Multidimensional risk assessment of yield-enhancing plant growth regulators in medicinal plants: A case study of paclobutrazol in Ophiopogon japonicus with metabolomics, bioactivity, and regulatory implications.

The illicit use of plant growth regulators in medicinal plant cultivation poses potential environmental and public health risks, exemplified by paclobutrazol (PBZ) application on Ophiopogon japonicus (OJ). The new Chinese Pharmacopoeia establishes the first mandatory standard limiting PBZ residues in OJ. This study aimed to evaluate the agronomic benefits, residue risks, metabolomic alterations, and preliminary biological consequences of PBZ application in OJ under field conditions to support the new standard's implementation. PBZ increased OJ yield by 43.7%-47.7% at medium concentrations but posed residue risks, with levels reaching 1.3- to 5.4-fold of the limit at medium-to-high concentrations. PBZ differentially regulated metabolite profiles, promoting representative homoisoflavonoids (8.9%-98.8% increase) while suppressing steroidal saponins (7.6%-32.8% decrease). PBZ enhanced anti-inflammatory activity (up to ∼40%) but attenuated antioxidant capacity (>20% reduction), exploratory correlation analysis suggested potential associations between activity changes and metabolite levels. In conclusion, PBZ impacts beyond residue concerns, inducing substantial alterations in metabolites, with preliminary observations suggesting that these changes may potentially affect the bioactivity and safety of the medicinal material. This study provides baseline data and directions for subsequent ecotoxicological and safety assessments, and may offer references to inform the potential development of evidence-based management policies regarding PGRs.