A Novel Salicylic Rice Safener Fulfilled through Supramolecular Capsulation

Abstract Rice, a major global food crop, faces considerable challenges from herbicide damage, particularly pre‐emergent herbicides like Pretilachlor (Pre). Herbicide‐resistant rice varieties and efficient, environmentally friendly safeners for Pre are still lacking. Substituted salicylic acid safeners show the potential to relieve herbicide damage but are limited by poor solubility and penetration. This study explores a novel substituted salicylic acid derivative salt, matrine (MT)‐3‐nitrosalicylic acid (3‐NO 2 SA) salt (MNS), as a safener for Pre. MNS, with enhanced solubility, demonstrated better penetration in rice cells than fenclorin (Fen), the only commercial safener for Pre, which is less effective and poses environmental risks. MNS activates the glutathione metabolism detoxification pathway more effectively than Fen, leading to a superior safening effect. To further enhance solubility and plant uptake, MNS is loaded into a supramolecular nanocarrier, beta‐hydroxycyclodextrin (HBPCD), to fabricate a nanoformulation (MNS@HBPCD). In field trials, MNS@HBPCD outperformed Fen, improving 26% seedlings number, 15% shoot height, 9% root length, 27% fresh weight, and 14% yield, while maintaining Pre's herbicidal efficacy. Toxicity tests indicated that it is significantly less toxic to zebrafish embryos, HepG2 cells, and HaCaT cells than Fen. Thus, MNS@HBPCD shows promise as an environmentally friendly crop protection material that effectively mitigates herbicide damage.