apigenin role against thioacetamide-triggered liver fibrosis: deciphering the pparγ/tgf-β1/nf-κb and the hif/fak/akt pathways

Introduction: liver tissue malfunction is a severe worldwide health concern that arises from various chronic liver conditions. the goal of this investigation was to look into the anti-fibrotic effect of apigenin (apg), an antioxidant found in various plants, versus thioacetamide (taa)-triggered hepatic scarring in rats and the potential mechanisms behind it. methods: taa was administered thrice weekly (100 mg/kg, i.p.) for two weeks to produce hepatic scarring. apg was administered after taa for 14 days (5 or 10 mg/kg, orally). thereafter, hepatic liver enzymes, inflammatory markers, fibrotic indicators, and histopathological changes were evaluated. results: taa increased the activities of aspartate aminotransferase (ast) and alanine aminotransferase (alt), reduced albumin and total protein, elevated hepatic level of lipid peroxidation, focal adhesion kinase (fak), hypoxia-inducible factor-1α (hif-1α), and inflammatory cytokines, decreased interleukin-10 (il-10), reduced hepatic expression of peroxisome proliferator-activated receptor gamma (pparγ) and nuclear factor-erythroid factor 2-related factor 2 (nrf2), and elevated serine-threonine protein kinase (akt) expression. furthermore, taa increased hepatic contents of collagen i, connective tissue growth factor (ctgf), hydroxyproline, and alpha-smooth muscle actin. on the other hand, apg evaded these changes and mitigated the harmful effects of taa in a dose-dependent way. histopathological and immunohistochemical observations reinforced these biochemical outcomes. conclusion: apg can potentially alleviate liver fibrosis mediated via fak and hif1 inhibiting signaling pathways.