Cited by 481Neuroinflammation and Neurodegeneration MechanismsImmune Response and InflammationFlavonoids in Medical Research

Targeting the TLR4 signaling pathway by polyphenols: A novel therapeutic strategy for neuroinflammation

Rahimifard, Mahban, Maqbool, Faheem, Moeini-Nodeh, Shermineh, Niaz, Kamal, Abdollahi, Mohammad, Braidy, Nady, Nabavi, Seyed Mohammad, Nabavi, Seyed Fazel·2017·Ageing Research Reviews

Abstract

A wide array of cell signaling mediators and their interactions play vital roles in neuroinflammation associated with ischemia, brain trauma, developmental disorders and age-related neurodegeneration. Along with neurons, microglia and astrocytes are also affected by the inflammatory cascade by releasing pro-inflammatory cytokines, chemokines and reactive oxygen species. The release of pro-inflammatory mediators in response to neural dysfunction may be helpful, neutral or even deleterious to normal cellular survival. Moreover, the important role of NF-κB factors in the central nervous system (CNS) through toll-like receptor (TLR) activation has been well established. This review demonstrates recent findings regarding therapeutic aspects of polyphenolic compounds for the treatment of neuroinflammation, with the aim of regulating TLR4. Polyphenols including flavonoids, phenolic acids, phenolic alcohols, stilbenes and lignans, can target TLR4 signaling pathways in multiple ways. Toll interacting protein expression could be modulated by epigallocatechin-3-gallate. Resveratrol may also exert neuroprotective effects via the TLR4/NF-κB/STAT signaling cascade. Its role in activation of cascade via interfering with TLR4 oligomerization upon receptor stimulation has also been reported. Curcumin, another polyphenol, can suppress overexpression of inflammatory mediators via inhibiting the TLR4-MAPK/NF-κB pathway. It can also reduce neuronal apoptosis via a mechanism concerning the TLR4/MyD88/NF-κB signaling pathway in microglia/macrophages. Despite a symphony of in vivo and in vitro studies, many molecular and pharmacological aspects of neuroinflammation remain unclear. It is proposed that natural compounds targeting TLR4 may serve as important pharmacophores for the development of potent drugs for the treatment of neurological disorders.

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Crossref · 10.1016/j.arr.2017.02.004

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Authors
Rahimifard, M., Maqbool, F., Moeini-Nodeh, S., Niaz, K., Abdollahi, M., Braidy, N., Nabavi, S. M., & Nabavi, S. F.
Affiliations
  • Pharmaceutical Sciences Research Center (IR)
  • UNSW Sydney (AU)
  • Baqiyatallah University of Medical Sciences (IR)
Corresponding author
  • Abdollahi, Mohammad
  • Nabavi, Seyed Mohammad
Venue
Ageing Research Reviews
Publisher
Elsevier BV
Published
2017-07
Volume
36
Pages
11-19
ISSN
1568-1637 (ISSN-L)
OpenAlex
W2589764628
Cited by
481
References
110
Citations by year
2026: 28 · 2025: 50 · 2024: 57 · 2023: 70 · 2022: 70 · 2021: 61 · 2020: 58 · 2019: 40 · 2018: 34 · 2017: 13
FWCI
3.81
Type
journal article
Language
en
Open access
closed
Locations
  • Ageing Research Reviews (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
  • Health Sciences › Medicine › Pharmacology › Flavonoids in Medical Research
Keywords
neuroinflammation, TLR4 signaling, polyphenols, NF-κB, TLR4, resveratrol, epigallocatechin gallate, curcumin, MyD88, MAPK signaling, neuroprotection, microglia, astrocytes, flavonoids, phenolic acids, stilbenes, lignans, neurodegeneration
MeSH terms
Animals, Astrocytes, Cell Survival, Humans, Inflammation, Neurons, Signal Transduction, Drug Delivery Systems, Microglia, Inflammation Mediators, Toll-Like Receptor 4, Polyphenols

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