Ginsenoside Rg1 attenuates diabetic vascular endothelial dysfunction by inhibiting the calpain-1/ROS/PKC-ß axis.
Life Sci
; 329: 121972, 2023 Sep 15.
Article
in En
| MEDLINE
| ID: mdl-37482213
ABSTRACT
AIMS:
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. MAINMETHODS:
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-ß inhibitor), NAC (ROS inhibitor) and calpain-1 overexpression. Then, factors related to mitochondrial dysfunction, oxidative stress and VED were measured. KEYFINDINGS:
The administration of Rg1 and calpain-1 knockout ameliorated diabetic mitochondrial dysfunction, oxidative stress and VED and inhibited the calpain-1/ROS/PKC-ß axis. LY-333531 and NAC treatment restored destructive endothelium-dependent vasodilation in mice with diabetes, while pyrogallol (ROS agonist), PMA (PKC-ß 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-ß in HAECs exposed to HG. Overexpression of calpain-1 abrogated the protective effect of Rg1 against HG-induced oxidative stress and VED.SIGNIFICANCE:
These findings reveal that Rg1 can protect against VED by suppressing the calpain-1/ROS/PKC-ß axis and alleviating the development of mitochondrial dysfunction and oxidative stress.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Vascular Diseases
/
Diabetes Mellitus, Experimental
/
Diabetes Mellitus, Type 2
Limits:
Animals
/
Humans
/
Male
Language:
En
Journal:
Life Sci
Year:
2023
Document type:
Article
Affiliation country:
China