{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T12:57:16Z","timestamp":1792155436123,"version":"4.4.0"},"reference-count":63,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,1,7]],"date-time":"2026-01-07T00:00:00Z","timestamp":1767744000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Fundamental Research Funds for the Central public welfare research institutes","award":["ZZ18-ND-12"],"award-info":[{"award-number":["ZZ18-ND-12"]}]},{"name":"Scientific Research Foundation for the introduction of talent","award":["QD-2024008B"],"award-info":[{"award-number":["QD-2024008B"]}]},{"name":"National key research and development program of China","award":["2017YFE0114400"],"award-info":[{"award-number":["2017YFE0114400"]}]},{"name":"Major scientific research tasks of the Science and Technology Innovation Project of the Chinese Academy of Agricultural Sciences","award":["CAAS-ZDRW202111"],"award-info":[{"award-number":["CAAS-ZDRW202111"]}]},{"name":"Major Output Research Topics of Chinese Academy of Agricultural Sciences","award":["CAAS-ZDXT2018008"],"award-info":[{"award-number":["CAAS-ZDXT2018008"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Salmonella typhimurium (S.T) infection of the central nervous system (CNS) induces severe inflammation, leading to elevated expression of inducible nitric oxide synthase (iNOS) in microglia. This process catalyzes excessive production of nitric oxide (NO), resulting in irreversible damage to neuronal mitochondria. Asiatic acid (AA) is a small molecule with neuroprotective potential; however, its ability to counteract nerve injury induced by S.T and the underlying mechanisms remain unclear. In this study, we established an S.T-infected mouse model (in vivo) and an S.T-stimulated microglial model using BV-2 cells (in vitro) and employed techniques including immunofluorescence (IF), Western blot, co-immunoprecipitation (Co-IP), and RNA extraction and quantitative reverse transcription PCR (RT-qPCR) to systematically evaluate the protective effects and mechanisms of AA. The results showed that pre-treatment with AA significantly reduced the expression of iNOS and the production of NO caused by S.T infection in mouse hippocampal tissue and BV-2 cells. Mechanistically, AA exerts its effects by inhibiting the upstream Toll-like receptor 2 (TLR2)\/Notch and nuclear factor-\u03baB (NF-\u03baB) signaling axis. It interferes with the nuclear translocation of Notch and p65 proteins and their complex formation under S.T stimulation, thereby blocking downstream expression of iNOS and production of NO. This study reveals a novel mechanism by which AA alleviates infection-related neuroinflammation through targeting Notch-p65 interactions, providing a new theoretical basis for its clinical application.<\/jats:p>","DOI":"10.3390\/ijms27020602","type":"journal-article","created":{"date-parts":[[2026,1,7]],"date-time":"2026-01-07T09:34:12Z","timestamp":1767778452000},"page":"602","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Asiatic Acid Attenuates Salmonella typhimurium-Induced Neuroinflammation and Neuronal Damage by Inhibiting the TLR2\/Notch and NF-\u03baB Pathway in Microglia"],"prefix":"10.3390","volume":"27","author":[{"given":"Wenshu","family":"Zou","sequence":"first","affiliation":[{"name":"Jiangxi Province Key Laboratory of Traditional Chinese Medicine Pharmacology, Institute of Traditional Chinese Medicine Health Industry, China Academy of Chinese Medical Sciences, Nanchang 330115, China"},{"name":"Postdoctoral Fluxion Station, China Academy of Chinese Medical Sciences, Beijing 100700, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianxi","family":"Li","sequence":"additional","affiliation":[{"name":"Key Laboratory of Veterinary Pharmaceutical Development of Ministry of Agriculture and Rural Affairs of China, Engineering and Technology Research Center of Traditional Chinese Veterinary Medicine of Gansu Province, Lanzhou Institute of Husbandry and Pharmaceutical Sciences of Chinese Academy of Agricultural Sciences, Lanzhou 730050, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,7]]},"reference":[{"key":"ref_1","unstructured":"World Health Organization (2022, April 27). 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