Cardioprotective function of mixed spices against myocardial infarction injury: In-vivo and In-silico study

Myocardial infarction is the permanent necrosis of heart tissue caused by an artery obstruction. It causes an inadequate delivery of oxygen and nutrients, resulting in muscle injury in the afflicted areas. Here, water extract of mixed spices-onion, garlic, ginger, red chili, turmeric, cumin seed, coriander, cardamom, black pepper, cloves, fenugreek, nigella, cinnamon, and carom seed-was prepared to evaluate cardioprotective function in albino rats. To systematically investigate cardioprotective efficacy, isoproterenol was injected into albino rats to induce myocardial injury. The prepared extract was administrated orally to rats daily for 28 days (200 mg/kg body weight) before infusion of isoproterenol (100 mg/kg body weight) on 29th and 30th days. The induced cardiac injury was significantly ameliorated in rats based on cardiac hypertrophy, histopathology, and Caspase-3 mRNA expression analysis by qRT-PCR. The Indian Medicinal Plants, Phytochemistry And Therapeutics (IMPPAT) chemical database of 820 natural compounds from the mixed spices was then screened against CASP-3 protein using cheminformatics tools, where thymohydroquinone, 4-isopropylbenzoic acid, and 1-naphthylacetic acid were found to be the best interacting ligands, with binding energy scores of -6.112 kcal/mol, -6.206 kcal/mol, and -6.112 kcal/mol, respectively. Notably, thymohydroquinone exhibited the lowest predicted cytotoxicity. Furthermore, molecular dynamic simulation was used to validate the binding stability of the thymohydroquinone with CASP-3 protein compared to CID-6167 (control). Thus, this study explored that mixed spices have cardioprotective effects in rats and identified thymohydroquinone as a natural lead compound against CASP-3, which may pave the way for the development of pharmacotherapy for myocardial damage.