Cardioprotective activity of synthetic guggulsterone (E and Z-isomers) in isoproterenol induced myocardial ischemia in rats: A comparative study

Guggulsterone, a mixture of cis (E) and trans (Z) isomers (7∶3 w/w) was synthesized from 16-DPA. The isomers were separated by column chromatography and evaluated for cardioprotective and antioxidant activities. Myocardial necrosis induced by isoproterenol in rats caused marked increase in serum creatine phosphokinase and glutamate pyruvate transaminase. Simultaneously in ischemic heart, Phospholipase, Xanthine Oxidase and lipid peroxides were enhanced following depletion of glycogen, Phospholipids and Cholesterol. Treatment with guggulsterone and its both isomers at the dose of 50 mg/kg po., significantly protected cardiac damage as assessed by the reversal of blood and heart biochemical parameters in ischemic rats. The cardioprotective activity of guggulsterone and of both the isomers were compared with that of gemfibrozil at the same doses. Guggulsterone and both the isomers at tested concentrations (5-20mM) inhibited oxidative degradation of lipids in human low-density lipoprotein and rat liver microsomes induced by metal ionsin vitro. The drug counteracted against the generation of superoxide anions (O(2)) and hydroxyl radicals (OH(-)) in non-enzymic test systems. It is suggested that cardioprotective and antioxidant activities of synthetic guggulsterone and guggulsterone obtained from gum resinCommiphora mukul that contains isomers E & Z in the ratio of 46∶54w/w are the same.

Cis and trans-guggulsterone; Isoproterenol cardiac; antioxidant property; cardiprotective activity.