Antioxidant and Hepatoprotective Effect of Swertiamarin on Carbon Tetrachloride-Induced Hepatotoxicity via the Nrf2/HO-1 Pathway

Background/aims: Swertiamarin (STM), the main bioactive component in Swertia mussotii Franch (Gentianaceae), has been shown to exert hepatoprotective effects on experimental liver injury. However, the effects and exact mechanisms of STM on carbon tetrachloride (CCl4) causing hepatotoxicity are still unknown. This study investigated the potential protective effects and mechanisms of STM on CCl4-induced liver injury in rats.

Methods: Adult male Sprague-Dawley (SD) rats were exposed to CCl4 with or without STM co-administration for consecutive eight weeks.

Results: STM significantly ameliorated CCl4-induced increase in serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and Alkaline Phosphatase (ALP) levels and histopathological changes in the liver. Hepatic oxidative stress was repressed by STM, as evidenced by the decrease in malondialdehyde (MDA), with concomitant increase in antioxidase activity (e.g. superoxide dismutase (SOD); Glutathione Peroxidase (GPx)), glutathione (GSH) level. STM also obviously attenuated inflammatory response in CCl4-lesioned livers as evidenced by the decrease in inflammatory cytokines/ chemokines (e.g. inducible nitric oxide synthase (iNOS), interleukin-1β (IL-1β)). Additionally, STM significantly induced the expression of CYPs, efflux transporters and PDZK1 as compared with the CCl4 group. Moreover, co-administration of STM with CCl4 remarkably up-regulated the expression of Nrf2, HO-1 and NQO1 compared with the CCl4 group.

Conclusions: The present study demonstrates that STM exerts a protective effect against CCl4-induced liver injury and inflammation with its antioxidant effects and induction of hepatic detoxification Enzymes and efflux transporters expression, at least in part, via the Nrf2/HO-1 pathway in rats.

Carbon tetrachloride; Efflux transporters; Inflammation; Nrf2; Oxidative stress; Swertiamarin.