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Res."],"published-print":{"date-parts":[[2024,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>AC-186 (4-[4-4-Difluoro-1-(2-fluorophenyl) cyclohexyl] phenol) is a neuroprotective non-steroidal selective oestrogen receptor modulator. This study investigated whether inhibition of neuroinflammation contributed to neuroprotective activity of this compound.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>BV-2 microglia were treated with AC-186 (0.65\u20135 \u03bcM) prior to stimulation with LPS\u00a0(100 ng\/mL). Levels of pro-inflammatory mediators and proteins were then evaluated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      Treatment of LPS-activated BV-2 microglia with AC-186 resulted in significant (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.05) reduction in TNF\u03b1, IL-6, NO, PGE\n                      <jats:sub>2<\/jats:sub>\n                      , iNOS and COX-2. Further investigations showed that AC-186 decreased LPS-induced elevated levels of phospho-p65, phospho-I\u03baB\u03b1 and acetyl-p65 proteins, while blocking DNA binding and luciferase activity of NF-\u03baB. AC-186 induced significant (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.05) increase in protein expression of ER\u03b2, while enhancing ERE luciferase activity in BV-2 cells. Effects of the compound on oestrogen signalling in the microglia was confirmed in knockdown experiments which revealed a loss of anti-inflammatory activity following transfection with ER\u03b2 siRNA. In vitro neuroprotective activity of AC-186 was demonstrated by inhibition of activated microglia-mediated damage to HT-22 neurons.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>This study established that AC-186 produces NF-\u03baB-mediated anti-inflammatory activity, which is proposed as a contributory mechanism involved in its neuroprotective actions. It is suggested that the anti-inflammatory activity of this compound is linked to its agonist effect on ER\u03b2.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s00011-024-01952-y","type":"journal-article","created":{"date-parts":[[2024,10,3]],"date-time":"2024-10-03T05:02:03Z","timestamp":1727931723000},"page":"2109-2121","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Inhibition of neuroinflammation and neuronal damage by the selective non-steroidal ER\u03b2 agonist AC-186"],"prefix":"10.1007","volume":"73","author":[{"given":"Folashade O.","family":"Katola","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Misturah Y.","family":"Adana","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olumayokun A.","family":"Olajide","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,10,3]]},"reference":[{"issue":"12","key":"1952_CR1","doi-asserted-by":"publisher","first-page":"965","DOI":"10.1016\/j.tins.2020.10.002","volume":"43","author":"A Podle\u015bny-Drabiniok","year":"2020","unstructured":"Podle\u015bny-Drabiniok A, Marcora E, Goate AM. 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