Hepatoprotective herbal drug, silymarin from experimental pharmacology to clinical medicine

Indian Journal of Medical Research

Volumn 124, Issue , 2006, Pages 491-504

  Pradhan, S C ^a   Girish, C ^a  

^a JAWAHARLAL INSTITUTE OF POSTGRADUATE MEDICAL EDUCATION AND RESEARCH   (India)

Author keywords

Hepatitis; Hepatoprotection; Hepatotoxicity; Herbal drugs; Milk thistle; Silymarin

Indexed keywords

ANDROGRAPHOLIDE; CAJANUS INDICUS EXTRACT; CI 1; CISPLATIN; DOXORUBICIN; GLUTATHIONE; GLYCYRRHIZIC ACID; HERBACEOUS AGENT; INTERFERON; ISONIAZID; LAMIVUDINE; LIVER PROTECTIVE AGENT; MERCAPTOPURINE; METHOTREXATE; MZ 80; NEUROLEPTIC AGENT; PENICILLIN G; PHENOTHIAZINE DERIVATIVE; PHYLLANTHIN; PLACEBO; RIBAVIRIN; RIFAMPICIN; SILIBININ; SILIBININ DIHEMISUCCINATE; SILIBININ PHOSPHATIDYLCHOLINE COMPLEX; SILICRISTIN; SILIDIANIN; SILYMARIN; TACRINE; UNCLASSIFIED DRUG; UNINDEXED DRUG; URSODEOXYCHOLIC ACID; WITHANIA SOMNIFERA EXTRACT;

ALCOHOL LIVER DISEASE; ALZHEIMER DISEASE; AMINOTRANSFERASE BLOOD LEVEL; ANTIINFLAMMATORY ACTIVITY; ANTIOXIDANT ACTIVITY; ANTIVIRAL ACTIVITY; ASTHENIA; BLOATING; CAJANUS INDICUS; CLINICAL TRIAL; COST EFFECTIVENESS ANALYSIS; DIABETES MELLITUS; DIARRHEA; DRUG ABSORPTION; DRUG ALCOHOL INTERACTION; DRUG ANTAGONISM; DRUG BILE LEVEL; DRUG BIOAVAILABILITY; DRUG BLOOD LEVEL; DRUG CONTAMINATION; DRUG COST; DRUG EFFICACY; DRUG ERUPTION; DRUG EXCRETION; DRUG HYPERSENSITIVITY; DRUG ISOLATION; DRUG MEGADOSE; DRUG SAFETY; DRUG STRUCTURE; DRUG TOLERABILITY; DRUG USE; DYSPEPSIA; GASTROENTERITIS; GASTROINTESTINAL DISEASE; HEADACHE; HEPATITIS; HEPATOBILIARY DISEASE; HUMAN; IMMUNOMODULATION; INTOXICATION; LIVER CELL CARCINOMA; LIVER CIRRHOSIS; LIVER DISEASE; LIVER INJURY; LIVER PROTECTION; LIVER REGENERATION; LIVER TOXICITY; LOW DRUG DOSE; MALAISE; MEDICINAL PLANT; NAUSEA; NEPHROTOXICITY; NONHUMAN; PRURITUS; QUALITY CONTROL; REVIEW; SIDE EFFECT; STANDARDIZATION; VERTIGO;

CLINICAL TRIALS; DRUG INTERACTIONS; HUMANS; LIVER; LIVER CIRRHOSIS; LIVER DISEASES; LIVER DISEASES, ALCOHOLIC; MUSHROOM POISONING; PROTECTIVE AGENTS; SILYMARIN;

EID: 33846519345     PISSN: 09715916     EISSN: 09715916     Source Type: Journal    
DOI: None     Document Type: Review

References (78)

1. Luper S. A review of plants used in the treatment of liver diseases: Part 1. Altern Med Rev 1998; 3: 410-21.
2. Schuppan D, Jia J, Brinkhaus B, Hahn EG. Herbal products for liver diseases: A therapeutic challenge for the new millennium. Hepatology 1999; 30: 1099-104.
3. Wagner H, Diesel P, Seitz M. The chemistry and analysis of silymarin from Silybum marianum Gaertn. Arzneimittelforschung 1974; 24: 466-71.
4. Flora K, Hahn M, Rosen H, Benner K. Milk thistle (Silybum marianum) for the therapy of liver disease. J Gastroenterol 1998; 93: 139-43.
5. Saller R, Meier R, Brignoli R. The use of silymarin in the treatment of liver diseases. Drugs 2001; 61: 2035-63.
6. Sonnenbichler J, Zetl I. Biochemical effects of the flavonolignan silibinin on RNA, protein, and DNA synthesis in rat liver. Progr Clin Biol Res 1986; 213: 319-31.
7. Vailati A, Aristia L, Sozze E, Milani F, Inglese V, Galenda P, et al. Randomized open study of the dose-effect relationship of a short course of IdB 1016 in patients with viral or alcoholic hepatitis. Fitoterapia 1993; 64: 219-31.
8. Thakur SK. Silymarin- A hepatoprotective agent. Gastroenterol Today 2002; 6: 78-82.
9. Morazzoni P, Montalbetti A, Malandrino S. Comparative pharmacokinetics of silipide and silymarin in rats. Eur J Drug Metab Pharmacokinet 1993; 18: 289-97.
10. Schandalik R, Gatti G, Perucca E. Pharmacokinetics of silybin in bile following administration of silipide and silymarin in cholecystectomy patients. Arzneimittelforschung 1992; 42: 964-8.
11. Weyhenmeyer R, Mascher H, Birkmayer J. Study on the dose-linearity of the pharmacokinetics of silybin diastereomers using a new stereospecific assay. Int J Clin Pharmacol Ther Toxicol 1992; 30: 134-8.
12. Lorenz D, Lucker PW, Mennicke WH, Wetzelsberger N. Pharmacokinetic studies with silymarin in human serum and bile. Methods find. Exp Clin Pharmacol 1984; 6: 655-61.
13. Barzaghi N, Crema F, Gatti G, Pifferi G, Perucca E. Pharmacokinetic studies on Idb 1016, a silybin-phosphatidylcholine complex, in healthy human subjects. Eur J Drug Meta Pharmacokinet 1990; 15: 333-8.
14. Carducci R, Armellino MF, Volpe C, Basile G, Caso N, Apicella A, et al. Silibinin and acute poisoning with Amanita phalloides. Minerva Anestesiol 1996; 62: 187-93.
15. Srivastava S, Srivastava AK, Srivastava S, Patnaik GK, Dhawan BN. Effect of picroliv and silymarin on liver regeneration in rats. Indian J Pharmacol 1994; 26: 19-22.
16. Srivastava S, Srivastava AK, Patnaik GK, Dhawan BN. Effect of picroliv on liver regeneration in rats. Fitoterapia 1996; 67: 252-6.
17. Sonnenbitchler J, Goldberg M, Hane L, Madubunyi I, Vogl S, Zetl I. Stimulatory effect of silybin on the DNA synthesis in partially hepatectomized rat livers: non-response in hepatoma and other malignant cell lines. Biochem Pharmacol 1986; 35: 538-41.
18. Schopen RD, Lange OK, Panne C. Searching for a new therapeutic principle. Experience with hepatic therapeutic agent legalon. Medical Welt 1969; 20: 888-93.
19. Sherlock S, Dooley J. Diseases of liver and biliary system. 11th ed. Oxford: Blackwell Scientific Publications; 2002 p. 322-56.
20. Subramonium A, Pushpangadan P. Development of phytomedicines for liver diseases. Indian J Pharmacol 1999; 31: 166-75.
21. Sharma A, Chakraborti KK, Handa SS. Anti hepatotoxic activity of some Indian herbal formulations as compared to silymarin. Fitoterapia 1991; 62: 229-35.
22. 4 liver damage. J Appl Toxicol 1990; 10: 275-9.
23. 4-chronic liver damage in rats. Arch Med Res 1997; 28: 11-7.
24. Ramellini G, Meldolesi J. Liver protection by silymarin: In vitro effect on dissociated rat hepatocytes. Arzneimittelforschung 1976; 26: 69-73.
25. Shukla B, Visen PKS, Patnaik GK, Dhawan BN. Choleretic effect of andrographolide in rats and guinea pigs. Planta Med 1992; 58: 146-9.
26. Renganathan A. Pharmaco dynamic properties of andrographolide in experimental animals. M.D. thesis. Pharmacology. Pondicherry: Jawaharlal Institute of Postgraduate Medical Education & Research (JIPMER), Pondicherry University; 1999.
27. Campos R, Garrido A, Guerra R, Valenzuela A. Silybin dihemisuccinate protects against glutathione depletion and lipid peroxidation induced by acetaminophen on rat liver. Planta Med 1989; 55: 417-9.
28. Neuman MG, Cameron RG, Haber JA, Katz GG, Malkiewicz IM, Shear NH. Inducers of cytochrome P4502E1 enhances methotrexate-induced hepatocytotoxicity. Clin Biochem 1999; 32: 519-36.
29. Deak G, Muzes G, Lang I, Nekam K, Gonzalez-Cabello R, Gergely P, et al. Effects of two bioflavonoids on certain cellular immune reactions in vitro. Acta Phsiol Hung 1990; 76: 113-21.
30. Wang M, Grange LL, Tao J. Hepatoprotective properties of Silybum marianum herbal preparation on ethanol-induced liver damage. Fitoterapia 1996; 67: 167-71.
31. Saraswat B, Visen PKS, Pataik GK, Dhawan BN. Effect of andrographolide against galactosamine-induced hepatotoxicity. Fitoterapia 1995; 66: 415-20.
32. Datta S, Sinha S, Bhattacharya P. Hepatoprotective activity of an herbal protein CI-1, purified from Cajanus indicus against α-galactosamine HCl toxicity in isolated rat hepatocytes. Phtother Res 1999; 13: 508-12.
33. PullaReddy A, Lokesh BR. Effect of curcumin and eugenol on iron-induced hepatic toxicities in rats. Toxicology 1996; 107: 39-45.
34. Bhattacharya A, Ramanathan M, Ghosal, Bhattacharya SK. Effect of Withania somnifera glycowithanolides on iron-induced heopatotoxicity in rats. Phytother Res 2000; 14: 568-70.
35. Desplaces A, Choppin J, Vogel G. The effects of silymarin on experimental phalloidine poisoning. Arzneimittelforschung 1975; 25: 89-96.
36. Vogel G, Tuchweber B, Trost W. Protection by silibinin against Amanita phalloides intoxication in beagles. Toxicol Appl Pharmacol 1984; 73: 355-62.
37. Wu CG, Chamuleau RA, Bosch KS. Protective effect of silymarin on rat liver injury induced by ischemia. Virchows Arch B Cell Pathol Incl Mot Pathol 1993; 64: 259-63.
38. Kropacova K, Misurova E, Hakova H. Protective and therapeutic effect of silymarin on the development of latent liver damage. Radiats Biol Radioecol 1998; 38: 411-5.
39. Kosina P, Kren V, Gebhardt R, Grambal F, Ulrichova J, Walterova D. Antioxidant properties of silybin glycosides. Phytother Res 2002; 16: S33-9.
40. Miguez MP, Anundi I, Sainz-Pardo LA, Lindros KO. Hepatoprotective mechanism of silymarin: no evidence for involvement of cytochrome P4502E1. Chem Biol Interact 1994; 91: 51-63.
41. Miller AL. Antioxidant flavonoids: Structure, function and clinical usage. Altern Med Rev 1996; 1: 103-11.
42. Wiseman H. Dietary influences on membrane function: Importance in protection against oxidative damage and disease. J Nutr Biochem 1996; 7: 2-5.
43. Dehmlow C, Eahard J, Goot HD. Inhibition of Kupffer cells as an explanation for the hepatoprotective properties of silibinin. Hepatology 1996; 23: 749-54.
44. Saliou C, Rihn B, Cillard J, Okamoto T, Packer L. Selective inhibition of NF-κB activation by the flavonoid hepatoprotector silymarin in HepG2. FEBS Lett 1998; 440: 8-12.
45. Johnson VJ, Osuchowski MF, He Q, Sharma RP. Physiological responses to a natural antioxidant flavonoids mixture, silymarin, in BALB/c mice: II. Alterations on thymic differentiation correlate with changes in c-myc gene expression. Planta Med 2002; 68: 961-5.
46. Gebhardt R. Oxidative stress, plant-derived antioxidants and liver fibrosis. Planta Med 2002; 68: 289-96.
47. Munter K, Mayer D, Faulstich H. Characterization of a transporting system in rat hepatocytes: studies with competitive and non-competitive inhibitors of phalloidin transport. Biochem Biophys Acta 1986; 860: 91-8.
48. Faulstich H, Jahn W, Wieland T. Silybin inhibition of amatoxin uptake in the perfused rat liver. Arzneimittelforschung 1980; 30: 452-4.
49. Aldersley MA, O'Grady JG. Hepatic disorders: features and appropriate management. Drugs 1995; 49: 83-102.
50. Salmi HA, Sarna S. Effects of silymarin on chemical, functional and morphological alterations of the liver. A double-blind controlled study. Scand J Gastroenterol 1982; 17: 517-21.
51. Feher I, Deak G, Muzes G. Liver protective action of silymarin therapy in chronic alcoholic liver diseases. Orv Hetil 1989; 130: 2723-7.
52. Trinchet IC, Coste T, Levy VG. Treatment of alcoholic hepatitis with silymarin. A double-blind comparative study in 116 patients. Gastroenterol Clin Biol 1989: 13: 120-4.
53. Varga M, Buris L, Fodor M. Ethanol elimination in man under influence of hepatoprotective silibinin. Blutalkohol 1991; 28: 405-8.
54. Ferenci P, Dragosics B, Dittrich H, Frank H, Benda L, Lochs H, et al. Randomized controlled trial of silymarin treatment in patients with cirrhosis of the liver. J Hepatol 1989; 9: 105-13.
55. Pares A, Planas R, Torres M, Caballera J, Viver JM, Acero D, et al. Effects of silymarin in alcoholic patients with cirrhosis of liver: results of a controlled double-blind randomized and multicenter trial. J Hepatol 1998; 28: 615-21.
56. Lucena MI, Andrade RJ, De la Cruz JP, Rodriguez-Mendizabal M, Blanco E, Sanchez de la Cuesta F. Effects of silymarin MZ-80 on oxidative stress in patients with alcoholic cirrhosis. Results of a randomized, double-blind, placebo-controlled clinical study. Int J Clin Pharmacol Ther 2002; 40: 2-8.
57. Enjalbert F, Rapior S, Nouguier-Soule J, Guillon S, Amouroux N, Cabot C. Treatment of amatoxin poisoning: 20-year retrospective analysis. J Toxicol Clin Toxicol 2002; 40: 715-57.
58. Lirussi F, Okolicsanyi L. Cytoprotection in the nineties: experience with ursodeoxycholic acid and silymarin in chronic liver disease. Acta Physiol Hung 1992; 80: 363-7.
59. Buzzelli G, Moscarella S, Giusti A, Duchini A, Marena C, Lampertico M. A pilot study on the liver protective effect of silybin-phosphatidylcholine complex (IdB 1016) in chronic active hepatitis. Int J Clin Pharmacol Ther Toxicol 1993; 31: 456-60.
60. Allain H, Schuck S. Lebreton S, Strenge-Hesse A, Braun W, Gandon JM, et al. Aminotransferase, levels and silymarin in de novo tacrine-treated patients with Alzheimer's disease. Dement Geriatr Cogn Disord 1999; 10: 181-5.
61. Saba P, Galeone F, Salvadorini F. Therapeutic actions of silymarin on chronic hepatopathies caused by psychopharmaceuticals. Gszz Med Ital 1976; 135: 236-51.
62. Khan MH, Farrell GC, Byth K, Lin R, Weltman M, George J, et al. Which patients with hepatitis C develops liver complications? Hepatology 2000; 31: 513-20.
63. Petrides AS, Vogt C, Schulze-Berge D, Matthews D, Strohmeyer G. Pathogenesis of glucose intolerance and diabetes mellitus in cirrhosis. Hepatology 1994; 19: 616-27.
64. Velussi M, Cernigoi AM, De Monte A, Dapas F, Caffau C, Zilli M. Long-term (12 months) treatment with an antioxidant drug (silymarin) is effective on hyperinsulinemia, exogenous insulin need and malondialdehyde levels in cirrhotic diabetic patients. J Hepatol 1997; 26: 871-9.
65. Silybum marianum (Milk thistle). Alt Med Rev 1999; 4: 272-4.
66. Jacobs PB, Dennehy C, Ramirez G, Sapp J, Lawrence VA. Milk thistle for the treatment of liver disease: A systematic review and meta-analysis. Am J Med 2002, 113: 506-15.
67. Adverse Reaction Advisory Committee. An adverse reaction to the herbal medication Milk thistle (Silybum marianum). Med J Aust 1999; 170: 218-9.
68. Sridar C, Goosen T, Kent UM, William JA, Hollenberg PF. Silybin inactivates cytochromes P450 3A4 and 2C9 and inhibits major hepatic glucuronosyltranferases. Drug Metab Dispos 2004; 32: 587-94.
69. Zuber R, Modriansky M, Dvorak Z, Robovsky P, Ulrichova J, Simanek V, et al. Effect of silybin and its congeners on human liver microsomal cytochrome P450 activities. Phytother Res 2002; 16: 632-8.
70. Kren V, Walterova D. Silybin and silymarin- New effects and applications. Biomed Papres 2005; 149: 29-41.
71. Kosina P, Maurel P, Ulrichova J, Dvorak Z. Effect of silybin and its glycosides on the expression of cytochromes P450 1A2 and 3A4 in primary cultures of human hepatocytes. J Biochem Mol Toxicol 2005; 19: 149-53.
72. Patrick L. Hepatitis C: Epidemiology and review of complementary/ alternative medicine treatments. Altern Med Rev 1999; 4: 220-38.
73. Jayaram S, Thyagarajan SP. Inhibition of HBsAg secretion from Alexander cell line by Phyllanthus amarus. Indian J Pathol Microbiol 1996; 39: 211-5.
74. Chander R, Kapoor NK, Dhawan BN. Hepatoprotective activity of silymarin against hepatic damage in Mastomys natalensis infected with Plasmodium berghei. Indian J Med Res 1989; 90: 472-7.
75. Mayer KE, Myers RP, Lee SS. Silymarin treatment of viral hepatitis: A systematic review. J Viral Hepatitis 2005; 12: 559-67.
76. Tyagi AK, Agarwal C, Chan DCF, Agarwal R. Synergistic anticancer effects of silibinin with conventional cytotoxic agents doxorubicin, cisplatin and carboplatin against human breast carcinoma MCF-7 and MDA-MB468 cells. Oncol Rep 2003; 11: 493-9.
77. Piscitelli SC, Formentini E, Burstein AH, Alfaro R, Jagannatha S, Falloon J. Effect of milk thistle on the pharmacokinetics of indinavir in healthy volunteers Pharmacotherapy 2002; 22: 551-6.
78. Wang MJ, Lin WW, Chen HL, Chang YH, Ou HC, Kuo JS, et al. Silymarin protects dopaminergic neurons against lipopolysaccharide-induced neurotoxicity by inhibiting microglia activation. Eur J Neurosci 2002; 16: 2103-12.