Geniposidic acid protects against D-galactosamine and lipopolysaccharide-induced hepatic failure in mice

Ethnopharmacological relevance: Geniposidic acid (GA) is an iridoid glucoside isolated from Gardeniae jasminoides Ellis (Rubiaceae) that has long been used to treat inflammation, jaundice and hepatic disorders.

Aims of the study: This study examined the cytoprotective properties of GA against D-galactosamine (GalN)/lipopolysaccharide (LPS)-induced fulminant hepatic failure.

Materials and methods: Mice were given an intraperitoneal injection of GA (12.5, 25, 50 mg/kg) 1h before receiving GalN (800 mg/kg)/LPS (40 μg/kg). Liver and blood samples were collected 1 and 8 h after GalN/LPS injection.

Results: The survival rate of the GA group was significantly higher than the control. GalN/LPS increased serum aminotransferase activity, serum tumor necrosis factor-α level and hepatic lipid peroxidation and decreased hepatic glutathione content. These changes were attenuated by GA. GA augmented increases in serum interleukin-6 level, heme oxygenase-1 and NF-E2-related factor 2 protein expression. Mice treated with GA decreased cleaved Caspase-8 and Caspase-3 protein expression and showed significantly fewer apoptotic cells. GA increased Bcl-xL protein expression and decreased Bax protein expression. Moreover, GA treatment enhanced phosphorylation of signal transducer and activator of transcription 3.

Conclusion: Our findings suggest that geniposidic acid alleviates GalN/LPS-induced liver injury by enhancing antioxidative defense system and reducing apoptotic signaling pathways.