Geniposide Treatment Research Articles

Effect of in vitro and in vivo aerosolized treatment with geniposide on tracheal permeability in ovalbumin-induced guinea pigs

The primary objective of this study was to investigate the effect of geniposide, a potent anti-inflammatory, on ovalbumin-antigen-induced tracheal permeability and transepithelial electrical resistance in guinea pigs. Two weeks after sensitization with ovalbumin (100 mg/ml), the permeability of guinea-pig tracheas was evaluated by flux measurements using the transcellular tracer, [ 14C]estradiol, and the paracellular tracer, [ 14C]mannitol. The effect of extracellular Ca 2+ with geniposide was also studied, using deletion of Ca 2+ in the donor chamber. The in vivo treatment effect of aerosolized geniposide on tracheal permeability in the ovalbumin-sensitized guinea pigs was also evaluated. The results indicate that tight junction permeability of ovalbumin-sensitized trachea was significantly dose dependent and decreased by geniposide (1–10 mM), as evidenced by substantial recovery of transepithelial electrical resistance and decreased transepithelial permeability of [ 14C]mannitol at (1.32±0.12)×10 −5 cm/s. The effect of combination of the removal of extracellular Ca 2+ with geniposide had no effect on tight junction permeability of ovalbumin-sensitized trachea and revealed that transepithelial electrical resistance and junction permeability did not recover. In addition, the cAMP levels and phosphodiesterase activity were not significantly influenced in ovalbumin-sensitized tracheal tissues after geniposide treatment. Inhaled geniposide (50 mM, 30 min after ovalbumin sensitization) significantly restored junction permeability induced by ovalbumin (100 mg/ml, 2 min). Junction permeability did not recover on pretreatment with geniposide (50 mM for 30 min over 16 days consecutive before ovalbumin sensitization) after exposure of conscious guinea pigs to aerosol ovalbumin. In conclusion, geniposide has inhibitory effects on ovalbumin-induced junction permeability and recovery of transepithelial electrical resistance in guinea pig trachea, showing its potential as anti-asthma therapy.

Suppressive effect of geniposide on the hepatotoxicity and hepatic DNA binding of aflatoxin B1 in rats

The effects of geniposide pretreatment on both hepatic aflatoxin B1 (AFB1)-DNA binding and AFB1 hepatotoxicity in rats has been examined. For these studies, male Sprague-Dawley rats were treated with AFB1 (2 mg/kg) by i.p. administration, and the different degrees of hepatic damage were revealed by the elevations of levels of serum marker enzymes such as aspartate aminotransferase (AST), alanine amino-transferase (ALT) and gamma-glutamyltranspeptidase (gamma-GT). After pretreatment of animals with geniposide (10 mg/kg) daily for 3 consecutive days, the enzyme elevations were significantly suppressed. This suggested that the geniposide possessed chemopreventive effects on the early acute hepatic damage induced by AFB1. Under these experimental conditions, consistent elevation of the activities of glutathione S-transferase (GST) and gamma-glutamylcysteine synthetase but not glutathione peroxidase (GSH-Px) and gamma-glutamyltranspeptidase were observed. Treatment of rats with geniposide significantly lowered hepatic GSH and GSSG levels, but the ratio of GSH to GSSG was not changed. Geniposide treatment also decreased AFB1-DNA adduct formation in AFB1-treated animals. From these results, we suggest that the protective effect of geniposide on AFB1 hepatotoxicity in rats might be due to the hepatic tissues' defense mechanisms that involve the enhanced GST activity for AFB1 detoxication and induction gamma-glutamylcysteine synthetase for GSH biosynthesis.