Mechanisms of Anemarrhenae Rhizoma Water Extract in Ameliorating Neuroinflammation in Alzheimer's Disease Model Rats via SIRT1/HMGB1/NF-κB Signaling Pathway
10.13422/j.cnki.syfjx.20251804
- VernacularTitle:基于SIRT1/HMGB1/NF-κB信号通路研究知母水提物改善阿尔茨海默病模型大鼠神经炎症作用机制
- Author:
Fei WU
1
;
Yuexia LI
1
;
Qi HUANG
2
;
Tianshi LI
3
;
Chuanshan JIN
2
;
Kai MA
3
Author Information
1. Bozhou Institute， Anhui Academy of Chinese Medicine， Bozhou 236800， China
2. Anhui University of Chinese Medicine， Hefei 230012， China
3. Bozhou Yonggang Decoction Pieces Factory Co. Ltd.， Bozhou 236800， China
- Publication Type:Journal Article
- Keywords:
Anemarrhenae Rhizoma;
Alzheimer's disease;
microglial polarization;
silent information regulator 1 （SIRT1）/high-mobility group box 1 （HMGB1）/nuclear factor-κB （NF-κB） signaling pathway
- From:
Chinese Journal of Experimental Traditional Medical Formulae
2026;32(7):230-240
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo investigate the therapeutic effects of the Anemarrhenae Rhizoma water extract （AR） on Alzheimer's disease （AD） model rats and to explore its potential underlying mechanisms. MethodsMale rats were intraperitoneally injected with D-galactose （100 mg·kg-1） for 42 days， and on day 14， 1 μL of β-amyloid （Aβ25-35， 2 g·L-1） solution was injected into the hippocampus. Rats were randomly divided into a model group， low-dose AR （0.6 g·kg-1）， medium-dose AR （1.2 g·kg-1）， high-dose AR （2.4 g·kg-1）， and a positive control group （donepezil， 5 mg·kg-1）. Healthy rats receiving only a hippocampal injection of 1 μL of sterile saline served as the sham-operated group. From day 21， rats in the treatment groups were administered the corresponding drugs by gavage once daily for 21 consecutive days， while the blank control and model groups received an equal volume of saline. Learning and memory abilities were assessed using the Morris water maze. Brain tissue damage was observed by hematoxylin and eosin （HE） staining， and neuronal apoptosis was evaluated by terminal deoxynucleotidyl transferase dUTP nick-end labeling （TUNEL） staining. Levels of interleukin-1β （IL-1β）， tumor necrosis factor-α （TNF-α）， and interleukin-10 （IL-10） in brain tissues were measured by enzyme-linked immunosorbent assay （ELISA）. BV2 microglial cells were co-cultured with Aβ25-35 （40 μmol·L-1） for 2 h， and cell viability was determined by the CCK-8 assay to screen the optimal concentration of AR-containing serum （S-AR）. Cells were divided into blank control， Aβ25-35， S-AR， EX527 ［silent information regulator 1 （SIRT1） inhibitor］， and S-AR+EX527 groups. Immunofluorescence staining was used to detect the expression of CD16， CD206， and high-mobility group box 1 （HMGB1）. Western blot analysis was performed to measure the protein expression of CD16， inducible nitric oxide synthase （iNOS）， CD206， arginase （Arg）， and proteins related to the SIRT1/HMGB1/nuclear factor-κB （NF-κB） signaling pathway. ResultsIn vivo experiments showed that， compared with the sham-operated group， the model group exhibited reduced platform crossings and time spent in the target quadrant （P<0.01）， prolonged escape latency， increased hippocampal neuronal apoptosis （P<0.01）， and obvious hippocampal damage. The expression levels of IL-6， TNF-α， IL-10， CD16， and iNOS in brain tissues were significantly elevated （P<0.01）， while CD206 and Arg protein expression showed an increasing trend without statistical significance. Compared with the model group， all AR-treated groups significantly increased platform crossings and target quadrant time （P<0.05， P<0.01）， alleviated hippocampal damage， reduced escape latency and neuronal apoptosis， downregulated the expression of TNF-α， IL-6， CD16， and iNOS （P<0.05， P<0.01）， and upregulated the expression of IL-10， CD206 and Arg （P<0.05， P<0.01）. In vitro experiments demonstrated that， compared with the blank control group， the Aβ25-35 group showed increased fluorescence intensity of CD206， CD16， and HMGB1， as well as elevated protein expression of iNOS and CD16 （P<0.01）， while CD206 and Arg protein expression exhibited an increasing trend without statistical significance. After S-AR intervention， CD206 fluorescence intensity and the protein expression of Arg and CD206 were significantly increased （P<0.01）， whereas the fluorescence intensity of CD16 and HMGB1 and the protein expression of iNOS and CD16 were significantly decreased （P<0.01）. These effects were reversed by EX527 （P<0.05， P<0.01）. Furthermore， compared with the blank control group， the Aβ25-35 group showed significantly increased cytoplasmic HMGB1 expression and p-p65/p65 ratio （P<0.01）， along with significantly decreased SIRT1 and nuclear HMGB1 expression （P<0.01）. In contrast， the S-AR group exhibited opposite trends compared with the Aβ25-35 group， and the regulatory effects of S-AR on these proteins were reversed by EX527 （P<0.01）. ConclusionAR exerts neuroprotective effects in AD model rats by regulating microglial polarization and alleviating neuroinflammation， potentially through modulation of the SIRT1/HMGB1/NF-κB signaling pathway.
