Isatidis Folium alleviates acetaminophen‐induced liver injury in mice by enhancing the endogenous antioxidant system

Abstract Isatidis Folium (IF) has been clinically combined with acetaminophen (APAP), but the rationality of combinational therapy is still ambiguous. In the present study, the protective effect and related mechanism of IF on APAP‐induced hepatotoxicity were evaluated. Hepatic histopathology and blood biochemistry investigations clearly demonstrated that IF could restore APAP‐induced hepatotoxicity. Liver distribution study indicated that the hepatoprotective effect of IF on APAP is attributed to the reduction of N‐acetyl‐p‐benzoquinone imine (NAPQI) in liver, which is a known hepatotoxic metabolite of APAP. Further study suggested the reduction is not via decreasing the generation of NAPQI through inhibiting the enzyme activities of CYP 1A2, 2E1, and 3A4 but via accelerating the transformation of NAPQI to NAPQI‐GSH by promoting GSH and decreasing GSSG contents in liver. Furthermore, IF significantly enhanced the hepatic activities of GSH‐associated enzymes in APAP‐treated mice. In summary, IF could alleviate APAP‐induced hepatotoxicity by reducing the content of NAPQI via enhancing the level of GSH and the followed generation of NAPQI‐GSH which might be ascribed to the upregulation of GSH‐associated enzymes.