Yimnual C.Sontikun J.Yaovakhan V.Kuno S.Pothipan P.Muanprasat C.Soontornniyomkij V.Moonwiriyakit A.Mahidol University2026-06-212026-06-212026-01-01Current Research in Pharmacology and Drug Discovery Vol.11 (2026)https://repository.li.mahidol.ac.th/handle/123456789/117443G-protein coupled receptor 40 (GPR40), also termed free fatty acid receptor 1 (FFAR1) is a promising molecular target for treating chronic metabolic and inflammatory diseases. Despite the antiasthmatic benefit of GPR40 agonists such as omega-3 polyunsaturated fatty acids, it remains unclear whether GPR40 activation improves allergic asthmatic outcomes. The present study investigated the ameliorative effect of GPR40 activation on IL-13-induced allergic inflammation in human bronchial epithelial 16HBE14o-cells and in the ovalbumin-induced asthmatic murine model. The increasing concentration of GPR40 agonists GW9508 and TAK875, markedly mitigated IL-13–induced STAT6 phosphorylation and MUC5AC hypersecretion, suggesting mitigated type 2 inflammation in 16HBE14o-cells. The selective GPR40 antagonists DC260126 and GW1100 both strikingly abolished the anti-inflammatory effect of GW9508. In the asthmatic mouse model, intraperitoneal administration of GW9508 (10 mg/kg) alleviated ovalbumin-induced mucus hypersecretion and airway inflammation, with a reduction in STAT6 phosphorylation in lung tissue. Our findings suggest that GPR40 activation represents a novel therapeutic strategy for STAT6-mediated or type-2-inflammation mediated diseases such as allergic asthma.Agricultural and Biological SciencesArticleSCOPUS10.1016/j.crphar.2026.1002602-s2.0-10504195261325902571