Fig. 6

Schematic representation of the proposed model for immune regulatory function of synaptamide-induced GPR110 activation in LPS-induced neuroinflammation exacerbated by ethanol. LPS activates peripheral immune cells such as macrophages and increases the level of pro-inflammatory mediators. Priming with ethanol exacerbates inflammatory responses induced by LPS. The cytokines produced by peripheral immune cells cross the blood–brain barrier and activate microglia, resulting in neuroinflammation through downregulating the cAMP system and activating NLRP3 inflammasome. Pharmacological administration of synaptamide exerts its therapeutic effect on central and peripheral targets that express GPR110 or induce GPR110 expression after LPS and/or ethanol challenge. By activating GPR110, synaptamide ameliorates neuroinflammation under ethanol exacerbated conditions by upregulating the cAMP production system and suppressing NLRP3 inflammasome activation. Ethanol and synaptamide can cross the blood–brain barrier