Ginsenoside Rb1 Ameliorates Diabetic Arterial Stiffening via AMPK Pathway

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.

Estimated pulse wave velocity is associated with all-cause mortality and cardiovascular mortality among adults with diabetes

“…The molecular mechanism of arterial stiffness caused by diabetes has also been widely investigated. Zhang et al found that diabetes can activate MMP2, MMP9, and TGFβ1/Smad2/3 pathways, leading to elevated blood pressure and arterial stiffness (46). Glucose fluctuations often occurs in patients with diabetes after meals.…”

Fermentation, Identification, and Antioxidant Activity of Saponins Produced by a Wild Ginseng Endophytic Fungus Umbelopsis dimorpha Strain NSJG

“…It may inhibit the increase in MDA content and the decrease in glutathione (GSH) levels in rat retinas and significantly increase the Nuclear Factor erythroid 2-Related Factor 2 (Nrf2) level and the expression of glutamate cysteine ligase catalytic subunit (GCLC) and glutamate cysteine ligase modifier subunit (GCLM) in rat retinal cell nuclei [57]. Ginsenoside Rb1 could also improve arteriosclerosis and prevent diabetic vasculopathy by reducing the inhibition of diabetes-induced Adenosine 5 ′ -monophosphate (AMP)-activated protein kinase (AMPK), regulating nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, alleviating oxidative stress, and inhibiting the TGFβ1/Smad2/3 pathway [58]. The mechanism of action of the fermentation extract in this experiment remains to be further explored.…”

Saponin monomers: Potential candidates for the treatment of type 2 diabetes mellitus and its complications

“…In summary, Rb1 can lower blood glucose levels by modulating gut microbes, regulating lipid metabolism, and increasing insulin sensitivity. Moreover, it showed great efficacy in alleviating the occurrence of T2DM‐related complications, including diabetic cardiomyopathy (Qin et al, 2019; C. Zhang et al, 2022), diabetic atherosclerosis (Z. C. Wang, Niu, et al, 2022; X. Zhang et al, 2021), high glucose‐induced kidney damage or DN (J. Y. He et al, 2022), and high glucose‐induced cognitive impairment (R. Yang et al, 2020).…”