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Core targets were evaluated by molecular docking and dynamics simulation. A\u03b21\u201342-induced AD mice and LPS-stimulated macrophages were used. Cognitive function, A\u03b2 deposition, tau phosphorylation, and inflammatory gene expression were measured.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key findings<\/jats:title>\n                    <jats:p>Network analysis highlighted inflammation-related pathways. Molecular dynamics simulations confirmed stable binding between active components and targets like STAT1, STAT3, JAK2, and TNF. In vivo, G. lucidum extract suppressed abnormal activation of microglia and astrocytes, and reduced pro-inflammatory factors. Following G. lucidum administration, mRNA levels of Jak2 and Stat1 in hippocampal tissue were significantly reduced, suggesting potential regulation of neuroinflammation via the JAK2\/STAT1 pathway. Concurrently, G. lucidum down-regulated transcription of key subunits (Ncstn, Aph-1, Pen-2) in the \u03b3-secretase complex, thereby reducing A\u03b21\u201342 production. In vitro experiments similarly confirmed G. lucidum\u2019s ability to inhibit LPS-induced IL-6 and TNF-\u03b1 release from macrophages.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Ganoderma lucidum extract alleviates neuroinflammation in AD models, providing experimental evidence for its potential application in AD prevention or therapy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/jpp\/rgag105","type":"journal-article","created":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T11:21:03Z","timestamp":1788520863000},"source":"Crossref","is-referenced-by-count":0,"title":["Integrating network pharmacology and experimental validation to uncover the mechanisms of\n                    <i>Ganoderma lucidum<\/i>\n                    in ameliorating neuroinflammation in Alzheimer\u2019s disease"],"prefix":"10.1093","volume":"78","author":[{"given":"Feiya","family":"Sheng","sequence":"first","affiliation":[{"name":"School of Preclinical Medicine, Chengdu University , No. 2025 Chengluo Avenue, Chengdu, Sichuan 610106 ,","place":["China"]},{"name":"Chinese Medicine Germplasm Resources Innovation and Effective Uses Key Laboratory of Sichuan Province, Chengdu University of Traditional Chinese Medicine , No. 1166 Liutai Avenue, Wenjiang District, Chengdu, Sichuan 611137 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia-Mei","family":"Yu","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Chengdu University , No. 2025 Chengluo Avenue, Chengdu, Sichuan 610106 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiao","family":"Yang","sequence":"additional","affiliation":[{"name":"School of Preclinical Medicine, Chengdu University , No. 2025 Chengluo Avenue, Chengdu, Sichuan 610106 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rigu","family":"Jipei","sequence":"additional","affiliation":[{"name":"School of Preclinical Medicine, Chengdu University , No. 2025 Chengluo Avenue, Chengdu, Sichuan 610106 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen-Qi","family":"Xie","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Chengdu University , No. 2025 Chengluo Avenue, Chengdu, Sichuan 610106 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gu","family":"Zhan","sequence":"additional","affiliation":[{"name":"Chinese Medicine Germplasm Resources Innovation and Effective Uses Key Laboratory of Sichuan Province, Chengdu University of Traditional Chinese Medicine , No. 1166 Liutai Avenue, Wenjiang District, Chengdu, Sichuan 611137 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