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Ginsenoside Rg1 attenuates diabetic vascular endothelial dysfunction by inhibiting the calpain-1/ROS/PKC-β axis.
- Source :
-
Life Sciences . Sep2023, Vol. 329, pN.PAG-N.PAG. 1p. - Publication Year :
- 2023
-
Abstract
- Vascular endothelial dysfunction (VED) is the onset event of cardiovascular complications in type 2 diabetes mellitus. Ginsenoside Rg1 (Rg1) can improve the cardiovascular system, but its mechanism in diabetic vascular endothelial dysfunction has received little attention. Male calpain-1-knockout and wild-type C57BL/6 J mice were intraperitoneally injected with streptozotocin and treated with Rg1 (10 and 20 mg/kg) for 8 weeks. Human aortic endothelial cells (HAECs) were incubated with high glucose (HG) and were pretreated with Rg1 (10, 20 μM), MDL-28170 (calpain-1 inhibitor), LY-333531 (PKC-β inhibitor), NAC (ROS inhibitor) and calpain-1 overexpression. Then, factors related to mitochondrial dysfunction, oxidative stress and VED were measured. The administration of Rg1 and calpain-1 knockout ameliorated diabetic mitochondrial dysfunction, oxidative stress and VED and inhibited the calpain-1/ROS/PKC-β axis. LY-333531 and NAC treatment restored destructive endothelium-dependent vasodilation in mice with diabetes, while pyrogallol (ROS agonist), PMA (PKC-β agonist) or L-NAME (eNOS inhibitor) treatment abrogated the protective effect of Rg1 against diabetic endothelial dysfunction. The administration of Rg1, MDL-28170, LY-333531 and NAC improved mitochondrial dysfunction, oxidative stress and VED, whereas the overexpression of calpain-1 amplified mitochondrial dysfunction, oxidative stress and VED and further upregulated the expression of PKC-β in HAECs exposed to HG. Overexpression of calpain-1 abrogated the protective effect of Rg1 against HG-induced oxidative stress and VED. These findings reveal that Rg1 can protect against VED by suppressing the calpain-1/ROS/PKC-β axis and alleviating the development of mitochondrial dysfunction and oxidative stress. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 00243205
- Volume :
- 329
- Database :
- Academic Search Index
- Journal :
- Life Sciences
- Publication Type :
- Academic Journal
- Accession number :
- 169832748
- Full Text :
- https://doi.org/10.1016/j.lfs.2023.121972