Aporocactus flagelliformis water extract and limonin suppresses P2Y purinoceptor 14-mediated proinflammatory features in 3D4/31 porcine alveolar macrophages.

Respiratory diseases have been recognized as a significant cause of reduced livestock productivity since 1995. Respiratory diseases in the swine industry caused by both biological and non-biological factors are collectively referred to as porcine respiratory disease complex (PRDC). However, there is a lack of eco-friendly anti-inflammatory drugs (AIDs) that can effectively control lung inflammation caused by PRDC. P2Y purinoreceptor 14 (P2Y(14)) has been identified as a key regulator of macrophage inflammatory responses; however, its regulatory role in porcine lung inflammation remains unclear. In this study, we investigated the role of P2Y(14) in inflammation in 3D4/31 porcine macrophages and attempted to develop a novel AID. An extract of the Mexican medicinal plant Aporocactus flagelliformis water extract (AFWE) reduced reactive oxygen species production and pro-inflammatory cytokine expression in phorbol myristate acetate-stimulated 3D4/31-PAMs. It also reduced glucose uptake, glycogen accumulation, and expression of genes related to the P2Y(14) cascade. Polarity-based fractionation and liquid chromatography-mass spectrometry identified limonin as an anti-inflammatory compound in AFWE. Limonin reduced P2RY(14) and proinflammatory gene expression induced by the P2Y(14) ligand UDPG in 3D4/31-PAMs, demonstrating its inhibitory effect on P2Y(14)-mediated inflammation. These results suggest that P2Y(14) is an inflammatory receptor in PAMs and an effective target for AID development. We also propose AFWE and limonin as candidate AIDs for pigs.