The effects of protein-rich extract from Rhizoma Gastrodiae against cerebral ischemia/reperfusion injury via regulating MAPK and PI3K/AKT signaling pathway

Xiaohua Duan; Nali Song; Kejian Ma; Ying Tong; Liping Yang

doi:10.1016/j.brainresbull.2023.110772

The effects of protein-rich extract from Rhizoma Gastrodiae against cerebral ischemia/reperfusion injury via regulating MAPK and PI3K/AKT signaling pathway

Brain Res Bull. 2023 Oct 15:203:110772. doi: 10.1016/j.brainresbull.2023.110772. Epub 2023 Oct 2.

Authors

Xiaohua Duan¹, Nali Song², Kejian Ma², Ying Tong¹, Liping Yang³

Affiliations

¹ Yunnan Key Laboratory of Dai and Yi Medicines, Yunnan University of Chinese Medicine, Kunming, Yunnan 650500, China.
² Yunnan Institute of Traditional Chinese Medicine, Kunming, Yunnan 650500, China.
³ Yunnan Key Laboratory of Dai and Yi Medicines, Yunnan University of Chinese Medicine, Kunming, Yunnan 650500, China. Electronic address: ynylp81@qq.com.

PMID: 37793596
DOI: 10.1016/j.brainresbull.2023.110772

Abstract

Background: Rhizoma Gastrodiae is a highly valuable traditional Chinese medicine and functional health food that has been used in China to treat neurological disorders for thousands of years. Rhizoma Gastrodiae contains various of biological activities, such as antioxidative, neuroprotective, learning improvement, anxiolytic, and antidepressant effects. However, no studies have been conducted to explore the effects of the protein components in Rhizoma Gastrodiae (GEPS) and its potential protective effects against ischemic stroke.Our main goal was to investigate the effects of GEPS on ischemia/reperfusion (I/R) injury and its possible mechanisms.

Methods: A middle cerebral artery occlusion (MCAO) induced focal cerebral ischemia mouse model and an oxygen-glucose deprivation (OGD/R) injury model in HT22 cells were established. A neurobehavioral test was performed 24 h after MCAO, and brain infarction was measured. A Morris water maze experiment was conducted on Day 14 after reperfusion in mice. Hematoxylin and eosin (HE) and TUNEL staining were performed to assess apoptotic neuronal death. Immunohistochemical analysis was used to detect BDNF and GAP43 expression. The content of SOD, MDA, GSH-PX and ROS were detected. The protein expression was analyzed using Western blotting. Cell viability was determined by MTT assay. Cell apoptosis was examined by flow cytometry.

Results: GEPS reduced apoptosis, decreased cerebral infarction, improved neurological defects, and ameliorated oxidative stress in the ischemic penumbra. In addition, GEPS increased the expression of BDNF and GA43 in the penumbra. Mechanistically, GEPS counteracted MCAO-induced PI3K/AKT inhibition and activation of MAPK signaling pathways.

Conclusion: GEPS has a clear neuroprotective effect on I/R injury, and its mechanism may be linked to the PI3K/AKT and MAPK signaling pathways.

Keywords: Antiapoptosis; Ischemic stroke; MAPK pathway; PI3K/AKT pathway; Protein from Rhizoma Gastrodiae.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Apoptosis
Brain Ischemia* / drug therapy
Brain Ischemia* / metabolism
Brain-Derived Neurotrophic Factor / metabolism
Infarction, Middle Cerebral Artery / drug therapy
Infarction, Middle Cerebral Artery / metabolism
Mice
Neuroprotective Agents* / pharmacology
Phosphatidylinositol 3-Kinases / metabolism
Proto-Oncogene Proteins c-akt / metabolism
Rats
Rats, Sprague-Dawley
Reperfusion Injury* / drug therapy
Reperfusion Injury* / metabolism
Signal Transduction

Substances

Proto-Oncogene Proteins c-akt
Phosphatidylinositol 3-Kinases
Brain-Derived Neurotrophic Factor
Neuroprotective Agents