Dodonaea viscosa (L.) Jaeq (Sapindaceae) is used in traditional medicine for the treatment of hemorrhoids, ulcer, and pains of hepatic or stomach origin. The current study was designed to investigate the phytochemical constituents of the plant and evaluate its activity against liver fibrosis induced by carbon tetrachloride (CCl4) in rats. The phytochemical analysis has afforded one flavanone; 5,7-dihydroxy flavanone (pinocembrin) (1) and eight flavones. The compounds were isolated and elucidated as; 5,7-dihydroxy-3,6,4'-trimethoxyflavone (santin) (2), 5,7,4'-trihydroxy-3-methoxy flavone (kaempferol 3-O-methyl ether) (3), 3,4',5-trihydroxy-7-methoxy flavone (kaempferol 7-O-methyl ether) (4), 3',4',5,7-tetrahydroxy-3-methoxy-flavone (quercetin 3'-O-methyl ether) (5), 3,3',4',5,7-pentahydroxyflavone (quercetin) (6), 5,7,4'-trihydroxy-3,6-dimethoxy flavone (7), 5,7-dihydroxy 3,6,3',4'-tetramethoxy flavone (8), and isorhamnetin-3-O-robinobioside (9).. In vitro screening of ethanol extract, fractions of toluene and ethyl acetate, the flavanone and major flavone compounds as antioxidants was carried out. In addition, D. viscosa ethanol extract and two fractions were examined in vivo against liver fibrosis induced by CCl4 in rats. The evaluation was done through measuring hepatic oxidative stress markers; malondialdehyde (MDA), glutathione (GSH) and superoxide dismutase (SOD). The work was extended to measure serum protein content and liver function enzymes; aspartate and alanine aminotransferases (AST and ALT), alkaline phosphatase (ALP) and gamma glutamyl transferase (GGT). Liver histopathological analysis was done for results confirmation. In conclusion, among the isolated flavones, compounds 3, 4, and 8 were isolated for the first time. The ethanol extract and compound of 6, 5 followed by 7 exhibited the strongest antioxidant activities. Treatment with D. viscosa extract and its fractions attenuates the increments of MDA, AST, ALT, ALP, GGT, total protein and increased GSH and SOD levels. The ethanol extract showed the most potent effect. The data confirmed the rationale for the traditional use of D. viscosa extracts to hepatic disorders. Further studies are needed in order to evaluate the isolated flavones as protective agents against liver injury and for their clinical application
