EVALUATION OF METHANOLIC EXTRACT OF SILYBUM MARIANUM FOR HEPATOPROTECTIVE ACTIVITY IN RATS.

The liver is a vital organ involved in metabolism, detoxification, protein synthesis, and maintenance of physiological homeostasis. Excessive exposure to hepatotoxic agents such as paracetamol can produce hepatic injury primarily through the formation of reactive metabolites and increased oxidative stress. The present study was undertaken to evaluate the hepatoprotective and antioxidant potential of a methanolic plant extract against paracetamol-induced hepatotoxicity in experimental animals. The animals were divided into five groups, consisting of six animals in each group. Group I served as the normal control and received distilled water orally. Group II served as the toxic control and received paracetamol at a dose of 2 g/kg, orally, to induce hepatotoxicity. Group III received the standard hepatoprotective drug silymarin at 50 mg/kg, orally. Groups IV and V received the methanolic extract at doses of 200 and 400 mg/kg, orally, respectively. Following treatment, biochemical parameters were evaluated to determine the protective effect of the test extract against paracetamol-induced hepatic injury. Paracetamol administration produced marked alterations in hepatic biochemical parameters, characterized by an increase in serum SGOT (AST), SGPT (ALT), ALP, and total bilirubin, together with a reduction in total protein, albumin, and globulin levels compared with the normal control group. Paracetamol also produced considerable oxidative stress, as demonstrated by a significant elevation of malondialdehyde (MDA) and depletion of endogenous antioxidant defenses, including reduced glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx). Treatment with silymarin significantly attenuated the paracetamol-induced alterations and restored the biochemical and antioxidant parameters toward normal values. The methanolic extract at both 200 and 400 mg/kg produced significant hepatoprotective effects, as evidenced by reduction of elevated hepatic enzyme and bilirubin levels and improvement in serum protein parameters. The extract also significantly reduced MDA levels and restored GSH, SOD, CAT, and GPx activities. The protective effect was more pronounced at 400 mg/kg than at 200 mg/kg, indicating a dose-related response. The hepatoprotective effect of the methanolic extract may be associated with its phytochemical constituents, particularly phenolic and flavonoid compounds, which may contribute to free-radical scavenging, inhibition of lipid peroxidation, and preservation of endogenous antioxidant defenses. Overall, the findings suggest that the methanolic extract possesses significant hepatoprotective and antioxidant activity against paracetamol-induced hepatic injury. Further studies involving histopathological evaluation, isolation of active phytoconstituents, and molecular investigations are warranted to establish the precise mechanisms responsible for the observed protective effects. Keywords: Paracetamol, hepatotoxicity, hepatoprotective activity, methanolic extract, silymarin, oxidative stress, MDA, GSH, SOD, catalase, glutathione peroxidase.