Harmalol mitigates liver fibrosis by alleviating oxidative stress associated with Nrf-2/HO-1 signaling activation

Liver fibrosis is characterized by the dysregulation of various signaling pathways that govern the process of extracellular matrix deposition. This study explores the protective effect of harmalol, a beta-carboline member of Peganum Harmala, in a rat model of hepatic fibrosis. Thioacetamide (TAA) administration (200 mg/kg/i.p, twice weekly for 8 weeks) induced hepatic fibrosis in rats. Harmalol (10 mg/kg, i.p) was co-administered with TAA and sera and hepatic tissue were collected for biochemical and histopathological investigation. Co-treatment with harmalol ameliorated hepatic dysfunction and attenuated fibrosis, as revealed by lowered serum levels of AST, ALT, Gamma-glutamyl transferase (GGT) and bilirubin, elevated serum albumin levels. Harmalol treatment reduced levels of malondialdehyde and nitric oxide while enhancing total antioxidant capacity and glutathione levels, indicating alleviated oxidative stress. Histopathological and immunohistochemical analysis showed attenuated fibrosis and inflammation. Harmalol upregulated Nrf-2 expression and suppressed NF-κB and TGF-ß1 hepatic expression. Consequently, HO-1 levels were elevated and hepatic TNF-α, IL-6, and α-SMA levels were attenuated. These findings propose that harmalol abrogates hepatic fibrosis by modulating inflammation and oxidative stress via targeting Nrf-2/NF-κB signaling.