期刊
PHYTOMEDICINE
卷 104, 期 -, 页码 -出版社
ELSEVIER GMBH
DOI: 10.1016/j.phymed.2022.154158
关键词
Alzheimer?s disease; Natural medicine; HlXL; Neuroinflammation; Innate immune response
This study investigated the mechanisms of HLXL, a Chinese medicine containing multiple bioactive components, in attenuating AD neuropathology. The results showed that HLXL significantly reduced amyloid neuropathology by regulating phagocytosis and energy metabolism pathways. This study provides a new avenue for the development of AD therapeutics.
Background: Based on the complex pathology of AD, a single chemical approach may not be sufficient to deal simultaneously with multiple pathways of amyloid-tau neuroinflammation. A polydrug approach which contains multiple bioactive components targeting multiple pathways in AD would be more appropriate. Here we focused on a Chinese medicine (HLXL), which contains 56 bioactive natural products identified in 11 medicinal plants and displays potent anti-inflammatory and immuno-modulatory activity.Hypothesis/Purpose: We investigated the neuroimmune and neuroinflammation mechanisms by which HLXL may attenuate AD neuropathology. Specifically, we investigated the effects of HLXL on the neuropathology of AD using both transgenic mouse models as well as microglial cell-based models.Study design: The 5XFAD transgenic animals and microglial cell models were respectively treated with HLXL and AI342, and/or lipopolysaccharide (LPS), and then analyzed focusing on microglia mediated AI3 uptake and clearance, as well as pathway changes.Methods: We showed that HLXL significantly reduced amyloid neuropathology by upregulation of microgliamediated phagocytosis of AI3 both in vivo and in vitro. HLXL displayed multi-modal mechanisms regulating pathways of phagocytosis and energy metabolism.Results: Our results may not only open a new avenue to support pharmacologic modulation of neuroinflammation and the neuroimmune system for AD intervention, but also identify HLXL as a promising natural medicine for AD. Conclusion: It is conceivable that the traditional wisdom of natural medicine in combination with modern science and technology would be the best strategy in developing effective therapeutics for AD.
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