AIM To investigate the antioxidant and hepatoprotective effects of Cortex Dictamni aqueous extract(CDAE) in carbon tetrachloride(CCl4)-induced liver damage in rats.METHODS The in vitro antioxidant effect of CDAE was investigated using α,α-diphenyl-β-picrylhydrazyl(DPPH), 2,2’-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid)(ABTS), β-carotene bleaching, reducing power, and thiobarbituric acid reactive substance assays. A linoleic acid system, including ferric thiocyanate(FTC) and thiobarbituric acid(TBA) assays, was used to evaluate the inhibition of lipid peroxidation. The in vivo hepatoprotective and antioxidant effects of CDAEagainst CCl4-induced liver damage were evaluated in Sprague-Dawley rats. Silymarin was used as a positive control. Liver damage was assessed by determining hepatic histopathology and liver marker enzymes in serum. Enzyme and non-enzyme antioxidant levels and lipid peroxide content were measured in the liver. Cytochrome P450 2E1(CYP2E1) protein expression was measured via immunohistochemical staining. Nuclear factor E2-related factor(Nrf2), heme oxygenase-1(HO-1), NAD(P)H quinine oxidoreductase 1(NQO1), and γ-glutamylcysteine synthetase catalytic subunit(γ-GCSc) protein expression was measured by Western blot.RESULTS Our results showed that CDAE exhibited a strong antioxidant activity in vitro. CDAE scavenged DPPH and ABTS radicals in a dose-dependent manner. CDAE inhibited lipid peroxidation with a lipid peroxide inhibition rate of 40.6% ± 5.2%. In the FTC and TBA assays, CDAE significantly inhibited lipid peroxidation(P < 0.01). In vivo histopathological studies indicated that CCl4-induced liver injury was alleviated following CDAE treatment in rats of both sexes. CDAE(160 and 320 mg/kg) significantly prevented CCl4-induced elevations of alkaline phosphatase, glutamate pyruvate transaminase, aspartate aminotransferase, and total bilirubin levels in rats of both sexes(P < 0.05, 0.01, or 0.001). Moreover, CDAE restored the decreased activities of hepatic antioxidant enzymes, including superoxide dismutase, catalase, and glutathione peroxidase, as well as non-enzyme antioxidant glutathione, which were induced by CCl4 treatment. CDAE significantly suppressed the up-regulation of CYP2E1 and promoted Nrf2, HO-1, NQO1, and γ-GCSc protein expression.CONCLUSION CDAE exhibits good antioxidant performance in vitro, with marked radical-scavenging and anti-lipid peroxidation activities. CDAE is effective in preventing CCl4-induced hepatic damage in rats of both sexes. The hepatoprotective activity of CDAE may be attributable to its antioxidant activity, which may involve Keap1-Nrf2-mediated antioxidant regulation. AIM To investigate the antioxidant and hepatoprotective effects of Cortex Dictamni aqueous extract (CDAE) in carbon tetrachloride (CCl4) -induced liver damage in rats. METHODS The in vitro antioxidant effect of CDAE was investigated using α, α-diphenyl-β-picrylhydrazyl DPPH, 2,2’-azino-bis (ABTS), β-carotene bleaching, reducing power, and thiobarbituric acid reactive substance assays. A linoleic acid system, including ferric thiocyanate (FTC ) and thiobarbituric acid (TBA) assays, was used to evaluate the inhibition of lipid peroxidation. The in vivo hepatoprotective and antioxidant effects of CDAEagainst CCl4-induced liver damage were evaluated in Sprague-Dawley rats. Silymarin was used as a positive control. Liver damage was assessed by hepatic histopathology and liver marker enzymes in serum. Enzyme and non-enzyme antioxidant levels and lipid peroxide content were measured in the liver. Cytochrome P450 2E1 (CYP2E1) protein expression was was measured by immunohistochemical staining. Nuclear factor E2-related factor (Nrf2), heme oxygenase-1 (HO-1), NAD (P) H quinine oxidoreductase 1 (NQO1), and γ-glutamylcysteine ​​synthetase catalytic subunit expression was measured by Western blot.RESULTS Our results showed that CDAE exhibited a strong antioxidant activity in vitro. CDAE inhibited lipid peroxidation with a lipid peroxide inhibition rate of 40.6% ± 5.2% In vivo histopathological studies indicated that CCl4-induced liver injury was alleviated following CDAE treatment in rats of both sexes. CDAE (160 and 320 mg / kg) significantly prevented CCl4-induced elevations of alkaline phosphatase, glutamate pyruvate transaminase, aspartate aminotransferase, and total bilirubin levels in rats of both sexes (P <0.05, 0.01, or 0.001) ivitiesof hepatic antioxidant enzymes, including superoxide dismutase, catalase, and glutathione peroxidase, which were induced by CCl4 treatment. CDAE significantly suppressed the up-regulation of CYP2E1 and promoted Nrf2, HO- 1, NQO1, and γ-GCSc protein expression. CONCLUSION CDAE exhibits good antioxidant performance in vitro, with marked radical-scavenging and anti-lipid peroxidation activities. CDAE is effective in preventing CCl4-induced hepatic damage in rats of both sexes. The hepatoprotective activity of CDAE may be attributable to its antioxidant activity, which may involve Keap1-Nrf2-mediated antioxidant regulation.