The Green Liver of the field: molecular transport, detoxification, and microbiome regulation of pharmaceutical fate in crops

Abstract Pharmaceutical residues are increasingly detected in agricultural soils and crops, largely due to the use of reclaimed wastewater and the application of organic amendments such as biosolids and manure. This review expands the classical Green Liver concept by proposing an integrated plant-microbe framework in which plant metabolism, transporter- and carrier-mediated routing, and microbiome-driven transformations collectively shape pharmaceutical fate in horticultural systems. Rather than acting as passive sinks, plants regulate xenobiotic uptake, transformation, redistribution, and sequestration through coordinated Phase I (functionalization), Phase II (conjugation), and Phase III (compartmentation) detoxification processes. We examine how pharmaceutical properties, particularly ionization and hydrophobicity, interact with soil conditions and plant physiology to influence root uptake, vascular transport, and tissue-specific accumulation. Membrane transporters, including ABCC/MRP, ABCG/PDR, and MATE families, are central to cellular efflux and vacuolar sequestration, while major latex-like proteins (MLPs) have been proposed as candidate soluble carriers for selected hydrophobic xenobiotics, although their role in pharmaceutical transport remains unverified. In parallel, rhizospheric and endophytic microbiomes contribute complementary transformation pathways and stress buffering, extending detoxification beyond individual plants into a distributed plant-microbe network. Together, these advances redefine the Green Liver framework as a mechanistic basis for understanding pharmaceutical behavior in horticultural crops and provide a foundation for safer water reuse, reduced residue accumulation, and sustainable crop production.