Pharmaceutical wastewater irrigation and metabolite-based environmental pharmacognosy: a perspective on quality and safety risks for medicinal plants.

Medicinal plants are increasingly cultivated in agroecosystems irrigated with treated or untreated wastewater, biosolids and contaminated surface water. Pharmaceutical residues are recognised contaminants of emerging concern, but their implications for botanical-drug quality, therapeutic consistency and safety remain insufficiently characterised. This Perspective argues that pharmaceutical wastewater irrigation is a plausible yet underexamined driver of metabolite reprogramming in medicinal plants. Chronic exposure to antibiotics, non-steroidal anti-inflammatory drugs, antiepileptics, antidepressants, hormones and transformation products may alter secondary metabolism through oxidative stress, xenobiotic detoxification, rhizosphere microbiome disturbance and modified nutrient signalling. These processes may change phenolic, flavonoid, alkaloid, terpenoid, glycoside and volatile metabolites that underpin pharmacognostic quality and ethnopharmacological reliability. Medicinal plants may also accumulate parent pharmaceuticals, transformation products and, under some conditions, microbial signatures associated with antibiotic resistance. Building on Carter et al.'s source-pathway-receptor framework and Helmecke et al.'s regulatory risk synthesis, we shift attention from residue burden to how exposure history alters the medicinal metabolome. Evidence from antibiotic-induced metabolite changes in Pinellia ternata supports this proposition, while indicating compound- and context-specific effects. We advance a balanced position: metabolite reprogramming is biologically credible, but food-crop studies often report de minimis residue risks and inconsistent rhizosphere-resistome effects. Future work should integrate wastewater profiling, matched controls, targeted and untargeted metabolomics, transformation-product discovery, microbiome analysis, digestion and bioaccessibility testing, bioactivity assays and probabilistic mixture-risk assessment.