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.

Abstract

To examine the protective effect of ginsenoside Rb1 (Rb1), the main component of Renshen (), 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). 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 insulin tolerance 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. 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. 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.