Shahrekord University of Medical Sciences Journal of Herbmed Pharmacology 2345-5004 12 2 2023 04 01 Apigenin role against thioacetamide-triggered liver fibrosis: Deciphering the PPARγ/TGF-β1/NF-κB and the HIF/FAK/ AKT pathways 202 213 10.34172/jhp.2023.21 EN Rehab F. Abdel-Rahman https://orcid.org/0000-0002-4341-4954 Hany M. Fayed https://orcid.org/0000-0002-3673-5733 Marwan Abd Elbaset Mohamed https://orcid.org/0000-0002-0861-6251 Alyaa F. Hessin https://orcid.org/0000-0002-7775-923X Gihan F. Asaad https://orcid.org/0000-0002-7679-5968 Sahar AbdelRahman https://orcid.org/0000-0001-8638-1737 Abeer A.A. Salama https://orcid.org/0000-0001-9870-5583 Mahmoud S. Arbid https://orcid.org/0000-0002-6773-3650 Hanan A. Ogaly https://orcid.org/0000-0002-0480-5127 Journal Article 10.34172/jhp.2023.21 2022 11 02 2022 12 24 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 antifibrotic 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.