{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T19:19:07Z","timestamp":1780082347889,"version":"3.54.0"},"reference-count":71,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2025,12,16]],"date-time":"2025-12-16T00:00:00Z","timestamp":1765843200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Key Research and Development Program of China","award":["2022YFD1600303"],"award-info":[{"award-number":["2022YFD1600303"]}]},{"name":"Agricultural Science and Technology Innovation Program, Institute of Food Science and Technology, Chinese Academy of Agricultural Sciences","award":["CAAS-ASTIP-IFST"],"award-info":[{"award-number":["CAAS-ASTIP-IFST"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Natural alkaloids derived from edible and medicinal plants have recently gained attention as bioactive molecules capable of modulating neuroinflammatory processes. Arecoline, the major alkaloid constituent of Areca catechu L. (betel nut), is well known for its cholinergic actions, yet its direct regulatory influence on microglial immune signaling has remained uncertain. In this study, murine BV2 microglial cells were employed to investigate whether arecoline could counteract lipopolysaccharide (LPS)-induced neuroinflammatory responses. Parameters including cell viability, nitric oxide (NO) production, cytokine secretion, and gene expression were assessed, and mechanistic analyses were focused on the Toll-like receptor 4 (TLR4)\/nuclear factor-\u03baB (NF-\u03baB) and phosphoinositide 3-kinase (PI3K)\/protein kinase B (AKT) pathways. Non-toxic doses of arecoline (10\u201340 \u03bcmol\/L) markedly decreased NO accumulation and reduced the expression of tumor necrosis factor-\u03b1 (TNF-\u03b1), interleukin-6 (IL-6), and interleukin-1\u03b2 (IL-1\u03b2). Western blot analysis further showed that arecoline suppressed LPS-activated microglial signaling by down-regulating TLR4, inhibiting NF-\u03baB p65 phosphorylation, and limiting PI3K\/AKT activation. Collectively, these data reveal that arecoline exerts immunomodulatory and neuroprotective effects through dual signaling regulation in microglia and may serve as a useful pharmacological tool or structural reference for elucidating microglial inflammatory regulation and for guiding the exploration of safer bioactive compounds.<\/jats:p>","DOI":"10.3390\/ijms262412097","type":"journal-article","created":{"date-parts":[[2025,12,16]],"date-time":"2025-12-16T12:47:26Z","timestamp":1765889246000},"page":"12097","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Protective Effects of Arecoline on LPS-Induced Neuroinflammation in BV2 Microglial Cells"],"prefix":"10.3390","volume":"26","author":[{"given":"Xiangfei","family":"Zhang","sequence":"first","affiliation":[{"name":"Institute of Food Science and Technology, Chinese Academy of Agricultural Sciences, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingwen","family":"Cui","sequence":"additional","affiliation":[{"name":"Institute of Food Science and Technology, Chinese Academy of Agricultural Sciences, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3569-7093","authenticated-orcid":false,"given":"Jing","family":"Sun","sequence":"additional","affiliation":[{"name":"Institute of Food Science and Technology, Chinese Academy of Agricultural Sciences, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bei","family":"Fan","sequence":"additional","affiliation":[{"name":"Institute of Food Science and Technology, Chinese Academy of Agricultural Sciences, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fengzhong","family":"Wang","sequence":"additional","affiliation":[{"name":"Institute of Food Science and Technology, Chinese Academy of Agricultural Sciences, Beijing 100193, China"},{"name":"Institute of Food and Nutrition Development, Ministry of Agriculture and Rural Affairs, Beijing 100081, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cong","family":"Lu","sequence":"additional","affiliation":[{"name":"Institute of Food Science and Technology, Chinese Academy of Agricultural Sciences, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,16]]},"reference":[{"key":"ref_1","first-page":"136","article-title":"Role of pro-inflammatory cytokines released from microglia in Alzheimer\u2019s disease","volume":"3","author":"Wang","year":"2015","journal-title":"Ann. 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