Hepatoprotective effects of cirsimaritin against CCl 4 -induced oxidative stress, inflammation, and apoptosis in rats

Background Carbon tetrachloride (CCl4) induces hepatotoxicity through oxidative stress, inflammation, and apoptosis. Cirsimaritin, a natural flavonoid with antioxidant and anti-inflammatory activity, has not been extensively investigated for hepatoprotection.Methods Male Wistar rats were allocated into four groups (n = 6): control, cirsimaritin-only (80 mg/kg/day), CCl4-only (1 mL/kg of 1:1 CCl4: olive oil, i.p., twice weekly), and cirsimaritin + CCl4. After four weeks, serum liver function markers, oxidative stress indices, cytokines, apoptotic markers, histology, and hepatic expression of Nrf2, HO-1, and NF-κB p65 were assessed.Results CCl4 significantly elevated ALT, AST, ALP, bilirubin, MDA, TNF-α, IL-6, caspase-3, and caspase-9, while reducing albumin, total protein, SOD, CAT, GPx, IL-4, and IL-10 (p < 0.05–0.001). Cirsimaritin co-treatment reversed these alterations by normalizing liver enzymes, restoring antioxidant activity, lowering lipid peroxidation and pro-inflammatory cytokines, elevating anti-inflammatory cytokines, and attenuating apoptosis. Histology confirmed preservation of hepatic architecture. qPCR analysis showed that CCl4 downregulated Nrf2/HO-1 and upregulated NF-κB p65, whereas cirsimaritin significantly counteracted these molecular changes.Conclusion Cirsimaritin protects against CCl4-induced hepatotoxicity by enhancing antioxidant defenses, correcting cytokine imbalance, and inhibiting apoptosis, at least partly via activation of Nrf2/HO-1 and suppression of NF-κB signaling. These findings highlight cirsimaritin as a promising natural hepatoprotective candidate.