Dietary Luteolin Reduces Proinflammatory Microglia in the Brain of Senescent Mice
Open accessAbstract
Brain microglia become dysregulated during aging and express proinflammatory cytokines that play a role in cognitive aging. Recent studies suggest the flavonoid luteolin reduces neuroinflammation and improves learning and memory in aged mice. However, if dietary luteolin reduces microglia activity in the brain of senescent mice is not known. We hypothesized that feeding aged mice a diet with luteolin would reduce microglia activity. Adult (3-6 months) and aged (22-24 months) mice were fed American Institute of Nutrition (AIN)-93M or AIN-93M with luteolin (6 g/kg) for 4 weeks and injected intraperitoneally with saline or lipopolysaccharide (LPS) before microglia were isolated and stained for major histocompatibility complex (MHC) class II, interleukin (IL)-1β, and IL-6 for flow cytometry. In saline-treated mice fed control diet, aging increased the proportion of microglia that stained for MHC class II (<3% for adults vs. 23% for aged), IL-1β (<2% for adults vs. 25% for aged), and IL-6 (<2% for adults vs. 25% for aged), indicating an age-related increase in proinflammatory microglia. In saline-treated aged mice fed luteolin, the proportion of microglia that stained for MHC class II, IL-1β, and IL-6 was reduced by nearly half (to 12%, 13%, and 12%, respectively). Interestingly, luteolin significantly reduced the proportion of microglia that stained for IL-1β and IL-6 in LPS-treated adult mice but not aged. Collectively, the results show that a diet supplemented with luteolin inhibited brain microglia activity during aging and activation by LPS in adults. Therefore, luteolin may inhibit neuroinflammation and improve cognition in the otherwise healthy aged by constraining brain microglia.
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Dietary administration of luteolin reduces microglial activation in senescent mice.
“a dietary administration of luteolin reduces microglial activation in senescent mice (Burton et al., 2016)”
From Exploring the Therapeutic Potential of Phytochemicals in Alzheimer’s Disease: Focus on Polyphenols and Monoterpenes (2022) · cites this paper as Burton et al., 2016
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“…derived primarily from fruits and vegetables such as celery, chrysanthemum flowers, sweet bell peppers, carrots, onion leaves, broccoli and parsley (Burton et al., 2016), and it has various pharmacological activities such as anti-oxidant, antiinflammatory, anti-allergic and anti-carcinogenic…”
BackgroundGut–Brain Inflammation and Disrupted Homeostasis Due to Activation of Mast Cells and Microglia
Katiraei, P., Frye, R. E., & Theoharides, T. C. (2026) · International Journal of Molecular Sciences · doi:10.3390/ijms27041768 · Cited by 3 · see citing works
“Luteolin can also enter the brain and reduce microglial activation [492], particularly as a result of LPS [493], as well as have antibacterial properties [494].”
Wang, S., Xiao, F., Yuan, Y., Li, J., Liang, X., Fan, X., Zhang, M., Yan, T., Yang, M., He, Z., et al. (2023) · Genomics · doi:10.1016/j.ygeno.2023.110751 · Cited by 3 · see citing works
Discovery of dietary beneficial compounds for healthy aging: From worm to human
Ye, X., Wang, H., Han, Y., Fu, X., Zhang, J., & Zhang, T. (2025) · Food Research International · doi:10.1016/j.foodres.2025.116916 · Cited by 2 · see citing works
Natural Molecules for Brain Health and Resilience
Venetsanaki, V., Pardali, E. C., Cholevas, C., Grammatikopoulou, M. G., Goulis, D. G., & Theoharides, T. C. (2026) · International Journal of Molecular Sciences · doi:10.3390/ijms27104343 · Cited by 2 · see citing works
Xing, C., Zeng, Z., Shan, Y., Guo, W., Shah, R., Wang, L., Wang, Y., & Du, H. (2024) · Combinatorial Chemistry & High Throughput Screening · doi:10.2174/0113862073276253231114063813 · Cited by 2 · see citing works
Mody, P. H., Santos, N. L. D., Lenert, M. E., Barron, L. R., Nottingham, B. A., & Burton, M. D. (2020) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2020.10.014 · Cited by 2 · see citing works
Wang, J., Li, X., Cui, S., Liu, J., Sun, C., Sui, L., Zhang, D., & Luan, T. (2025) · Chemistry & Biodiversity · doi:10.1002/cbdv.202500272 · Cited by 1 · see citing works
“Among them, flavonoids are naturally present in many plants and possess a wealth of pharmacological activities, including antibacterial [6], anti-aging [7, 8], antioxidant [9], antiviral [10, 11], and central nervous system regulatory properties [12].”
Long COVID neuropathy: The role of mast cells
Morcos, Z. L., & Theoharides, T. C. (2026) · Journal of Neuropathology & Experimental Neurology · doi:10.1093/jnen/nlag016 · Cited by 1 · see citing works
Shaji, D., Nagura, Y., Sabishiro, H., Suzuki, R., & Kurita, N. (2023) · Molecules · doi:10.3390/molecules28248035 · Cited by 1 · see citing works
“Previous studies [60,61] found that luteolin inhibited aging-related brain microglia activity and neuroinflammation, resulting in improved cognitive functions.”
ResultNeurotrophins and Phytochemicals: Potential Partners to Combat Neurodegenerative Diseases
Jayaraman, M., Dutta, A., Mahanta, S., Sivakumar, D., & Raghavendran, H. R. B. (2024) · Springer eBooks · doi:10.1007/978-981-99-7269-2_13
Galvani, G., Mottolese, N., Gennaccaro, L., Loi, M., Medici, G., Tassinari, M., Fuchs, C., Ciani, E., & Trazzi, S. (2021) · Figshare · doi:10.6084/m9.figshare.14936176
Galvani, G., Mottolese, N., Gennaccaro, L., Loi, M., Medici, G., Tassinari, M., Fuchs, C., Ciani, E., & Trazzi, S. (2021) · Figshare · doi:10.6084/m9.figshare.14936179
Combating Blue Light Pollution With Flavonoids: Implications for Environmental Health and Aging
Yang, Y., Li, X., He, J., & Shen, J. (2026) · Archives of Insect Biochemistry and Physiology · doi:10.1002/arch.70122
Abdullah, A. N., Ariffin, H., & Azanan, M. S. (2026) · ONCOLOGIE · doi:10.1515/oncologie-2025-0514
“In murine models, luteolin reduces microglial activation during aging and in fl ammatory stimulation [101], suggesting potential bene fi ts for neuroin fl ammation and cognition.”
- Authors
- Burton, M. D., Rytych, J. L., Amin, R., & Johnson, R. W.
- Affiliations
- University of Illinois Urbana-Champaign (US)
- Corresponding author
- Johnson, Rodney W.
- Venue
- Rejuvenation Research
- Publisher
- SAGE Publications
- Published
- 2016-08
- Volume
- 19
- Issue
- 4
- Pages
- 286-292
- ISSN
- 1094-5458 (ISSN-L)
- 1549-1684
- 1557-8577
- PMC
- PMC4971424
- OpenAlex
- W1663431763
- Cited by
- 69
- References
- 35
- Citations by year
- 2026: 5 · 2025: 3 · 2024: 8 · 2023: 6 · 2022: 9 · 2021: 9 · 2020: 9 · 2019: 5 · 2018: 9 · 2017: 4 · 2016: 2
- FWCI
- 2.67
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Rejuvenation Research (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (AG16710)
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Pharmacology › Flavonoids in Medical Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Antioxidants, Aging, Portulaca oleracea
- Keywords
- luteolin, dietary flavonoids, microglia, neuroinflammation, brain aging, cognitive aging, IL-1β, interleukin-6, MHC class II, lipopolysaccharide, microglial activation, aged mice
- MeSH terms
- Age Factors, Aging, Animals, Animal Feed, Anti-Inflammatory Agents, Brain, Diet, Endotoxins, Male, Mice, Inbred BALB C, Cytokines, Microglia, Inflammation Mediators, Dietary Supplements, Models, Animal, Luteolin
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