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Background: Nickel (Ni) contamination is a significant constraint to agricultural sustainability and medicinal plant productivity, leading to oxidative stress, nutrient imbalance, and disruption of secondary metabolism. Dopamine (DA) has been reported as a stress-mitigating agent in plants. Still, its role in shaping antioxidants and phenolic responses to Ni toxicity in medicinal species, such as Salvia officinalis, remains poorly understood.

Results: Exposure to increasing Ni concentrations (0–1000 µM) significantly reduced biomass (-46%), chlorophyll b (-57%), and shoot Ca and Fe contents (-50% and − 63%, respectively), while elevating oxidative markers (hydrogen peroxide (H2O2), malondialdehyde (MDA); 2.6-fold increase). Foliar DA application (0-100 µM) partially alleviated these effects by restoring biomass (+ 42%), enhancing Ca and Fe translocation (up to 1.7-fold), and maintaining carotenoid levels at nearly twice the control level under moderate stress. DA reduced oxidative markers by 16–24% and moderated the over-accumulation of superoxide dismutase (SOD), catalase (CAT), and peroxidase (POD) activities. Significantly, DA promoted phenolic-based antioxidant responses, increasing phenylalanine ammonia-lyase (PAL) (3.8-fold) and tyrosine aminotransferase (TAT) (1.5-fold) activities and stimulating rosmarinic acid accumulation (up to 91% above control). Multivariate analyses (principal component analysis (PCA), heatmap clustering, correlation networks, random forest) supported these findings, indicating that DA-treated plants clustered with low-stress phenotypes and shifted their defense balance toward phenolic rather than enzyme-dominated strategies.

Conclusions: This study provides integrative physiological and metabolic evidence that DA enhances Ni tolerance in sage by reducing oxidative damage, supporting nutrient uptake, and reinforcing phenolic metabolism. These results highlight DA as a promising candidate biostimulant under controlled conditions, with relevance to the sustainable cultivation of medicinal plants in metal-contaminated soils, pending further validation.