Abstract
Background and Purpose: Macrovascular complication of diabetes mellitus, characterized by increased aortic stiffness, is a major cause leading to many adverse clinical outcomes. It has been reported that ginsenoside Rb1 (Rb1) can improve glucose tolerance, enhance insulin activity, and restore the impaired endothelial functions in animal models. The aim of this study was to explore whether Rb1 could alleviate the pathophysiological process of arterial stiffening in diabetes and its potential mechanisms. Experimental Approach: Diabetes was induced in male C57BL/6 mice by administration of streptozotocin. These mice were randomly selected for treatment with Rb1 (10−60 mg/kg, i. p.) once daily for 8 weeks. Aortic stiffness was assessed using ultrasound and measurement of blood pressure and relaxant responses in the aortic rings. Mechanisms of Rb1 treatment were studied in MOVAS-1 VSMCs cultured in a high-glucose medium. Key Results: Rb1 improved DM-induced arterial stiffening and the impaired aortic compliance and endothelium-dependent vasodilation. Rb1 ameliorated DM-induced aortic remodeling characterized by collagen deposition and elastic fibers disorder. MMP2, MMP9, and TGFβ1/Smad2/3 pathways were involved in this process. In addition, Rb1-mediated improvement of arterial stiffness was partly achieved via inhibiting oxidative stress in DM mice, involving regulating NADPH oxidase. Finally, Rb1 could blunt the inhibition effects of DM on AMPK phosphorylation. Conclusion and Implications: Rb1 may represent a novel prevention strategy to alleviate collagen deposition and degradation to prevent diabetic macroangiopathy and diabetes-related complications.
Highlights
Diabetes mellitus (DM) is one of the costliest and most burdensome chronic diseases worldwide
Characteristics of the Mice at the End of Experiments. These groups showed no difference in BP, blood glucose, and body weight
We found that Rb1 could reduce the suppression of AMPK caused by hyperglycemia
Summary
Diabetes mellitus (DM) is one of the costliest and most burdensome chronic diseases worldwide It has become a pandemic health disaster, especially among the elderly. Increased aortic stiffness independently predicts future cardiovascular disease, especially in women (Laurent et al, 2012; Ben-Shlomo et al, 2014). It leads to many adverse clinical outcomes, including impaired coronary perfusion and subsequent cardiovascular mortality. Macrovascular complication of diabetes mellitus, characterized by increased aortic stiffness, is a major cause leading to many adverse clinical outcomes. Experimental Approach: Diabetes was induced in male C57BL/6 mice by administration of streptozotocin These mice were randomly selected for treatment with Rb1 Mechanisms of Rb1 treatment were studied in MOVAS-1 VSMCs cultured in a highglucose medium
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