{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T06:00:17Z","timestamp":1785218417147,"version":"3.55.0"},"reference-count":70,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T00:00:00Z","timestamp":1785196800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Neuroinflammation plays an important role in the initiation and progression of central nervous system (CNS) disorders. Calycosin (Caly) has been reported to exert anti-inflammatory and neuroprotective effects. However, little is known about its potential role in microglia-mediated neurotoxicity and the underlying mechanism. The aim of the present study is to investigate whether Caly attenuates LPS-induced inflammatory response in BV2 microglial cells and microglia-mediated neuronal injuries in HT-22 cells.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      BV2 cells were stimulated with LPS (1\u00a0\u03bcg\/mL, 24\u00a0h) and treated with Caly (5, 10, or 20\u00a0\u03bcM) or Dex (2\u00a0\u03bcM). Molecular docking, CETSA, ITDRF\n                      <jats:sub>CETSA<\/jats:sub>\n                      and DARTS assays were used to evaluate the potential target engagement between Caly and TLR4. Cell viability, microglial activation, inflammatory mediator expression, secreted cytokine levels, and TLR4\/MyD88\/NF-\u03baB signaling pathway were examined. HT-22 cells were cultured with conditioned medium (CM) derived from LPS-stimulated or Caly-treated BV2 cells, cell viability and expression of synaptic plasticity-related proteins were evaluated. Supplementary validation was also performed in HMC3 human microglial cells and SH-SY5Y human neuronal cells.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Stimulation with LPS could induce BV2 microglial activation, accompanied by the increased expression and secretion of pro-inflammatory mediators, and dysregulation of TLR4\/MyD88\/NF-\u03baB signaling pathway. CM derived from LPS-stimulated BV2 cells decreased HT-22 cell viability and reduced synaptic plasticity-related protein expression levels. Caly treatment attenuated LPS-induced cytotoxicity and inflammatory responses, and reversed imbalanced expression of TLR4\/MyD88\/NF-\u03baB signaling pathway in LPS-challenged BV2 cells, as indicated by the reduced Iba-1 fluorescence intensity, decreased mRNA expression levels and secretion of IL-1\u03b2, IL-6, and TNF-\u03b1, and decreased proteins expression of IL-17, TLR4, MyD88, p-NF-\u03baB\/NF-\u03baB and p-IKB\/IKB. Caly also increased the expression of the anti-inflammatory phenotype-associated markers CD206 and Arg1, while reducing the pro-inflammatory markers CD86 and iNOS. Moreover, CM derived from Caly-treated BV2 cells partially restored HT-22 cell viability and protein expression of \u03b2-Tubulin, PSD95, and Synapsin I. Supplementary experiments in HMC3 and SH-SY5Y cells showed similar anti-inflammatory and synaptic protein-preserving effects.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Caly could exert potential effects on suppressing LPS-induced microglia activation and inflammatory responses in immortalized BV2 cells by regulating TLR4\/MyD88\/NF-\u03baB signaling pathway, and attenuating microglia-mediated neuronal injury and synaptic impairment in immortalized HT-22 cells.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1817366","type":"journal-article","created":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T05:37:08Z","timestamp":1785217028000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Calycosin attenuates LPS-induced microglia inflammatory responses and microglia-mediated synaptic impairment via modulation of TLR4\/MyD88\/NF-\u03baB signaling pathway"],"prefix":"10.3389","volume":"17","author":[{"given":"Xinran","family":"Gao","sequence":"first","affiliation":[{"name":"The First Affiliated Hospital of Anhui University of Science and Technology","place":["Huainan, China"]},{"name":"The First Clinical Medical School, Anhui University of Science and Technology","place":["Huainan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruiyang","family":"Wang","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital of Anhui University of Science and Technology","place":["Huainan, China"]},{"name":"The First Clinical Medical School, Anhui University of Science and Technology","place":["Huainan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hejuntao","family":"Chen","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital of Anhui University of Science and Technology","place":["Huainan, China"]},{"name":"The First Clinical Medical School, Anhui University of Science and Technology","place":["Huainan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xu","family":"Chen","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital of Anhui University of Science and Technology","place":["Huainan, China"]},{"name":"The First Clinical Medical School, Anhui University of Science and Technology","place":["Huainan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaojuan","family":"Wang","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital of Anhui University of Science and Technology","place":["Huainan, China"]},{"name":"The First Clinical Medical School, Anhui University of Science and Technology","place":["Huainan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,28]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"923","DOI":"10.1007\/s12035-022-03102-z","article-title":"The dialogue between neuroinflammation and adult neurogenesis: mechanisms involved and alterations in neurological diseases","volume":"60","author":"Amanollahi","year":"2023","journal-title":"Mol. 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