Natural Products as a Potential Modulator of Microglial Polarization in Neurodegenerative Diseases
Abstract
Neurodegenerative diseases (NDs) are characterized by the progressive loss of structure and function of neurons most common in elderly population, mainly including Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS) and multiple sclerosis (MS). Neuroinflammation caused by microglia as the resident macrophages of the central nervous system (CNS) plays a contributory role in the onset and progression of NDs. Activated microglia, as in macrophages, to be heterogeneous, can polarize into M1 (pro-inflammatory) and M2 (anti-inflammatory) functional phenotypes. The former elaborate pro-inflammatory mediators promoting neuroinflammation and neuronal damage. In contrast, the latter generate anti-inflammatory mediators and neurotrophins that inhibit neuroinflammation and promote neuronal healing. Consistently, the regulation of microglial polarization from M1 to M2 phenotype appears as an outstanding therapeutic and preventive approach for NDs treatment. Although non-steroidal anti-inflammatory drugs (NSAIDs) currently used to alleviate M1 microglia-associated neuroinflammation responsible for the development of NDs, these drugs have different degrees of adverse effects and limited efficacy. As the advantages of novel structure, multi-target, high efficiency and low toxicity, natural products as the modulators of microglial polarization have attracted considerable concerns in the therapeutic areas of NDs. In this review, we mainly summarized the therapeutic potential of natural products and their various molecular mechanisms for NDs treatment through modulating microglial polarization. The aim of the current review is expected to be useful to develop innovative modulators of microglial polarization from natural products for the amelioration and treatment of NDs.
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Phytochemicals including flavonoids, polyphenols, terpenoids, and carotenoids target multiple signaling pathways responsible for microglial activation and release of pro-inflammatory mediators, or NF-κB and p38 MAPK activation.
“Many phytochemicals including flavonoids and other polyphenols, terpenoids, and carotenoids have indeed the ability to target multiple signaling pathways responsible for microglial activation and the subsequent release of pro-inflammatory mediators, or those involved in the activation of NF-κB and p38 MAPK”
From Exploring the Therapeutic Potential of Phytochemicals in Alzheimer’s Disease: Focus on Polyphenols and Monoterpenes (2022) · cites this paper as Jin et al., 2019
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Zhang, J., Zheng, Y., Luo, Y., Du, Y., Zhang, X., & Fu, J. (2019) · Molecular Immunology · doi:10.1016/j.molimm.2019.09.020 · Cited by 464 · see citing works
Henríquez, G., Gomez, A., Guerrero, E., & Narayan, M. (2020) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.0c00381 · Cited by 83 · see citing works
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Dong, H., Zhang, X., Duan, Y., He, Y., Zhao, J., Wang, Z., Wang, J., Li, Q., Fan, G., Liu, Z., et al. (2024) · Journal of Neuroinflammation · doi:10.1186/s12974-024-03070-2 · Cited by 49 · see citing works
Huang, R., Zhu, Z., Wu, Q., Bekhit, A. E.-D. A., Wu, S., Chen, M., Wang, J., & Ding, Y. (2023) · Critical Reviews in Food Science and Nutrition · doi:10.1080/10408398.2021.1975093 · Cited by 23 · see citing works
Blood brain barrier inflammation and potential therapeutic role of phytochemicals
Welcome, M. O. (2020) · PharmaNutrition · doi:10.1016/j.phanu.2020.100177 · Cited by 22 · see citing works
- Authors
- Jin, X., Liu, M.-Y., Zhang, D.-F., Zhong, X., Du, K., Qian, P., Gao, H., & Wei, M.-J.
- Affiliations
- China Medical University (CN)
- National Institutes for Food and Drug Control (CN)
- Venue
- Pharmacological Research
- Publisher
- Elsevier BV
- Published
- 2019-07
- Volume
- 145
- Pages
- 104253
- ISSN
- 1043-6618 (ISSN-L)
- OpenAlex
- W2943027232
- Cited by
- 109
- References
- 263
- Citations by year
- 2026: 6 · 2025: 13 · 2024: 15 · 2023: 16 · 2022: 21 · 2021: 17 · 2020: 15 · 2019: 5
- FWCI
- 1.53
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Pharmacological Research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Shenyang Science and Technology Bureau
- China Postdoctoral Science Foundation
- Department of Science and Technology of Liaoning Province
- Ministry of Science and Technology of the People's Republic of China
- Scientific Research Fund of Liaoning Provincial Education Department
- National Natural Science Foundation of China
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Neurology › Neurological Disease Mechanisms and Treatments
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Keywords
- natural products, microglial polarization, neurodegenerative diseases, neuroinflammation, M1/M2 microglia, Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, multiple sclerosis, anti-inflammatory agents, neuroprotection
- MeSH terms
- Animals, Biological Products, Humans, Phenotype, Microglia, Neuroprotective Agents, Neurodegenerative Diseases
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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