Trigonelline isolated from fenugreek seed protects against isoproterenol-induced myocardial injury through down-regulation of Hsp27 and αB-crystallin

Abstract

ObjectiveProtective effects of trigonelline (TRG) isolated from fenugreek seed were evaluated in isoproterenol (ISO)-induced myocardial dysfunctions in adult rats and a proteomic approach was applied to understand its mechanism of action. MethodsIn a preliminary experiment, effects of TRG at 20, 40, and 80 mg/kg for 20 d were studied in ISO-induced (100 mg/kg) adult rats. As 40 mg/kg was found the most effective concentration, in the final experiment, effects of 40 mg/kg of the test drug were investigated using different indices including cardiac marker enzymes, lipid peroxidation, antioxidants, cardiac histology, and electrocardiogram. Proteomic analyses were also done in cardiac myocytes. ResultsISO administration increased serum levels of cardiac markers (creatine kinase-MB, glutamate pyruvate transaminase, and lactate dehydrogenase) and exhibited a positive reaction in the TROP-T test. It also increased the cardiac lipid peroxidation and decreased the cellular antioxidants. Proteomic data revealed nine protein spots, seven were down-regulated and two up-regulated. The overexpressions of two small stress proteins, heat shock protein (Hsp)27 and αB crystallin were confirmed by Western blot analysis. All these alterations were restored to nearly normal values in 40 mg/kg of TRG-pretreated animals, suggesting its cardioprotective effects, which were further confirmed by histologic examinations and triphenyl tetrazolium chloride staining assay. ConclusionFor the first time, our study revealed the down-regulation of Hsp27 and αB-crystallin and (CaMKII delta) isoform by TRG. As the test compound prevented the ISO-induced myocardial injury, its therapeutic use may further be explored.