AMMANNIA BACCIFERA CONFERS CARDIOPROTECTION AGAINST ISOPROTERENOL-INDUCED TOXICITY VIA NRF2/HO-1 PATHWAY ACTIVATION

Abstract

Myocardial infarction remains a serious global health issue; thus, innovative therapeutic strategies are warranted. This study assessed whether isoproterenol-induced cardiac damage in Wistar rats was mitigated by ethanolic extract of Ammannia baccifera (EAB). In vitro and in vivo studies were conducted to evaluate the cardioprotective properties of EAB, and LC-MS was used to identify its bioactive constituents. Experimental rats were used to evaluate the effects of EAB (50 and 100 mg/kg) on cardiac biomarkers, lipid profiles, oxidative stress indicators, inflammatory cytokines, the Nrf2/Keap1/HO-1 pathway, and cardiac histology of the heart. LC-MS analysis revealed the presence of bioactive phytochemicals, including phenolic acids, flavonoids, coumarins, terpenoids, and sesquiterpenoids. (-)-Epigallocatechin gallate, curcumin, oxyresveratrol, and eugenol sulfate, known antioxidants that activate the Nrf2/HO-1 pathway, were identified. EAB markedly decreased the levels of cardiac biomarkers, such as cardiac troponin T, lactate dehydrogenase, and creatine kinase-MB. EAB also reduced malondialdehyde levels and increased antioxidant enzyme activity in the heart. EAB increased the levels of the anti-inflammatory interleukin-10 and decreased the levels of inflammatory mediators TNF-α, IL-1β, IL-6, NF-κB, and C-reactive protein. Gene expression analysis revealed that EAB restored redox homeostasis by activating the Nrf2/HO-1 antioxidant axis and suppressing Keap1 expression in a dose-dependent manner. The preservation of cardiac architecture in the EAB-treated groups was confirmed by histopathological investigation. By reducing oxidative stress, inflammation, reactivating Nrf2 signalling, and minimizing myocardial damage in ISO-induced MI in Wistar rats, these results support the development of EAB as a natural cardioprotective agent and provide a rationale for additional research.