Forsythiaside B inhibits cerebral ischemia/reperfusion-induced oxidative stress injury in mice via the AMPK/DAF-16/FOXO3 pathway.
10.12122/j.issn.1673-4254.2023.02.06
- Author:
Xing CHEN
1
;
Kai Fang WANG
1
;
De Hai CHU
1
;
Yu ZHU
1
;
Wen Bing ZHANG
1
;
Hui Ping CAO
1
;
Wen Yu XIE
2
;
Chuan Hao LU
2
;
Xia LI
2
Author Information
1. Department of Critical Care Medicine, Hanbin District Third People's Hospital, Ankang 725000, China.
2. Department of Neurosurgery, Xijing Hospital, Air Force Medical University, Xi'an 710032, China.
- Publication Type:Journal Article
- Keywords:
AMPK/DAF-16/FOXO3 pathway;
cerebral ischemia/reperfusion;
forsythiaside B;
oxidative stress
- MeSH:
Mice;
Animals;
AMP-Activated Protein Kinases/metabolism*;
Antioxidants/metabolism*;
Reactive Oxygen Species;
Mice, Inbred C57BL;
Brain Ischemia;
Oxidative Stress;
Infarction, Middle Cerebral Artery;
Reperfusion Injury;
Reperfusion;
Superoxide Dismutase/metabolism*
- From:
Journal of Southern Medical University
2023;43(2):199-205
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE:To study the protective effect of forsythiaside B (FB) against cerebral oxidative stress injury induced by cerebral ischemia/reperfusion (I/R) in mice and explore the underlying mechanism.
METHODS:Ninety C57BL/6 mice were randomized into sham-operated group, middle cerebral artery occlusion (MCAO) model group, and low-, medium and highdose (10, 20, and 40 mg/kg, respectively) FB groups. The expression levels of MDA, ROS, PCO, 8-OHdG, SOD, GSTα4, CAT and GPx in the brain tissue of the mice were detected using commercial kits, and those of AMPK, P-AMPK, DAF-16, FOXO3 and P-FOXO3 were detected with Western blotting. Compound C (CC), an AMPK inhibitor, was used to verify the role of the AMPK pathway in mediating the therapeutic effect of FB. In another 36 C57BL/6 mice randomized into 4 sham-operated group, MCAO model group, FB (40 mg/kg) treatment group, FB+CC (10 mg/kg) treatment group, TTC staining was used to examine the volume of cerebral infarcts, and the levels of ROS and SOD in the brain were detected; the changes in the protein expressions of AMPK, P-AMPK, DAF-16, FOXO3 and P-FOXO3 in the brain tissue were detected using Western blotting.
RESULTS:In mice with cerebral IR injury, treatment with FB significantly reduced the levels of ROS, MDA, PCO and 8-OHdG, increased the activities of antioxidant enzymes SOD, GSTα4, CAT and GPx, and enhanced phosphorylation of AMPK and FOXO3 and DAF-16 protein expression in the brain tissue (P < 0.01). Compared with FB treatment alone, the combined treatment with FB and CC significantly reduced phosphorylation of AMPK and FOXO3, lowered expression of DAF-16 and SOD activity, and increased cerebral infarction volume and ROS level in the brain tissue of the mice (P < 0.01).
CONCLUSION:FB inhibits oxidative stress injury caused by cerebral I/R in mice possibly by enhancing AMPK phosphorylation, promoting the downstream DAF-16 protein expression and FOXO3 phosphorylation, increasing the expression of antioxidant enzymes, and reducing ROS level in the brain tissue.
