{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T15:41:12Z","timestamp":1787499672835,"version":"build-2736575974"},"reference-count":145,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T00:00:00Z","timestamp":1776816000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82575038"],"award-info":[{"award-number":["82575038"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"award":["82575038"],"award-info":[{"award-number":["82575038"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Science and Technology Innovation Program of Hunan Province","award":["2023RC3166"],"award-info":[{"award-number":["2023RC3166"]}]},{"name":"Natural Science Foundation of Hunan Province for Excellent Youth","award":["2023JJ20033"],"award-info":[{"award-number":["2023JJ20033"]}]},{"name":"Outstanding Youth Project for Scientific Research of the Hunan Provincial Department of Education","award":["23B0373"],"award-info":[{"award-number":["23B0373"]}]},{"name":"Youth Student Basic Research Project of the Natural Science Foundation of Hunan Province","award":["2025JJ60910"],"award-info":[{"award-number":["2025JJ60910"]}]},{"name":"Hunan Provincial College Students\u2019 Innovation and Entrepreneurship Training Program","award":["S202410541053"],"award-info":[{"award-number":["S202410541053"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brain Sciences"],"abstract":"<jats:p>Background\/Objectives: Alzheimer\u2019s disease (AD) is a neurodegenerative disorder characterized by progressive cognitive decline and chronic neuroinflammation. Increasing evidence suggests that the imbalance between pro-inflammatory Th17 cells and anti-inflammatory regulatory T (Treg) cells plays a critical role in AD pathogenesis. However, a comprehensive synthesis of how natural compounds modulate Th17\/Treg balance in AD remains lacking. This review aims to summarize current preclinical evidence on Th17\/Treg dysregulation and evaluate the immunomodulatory potential of natural compounds in AD. Methods: This review focuses on preclinical evidence derived from experimental AD models and related inflammatory models to evaluate how natural compounds modulate Th17\/Treg balance, neuroinflammation, and cognitive function, with an emphasis on underlying molecular and immunometabolic mechanisms. Results: Th17\/Treg imbalance contributes significantly to AD-associated neuroinflammation and disease progression. Representative natural compounds, including paeoniflorin, quercetin, and ganoderic acid A, have demonstrated the ability to rebalance Th17\/Treg responses, suppress neuroinflammation, and improve neuronal survival in experimental models. These compounds are highlighted due to their relatively stronger evidence in AD-related models and more clearly defined immunomodulatory mechanisms. These effects are partially mediated through modulation of key signaling pathways and immunometabolic reprogramming. Conclusions: Targeting Th17\/Treg balance with natural compounds represents a promising multi-target immunomodulatory strategy for AD. However, most current evidence is derived from preclinical or non-AD models, and clinical validation remains limited. Future studies should prioritize AD-specific models and translational research to evaluate therapeutic potential in humans.<\/jats:p>","DOI":"10.3390\/brainsci16050443","type":"journal-article","created":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T08:11:14Z","timestamp":1776931874000},"page":"443","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Modulating Th17\/Treg Balance in Alzheimer\u2019s Disease: Therapeutic Insights from Natural Compounds and Immunometabolism"],"prefix":"10.3390","volume":"16","author":[{"given":"Shuyao","family":"Tang","sequence":"first","affiliation":[{"name":"Key Laboratory of Hunan Province for Integrated Traditional Chinese and Western Medicine on Prevention and Intervention of Cardio-Cerebral Diseases, School of Integrated Chinese and Western Medicine, Hunan University of Chinese Medicine, Changsha 410208, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gangying","family":"Fu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Hunan Province for Integrated Traditional Chinese and Western Medicine on Prevention and Intervention of Cardio-Cerebral Diseases, School of Integrated Chinese and Western Medicine, Hunan University of Chinese Medicine, Changsha 410208, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenjing","family":"Yu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Hunan Province for Integrated Traditional Chinese and Western Medicine on Prevention and Intervention of Cardio-Cerebral Diseases, School of Integrated Chinese and Western Medicine, Hunan University of Chinese Medicine, Changsha 410208, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengfen","family":"Zhou","sequence":"additional","affiliation":[{"name":"Key Laboratory of Hunan Province for Integrated Traditional Chinese and Western Medicine on Prevention and Intervention of Cardio-Cerebral Diseases, School of Integrated Chinese and Western Medicine, Hunan University of Chinese Medicine, Changsha 410208, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5966-3958","authenticated-orcid":false,"given":"Ting","family":"Chen","sequence":"additional","affiliation":[{"name":"Key Laboratory of Hunan Province for Integrated Traditional Chinese and Western Medicine on Prevention and Intervention of Cardio-Cerebral Diseases, School of Integrated Chinese and Western Medicine, Hunan University of Chinese Medicine, Changsha 410208, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0758-7484","authenticated-orcid":false,"given":"Zhenyan","family":"Song","sequence":"additional","affiliation":[{"name":"Key Laboratory of Hunan Province for Integrated Traditional Chinese and Western Medicine on Prevention and Intervention of Cardio-Cerebral Diseases, School of Integrated Chinese and Western Medicine, Hunan University of Chinese Medicine, Changsha 410208, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6148-9565","authenticated-orcid":false,"given":"Shaowu","family":"Cheng","sequence":"additional","affiliation":[{"name":"Key Laboratory of Hunan Province for Integrated Traditional Chinese and Western Medicine on Prevention and Intervention of Cardio-Cerebral Diseases, School of Integrated Chinese and Western Medicine, Hunan University of Chinese Medicine, Changsha 410208, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Li","sequence":"additional","affiliation":[{"name":"Key Laboratory of Hunan Province for Integrated Traditional Chinese and Western Medicine on Prevention and Intervention of Cardio-Cerebral Diseases, School of Integrated Chinese and Western Medicine, Hunan University of Chinese Medicine, Changsha 410208, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,22]]},"reference":[{"key":"ref_1","unstructured":"World Health Organization (2025). 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