Si Junzitang Ameliorates Alzheimer's Disease by Regulating Keap1/Nrf2/HO-1 Signaling Pathway
10.13422/j.cnki.syfjx.20250916
- VernacularTitle:基于Keap1/Nrf2/HO-1信号通路探讨四君子汤改善阿尔茨海默病的作用机制
- Author:
Minyan SUN
1
;
Shaofeng WEI
1
;
Xiaomin WANG
2
;
Kehan GAO
2
;
Jianhao YANG
1
;
Ziran XIE
3
;
Yu ZHANG
3
;
Qin ZHENG
1
Author Information
1. Jiangxi Key Laboratory for Innovation and Improvement of Traditional Chinese Medicine（TCM）， Key Laboratory of Modern Chinese Medicine Preparation， Ministry of Education， Jiangxi University of Chinese Medicine， Nanchang 330004， China
2. College of TCM， Jiangxi University of Chinese Medicine， Nanchang 330004， China
3. Nanchang Medical College， Nanchang 330052， China
- Publication Type:Journal Article
- Keywords:
Si Junzitang;
Alzheimer's disease;
oxidative stress;
Kelch-like ECH-associated protein 1 （Keap1）/nuclear factor erythroid 2-related factor 2 （Nrf2）/heme oxygenase-1 （HO-1） signaling pathway
- From:
Chinese Journal of Experimental Traditional Medical Formulae
2026;32(17):23-37
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo explore the mechanisms through which Si Junzitang （SJZD） ameliorates Alzheimer's disease （AD） induced by scopolamine （SCOP） in mice and the PC12 cell model induced by H2O2 based on the Kelch-like ECH-associated protein 1 （Keap1）/nuclear factor erythroid 2-related factor 2 （Nrf2）/heme oxygenase-1 （HO-1） signaling pathway. MethodsIn the animal experiments， an AD model was established in mice by intraperitoneal injection of SCOP （3 mg·kg-1）. Morris water maze and open field tests （OFT） were conducted to assess learning and memory abilities. Hematoxylin-eosin （HE） staining and Nissl staining were performed to observe pathological changes in neurons. Immunofluorescence was used to detect amyloid β-protein1-42 （Aβ1-42） expression， and immunohistochemistry was employed to detect phosphorylated （p）-Tau expression. Transmission electron microscopy （TEM） was employed to observe ultrastructural changes in hippocampal neurons and synapses. Biochemical methods were used to measure the levels of acetylcholine （ACh）， acetylcholinesterase （AChE）， superoxide dismutase （SOD）， malondialdehyde （MDA）， catalase （CAT）， and lactate dehydrogenase （LDH）. Real-time PCR and Western blot were employed to measure the mRNA and protein levels of molecules in the Keap1/Nrf2/HO-1 pathway in the hippocampus. In the cell experiments， a PC12 cell model of oxidative damage model was established with H2O2. Cell count kit-8 （CCK-8） assays and flow cytometry were adopted to measure cell viability and apoptosis rates， and Western blot was employed to quantify the expression levels of proteins in the Keap1/Nrf2/HO-1 pathway. ResultsThe animal experiments showed that compared with the model group， the SJZD and donepezil groups showed shortened escape latency （P<0.01）， increased time in the target quadrant and platform crossings， and increased movement distance and duration in the central area of the open field （P<0.05， P<0.01）. HE and Nissl staining showed more organized neurons and increased Nissl bodies in the drug intervention groups （P<0.05， P<0.01）， and the Aβ1-42 and p-Tau expression levels were downregulated （P<0.05， P<0.01）. TEM revealed reduced ultrastructural damage in hippocampal neurons and synapses in the drug intervention groups. In addition， the drug intervention groups showed declined levels of MDA， LDH， and AChE （P<0.05， P<0.01）， elevated levels of SOD， CAT， and ACh （P<0.05， P<0.01）， reduced Keap1 expression and increased Nrf2， HO-1， and NQO1 expression in the hippocampus （P<0.05， P<0.01）. The cell experiments showed that compared with the model group， the SJZD-containing serum increased the cell viability （P<0.05， P<0.01）， and decreased total apoptosis rates （P<0.05， P<0.01）. The drug intervention groups showed upregulated protein levels of Nrf2 and HO-1 and downregulated protein level of Keap1 （P<0.05， P<0.01）. ConclusionSJZD demonstrates protective effects against SCOP-induced AD in mice and H2O2-induced damage in PC12 cells through antioxidant mechanisms mediated by the Keap1/Nrf2/HO-1 pathway.
