摘要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 Decoc-tion(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 us-ing high-performance liquid chromatography(HPLC)and enzyme-linked immunosorbent as-say(ELISA)kits.The TREM2/protein kinase B(Akt)/mammalian target of rapamycin(mTOR)/hypoxia-inducible factor-1α(HIF-1α)signaling pathway was analyzed using West-ern 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 evalu-ated 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 el-evated TREM2 expression,adenosine triphosphate(ATP)levels,and microglial phagocytosis in APP/PS1 mice.Additionally,JWXG reduced Aβ-burden,neuropathological lesions,and cog-nitive deficits in APP/PS1 mice.In conclusion,JWXG promoted TREM2-induced EMR and en-hanced microglial phagocytosis,thereby reducing Aβ deposition,improving neuropathologic-al lesions,and alleviating cognitive deficits.