Puerarin-V Improve Mitochondrial Respiration and Cardiac Function in a Rat Model of Diabetic Cardiomyopathy via Inhibiting Pyroptosis Pathway through P2X7 Receptors

Abstract

There is a new form of puerarin, puerarin-V, that has recently been developed, and it is unclear whether puerarin-V has a cardioprotective effect on diabetic cardiomyopathy (DCM). Here, we determined whether puerarin-V had any beneficial influence on the pathophysiology of DCM and explored its possible mechanisms. By injecting 30 mg/kg of STZ intraperitoneally, diabetes was induced in rats. After a week of stability, the rats were injected subcutaneously with ISO (5 mg/kg). We randomly assigned the rats to eight groups: (1) control; (2) model; (3) metformin; (4–6) puerarin-V at different doses; (7) puerarin (API); (8) puerarin injection. DCM rats were found to have severe cardiac insufficiency (arrythmia, decreased LVdP/dt, and increased E/A ratio). In addition, cardiac injury biomarkers (cTn-T, NT-proBNP, AST, LDH, and CK-MB), inflammatory cytokines (IL-1β, IL-18, IL-6, and TNF-α), and oxidative damage markers (MDA, SOD and GSH) were markedly increased. Treatment with puerarin-V positively adjusts these parameters mentioned above by improving cardiac function and mitochondrial respiration, suppressing myocardial inflammation, and maintaining the structural integrity of the cardiac muscle. Moreover, treatment with puerarin-V inhibits the P2X7 receptor-mediated pyroptosis pathway that was upregulated in diabetic hearts. Given these results, the current study lends credence to the idea that puerarin-V can reduce myocardial damage in DCM rats. Furthermore, it was found that the effect of puerarin-V in diabetic cardiomyopathy is better than the API, the puerarin injection, and metformin. Collectively, our research provides a new therapeutic option for the treatment of DCM in clinic.

Investigation of Immunohistochemical Localization of Oxytocin Receptor in Diabetic and Non-Diabetic Mouse Heart

“…Contrary to this study, Cai et al (1989) stated that myocardia layer was thinner in diabetic male rat heart (28). Cai et al (1989) and Sun et al (1993) expressed that there was damage to myofibrils in the heart muscle cell (28,29). Çetin et al (2013) mentioned that pycnotic nuclei and eosinophilic cytoplasm were observed in myocyte of heart in the experimental diabetic group (30).…”

Gasdermin D-Mediated Pyroptosis in Diabetic Cardiomyopathy: Molecular Mechanisms and Pharmacological Implications

“…Specifically, the dose of 25 µL/mL of DHI exhibited more significant suppression of cell pyroptosis compared to a normal dosage of NSA [118]. Puerarin V is a newly identified form of puerarin that has been shown to ameliorate myocardial injury in DCM rats by regulating NLRP3/caspase-1/GSDMD-dependent pyroptosis, and it was further reported that puerarin-V exhibits a greater effect than puerarin, puerarin injections, or metformin in DCM [125]. Gypenosides, which are the main components of Gynostemma pentaphyllum, can inhibit ROS-induced activation of the NLRP3 inflammasome caused by cytochrome c, improve myocardial cell injury in H9c2 cells, and inhibit the development of DCM in vivo [126].…”

Targeting the programmed cell death (PCD) signaling mechanism with natural substances for the treatment of diabetic cardiomyopathy (DCM)

“…A new crystal form of puerarin, puerarin‐V, has been developed. Sun et al (2022) reported that puerarin‐V could regulate lipid metabolism in DCM rats, inhibit myocardial inflammation and fibrosis, improve antioxidant levels, and enhance cardiac function and mitochondrial respiratory function. Its possible mechanism involves inhibiting the expression of the P2X7 receptor, blocking the NLRP3‐Caspase‐1‐GSDMD pathway, thereby reducing pyroptosis and myocardial injury.…”