Mechanism of Tibetan Medicine Sanwei Doukoutang to Improve Cognitive Dysfunction in 5×FAD Mice Based on Wnt/β-catenin Signaling Pathway
10.13422/j.cnki.syfjx.20251736
- VernacularTitle:基于Wnt/β-catenin信号通路探讨藏药三味豆蔻汤改善5×FAD小鼠认知功能障碍的作用机制
- Author:
Shuran LI
1
;
Yaxin WANG
1
;
Jing SUN
1
;
Lei BAO
1
;
Zihan GENG
1
;
Dan XIE
1
;
Ronghua ZHAO
1
;
Yanyan BAO
1
;
Qiyue SUN
1
;
Jingsheng ZHANG
1
;
Xinwei WANG
1
;
Xinying LI
1
;
Xihe CUI
1
;
Xiaowei YANG
1
;
LIUXIAN
1
;
Mengyao CUI
1
;
Qingshan LIU
2
;
Shanshan GUO
1
Author Information
1. Institute of Chinese Materia Medica， China Academy of Chinese Medical Sciences， Beijing 100700，China
2. School of Pharmacy， Minzu University of China， Beijing 100081，China
- Publication Type:Journal Article
- Keywords:
Sanwei Doukoutang;
Tibetan medicine;
brain derived neurotrophic factor（BDNF）;
synaptic plasticity;
cognitive dysfunction
- From:
Chinese Journal of Experimental Traditional Medical Formulae
2025;31(21):54-60
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo explore the effects of the Tibetan medicine Sanwei Doukoutang （SWDK） on cognitive dysfunction in mice suffering from Alzheimer's disease （AD） and its related mechanism. MethodsFifty SPF 5 × FAD mice were randomly divided into model group， total ginsenoside group（0.04 g·kg-1）， high-， medium-， and low-dose groups of SWDK （32.60， 16.30， 8.15 g·kg-1）， with 10 mice in each group， and ten wild-type mice of the same age were used as the normal group， male and female in 1∶1. Gavage administration was performed once daily for 8 weeks. The Morris water maze test and contextual fear memory experiment were used to observe learning and memory function. Hematoxylin-eosin （HE） staining was utilized to observe the changes in the pathomorphology of brain tissue in mice. The levels of synaptophysin （SYP） and postsynaptic dense substance 95 （PSD95） in mice serum were detected by enzyme-linked immunosorbent assay （ELISA）. The positive expression of brain-derived neurotrophic factor（BDNF） in the dentate gyrus （DG） region of mouse brain tissue was observed by immunohistochemistry （IHC）. The protein levels of BDNF， Wnt family member 3A（Wnt3a）， and β-catenin were detected in the hippocampus of mice by Western blot. ResultsCompared with the normal group of mice， the model group of mice had significantly more complex swimming routes and lower swimming speed （P<0.01）， significantly lower percentage of time spent in the target quadrant （P<0.01）， and a significantly lower percentage of freezing time （P<0.05）. The number of neurons in the hippocampal region of mice was obviously reduced and unevenly arranged. The levels of SYP and PSD95（P<0.01） in the serum of mice were reduced， and the positive expression of BDNF in the DG region of the brain tissue of mice was reduced. The levels of hippocampal BDNF， Wnt3a， and β-catenin proteins in the hippocampus of mice were obviously reduced （P<0.05， P<0.01）. Compared with the model group， the mice in the SWDK group and the total ginsenoside group had significantly shorter swimming routes， the high- and medium- dose SWDK groups significantly higher swimming speeds （P<0.01）， significantly higher percentage of time spent in the target quadrant （P<0.01）， obviously higher percentage of Freezing time （P<0.05）， and obviously more neurons in the hippocampal region of the mice with tighter arrangement. The mice had elevated levels of serum SYP （P<0.05， P<0.01）， PSD95 （P<0.01）， increased BDNF-positive cells in the DG region of brain tissue， and obviously elevated levels of BDNF， Wnt3a， and β-catenin proteins in the hippocampus of mice （P<0.05， P<0.01）. ConclusionSWDK can significantly improve the cognitive dysfunction of AD mice， and its mechanism may be related to regulating the Wnt/β-catenin signaling pathway， which promotes BDNF expression and thereby enhances synaptic plasticity， allowing neuronal signaling to be restored.
