Danggui-Shaoyao-San Promotes Amyloid-β Clearance through Regulating Microglia Polarization via Trem2 in BV2 Cells
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 aggravat...
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| Format: | Article |
| Language: | English |
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IMR Press
2023-05-01
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| Series: | Journal of Integrative Neuroscience |
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| Online Access: | https://www.imrpress.com/journal/JIN/22/3/10.31083/j.jin2203072 |
| _version_ | 1797814527290507264 |
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| author | Gongcan Chen Mengmeng Han Yi Chen Yaling Lei Min Li Li Wang Chen Wang Yangxue Hu Jinghu Niu Cong Yang Yousheng Mo Qi Wang Lin Yang Xiang Chang |
| author_facet | Gongcan Chen Mengmeng Han Yi Chen Yaling Lei Min Li Li Wang Chen Wang Yangxue Hu Jinghu Niu Cong Yang Yousheng Mo Qi Wang Lin Yang Xiang Chang |
| author_sort | Gongcan Chen |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-13T08:08:57Z |
| format | Article |
| id | doaj.art-f9308dcb21174a6584a9b17febc16a5f |
| institution | Directory Open Access Journal |
| issn | 0219-6352 |
| language | English |
| last_indexed | 2024-03-13T08:08:57Z |
| publishDate | 2023-05-01 |
| publisher | IMR Press |
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| series | Journal of Integrative Neuroscience |
| spelling | doaj.art-f9308dcb21174a6584a9b17febc16a5f2023-06-01T01:59:17ZengIMR PressJournal of Integrative Neuroscience0219-63522023-05-012237210.31083/j.jin2203072S0219-6352(22)00497-1Danggui-Shaoyao-San Promotes Amyloid-β Clearance through Regulating Microglia Polarization via Trem2 in BV2 CellsGongcan Chen0Mengmeng Han1Yi Chen2Yaling Lei3Min Li4Li Wang5Chen Wang6Yangxue Hu7Jinghu Niu8Cong Yang9Yousheng Mo10Qi Wang11Lin Yang12Xiang Chang13Encephalopathy Department, Xi’an Hospital of Traditional Chinese Medicine, 710021 Xi’an, Shaanxi, ChinaEndocrinology Department of Shenzhen Hospital, Beijing University of Chinese Medicine, 518172 Shenzhen, Guangdong, ChinaScience and Technology Innovation Center, Guangzhou University of Chinese Medicine, 510405 Guangzhou, Guangdong, ChinaEncephalopathy Department, Shaanxi Provincial Hospital of Chinese Medicine, 710003 Xi’an, Shaanxi, ChinaEncephalopathy Department, Xi’an Hospital of Traditional Chinese Medicine, 710021 Xi’an, Shaanxi, ChinaEncephalopathy Department, Xi’an Hospital of Traditional Chinese Medicine, 710021 Xi’an, Shaanxi, ChinaEncephalopathy Department, Xi’an Hospital of Traditional Chinese Medicine, 710021 Xi’an, Shaanxi, ChinaEncephalopathy Department, Xi’an Hospital of Traditional Chinese Medicine, 710021 Xi’an, Shaanxi, ChinaEncephalopathy Department, Xi’an Hospital of Traditional Chinese Medicine, 710021 Xi’an, Shaanxi, ChinaScience and Technology Innovation Center, Guangzhou University of Chinese Medicine, 510405 Guangzhou, Guangdong, ChinaScience and Technology Innovation Center, Guangzhou University of Chinese Medicine, 510405 Guangzhou, Guangdong, ChinaScience and Technology Innovation Center, Guangzhou University of Chinese Medicine, 510405 Guangzhou, Guangdong, ChinaEncephalopathy Department, Xi’an Hospital of Traditional Chinese Medicine, 710021 Xi’an, Shaanxi, ChinaEncephalopathy Department, Xi’an Hospital of Traditional Chinese Medicine, 710021 Xi’an, Shaanxi, ChinaBackground: 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.https://www.imrpress.com/journal/JIN/22/3/10.31083/j.jin2203072danggui-shaoyao-santriggering receptor expressed on myeloid cells-2microglia polarizationamyloid-β depositionalzheimer's disease |
| spellingShingle | Gongcan Chen Mengmeng Han Yi Chen Yaling Lei Min Li Li Wang Chen Wang Yangxue Hu Jinghu Niu Cong Yang Yousheng Mo Qi Wang Lin Yang Xiang Chang Danggui-Shaoyao-San Promotes Amyloid-β Clearance through Regulating Microglia Polarization via Trem2 in BV2 Cells Journal of Integrative Neuroscience danggui-shaoyao-san triggering receptor expressed on myeloid cells-2 microglia polarization amyloid-β deposition alzheimer's disease |
| title | Danggui-Shaoyao-San Promotes Amyloid-β Clearance through Regulating Microglia Polarization via Trem2 in BV2 Cells |
| title_full | Danggui-Shaoyao-San Promotes Amyloid-β Clearance through Regulating Microglia Polarization via Trem2 in BV2 Cells |
| title_fullStr | Danggui-Shaoyao-San Promotes Amyloid-β Clearance through Regulating Microglia Polarization via Trem2 in BV2 Cells |
| title_full_unstemmed | Danggui-Shaoyao-San Promotes Amyloid-β Clearance through Regulating Microglia Polarization via Trem2 in BV2 Cells |
| title_short | Danggui-Shaoyao-San Promotes Amyloid-β Clearance through Regulating Microglia Polarization via Trem2 in BV2 Cells |
| title_sort | danggui shaoyao san promotes amyloid β clearance through regulating microglia polarization via trem2 in bv2 cells |
| topic | danggui-shaoyao-san triggering receptor expressed on myeloid cells-2 microglia polarization amyloid-β deposition alzheimer's disease |
| url | https://www.imrpress.com/journal/JIN/22/3/10.31083/j.jin2203072 |
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