Investigation of the Inhibition of IRE-1/XBP-1 Pathway in the Multiple Nematicidal Mechanisms of Isobavachalcone against <i>Meloidogyne incognita</i>

A natural compound isobavachalcone (IBC) from <i>Crotalaria juncea</i>exhibited an excellent nematicidal effect against <i>Meloidogyne incognita</i>, with an LC₅₀ value of 53.30 mg/L (24 h), which was validated through pot experiments. Further, a novel, multiple nematicidal mechanism of IBC was investigated. We discovered that it simultaneously induced oxidative stress and downregulated key lipid metabolism genes (e.g., <i>fat-5</i>, <i>acox-1.2</i>), leading to a significant reduction in triglyceride and fat content. Notably, IBC was also found to inhibit IRE-1/XBP-1 pathway of the endoplasmic reticulum unfolded protein response (UPR^ER), as evidenced by suppressed IRE-1 phosphorylation, blocked XBP-1 splicing, and reduced expression of the endoplasmic reticulum chaperone gene <i>hsp-4</i>. Moreover, molecular docking and dynamics simulations confirmed that IBC stably bound to the ATP-binding pocket of IRE-1. Importantly, the inhibition of IRE-1/XBP-1 pathway was revealed for the first time in nematode lethality. These findings indicate its potential for development as a novel nematicide.