Ginsenoside-Rb1 (Rb1), a major active component of ginseng, has many benefits for cardiovascular disease and diabetes mellitus (DM), but the effect and mechanism on diabetic cardiomyopathy are not clear. In the present study, we found that Rb1-feeding significantly improved cardiac dysfunction and abnormal cardiomyocytes calcium signaling caused by diabetes. This improved calcium signaling was because Rb1 reduced Ca leakage caused by overactivated ryanodine receptor 2 (RyR2) and increased Ca uptake by sarcoplasmic reticulum Ca-ATPase 2a (SERCA 2a). Furthermore, we found that Rb1 not only enhanced energy metabolism like metformin and eliminated O-GlcNAcylation of calcium handling proteins to regulate calcium signaling but also directly inhibited RyR2 activity to regulate calcium signaling. The present study indicated that as a health supplement or drug, Rb1 was a relatively effective auxiliary therapeutic substance for diabetic cardiomyopathy.
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