Zuoming Cao, Yan Wang, Zuoting Yang, Xiaoyu Gao, Jun Sheng, Yang Tian, Lei Peng
Panax notoginseng stems and leaves are abundant agricultural residues generated during root harvest, rich in flavonoids yet remain largely underutilized as a valuable phytochemical source. This study optimized a green steaming-sodium bicarbonate aqueous extraction process via orthogonal design. Optimal conditions (steaming 1 h, 1.0% food-grade NaHCO3, boiling extraction 2 h, 1:20 g/mL) achieved a solid yield of 13.50 ± 0.41%, significantly higher than conventional water extraction (7.98 ± 0.41%, p < 0.05), demonstrating enhanced recovery of bioactive compounds. The extract exhibited 91.95 ± 0.08% xanthine oxidase inhibition (IC50 = 5.0 mg/mL) with reversible mixed-type inhibition (Ki = 4.99 mg/mL). UHPLC-MS/MS identified 3392 metabolites, predominantly flavonoids, alkaloids, and organic acids with potential XO inhibitory activity. Network pharmacology and molecular docking revealed multi-target interactions involving ADRA2A, ADA, GAA, PNP, and PTGS2 enriched in purine metabolism and AGE-RAGE signaling pathways, with quercetin 3-Gentiobioside exhibiting the strongest binding affinity and favorable ligand-target interactions (ΔG = -12.91 kcal/mol). This eco-friendly strategy employs only pure water and food-grade additives, efficiently concentrating xanthine oxidase inhibitors and offering a clean-label, sustainable approach for high-value utilization of P. notoginseng agricultural residues. These findings provide a pharmacological basis for developing functional foods targeting hyperuricemia and associated metabolic disorders.