Chinese Journal of Tissue Engineering Research ›› 2022, Vol. 26 ›› Issue (26): 4166-4172.doi: 10.12307/2022.819

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Bushen Yizhi Anti-aging Prescription improves cognitive function of APP/PS1 mice by regulating microglia and macrophage polarization

Wang Yuyin1, 2, Wei Wenyue2, 3, Guo Minfang2, Li Hongxia2, Zhang Jing1, Gu Qingfang2, Liu Xiaoqin2, Guo Xiaoping2, Song Lijuan1, 3, Chai Zhi1, Ma Cungen1, 2, Wei Jiezhong1, 2, 4   

  1. 1Neurobiology Research Center, Shanxi University of Chinese Medicine, Jinzhong 030619, Shanxi Province, China; 2Institute of Brain Science, Shanxi Datong University, Datong 037009, Shanxi Province, China; 3Department of Neurology, First Clinical College of Shanxi Medical University, Taiyuan 030001, Shanxi Province, China; 4Department of Neurology, Datong Fifth People's Hospital, Datong 037009, Shanxi Province, China
  • Received:2020-11-04 Accepted:2021-01-16 Online:2022-09-18 Published:2022-03-08
  • Contact: Wei Jiezhong, MD, Professor, Doctoral supervisor, Neurobiology Research Center, Shanxi University of Chinese Medicine, Key Laboratory of Replenishing Qi and Activating Blood for the Treatment of Multiple Sclerosis, State Administration of Traditional Chinese Medicine, Jinzhong 030619, Shanxi Province, China; Institute of Brain Science, Shanxi Datong University, Shanxi Provincial Key Laboratory of Inflammatory Neurodegenerative Disease, Datong 037009, Shanxi Province, China; Department of Neurology, Datong Fifth People’s Hospital, Datong 037009, Shanxi Province, China Ma Cungen, MD, Professor, Doctoral supervisor, Neurobiology Research Center, Shanxi University of Chinese Medicine, Key Laboratory of Replenishing Qi and Activating Blood for the Treatment of Multiple Sclerosis, State Administration of Traditional Chinese Medicine, Jinzhong 030619, Shanxi Province, China; Institute of Brain Science, Shanxi Datong University, Shanxi Provincial Key Laboratory of Inflammatory Neurodegenerative Disease, Datong 037009, Shanxi Province, China
  • About author:Wang Yuyin, Master candidate, Neurobiology Research Center, Shanxi University of Chinese Medicine, Key Laboratory of Replenishing Qi and Activating Blood for the Treatment of Multiple Sclerosis, State Administration of Traditional Chinese Medicine, Jinzhong 030619, Shanxi Province, China; Institute of Brain Science, Shanxi Datong University, Shanxi Provincial Key Laboratory of Inflammatory Neurodegenerative Disease, Datong 037009, Shanxi Province, China Wei Wenyue, Master candidate, Institute of Brain Science, Shanxi Datong University, Shanxi Provincial Key Laboratory of Inflammatory Neurodegenerative Disease, Datong 037009, Shanxi Province, China; Department of Neurology, First Clinical College of Shanxi Medical University, Taiyuan 030001, Shanxi Province, China Wang Yuyin and Wei Wenyue contributed equally to this work.
  • Supported by:
    the National Natural Science Foundation of China (General Program), No. 81473577 (to MCG); Open Project of the State Key Laboratory of Molecular Developmental Biology, Chinese Academy of Sciences, No. 2020-MDB-KF-09 (to SLJ); Shanxi Natural Science Foundation, No. 201805D111009 (to MCG) and 201805D131005 (WJZ); Shanxi Provincial Applied Basic Research Project, No. 201901D211538 (to SLJ); Zhendong Special Project of Shanxi Provincial Traditional Chinese Medicine Modernization Key Technology Research, No. 2106ZD0505 (to WJZ); Shanxi Datong University School-level Scientific Research Project, No. 2019K18 (to LHX)

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Abstract: BACKGROUND: Bushen Yizhi Anti-aging Prescription exerts different therapeutic effects on Alzheimer′s disease, and our previous studies have suggested that Bushen Yizhi anti-aging prescription can significantly improve the cognitive function of APP/PS1 Tg mice by simultaneously promoting the polarization of spleen macrophages and central microglia to M2 type.  
OBJECTIVE: To explore the therapeutic effect and mechanisms of Bushen Yizhi Anti-aging Prescription on Alzheimer’s disease model mice (APP/PS1 Tg).
METHODS: Totally 20 male APP/PS1 transgene mice aged 8 months were randomly assigned to APP/PS1 transgenic model group and Bushen Yizhi Anti-aging Prescription intervention group. Another age- and sex-matched wild-type male mice were used as wild-type control group. All mice were fed for 8 weeks. Morris Water Maze and Y-maze test were used to evaluate cognitive function of mice in the three groups. M1 microglial surface marker nitric oxide synthase, interleukin-6 and M2 microglial surface marker arginase-1 and interleukin-10 in mouse hippocampus were analyzed by immunohistochemistry. Expressions of Iba-1, inducible nitric oxide synthase, arginase-1, interleukin-6, interleukin-10, Toll-like receptor 4, myeloid differentiation factor 88 and nuclear factor-κB were examined by western blot. Flow cytometry was used to analyze the expression of M1 (CD16/32, interleukin-12) and M2-type mononuclear macrophages (CD206, interleukin-10) in mouse spleen. The study protocol was approved by the Animal Ethics Committee of Shanxi Datong Univerisity. 
RESULTS AND CONCLUSION: Compared the wild-type control group, the model group showed decreased cognitive function and the microglia in the brain were activated and transformed into M1, while the mononuclear macrophages in the spleen also transformed into M1. After treatment with Bushen Yizhi Anti-aging Prescription, the cognitive function of APP/PS1 Tg mice was significantly improved (P < 0.05), the activation of microglia was inhibited (P < 0.01), the transformation from M1 microglia to M2 was promoted (P < 0.05), and the expressions of Toll-like receptor 4, myeloid differentiation factor 88 and nuclear factor-κB were down-regulated (P < 0.01). All these findings indicate that Bushen Yizhi Anti-aging Prescription reverses cognitive impairment and facilitates microglia M2 polarization via the Toll-like receptor 4/myeloid differentiation factor 88/nuclear factor-κB signaling pathway in APP/PS1 transgenic mice.

Key words: Alzheimer’s disease, Bushen Yizhi Anti-aging Prescription, inflammatory cytokines, microglia, macrophage

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