Potential protective effects of Pistacia lentiscus L. var. latifolius coss extract against carbon tetrachloride-induced liver injury: Biochemical, histopathological, and computational insights.

The investigation of natural products for liver fibrosis prevention is essential for advancing therapeutic strategies. This study investigates the hepatoprotective effects of Mastic extract against CCl4-induced liver fibrosis in mice and explores its underlying molecular mechanisms. Mice were divided into four groups: (1) negative control (corn oil only), (2) CCl4-induced fibrosis, (3) CCl4 + Mastic extract treatment, and (4) Mastic extract alone. Hepatic function and oxidative stress were assessed by measuring serum ALT, AST, malondialdehyde (MDA), and catalase activity. Gene expression analysis focused on epithelial-mesenchymal transition (EMT) and fibrosis-related genes (E-cadherin, vimentin, and Sirt1) at both mRNA and protein levels. Histopathology and immunohistochemistry examined liver architecture and TGF-β/E-cadherin expression. Network pharmacology identified 32 fibrosis-related genes targeted by Mastic extract's bioactive compounds, with key targets being CYP1A1, CYP2C9, and HMGCR. Secondary targets included CYP2C19, PPARA, and CYP2D6. Bioinformatics analysis predicted favorable drug-likeness and ADME properties of these compounds. Treatment with CCl4 led to elevated ALT, AST, increased MDA levels, and reduced catalase activity, indicating liver injury and oxidative stress. Mastic extract significantly restored these markers to near-normal levels. Additionally, Mastic extract reversed EMT-related changes, increasing E-cadherin and Sirt1 expression while reducing vimentin and TGF-β. Histological analysis showed reduced fibrosis, necrosis, and steatosis in treated livers. In conclusion, Mastic extract provides significant hepatoprotection against CCl4-induced liver fibrosis by modulating EMT, enhancing Sirt1 expression, and reducing oxidative stress. These findings support its potential as a natural therapeutic agent for liver fibrosis prevention and treatment.