Plant-Derived Isoferulic Acid and RNAi Synergize to Overcome Detoxification Defenses in the Bird Cherry–Oat Aphid ( <i>Rhopalosiphum padi</i> )

Sustainable management of insect pests is threatened by insecticide resistance, driving demand for effective, environmentally safe tools. The bird cherry-oat aphid (<i>Rhopalosiphum padi</i>), a major cereal pest, shows resistance to pyrethroids, neonicotinoids, and other insecticide classes. We identified isoferulic acid, a phenolic compound from <i>Prunus padus</i>, as a potent aphicide with lethal and sublethal impacts. Bioassays showed dose-dependent lethality (LC₅₀ = 1.74 mg/L at 48 h), while sublethal exposure shortened adult longevity (17.7 to 10.2 d) and reduced fecundity (81 to 53 nymphs/female). Transcriptomic and enzymatic analyses revealed broad induction of detoxification pathways, with <i>RpLipase</i> consistently upregulated. RNAi-mediated knockdown of <i>RpLipase</i> enhanced susceptibility, lowering the LC₅₀ to 0.85 mg/L and confirming its role in tolerance. Nontarget assays with the predator <i>Harmonia axyridis</i> revealed no acute toxicity. Collectively, isoferulic acid is a promising plant-derived insecticide, and silencing induced detoxification genes enhances its potency, providing a foundation for developing novel resistance-breaking strategies.