Integrative screening of Phytolacca americana extracts: Chromatography, bioassays, and in silico analysis

Phytolacca americana L. (American pokeweed, Phytolaccaceae) is a perennial herb traditionally used for its medicinal properties, yet comprehensive studies on its organ-specific bioactivity remain limited. This study provides an integrative evaluation of the chemical composition and biological activities of fruit and leaf extracts, employing solvent-dependent extraction (methanol, ethyl acetate, water), LC-MS profiling, in vitro antioxidant assays (DPPH, ABTS, CUPRAC, FRAP, metal chelation, phosphomolybdenum), enzyme inhibition assays (cholinesterases, α-amylase, α-glucosidase, tyrosinase), and in silico modeling. Methanol fruit extracts demonstrated exceptional radical scavenging and electron-donating capacity, particularly in the CUPRAC assay (310.62 mg TE/g), whereas leaf extracts excelled in metal chelation and total antioxidant capacity. Methanol extracts also showed the highest inhibitory activity against tyrosinase (54.77 mg KAE/g), alongside significant modulation of other key enzymes. Correlation analyses revealed that bioactivity is strongly influenced by organ-specific metabolite distribution and solvent selectivity. These findings provide a comprehensive integrative characterization of P. americana, highlighting its ethnopharmacological relevance and potential as a source of multifunctional bioactive compounds for neuroprotection, metabolic regulation, dermatology, and functional food development.