Hepatoprotective Effects of Rotula Aquatica Lour Against Acetaminophen Induced Liver Injury: Phytochemical and Mechanistic Insights

Abstract

Background: Drug-induced liver injury is one of the major clinical concerns and the reason for the search for effective natural hepatoprotective agents. Objective: This study is done to assess the ameliorative effect of ethanolic extract of Rotula aquatica Lour (EERA) in paracetamol induced liver damage in Wistar albino rats. Methods: This experimental animal study was conducted using Wistar albino rats to evaluate the hepatoprotective potential of ethanolic extract of EERA (EERA) against paracetamol-induced liver injury. Preliminary phytochemical screening of the ethanolic extract was performed to identify its bioactive constituents. The antioxidant potential was assessed using standard free radical scavenging assays. The cytotoxic safety profile of the extract was evaluated using the MTT (methylthiazol tetrazolium) assay in Chang human liver cell lines. Hepatotoxicity was induced in Wistar albino rats through administration of paracetamol. In the curative model, animals received EERA at doses of 200 mg/kg and 400 mg/kg (p.o.), or silymarin at 100 mg/kg (p.o.), for seven consecutive days following induction of liver injury. In the preventive model, EERA or silymarin was co administered with paracetamol for three days. Each experimental group consisted of six animals (n = 6 per group). Silymarin (100 mg/kg) was used as the standard reference drug. Biochemical evaluation included analysis of serum liver function markers, assessment of endogenous antioxidant enzymes such as superoxide dismutase and catalase, measurement of lipid peroxidation levels, and detailed histopathological examination of liver tissues. Results: Analysis of phytochemical constituents revealed the presence of flavonoids, triterpenoids, alkaloids and steroids. EERA exhibited marked antioxidant activity (p < 0.05). In the in vivo study model, EERA significantly improved serum biochemical parameters, enhanced antioxidant enzyme levels and reduced lipid peroxidation compared to the toxic control group (p < 0.05). In the curative model, treatment with EERA at 400 mg/kg markedly restored altered liver enzyme levels, with SGOT decreasing from 3.3 ± 0.139 in the toxic control group to 2.25 ± 0.07 and SGPT improving toward near-normal values compared with the paracetamol-treated group. Histopathological findings confirmed its hepatoprotective effects. Treatment with 400 mg/kg EERA produced effects similar to Silymarin at 100 mg/kg (p < 0.05). This shows that EERA protects the liver from damage, which is further confirmed by histopathological analysis. Conclusion: The findings suggest that EERA exhibits promising hepatoprotective and antioxidant activity against paracetamol-induced liver injury in rats, warranting further molecular and clinical investigation.