Huang-Lian-Jie-Du decoction alleviates cognitive deficits in Alzheimer’s disease model 5xFAD mice by inhibiting Trem2/Dap12 signaling pathway

作者：Rui-Kang Pang, Jia Shi, Xiang-Yu Peng, Shan Su, Jiayi Zheng, Kai Le, Vincent W. Keng, Shijie Zhang, Xiao-Xiao Li · 发表于：Chinese Medicine · 年份：2025 · DOI：10.1186/s13020-025-01098-x · 被引用次数：4 · 研究领域：Neuroinflammation and Neurodegeneration Mechanisms、Alzheimer's disease research and treatments、Neurological Disease Mechanisms and Treatments

BACKGROUND: Alzheimer's disease (AD) is a progressive neurodegenerative disorder predominantly affecting the elderly population. It is characterized by cognitive deficits associated with the accumulation of amyloid-beta plaques and neurofibrillary tangles. Huang-Lian-Jie-Du (HLJD) decoction, recognized as a representative formulation with heat-clearing and detoxification effects, has been demonstrated to be effective in treating AD. However, the underlying mechanisms require further investigation. METHODS: 5xFAD mice were administrated low and high doses of HLJD. The Morris water maze test was conducted to assess the effects of HLJD. Aβ42 and total tau protein levels were evaluated. Additionally, network pharmacology analysis was performed to identify therapeutic targets of HLJD's active components and their relevance to AD. ELISA, qPCR, Western Blot, and immunofluorescence assays were employed to confirm the identified pathways. Finally, primary microglia isolated from 5xFAD mice were used to validate the candidate targets of HLJD. RESULTS: HLJD improved cognitive deficits in 5xFAD mice and reduced amyloid plaque deposition and tau protein levels. Network pharmacology analysis indicated that HLJD influences the neuroinflammatory response, particularly through the Dap12 signaling pathway. This was confirmed by reduced levels of neuroinflammation markers, including TNF-α, IL-1β, IL-6, and indicators of microglial activation and polarization. The expression of Trem2 and Dap12 i...