Geniposidic acid protects against d-galactosamine and lipopolysaccharide-induced hepatic failure in mice
2013
Kim, So-jin | Kim, Kang-min | Park, Juhyun | Kwak, Jong-Hwan | Kim, Yeong Shik | Lee, Sun-Mee
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, 50mg/kg) 1h before receiving GalN (800mg/kg)/LPS (40μg/kg). Liver and blood samples were collected 1 and 8h 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.
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