Therapeutic potential of plant-derived natural compounds in Alzheimer’s disease: Targeting microglia-mediated neuroinflammation

Aug 2, 2024Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie

Plant-based natural compounds may help Alzheimer's by reducing brain immune cell inflammation

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Circadian Biology on OpenScience ↗PubMed ↗DOI ↗

Abstract

Dysregulated activation of microglial receptors and their downstream pathways is associated with impaired immune homeostasis in animal models of Alzheimer's disease.

Abnormal microglial activation contributes to the neuroinflammatory response observed in Alzheimer's disease.
Key signaling pathways, including MAPK and NF-κB, are involved in exacerbating microglia-mediated neuroinflammation.
Plant-derived natural compounds (PDNCs) may inhibit proinflammatory receptors in microglia and activate their anti-inflammatory counterparts.
Certain PDNCs, like magnolol and resveratrol, have potential to delay Alzheimer's progression by regulating receptors linked to β-amyloid clearance.
This review highlights the role of microglia in chronic inflammation specific to Alzheimer's disease and the immune regulatory effects of PDNCs.

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Microglia are resident immune cells of the central nervous system (CNS) with roles in sensing, housekeeping, and defense. Exploring the role of microglia in the occurrence and development of Alzheimer's disease (AD) and the possible therapeutic mechanism of plant-derived natural compounds (PDNCs) that regulate microglia-associated neuroinflammation may potentially help in elucidating the pathogenesis of AD and provide novel insights for its treatment. This review explores the role of abnormal microglial activation and its dominant neuroinflammatory response, as well as the activation of their target receptors and signaling pathways in AD pathogenesis. Additionally, we report an update on the potential pharmacological mechanisms of multiple PDNCs in modulating microglia-associated neuroinflammation in AD treatment. Dysregulated activation of microglial receptors and their downstream pathways impaired immune homeostasis in animal models of AD. Multiple signaling pathways, such as mitogen-activated protein kinase (MAPK), nuclear factor kappa light chain enhancer of activated B cells (NF-κB), and Toll-like receptors, play important roles in microglial activation and can exacerbate microglia-mediated neuroinflammation. PDNCs, such as magnolol, stigmasterol, matrine, naringenin, naringin, and resveratrol, can delay the progression of AD by inhibiting the proinflammatory receptors of microglia, activating its anti-inflammatory receptors, regulating the receptors related to β-amyloid (Aβ) clearance, reversing immune dysregulation, and maintaining the immune homeostasis of microglial downstream pathways. This review summarizes the mechanisms by which microglia cause chronic inflammation in AD and evaluates the beneficial effects of PDNCs on immune regulation in AD by regulating microglial receptors and their downstream pathways.

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Therapeutic potential of plant-derived natural compounds in Alzheimer’s disease: Targeting microglia-mediated neuroinflammation

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