Natural medicine HLXL targets multiple pathways of amyloid-mediated neuroinflammation and immune response in treating alzheimer's disease.

Autor:	Liang Y; Genetics and Aging Research Unit, McCance Center for Brain Health, Mass General Institute for Neurodegenerative Disease, Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, USA; Department of Anesthesiology, Weifang Medical University, Weifang, Shandong, China., Lee DYW; Bio-Organic and Natural Products Research Laboratory, Department of Psychiatry, McLean Hospital and Harvard Medical School, Belmont, MA, USA. Electronic address: dlee@mclean.harvard.edu., Zhen S; Genetics and Aging Research Unit, McCance Center for Brain Health, Mass General Institute for Neurodegenerative Disease, Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, USA., Sun H; Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, USA., Zhu B; Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, USA., Liu J; Bio-Organic and Natural Products Research Laboratory, Department of Psychiatry, McLean Hospital and Harvard Medical School, Belmont, MA, USA; Natural Pharmacia International Inc., Burlington, MA 01803, USA., Lei D; Genetics and Aging Research Unit, McCance Center for Brain Health, Mass General Institute for Neurodegenerative Disease, Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, USA., Lin CJ; Genetics and Aging Research Unit, McCance Center for Brain Health, Mass General Institute for Neurodegenerative Disease, Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, USA., Zhang S; Genetics and Aging Research Unit, McCance Center for Brain Health, Mass General Institute for Neurodegenerative Disease, Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, USA., Jacques NA; Genetics and Aging Research Unit, McCance Center for Brain Health, Mass General Institute for Neurodegenerative Disease, Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, USA., Quinti L; Genetics and Aging Research Unit, McCance Center for Brain Health, Mass General Institute for Neurodegenerative Disease, Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, USA., Ran C; Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, USA., Wang C; Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, USA., Griciuc A; Genetics and Aging Research Unit, McCance Center for Brain Health, Mass General Institute for Neurodegenerative Disease, Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, USA., Choi SH; Genetics and Aging Research Unit, McCance Center for Brain Health, Mass General Institute for Neurodegenerative Disease, Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, USA., Dai RH; Bio-Organic and Natural Products Research Laboratory, Department of Psychiatry, McLean Hospital and Harvard Medical School, Belmont, MA, USA; Natural Pharmacia International Inc., Burlington, MA 01803, USA., Efferth T; Department of Pharmaceutical Biology, Institute of Pharmaceutical and Biomedical Sciences, Johannes Gutenberg University, Mainz 55128, Germany., Tanzi RE; Genetics and Aging Research Unit, McCance Center for Brain Health, Mass General Institute for Neurodegenerative Disease, Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, USA. Electronic address: rtanzi@mgh.harvard.edu., Zhang C; Genetics and Aging Research Unit, McCance Center for Brain Health, Mass General Institute for Neurodegenerative Disease, Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, USA. Electronic address: Zhang.Can@mgh.harvard.edu.
Jazyk:	angličtina
Zdroj:	Phytomedicine : international journal of phytotherapy and phytopharmacology [Phytomedicine] 2022 Sep; Vol. 104, pp. 154158. Date of Electronic Publication: 2022 May 13.
DOI:	10.1016/j.phymed.2022.154158
Abstrakt:	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 Aβ42, and/or lipopolysaccharide (LPS), and then analyzed focusing on microglia mediated Aβ uptake and clearance, as well as pathway changes. Methods: We showed that HLXL significantly reduced amyloid neuropathology by upregulation of microglia-mediated phagocytosis of Aβ 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. (Copyright © 2022. Published by Elsevier GmbH.)
Databáze:	MEDLINE
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