Synergistic effect of silymarin and standardized extract of Phyllanthus amarus against [CCl.sub.4]-induced hepatotoxicity in Rattus norvegicus.(silymarin)(Clinical report)

Abstract

In search of the effective and standardized hepatoprotective combination therapy, silymarin and standardized extract of Phyllanthus amarus has been evaluated against [CCl.sub.4]-induced hepatotoxicity in rats. Eight groups of rats were used. The animals of group A served as normal and were given only vehicle. The animals of group B served as toxin control and were administered with CC[1.sub.4] (50% solution of C[C1.sub.4] in liquid paraffin, 2ml/kgb.w., intraperitoneally). The animals of groups C-H received silymarin (100 mg/kg b.w.), Phyllanthus amarus aqueous extract (l00 mg/kg b.w.), Phyllanthus amarus ethanolic extract (100 mg/kgb.w.), silymarin (50 mg/kg b.w.) + P. amarus aq. ext. (50 mg/kg b.w.), silymarin (50mg/kgb.w.)+ P. amarus eth. ext. (50 mg/kg b.w.) and marketed formulation (M.F.) 5 ml/kg b. w. for 6 days orally as well as CC[l.sub.4](2ml/kgb.w.) on 4th day intraperitoneally. The test materials were found effective as hepatoprotective as evidenced by plasma and liver biochemical parameters. The combination of silymarin and Phyllanthus amarus showed synergistic effect for hepatoprotection and silymarin with ethanolic extract of P. amarus showed better activity due to the higher concentration of phyllanthin in ethanolic extract in comparison to aqueous extract of P. amarus as estimated by HPLC.

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Keywords: Phyllanthus amarus; Silymarin; CC[1.sub.4]; Synergistic effect; Hepatotoxicity

Introduction

Living in a world of inadequately controlled environmental pollution and expanding therapy with potent drugs, the liver, which is the key organ of metabolism and excretion, is continually exposed to a variety xenobiotics and therapeutic agents. Thus the disorders associated with this organ are numerous and varied. An actual curative therapeutic agent has not yet been found. In fact, most of the available remedies support or promote the process of healing or regeneration of the liver.

Silymarin is a flavonoid extracted from the milk thistle Silybum marianum. It has been reported to prevent liver injuries induced by various chemicals or toxins including ethanol (Farghali et al., 2000; Halim et al., 1997; Lieber et al., 2003). Although the hepatoprotective properties of silymarin have been reported both from in vitro and in vivo studies, its mechanism of action still has not been established. Two major mechanisms that have been proposed include functioning as an antioxidative scavenger of free radicals (mainly active toward HO and HOC1 and less so for [H.sub.2][O.sub.2] or [O.sub.[bar.2]]) and as a regulator of immune functions by modulating cytokine production (Ferenci etal., 1989; Luper, 1998).