Protective effect of Ornithogalum saundersiae Ait (Liliaceae) against acetaminophen-induced acute liver injury via CYP2E1 and HIF-1α

Abstract

AimTo investigate the hepatoprotective effect of total saponin from Ornithogalum saundersiae Ait (Liliaceae) (OC) against acetaminophen (APAP)-induced acute liver injury in vivo and in vitro. MethodsMice were pretreated with OC (300, 200 or 100 mg·kg−1, body weight) or N-acetyl-L-cysteine (NAC) (300 mg·kg−1, body weight) for 3 times at 24 h intervals. APAP was administered 2 h after OC last dose. Chang liver cells were incubated with the medium containing OC (50, 100, 200 mg·mL−1) or NAC (10 mmol·L−1) with the presence or absence of APAP (10 mmol·L−1) for 24 h. ResultsOC showed remarkable hepatoprotective effect 12 h after APAP administration by decreased aspartate aminotransferase and alanine aminotransferase levels, reduced the products of lipid peroxidation, improved the activity of catalase, superoxide dismutase and glutathione peroxidase, inhibited the caspase-3 cleavage and hypoxia inducible factor-1α accumulation in vivo. In vitro, OC significantly decreased the activities of metabolism enzyme cytochrome P450 2E1 (CYP2E1) and cyclooxygenase-2 (COX-2) induced by APAP. ConclusionOC possesses the ability to protect hepatocyte from APAP-induced liver damage, suggesting that the hepatoprotective mechanism of OC might be related to antioxidation via blocking the CYP2E1, and mediating reactive oxygen species scavenging and accumulation of hypoxia-inducible factor (HIF)-1α.