Danggui Shaoyaosan Inhibits Neuroinflammation in AD Rats by Regulating NLRP3/Caspase-1 Pathway
10.13422/j.cnki.syfjx.20211802
- VernacularTitle:当归芍药散通过调控NLRP3/Caspase-1信号通路抑制AD大鼠神经炎症的作用
- Author:
Zhen-yan SONG
1
;
Xiao-fang XIA
1
;
Yu-ke WANG
1
;
Yu-shan ZHENG
1
;
Pei-ying CHEN
1
;
De-yong LUO
1
;
Chun-xiang HE
1
;
Wen-jing YU
1
;
Ping LI
1
;
Shao-wu CHENG
1
Author Information
1. Key Laboratory of Hunan Province for Integrated Traditional Chinese and Western Medicine on Prevention and Treatment of Cardio-Cerebral Diseases，Hunan University of Chinese Medicine， Changsha 410208，China
- Publication Type:Research Article
- Keywords:
Danggui Shaoyaosan;
Alzheimer's disease （AD）;
amyloid-β-peptide （Aβ1-42）;
NOD-like receptor protein 3 （NLRP3） inflammasomes;
cysteinyl aspartate-specific protease-1 （Caspase-1）
- From:
Chinese Journal of Experimental Traditional Medical Formulae
2021;27(19):1-8
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the neuroprotective effect of Danggui Shaoyaosan （DSS） in a rat model of amyloid-β-peptide1-42 （Aβ1-42）-induced Alzheimer's disease （AD） as well as its regulatory effect on NOD-like receptor protein 3 （NLRP3）/cysteinyl aspartate-specific protease-1 （Caspase-1） signaling pathway. Method:The AD animal model was established via intracerebral injection of Aβ1-42 and treated with different concentrations of DSS after the division of rats into the sham operation group， model group， as well as the high-， medium-， and low-dose DSS groups. Morris water maze test was conducted to determine the learning and memory abilities of rats. The morphology and function of neurons were detected by hematoxylin-eosin （HE） staining and Golgi staining， followed by immunofluorescence co-localization of NLRP3 inflammasome activation. The mRNA expression levels of interleukin （IL）-1β and IL-18 were measured by Real-time polymerase chain reaction （Real-time PCR）， and the protein expression levels of NLRP3， Caspase-1， and IL-1β were assayed by Western blot. Result:Compared with the sham operation group， the model group exhibited significantly decreased learning and memory abilities （P<0.01）， impaired neuronal morphology and function， up-regulated IL-1β and IL-18 mRNA expression， enhanced NLRP3 inflammasome activation， and elevated NLRP3， Caspase-1， and IL-1β protein expression （P<0.01）. Compared with the model group， DSS at both medium and high doses remarkably improved the learning and memory abilities of AD rats （P<0.05， P<0.01）， restored neuronal morphology and function， down-regulated the mRNA expression levels of inflammatory factors IL-1β and IL-18， reduced the activation of NLRP3 inflammasomes， and lowered the protein expression levels of NLRP3， Caspase-1， and IL-1β （P<0.01）. Conclusion:DSS inhibits inflammasome activation and neuroinflammatory response possibly by regulating the NLRP3/Caspase-1 signaling pathway， thus exerting the neuroprotective effect.
