BERGAPTEN FROM LEUCAS URTICIFOLIA MITIGATES ISOPROTERENOL-INDUCED CARDIOTOXICITY THROUGH NRF2/HO-1 SIGNALLING PATHWAY
DOI:
https://doi.org/10.22159/ajpcr.2026v19i3.57402Keywords:
Isoproterenol, Leucas urticifolia, Gas chromatography-mass spectrometry, Cardiac markersAbstract
Objective :.This study evaluated whether an ethanolic extract of Leucas urticifolia(ELU) attenuates isoproterenol-induced cardiac damage in Wistar rats.
Method: The cardioprotective potential of ELU was assessed using in vitro and in vivo experiments, and its bioactive component bergapten was identified using GC-MS and quantified by RPHPLC.The safety profile and effects of ELU (50 and 100 mg/kg) on cardiac biomarkers, lipid profiles, oxidative stress markers, inflammatory cytokines, Nrf2/Keap1/HO-1 pathway, and cardiac histopathology were evaluated in experimental rats.
Results: ELU showed significant tissue antioxidant activity, no substantial cytotoxicity in H9C2 cells (IC₅₀: 82.04 µg/mL), and was safe in acute oral toxicity studies up to 2000 mg/kg in rats. ELU significantly reduced the levels of cardiac biomarkers, including creatine kinase-MB, lactate dehydrogenase, and cardiac troponin T. ELU also enhanced myocardial antioxidant enzyme activity and decreased malondialdehyde levels.ELU downregulated the inflammatory mediators TNF-α, IL-1β, IL-6, NF-κB, and C-reactive protein, while upregulating anti-inflammatory interleukin-10.Gene expression and western blot analysis showed that ELU restored redox homeostasis by activating the Nrf2/HO-1 antioxidant axis and suppressing Keap1 expression in a dose-dependent manner.Histopathological analysis confirmed cardiac architecture preservation in the ELU-treated groups.
Conclusion: ELU exerts cardioprotective effects by attenuating oxidative stress, suppressing inflammation, reactivating Nrf2 signalling, and minimizing myocardial injury in ISO-induced MI in Wistar rats, supporting its development as a natural cardioprotective agent and providing a rationale for further investigations.
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