التفاصيل البيبلوغرافية
| العنوان: |
Inhibition of neuroinflammation and neuronal damage by the selective non-steroidal ERβ agonist AC-186: Inhibition of neuroinflammation and neuronal damage by the selective non-steroidal ERβ agonist AC-186: F. O. Katola et al. |
| المؤلفون: |
Katola, Folashade O.1,2 (AUTHOR), Adana, Misturah Y.1,3 (AUTHOR), Olajide, Olumayokun A.1 (AUTHOR) o.a.olajide@hud.ac.uk |
| المصدر: |
Inflammation Research. Dec2024, Vol. 73 Issue 12, p2109-2121. 13p. |
| مصطلحات موضوعية: |
*ANTI-inflammatory agents, *PROTEIN expression, *MICROGLIA, *CYCLOOXYGENASE 2, *NEUROINFLAMMATION, *ESTROGEN |
| مستخلص: |
Background: 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. Methods: BV-2 microglia were treated with AC-186 (0.65–5 μM) prior to stimulation with LPS (100 ng/mL). Levels of pro-inflammatory mediators and proteins were then evaluated. Results: Treatment of LPS-activated BV-2 microglia with AC-186 resulted in significant (p < 0.05) reduction in TNFα, IL-6, NO, PGE2, iNOS and COX-2. Further investigations showed that AC-186 decreased LPS-induced elevated levels of phospho-p65, phospho-IκBα and acetyl-p65 proteins, while blocking DNA binding and luciferase activity of NF-κB. AC-186 induced significant (p < 0.05) increase in protein expression of ERβ, 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 ERβ siRNA. In vitro neuroprotective activity of AC-186 was demonstrated by inhibition of activated microglia-mediated damage to HT-22 neurons. Conclusions: This study established that AC-186 produces NF-κB-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 ERβ. [ABSTRACT FROM AUTHOR] |
| قاعدة البيانات: |
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