Effect of Euphorbia Milii Extract on Cytotoxicity and Hepatoprotective Activity Against Paracetamol-Induced Hepatic Damage in Wistar Rats

Objectives: The objective of the study is to evaluate the hepatoprotective potential of the alcoholic extract of Euphorbia milii (AEEM) (family: Euphorbiaceae) against paracetamol (PCM)-induced acute liver damage, in support of its traditional use in Indian medicine. Methods: An in vitro cytotoxicity test was conducted following ISO guidelines to assess the safety profile of the extract. Hepatotoxicity was induced in experimental models using PCM, and the protective effects of the Euphorbia milii (EM) extract were assessed by measuring liver function markers, including serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), and total serum bilirubin (SB). Levels of lipid peroxidation (LPO) and glutathione (GSH) were also evaluated. Histopathological examination of liver tissues was performed to corroborate the biochemical findings. Results: The in vitro cytotoxicity of AEEM reveals that the % viability of test item concentration observed as 105.06%, 103.12%, 100.05%, and 83.75% at 12.5%, 25%, 50%, and 100%, respectively. The % viability of positive control concentration observed as 47.11%, 8.92%, 0.51%, and 0.71% at 12.5%, 25%, 50%, and 100%, respectively. The test compound (AEEM extract) % viability was observed ˃70% of the blank, so the test item is concluded as “Non-Cytotoxic”. EM alcoholic extract exhibited dose-dependent hepatoprotective effects. The high dose (Group III) significantly improved liver enzyme profiles and bilirubin levels, almost matching the standard treatment (Group VI), indicating its strong therapeutic potential against PCM-induced liver damage. The extract also enhanced hepatic antioxidant status by reducing LPO and increasing GSH levels. Histopathological analysis supported these findings by demonstrating preserved liver architecture and reduced cellular damage in extract-treated groups. This confirms the protective action of AEEM against experimentally induced liver damage in rats. Conclusion: The present study confirms the hepatoprotective potential of the AEEM against PCM-induced liver damage. Preliminary phytochemical screening revealed the presence of bioactive constituents such as glycosides, proteins, terpenoids, phenols, and flavonoids, which may contribute to its pharmacological activity. The in vitro cytotoxicity assay demonstrated more than 70% cell viability, indicating the extract is non-cytotoxic and safe for biological use. The extract significantly attenuated elevated serum markers (AST, ALT, ALP, and SB) and preserved normal liver architecture in histopathological evaluations, comparable to the standard drug silymarin. These findings support the traditional use of EM in the management of hepatic disorders and suggest its potential as a natural hepatoprotective agent with antioxidant properties. Further studies are warranted to isolate the active constituents and elucidate the precise mechanisms of action.