Although multiple studies have shown that Angelica keiskei of the Umbelliferae family has potent anti-inflammatory and antioxidative activities and that it reduces the serum bile acids in humans, whether A. keiskei has protective effects against cholestasis-induced liver injury remains unexplored until now. This study tests the hypothesis that Angelica keiskei root extract (AKE) alleviates liver injury, inflammation, and fibrosis in mouse models of acute cholestasis induced by bile duct ligation (BDL). Oral administration of AKE (200 or 500 mg/kg) attenuated hepatocellular necrosis and significantly reduced serum levels of bile acids and bilirubin in BDL mice. The critical enzyme of bile acid synthesis, CYP7A1, was repressed by AKE, suggesting that reduced bile acid production may contribute to liver protection. Moreover, we determined through gene expression and cytokine analysis and histological examination that AKE treatment decreased liver inflammation, oxidative stress, and fibrosis. AKE also suppressed the NF-κB pathway, suggesting this as a possible mediator of its anti-inflammatory effect. Our findings substantiate that AKE may be promising for treating cholestatic liver diseases in the future.
Keywords: NF-κB; Sirt1; cholestasis; fibrosis; inflammation; oxidative stress.