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Honokiol Restores Microglial Phagocytosis by Reversing Metabolic Reprogramming.

Wenwen Li1, Shiyuan Wang1, Heng Zhang1

  • 1Innovation Center for Neurological Disorders and Department of Neurology, Xuanwu Hospital, Capital Medical University, National Clinical Research Center for Geriatric Diseases, Beijing, China.

Journal of Alzheimer'S Disease : JAD
|June 21, 2021
PubMed
Summary

Honokiol, a natural compound, enhances microglial phagocytosis by improving mitochondrial function and energy metabolism. This finding offers a promising therapeutic strategy for Alzheimer's disease (AD) by restoring essential brain cell functions.

Keywords:
Honokiolmetabolic reprogrammingmicroglial phagocytosismitochondria

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Area of Science:

  • Neuroscience
  • Pharmacology
  • Cell Biology

Background:

  • Microglial dysfunction is a key factor in Alzheimer's disease (AD) pathogenesis.
  • Restoring microglial function presents a promising therapeutic avenue for AD.
  • Honokiol, a natural compound from Magnolia officinalis, shows potential in AD therapy.

Purpose of the Study:

  • To investigate the role of honokiol in microglial phagocytosis.
  • To elucidate the underlying mechanisms by which honokiol affects microglial function.

Main Methods:

  • Assessed cell viability and apoptosis using MTT and flow cytometry.
  • Evaluated phagocytic capacity, mitochondrial reactive oxygen species, and membrane potential via fluorescence microscopy.
  • Analyzed cellular glycolysis, oxidative phosphorylation, and metabolites using Seahorse XF24 and mass spectrometry.
  • Quantified PPARγ and PGC1α expression at mRNA and protein levels via qRT-PCR and Western blotting.

Main Results:

  • Honokiol mitigated amyloid-beta 42 (Aβ42)-induced neurotoxicity in BV2 microglial cells.
  • Promoted microglial phagocytic efficiency by shifting metabolism from oxidative phosphorylation to anaerobic glycolysis, boosting ATP production.
  • Reduced mitochondrial reactive oxygen species and increased mitochondrial membrane potential.
  • Upregulated peroxisome proliferator-activated receptor gamma (PPARγ) and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α) expression.

Conclusions:

  • Honokiol enhances microglial phagocytic function by improving mitochondrial function.
  • The natural compound honokiol demonstrates efficacy in promoting essential microglial activities.
  • Honokiol represents a potential therapeutic agent for neurodegenerative diseases like Alzheimer's.