Effect of Wenpi tongluo kaiqiao formula against neuronal necroptosis in mice with Alzheimer’s disease and its mechanism
- VernacularTitle:温脾通络开窍方抑制AD小鼠神经元坏死性凋亡的作用及机制
- Author:
Xiaomin ZHU
1
;
Wei CHEN
2
;
Yulan FU
1
;
Guifeng ZHUO
1
;
Yingrui HUANG
1
;
Ying ZHANG
1
;
Lin WU
1
Author Information
1. The First Clinical College of Medicine，Guangxi University of Chinese Medicine，Nanning 530022，China
2. Ward 1，Department of Encephalopathy，the First Affiliated Hospital of Guangxi University of Chinese Medicine，Nanning 530022，China
- Publication Type:Journal Article
- Keywords:
Wenpi tongluo kaiqiao formula;
Alzheimer’s disease;
ZBP1/MLKL signaling pathway;
necroptosis
- From:
China Pharmacy
2025;36(9):1046-1051
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE To investigate the effects and mechanism of Wenpi tongluo kaiqiao formula （WPTL） against neuronal necroptosis in Alzheimer’s disease （AD） mice based on the Z-DNA binding protein 1 （ZBP1）/mixed lineage kinase domain-like protein （MLKL） signaling pathway. METHODS Forty APP/PS1 transgenic AD mice were randomly divided into model group， WPTL low-dose （WPTL-L） group （10.4 g/kg， calculated by the raw medicine）， WPTL high-dose （WPTL-H） group （20.8 g/kg， calculated by the raw medicine） and donepezil hydrochloride group （3 mg/kg）， with 10 mice in each group； another 10 C57BL/6J mice were selected as normal control group. Intragastric administration， once a day， for 30 consecutive days. Twenty-four hours after the last administration， Morris water maze test was performed to evaluate learning and memory abilities； the pathological morphology of hippocampal tissues was observed； the serum levels of tumor necrosis factor-α （TNF-α） and interleukin-4 （IL-4） were determined； the expressions of amyloid precursor protein （APP）， Tau protein， and ZBP1/MLKL signaling pathway-related proteins in hippocampal tissues were detected； the positive expression of phosphorylated receptor-interacting protein kinase 3 （p-RIPK3） in the neurons of hippocampal tissues and mRNA expression of ZBP1 were measured in hippocampal tissues. RESULTS Compared with normal control group， the escape latency of mice in model group was prolonged significantly on day 3 to 5 （P＜0.05）， the times of crossing platform reduced significantly （P＜0.05）， and obvious pathological changes were observed in the hippocampal tissue. The level of TNF- α， the expressions of APP， p-Tau and ZBP1， the phosphorylation levels of RIPK1， RIPK3 and MLKL， the fluorescence intensity of p-RIPK3 as well as the mRNA expression of ZBP1 were significantly increased （P＜0.05）， while the serum level of IL-4 was decreased significantly （P＜0.05）. Compared with model group， above indexes were reversed significantly in administration groups （P＜0.05）， and pathological damage of hippocampal tissue was alleviated. CONCLUSIONS WPTL can inhibit the ZBP1/MLKL signaling pathway， reduce neuronal necroptosis in AD mice， and inhibit inflammatory responses， thereby improving learning and spatial memory abilities in AD mice.
