Celastrol attenuates streptozotocin-induced diabetic cardiomyopathy in mice by inhibiting the ACE / Ang II / AGTR1 signaling pathway

Abstract

Background Heart failure is closely correlated with diabetic cardiomyopathy (DCM) and can lead to mortality. Celastrol has long been utilized for the treatment of immune and inflammatory disorders. However, whether celastrol would exert protective effects on DCM has not been determined. This work aimed to explore the protective actions of celastrol on DCM and unravel the underlying mechanisms involved. Methods A DCM model was constructed in mice by intraperitoneal administration of streptozotocin. ELISA and echocardiography were performed to examine myocardial injury markers and cardiac function, respectively. Morphological changes and fibrosis were assessed using H&E staining and Masson’s staining. Inflammatory cytokines and fibrotic markers were detected by ELISA and RT-PCR. Endothelial nitric oxide synthase, apoptosis, and reactive oxygen species were detected by microscopic staining. Network pharmacology approaches, molecular docking analysis, ELISA, and Western blot were used for mechanism studies. Results Celastrol alleviated diabetes-induced cardiac injury and remodeling. Celastrol also suppressed diabetes-induced production of inflammatory cytokines and reactive oxygen species, as well as cardiomyocyte apoptosis. The cardioprotective effects of celastrol were associated with its inhibition on the angiotensin-converting enzyme / angiotensin II / angiotensin II receptor type 1 signaling pathway. Conclusion Celastrol exhibits significant potential as an effective cardioprotective drug for DCM treatment. The underlying mechanisms can be attributed to the blockage of celastrol on the angiotensin-converting enzyme signaling pathway.

Diabetes cardiomyopathy: targeted regulation of mitochondrial dysfunction and therapeutic potential of plant secondary metabolites

“…In another study, celastrol can also alleviate diabetes-induced cardiac damage, inhibit mitochondrial ROS production, and suppress the release of inflammatory factors. The research results indicate that celastrol shows great potential as an effective cardiac protective drug for treating DCM ( Zhao et al, 2023 ).…”