Isolation of Phenolic Metabolites and Evaluation of the Antioxidant and Metabolic Enzyme-Inhibitory Activities of Polygonum equisetiforme Sm.

Polygonum equisetiforme Sm. is traditionally used in the Mediterranean region as a medicinal plant and herbal tea ingredient. This study aimed to characterize its phenolic constituents and evaluate its in vitro potential against metabolic targets associated with obesity and diabetes. Methanolic and defatted aqueous extracts of the aerial parts were prepared, and the aqueous extract was fractionated using chromatographic techniques. The isolated compounds were characterized by one- and two-dimensional NMR spectroscopy, supported by mass spectrometry where available, and compared with published spectroscopic data. Antioxidant activity was evaluated using 2,2-diphenyl-1-picrylhydrazyl (DPPH), superoxide anion radical (O₂•⁻), nitric oxide (NO), cupric ion reducing antioxidant capacity (CUPRAC), ferric reducing antioxidant power (FRAP), and Trolox equivalent antioxidant capacity (TEAC) assays. Inhibitory effects against α-amylase, α-glucosidase, and pancreatic lipase were determined, and glucose uptake was assessed in 3T3-L1 cells. Seven phenolic compounds were identified: 3-O-acetyl-(−)-epicatechin, liquiritin, catechin, tamarixetin, quercetin, quercetin-3-O-glucoside, and quercetin-3-O-galactoside. Among these, 3-O-acetyl-(−)-epicatechin and tamarixetin are reported for the first time in the genus Polygonum. The phenolic-rich fractions exhibited pronounced antioxidant activity, with Fr. E showing the strongest DPPH radical-scavenging activity (IC₅₀ = 6.00 µg/mL). The methanolic and aqueous extracts inhibited α-amylase (IC₅₀ = 310.95 and 285.00 µg/mL), α-glucosidase (IC₅₀ = 374.04 and 362.82 µg/mL), and pancreatic lipase (IC₅₀ = 519.20 and 868.50 µg/mL), respectively. At 100 µg/mL, both extracts enhanced glucose uptake in 3T3-L1 cells, with a further significant increase observed in the presence of insulin. These findings expand the phytochemical knowledge of P. equisetiforme and demonstrate its multi-target in vitro potential against metabolic processes associated with obesity and diabetes.