Mechanism of (+)-Isoaltholactone from <i>Goniothalamus griffithii</i> with Excellent Nematicidal Activity against <i>Meloidogyne incognita</i>

To obtain natural nematicides from plants is thought to be an efficient way to manage root-knot nematodes, and (+)-isoaltholactone isolated from <i>Goniothalamus griffithii</i> showed excellent bioactivity against <i>Meloidogyne incognita</i> in vitro, with the LC₅₀ value of 25.19 mg/L (24 h). Importantly, it also exhibited a significant control effect against <i>M. incognita</i> in tobacco pot experiments. Additionally, <i>Caenorhabditis elegans</i> was used as a model organism to investigate the mechanism of action of this nematicidal compound. We found that exposure to (+)-isoaltholactone destroyed the stratum corneum and caused reproductive toxicity, neurotoxicity, and oxidative stress in the worms. Furthermore, based on MolTrans' prediction, molecular docking, and molecular dynamics simulation studies, the results indicated that (+)-isoaltholactone may interact with the target GAR-3. The expression of genes associated with oxidative stress and neurotoxicity was significantly influenced. These findings indicated that (+)-isoaltholactone may cause oxidative stress and neurotoxicity by interfering with the function of the target GAR-3, which would impact the nervous system and muscular activity, ultimately leading to the death of nematodes.