Facilitating microglial phagocytosis by which Jiawei Xionggui Decoction alleviates cognitive impairment via TREM2-mediated energy metabolic reprogramming.
10.1016/S1875-5364(25)60927-7
- Author:
Wen WEN
1
;
Jie CHEN
1
;
Junbao XIANG
1
;
Shiqi ZHANG
1
;
Jingru LIU
2
;
Jie WANG
1
;
Ping WANG
3
;
Shijun XU
4
Author Information
1. State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China; School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China; Institute of Material Medica Integration and Transformation for Brain Disorders, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China.
2. Division of Biosciences, University College London, London WC1E6BT, UK.
3. State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China; School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China; Institute of Material Medica Integration and Transformation for Brain Disorders, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China. Electronic address: viviansector@aliyun.com.
4. State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China; School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China; Institute of Material Medica Integration and Transformation for Brain Disorders, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China. Electronic address: xushijun@cdutcm.edu.cn.
- Publication Type:Journal Article
- Keywords:
Akt/mTOR/HIF-1α;
Energy metabolic reprogramming;
Jiawei Xionggui Decoction;
Microglial phagocytosis;
Triggering receptor expressed on myeloid cells 2 (TREM2)
- MeSH:
Drugs, Chinese Herbal/pharmacology*;
Microglia/drug effects*;
Phagocytosis;
Cognitive Dysfunction/drug therapy*;
Metabolic Reprogramming;
Animals;
Mice;
Cell Line;
Receptors, Immunologic/metabolism*;
Membrane Glycoproteins/metabolism*;
Signal Transduction;
Amyloid beta-Peptides/metabolism*;
Energy Metabolism
- From:
Chinese Journal of Natural Medicines (English Ed.)
2025;23(8):909-919
- CountryChina
- Language:English
-
Abstract:
Triggering receptor expressed on myeloid cells 2 (TREM2)-mediated microglial phagocytosis is an energy-intensive process that plays a crucial role in amyloid beta (Aβ) clearance in Alzheimer's disease (AD). Energy metabolic reprogramming (EMR) in microglia induced by TREM2 presents therapeutic targets for cognitive impairment in AD. Jiawei Xionggui Decoction (JWXG) has demonstrated effectiveness in enhancing energy supply, protecting microglia, and mitigating cognitive impairment in APP/PS1 mice. However, the mechanism by which JWXG enhances Aβ phagocytosis through TREM2-mediated EMR in microglia remains unclear. This study investigates how JWXG facilitates microglial phagocytosis and alleviates cognitive deficits in AD through TREM2-mediated EMR. Microglial phagocytosis was evaluated through immunofluorescence staining in vitro and in vivo. The EMR level of microglia was assessed using high-performance liquid chromatography (HPLC) and enzyme-linked immunosorbent assay (ELISA) kits. The TREM2/protein kinase B (Akt)/mammalian target of rapamycin (mTOR)/hypoxia-inducible factor-1α (HIF-1α) signaling pathway was analyzed using Western blotting in BV2 cells. TREM2-/- BV2 cells were utilized for reverse validation experiments. The Aβ burden, neuropathological features, and cognitive ability in APP/PS1 mice were evaluated using ELISA kits, immunohistochemistry (IHC), and the Morris water maze (MWM) test. JWXG enhanced both the phagocytosis of EMR disorder-BV2 cells (EMRD-BV2) and increased EMR levels. Notably, these effects were significantly reversed in TREM2-/- BV2 cells. JWXG elevated TREM2 expression, adenosine triphosphate (ATP) levels, and microglial phagocytosis in APP/PS1 mice. Additionally, JWXG reduced Aβ-burden, neuropathological lesions, and cognitive deficits in APP/PS1 mice. In conclusion, JWXG promoted TREM2-induced EMR and enhanced microglial phagocytosis, thereby reducing Aβ deposition, improving neuropathological lesions, and alleviating cognitive deficits.
