Anti-inflammatory effects of Pyrus pyrifolia extract via modulation of Src/Syk-mediated NF-κB signaling.

Pyrus pyrifolia (Asian pear) is widely consumed in East Asia and has reported anti-inflammatory properties, but its molecular mechanisms remain unclear. In this study, we investigated the anti-inflammatory effects of an ethanol extract of P. pyrifolia (Pp-EE) using cellular and animal models. Network pharmacology predicted NF-κB signaling as a major target. In macrophages stimulated with Toll-like receptor ligands, Pp-EE suppressed nitric oxide production, reduced iNOS, IL-6, and COX-2 expression, and inhibited NF-κB activity without cytotoxicity. Mechanistically, Pp-EE attenuated early activation of Src and Syk kinases and inhibited downstream PI3K-AKT-IKK signaling. Molecular docking and cellular thermal shift assays supported interactions between phenolic constituents and these kinases. In vivo, Pp-EE alleviated gastric mucosal injury and reduced neutrophil infiltration in inflammatory models. These findings suggest that P. pyrifolia exerts anti-inflammatory effects through modulation of Src/Syk-mediated NF-κB signaling. The online version contains supplementary material available at 10.1007/s10068-026-02241-6.