IMR Press / JIN / Volume 22 / Issue 3 / DOI: 10.31083/j.jin2203072
Open Access Original Research
Danggui-Shaoyao-San Promotes Amyloid-β Clearance through Regulating Microglia Polarization via Trem2 in BV2 Cells
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1 Encephalopathy Department, Xi’an Hospital of Traditional Chinese Medicine, 710021 Xi’an, Shaanxi, China
2 Science and Technology Innovation Center, Guangzhou University of Chinese Medicine, 510405 Guangzhou, Guangdong, China
3 Endocrinology Department of Shenzhen Hospital, Beijing University of Chinese Medicine, 518172 Shenzhen, Guangdong, China
4 Encephalopathy Department, Shaanxi Provincial Hospital of Chinese Medicine, 710003 Xi’an, Shaanxi, China
*Correspondence: (Qi Wang); (Lin Yang); (Xiang Chang)
J. Integr. Neurosci. 2023, 22(3), 72;
Submitted: 14 October 2022 | Revised: 29 November 2022 | Accepted: 7 December 2022 | Published: 15 May 2023
(This article belongs to the Special Issue Alzheimer’s disease (AD))
Copyright: © 2023 The Author(s). Published by IMR Press.
This is an open access article under the CC BY 4.0 license.

Background: Alzheimer’s disease (AD) is a chronic neurodegenerative brain disorder currently without satisfactory therapeutic treatments. Triggering receptors expressed on a myeloid cells-2 (Trem2) gene mutation has been reported as a powerful AD risk factor that induces Trem2 gene deletion aggravated microglia disfunction and Amyloid-β (Aβ) aggregation in the brain. The traditional Chinese medicine (TCM) formula Danggui-Shaoyao-San (DSS) has shown therapeutic effect on alleviating the symptoms of AD. However, the neuroprotective effect and underlying mechanism of DSS against AD is still far from fully understood. Methods: Double-label immunofluorescence and Western blotting were employed to evaluate the different polarization states of mouse BV2 microglial (BV2) cells after lipopolysaccharide (LPS) or interleukin (IL)-4 treatment. Trem2 over-expression lentiviral vector and Trem2 siRNA were used respectively to evaluate the effect of Trem2 on microglia polarization via detecting the proteins expression of iNOS and arginase1 (Arg1) by Western blotting while the Aβ-scavenging capacity of BV2 cells was assessed by flow cytometry. Cell counting kit-8 (CCK8) assay was performed to assess the effect of DSS on the viability of BV2 cells. Flow cytometry was used to investigate the effect of DSS on the Aβ-scavenging capacity of BV2 cells treated with corresponding concentration of DSS-containing serum. Protein of Trem2 and the gene expression of the M1 or M2 phenotype in BV2 cells treated with DSS after Trem2 over-expression or silence were detected by Western blot and RT-qPCR, respectively. Results: In vitro experiments. DSS exhibited anti-inflammatory and neuroprotective functions. It was found that Trem2 had an effect on inducing a shift of M1 microglia towards the M2 phenotype and enhanced the Aβ-scavenging capacity of BV2 cells, further that DSS administration relieved inflammation by engulfing Aβ through the activities of Trem2. Importantly, DSS treatment effectively increased the Aβ-scavenging capacity of BV2 cells through accelerating the shift of M1 microglia towards an M2 phenotype via increasing Trem2 expression. Conclusions: Results demonstrated that DSS promoted the clearance of Aβ through the regulation of microglia polarization via increased expression of Trem2 in BV2 cells.

triggering receptor expressed on myeloid cells-2
microglia polarization
Amyloid-β deposition
Alzheimer's disease
81704131/National Natural Science Foundation of China
81904168/National Natural Science Foundation of China
2019KSYS005/Key laboratory project of colleges and universities in Guangdong province
2020A0505100052/Guangdong province science and technology plan international cooperation project
Fig. 1.
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