Oridonin ameliorates lipopolysaccharide/D-galactosamine-induced acute liver injury in mice via inhibition of apoptosis

摘要

We investigated the protective effects exerted by oridonin, the main active constituent of the Chinese medicinal herb Rabdosiarubescens, against lipopolysaccharide (LPS)/D-galactosamine (D-Gal)-induced acute liver injury (ALI). An ALI model was induced in mice using LPS (40 μg/0.5 ml) and D-Gal (5 mg/0.5 ml). The mice were randomly divided into the following five groups of six mice each: one control group (a), one ALI group (b), two oridonin treatment groups (c and d), and one oridonin control group (e). Oridonin (0.2 mg/0.5 ml) was administered once 1 h prior to the LPS/D-Gal challenge in group c and a total of three times over a period of four days, with the last dose given at 1 h before the LPS/D-Gal challenge, in group d. Pretreatment with oridonin improved the survival rate, alleviated histopathological abnormalities, and suppressed plasma aminotransferases in the LPS/D-Gal-challenged mice. Importantly, oridonin attenuated LPS/D-Gal-induced apoptosis in hepatocytes by reducing pro-apoptotic signals (P<0.05), such as tumor necrosis factor-α (TNF-α) and c-Jun N-terminal kinases (JNK). Furthermore, JNK-associated mitochondrial pro-apoptotic proteins were also suppressed by pretreatment with oridonin. Taken together, these data show that oridonin exerts protective effects against LPS/D-Gal-induced ALI in mice via a mechanism that may involve the suppression of the pro-apoptotic cytokine TNF-α and JNK-associated pro-apoptotic signaling.