targeting cell cycle regulators, angiogenic biomarkers and induction of apoptosis. Mol Carcinog 2014 Aug 30. doi: 10.1002/mc.22208.
25. Mohan S, Dhanalakshmi S, Mallikarjuna GU, Singh RP, Agarwal R. Silibinin modulates UVB-induced apoptosis via mitochondrial proteins, caspases activation, and mitogenactivated protein kinase signaling in human epidermoid carcinoma A431 cells. Biochem Biophys Res Commun 2004; 320: 183-9.
26. Kang JS, Park SK, Yang KH, Kim HM. Silymarin inhibits TNF-α induced expression of adhesion molecules in human umbilical vein endothelial cells. FEBS Lett 2002; 550: 89-93.
27. De Groot H, Rauen U. Tissue injury by reactive oxigen species and the protective effect of flavanoids, Fundam. Clin. Pharmacol 1998; 12: 249-55.
28. Flora K, Hanh M, Rosen H, Benner K. Milk thistle (Silybum marianum) for the therapy of liver disease. Am J Gastroenterol 1998; 93: 139-43.
29. Saller R, Meier R, Brignoli R. The use of silymarin in the treatment of liver diseases 2001; 61: 2035-63.
30. Abenavoli L, Capasso R, Milic N, Capasso F. Milk thistle in liver diseases: past, present, future. Phytother Res 2010; 24: 1423-32
31. Hackett ES, Twedt DC, Gustafson DL. Milk thistle and its derivative compounds: a review of opportunities for treatment of liver disease. J Vet Intern Med 2013; 27: 10-6.
32. Rolo AP, Oliveira PJ, Moreno AJM, Palmeira CM. Protection against post-ischemic mitochondrial injury in rat liver by silymarin or TUDC. Hepatology Research 2003; 26: 217-24.
33. Veena J, Muragundla A, Sidgiddi S, Subramaniam S. Nonalcoholic fatty liver disease: need for a balanced nutritional source. Br J Nutr 2014; 112: 1858-72.
34. Yang Z, Zhuang L, Lu Y, Xu Q, Chen X. Effects and tolerance of silymarin (milk thistle) in chronic hepatitis C virus infection patients: a meta-analysis of randomized controlled trials. Biomed Res Int 2014; doi: 10.1155/2014/941085.
35. Baretto R, Kawakita S, Tsuchiya J, et al. Metal-induced oxidative damage in cultured hepatocytes and hepatic lysosomal fraction: beneficial effect of a curcumin/absinthium compound. Chin J Dig Dis 2005; 6: 31-6.
36. Ahmad N, Fazal H, Abbasi BH, Anwar S, Basir A. DPPH free radical scavenging activity and phenotypic difference in hepatoprotective plant (Silybum marianum L.) Toxicol Ind Health 2013; 29: 460-7.
37. Farghali H, Kamenikova L, Hynie S, Kmonickova E. Silymarin effects on intracellular calcium and cytotoxicity: A Study in perfused rat hepatocytes after oxidative stres injury. Pharmacol Res 2000; 41: 231-37.
38. Matsuda T, Ferreri K, Todorov I, et al. Silymarin protects pancreatic β-cells against cytokine mediated toxicity: Implication of c-Jun NH2-Terminal Kinase and Janus Kinase/Signal transducer and activator of transcription pathways. Endocrinology 2004; 146: 175-85.
39. Luper S. A review of plants used in the treatment of liver disease: Part 1. Altern Med Rev 1998; 3: 410-21.
40. Burczynski FJ, Wang G, Nguyen D, Chen Y, Smith HJ, Gong Y. Silymarin and hepatoprotection. Zhong Nan Da Xue Xue Bao Yi Xue Ban 2012; 37: 6-10.
41. Desplaces A, Choppin J, Vogel G. The effects of silymarin on experimental phalloidine poisoning. Arzneimittelforschung 1975; 25: 89-96.
42. Dehmlow C, Erhard J, de Groot H. Inhibition of Kupffer cell functions as an explanation for the hepatoprotective properties of silibinin. Hepatology 1996; 23: 749-54.
43. Baer-Dubowska W, Szafer H, Krajkakuzniak V. Inhibition of murine hepatic cytochrome P450 activities by natural and synthetic phenolic compounds. Xenobiotica 1998; 28: 735-43.
44. Muriel P, Mourelle M. Prevention by silymarin of membrane alterations in acute CCl4 liver damage. J Appl Toxicol 1990; 10: 275-9.
45. Matveev AV, Koniaeva EI, Kurchenko VP, Shchekatikhina AS. Hepatoprotective properties of silymarin. Eksp Klin Gastroenterol 2011; 2: 130-5.
46. Salmi HA, Sarna S. Effect of silymarin on chemical, functional, and morphological alterations of the liver; A double blind controlled study. Scand J Gastroenterol 1982; 17: 517-21.
47. Ferenci P, Dragosics B, Dittrich H. Randomized controlled trial of silymarin treatment in patients with cirrhosis of the liver. J. Hepatol 1989; 9: 105-13.
48. Sonnenbichler J, Zetl I. Biochemical effects of the flavolignane silibinin on RNA, protein and DNA synthesis in rat liver. Prog. Clin. Biol. Res 1986; 213: 319-31.
49. Magliulo E, Carosi PG, Minoli L. St and treated with silymarin. Arzneimittelforschung 1973; 23: 161-67.
50. Davis-Searles PR, Nakanishi Y, Kim NC, et al. Milk thistle and prostate cancer: differential effects of pure flavonolignans from Silybum marianum on antiproliferative end points in human prostate carcinoma cells. Cancer Res 2005; 15: 4448-57.
51. Gupta OP, Sing S, Bani S, et al. Anti-inflammatory and antiarthritic activities of silymarin acting through inhibition of 5- lipoxygenase. Phytomedicine 2000; 7: 21-4.