Ginsenoside Rb1 alleviates chronic intermittent hypoxia-induced diabetic cardiomyopathy in db/db mice by regulating the adenosine monophosphate-activated protein kinase/Nrf2/heme oxygenase-1 signaling pathway

OBJECTIVE: To examine the protective effect of ginsenoside Rb1 (Rb1), the main component of Renshen (Radix Ginseng), on cardiomyopathy in db/db mice exposed to chronic intermittent hypoxia (CIH) and explore the potential underlying mechanism of Rb1 in treating diabetic cardiomyopathy (DCM). METHODS: The db/db mice were randomly separated into five groups: normal control group, model group, Rb1 20 mg/kg group, Rb1 40 mg/kg group, and glucagon-like peptide-1 (GLP-1) group. Mice were exposed to air -condition or CIH for 8 weeks, and Rb1 and GLP-1 were administrated before CIH exposure every day. Oral glucose tolerance test (OGTT), intraperitoneal insulintolerance test (IPITT), total cholesterol (TC), triglyceride (TG), and high-density lipoprotein cholesterol (HDL-C) were detected to evaluate glycolipid metabolism. The level of insulin was detected by a mouse enzyme-linked immunosorbent assay (ELISA). Cardiac function was detected by echocardiography, and myocardial pathology was observed by hematoxylin-eosin and Masson staining. The expression of collagen I and collagen III was detected by immunohistochemistry. Adenosine monophosphate-activated protein kinase (AMPK)/Nrf2/heme oxygenase-1 (HO-1) signaling pathway was detected by Western blot and immunofluorescence. RESULTS: Rb1 treatment could improve glucose tolerance and the level of cardiac function indexes, and inhibit the level of oxidative stress indexes and the expression of collagen I and collagen III. Moreover, Rb1 treatment enhanced AMPK phosphorylation and increased Nrf2 and HO-1 expression. CONCLUSION: Rb1 treatment alleviated CIH-induced diabetic cardiomyopathy and glycolipid metabolism disorders in db/db mice by inhibiting oxidative stress and regulating the AMPK/Nrf2/HO-1 signaling pathway.(c) 2023 JTCM. All rights reserved.