Studies On Pharmacodynamics Of Glycarrhetic Acid Derivatives(TY501)

BACKGROUND&OBJECTIVEGlycyrrhetic acid derivatives possess a wide range of pharmacological properties and the activities of anti-inflammatory, hepatoprotection and anti-gastric ulcer are also used in clinic. TY501is a series of new glycyrrhetic acid derivatives.Its anti-inflammatory, analgesic, antibechic effect had been confirmed in the past studies. Considering the lack of ideal drugs about anti-kidney damage, hepatoprotection, anti-gastric ulcer and relative records about the actives of glycyrrhetic acid, multiple kinds of animal models were used to evaluate the effects in order to lay the foundation of searching for new drugs.METHODS&RESULTS1. Anti-kidney damage activityIn Anti-kidney damage experiments, we used two animal models, respectively rats acute renal injury induced by gentamicin and rats acute renal injury induced by cisplatin. Glycyrrhetic acid derivatives-TY501-0, TY501-1, TY501-3, TY501-4, TY501-6, TY501-7, TY501-9exhibited inhibitory activities on100mg/kg dose not only in the model of rats acute renal injury induced by gentamicin but also rats acute renal injury induced by cisplatin.Especially,TY501-0, TY501-9, TY501-7, TY501-6, TY501-3can protect kidney obviously in the two models and the anti-kidney damage intensity were almost similar to conventional-dose Nephritis rehabilitation tablets. Moreover, TY501-0, which had a better activity compared to others, showed dose dependent on10,30,100mg/kg. Rusults in our study showed that glycyrrhetic acid derivatives in our study possessed higher anti-kidney damage activity.2. Hepatoprotective activityWe selected two animal models-CCl4induced acute hepatic injury of rats and D-Ga1N induced acute hepatic injury of rats to observe the protective effects of glycyrrhetic acid derivatives. Glycyrrhetic acid derivatives-TY501-0, TY501-1, TY501-3, TY501-4, TY501-6, TY501-7, TY501-9exhibited inhibitory activities on100mg/kg dose in the two models. TY501-0, TY501-9, TY501-7, TY501-6, TY501-3could protect hepatic injury obviously both in the model of CCl4induced acute hepatic injury of rats and the model of D-GalN induced acute hepatic injury of rats and the hepatoprotective effect intensity were almost similar to50mg/kg dose Silybum marianum. TY501-0, which had a better activity compared to others, was found dose dependent on10,30,100mg/kg. The rusults showed that glycyrrhetic acid derivatives in our study possessed higher hepatoprotective activity.3. Anti-gastric ulcer activityThe rats experimental gastric ulcer models were induced by pylorus ligation, alcohol and water immersion stress were adopted to observe the therapeutic effect of glycyrrhetic acid derivatives. TY501-0, TY501-9exhibited inhibitory activities on50mg/kg dose in the model of rats gastric ulcer induced by pylorus ligation. TY501-0also showed anti-gastric ulcer effect in the other two models and the other compounds had weak or almost no inhibitory activities. Therefore, glycyrrhetic acid derivatives in our study could anti-gastric ulcer, but the intensity is moderate.CONCLUSIONSGlycyrrhetic acid derivatives exhibited higher anti-kidney damage activity and hepatoprotective activity, and they also had anti-gastric ulcer activity. As our studies were still at the initial stage, the results provided better evidences to illustrate further mechanism, which was worth to be explored deeply.