Synergistic effects of melatonin and zinc oxide nanoparticles on oxidative stress mitigation, nutrient accumulation, and secondary metabolite enhancement in Cannabis sativa L

The synergistic interaction between melatonin and zinc oxide nanoparticles (ZnO-NPs) represents a promising approach to enhancing plant performance under physiological stress. This study evaluated the individual and combined effects of melatonin and ZnO-NPs on growth, physiological attributes, oxidative stress mitigation, nutrient uptake, and secondary metabolite production in Cannabis sativa L. Plants were treated with melatonin and ZnO-NPs (5 and 10 ppm) under controlled greenhouse conditions, and responses were analyzed using two-way ANOVA followed by the Least Significant Difference (LSD) test to compare treatment means. Significant interaction effects between melatonin and ZnO-NPs were detected for most parameters. The co-application of melatonin and 10 ppm ZnO-NPs produced the greatest improvements in shoot and root biomass, relative water content, membrane stability, and photosynthetic pigments. Combined treatments markedly reduced hydrogen peroxide (H₂O₂) and malondialdehyde (MDA) levels, indicating enhanced oxidative stress tolerance. ZnO-NPs promoted nutrient accumulation (Ca, K, Mg, Fe, Mn, Cu, and Zn), while melatonin contributed to improved nitrogen metabolism. The joint application further elevated secondary metabolites, including flavonoids, phenolics, alkaloids, cannabidiol (CBD), and tetrahydrocannabinol (THC). These findings demonstrate that melatonin and ZnO-NPs act synergistically to optimize growth, strengthen antioxidant defense, and enhance bioactive metabolite synthesis in hemp, offering potential strategies for sustainable improvement of high-value crops. • Melatonin and ZnO-NPs synergistically reduce oxidative stress in Cannabis sativa . • Combined treatment enhances root growth, protein content, and chlorophyll levels. • Secondary metabolites (CBD, THC, flavonoids, phenolics) significantly increased. • Uptake of essential nutrients (Ca, K, Mg, Fe, Zn) improved under stress conditions. • Melatonin modulates ZnO-NP homeostasis, boosting plant resilience and productivity.