Browsing by Author "Olajide, O. A."

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    Inhibition of neuroinflammation and neuronal damage by the selective non-steroidal ERβ agonist AC-186.
    (2024) Adana, M. Y.; Katola, F. O.; Olajide, O. A.
    Background: AC-186 (4-[4-4-Difuoro-1-(2-fuorophenyl) cyclohexyl] phenol) is a neuroprotective non-steroidal selective oestrogen receptor modulator. This study investigated whether inhibition of neuroinfammation contributed to neuroprotec tive 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-infammatory mediators and proteins were then evaluated. Results: Treatment of LPS-activated BV-2 microglia with AC-186 resulted in signifcant (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 signifcant (p<0.05) increase in protein expression of ERβ, while enhancing ERE luciferase activity in BV-2 cells. Efects of the compound on oestrogen signalling in the microglia was confrmed in knockdown experiments which revealed a loss of anti-infammatory 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-infammatory activity, which is proposed as a contributory mechanism involved in its neuroprotective actions. It is suggested that the anti-infammatory activity of this compound is linked to its agonist efect on ERβ