Betulin protects against isoproterenol-induced myocardial injury by inhibiting NF-κB signaling and attenuating cardiac inflammation and oxidative stress in rats

Abstract

Objective: To investigate the cardioprotective potential of betulin in isoproterenol (ISO)-induced myocardial injury in rats. Methods: Wistar rats were divided into five groups (n=10): normal, ISO, nebivolol 5 mg/kg, and betulin (20 & 40 mg/kg). Nebivolol and betulin were administered orally for 29 days. ISO (85 mg/kg) was administered subcutaneously on day 27 and day 28 to induce myocardial injury. On day 29, blood was collected for determination of cardiac markers, and hemodynamic parameters were investigated. The levels of oxidative stress markers and the gene expressions of apoptotic markers and inflammatory mediators were evaluated. Moreover, 2,3,5-triphenyltetrazolium chloride staining and histopathological analysis were also performed. Results: Betulin reduced the size of myocardial infarction, decreased elevated levels of cardiac enzymes, and maintained hemodynamic functions. It also inhibited ISO-induced upregulation of Bax, caspase-3, NF-κB, and IL-6, enhanced endogenous antioxidant enzymes, and reduced lipid peroxidation. Additionally, pretreatment with betulin alleviated myocardial ischemic damage, as reflected by reduced myonecrosis, edema, and inflammatory changes. Conclusions: Betulin exhibits strong cardioprotective activity against ISO-induced myocardial injury by anti-inflammatory, anti-apoptotic, and antioxidant activities.

Keywords

NF-κB / Isoproterenol / Betulin / Myocardial injury / Oxidative stress / Inflammation / Apoptosis

Acknowledgments

The author would like to thank Anand Pharmacy College, Anand, Gujarat, India for providing the animal house facility and research facility for this study.

Conflict of interest statement

The authors declared no conflict of interest.

Funding

The authors received no extramural funding for the study.

Data availability statement

The data supporting the findings of this study are available from the corresponding authors upon request.

Authors’ contributions

HS and TG developed the project conceptualization, experimental design, and protocol preparation, and obtained ethical approval. HS conducted the experimental work, analyzed the data, prepared the draft manuscript, and revised manuscript. TG monitored and supervised the project, reviewed the draft manuscript, and provided research facilities and resources.

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