Neuroprotective and mechanistic study of GJ-4 on okadaic acid-induced memory impairment in mice
10.16438/j.0513-4870.2023-1201
- VernacularTitle:GJ-4对冈田酸诱发小鼠学习记忆障碍的神经保护作用和机制研究
- Author:
Yang YANG
;
Chan-juan SHENG
;
Cai-xia ZANG
;
Jun-mei SHANG
;
Xiu-qi BAO
;
Dan ZHANG
- Publication Type:Research Article
- Keywords:
Alzheimer disease;
GJ-4;
Tau protein;
okadaic acid;
neuroinflammation
- From:
Acta Pharmaceutica Sinica
2023;58(12):3628-3636
- CountryChina
- Language:Chinese
-
Abstract:
GJ-4 is crocin enrichments extracted from Gardenia jasminoides J. Ellis, and our previous studies have shown that GJ-4 significantly improved learning and memory impairment induced by Aβ in mice. Herein, a memory deficit model was developed by injecting okadaic acid (OA) into the lateral ventricle of mice, and the neuroprotection and underlying mechanism of GJ-4 on neuronal injury caused by Tau hyperphosphorylation were investigated. The Animal Care & Welfare Committee, Institute of Materia Medica, CAMS & PUMC has approved all procedures (No.00000318). GJ-4 at different doses was intragastric administration to mice for 16 days. Step-down test and Morris water maze test showed that GJ-4 could significantly improve OA-induced memory impairment in mice, and reduced the loss of Nissl bodies in the hippocampus of mice. GJ-4 could also decrease the phosphorylation level of Tau protein at Ser396, Thr231 and Ser404 via increasing protein phosphatase 2A (PP2A) activity and inhibiting glycogen synthase kinase-3β (GSK-3β) activity. Besides, further researches indicated that GJ-4 could inhibit the level of oxidative stress in the brain of OA mice, reduce neuronal apoptosis and inhibit the neuroinflammation mediated by activation of astrocytes in the hippocampus of mice, and eventually achieve its effects in improving learning and memory impairment in mice. According to these findings, we anticipated that GJ-4 might be a potential therapeutic drug for Alzheimer's disease.
