Effects of Schisandrae Chinensis Fructus induced CYPs and Nrf2 activation on acute liver injury induced by acetaminophen / 中国中药杂志

ABSTRACT

Schisandra chinensis is a commonly used hepatoprotective medicine in clinic. Previous studies have showed that Schisandrae Chinensis Fructus has dual effects on the activity of CYPs. Short-term administration of Schisandrae Chinensis Fructus may inhibit CYP450s activity, while long-term administration may up-regulate CYP activity. High CYP450s activity level may increase the frequency of reactive metabolites-induced liver injury. It remains unclear how long-term administration of Schisandrae Chinensis Fructus may affect acetaminophen-induced acute hepatotoxicity. After oral administration of Schisandrae Chinensis Fructus extract (0.5-2.0 g·kg⁻¹) for 21 d, the activity of CYPs, Nrf2, HO-1, GST expressions, SOD and GST activity as well as glutathione level of SD rats were up-regulated. Besides, Schisandrae Chinensis Fructus extract ameliorated APAP (500 mg·kg⁻¹)-induced acute hepatotoxicity in a dose-dependent manner, as evidenced by decrease in ALT, AST, and MDA level and increase in GSH level (<0.05). What's more, the liver histopathology was alleviated, and cleaved caspase-3 expression was decreased. Besides, the increase of N-acetyl-p-benzoquinoneimine-GSH (reactive metabolite of acetaminophen) formation was observed in Schisandrae Chinensis Fructus extract groups. In conclusion, the present study indicated that the effects of Schisandrae Chinensis Fructuson acetaminophen-induced hepatotoxicity may rely on the Nrf2 signal pathway activation, and less depends on the increase in CYP450s activity.