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Danggui Shaoyaosan Inhibits Neuroinflammation in AD Rats by Regulating NLRP3/Caspase-1 Pathway / 中国实验方剂学杂志
Article in Chinese | WPRIM | ID: wpr-906044
Responsible library: WPRO
ABSTRACT

Objective:

To investigate the neuroprotective effect of Danggui Shaoyaosan (DSS) in a rat model of amyloid-<italic>β</italic>-peptide<sub>1-42</sub> (A<italic>β</italic><sub>1-42</sub>)-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 A<italic>β</italic><sub>1-42</sub> 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)-1<italic>β</italic> and IL-18 were measured by Real-time polymerase chain reactionReal-time PCR), and the protein expression levels of NLRP3, Caspase-1, and IL-1<italic>β </italic>were assayed by Western blot.

Result:

Compared with the sham operation group, the model group exhibited significantly decreased learning and memory abilities (<italic>P</italic><0.01), impaired neuronal morphology and function, up-regulated IL-1<italic>β</italic> and IL-18 mRNA expression, enhanced NLRP3 inflammasome activation, and elevated NLRP3, Caspase-1, and IL-1<italic>β</italic> protein expression (<italic>P</italic><0.01). Compared with the model group, DSS at both medium and high doses remarkably improved the learning and memory abilities of AD rats (<italic>P</italic><0.05, <italic>P</italic><0.01), restored neuronal morphology and function, down-regulated the mRNA expression levels of inflammatory factors IL-1<italic>β</italic> and IL-18, reduced the activation of NLRP3 inflammasomes, and lowered the protein expression levels of NLRP3, Caspase-1, and IL-1<italic>β</italic> (<italic>P</italic><0.01).

Conclusion:

DSS inhibits inflammasome activation and neuroinflammatory response possibly by regulating the NLRP3/Caspase-1 signaling pathway, thus exerting the neuroprotective effect.

Full text: Available Index: WPRIM (Western Pacific) Language: Chinese Journal: Chinese Journal of Experimental Traditional Medical Formulae Year: 2021 Type: Article

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Full text: Available Index: WPRIM (Western Pacific) Language: Chinese Journal: Chinese Journal of Experimental Traditional Medical Formulae Year: 2021 Type: Article