Polyporus species is a valuable species of the Polyporaceae family with defined bioactive properties among medicinal mushrooms. This study was undertaken to investigate the antioxidant, anticholinesterase and antidiabetic activities of Polyporus squamosus (Huds.) Fr. with characterization of phenolic profile by HPLC-DAD. Fumaric acid (190.07±0.08 µg/g), catechin hydrate (46.96±0.02 µg/g), ferulic acid (21.98±0.03 µg/g), trans-cinnamic acid (16.66±0.02 µg/g), and protocatechuic acid (13.29±0.06 µg/g) were detected as the most abundant compounds in P. squamosus by HPLC-DAD. P. squamosus methanol extract exhibited higher antioxidant activity than the hexane extract in β-carotene linoleic acid (IC50: 73.75±0.28 µg/mL), DPPH• scavenging (7.56±0.00% inhibition at 400 µg/mL), ABTS•+ scavenging (IC50: 154.30±0.55 µg/mL), and metal chelating (35.61±1.20% inhibition at 400 µg/mL) assays. P. squamosus hexane extract was determined as the stronger inhibitor than the methanol extract against all enzymes with inhibition values of 39.48±0.45% on AChE at 200 µg/mL, 28.02±1.34% on BChE at 200 µg/mL, 96.70±0.80% on α-amylase at 1000 µg/mL, and 39.93±0.52% on α-glucosidase at 500 µg/mL. The present study highlighted the importance of P. squamosus as a promising source of valuable therapeutic compounds that could be considered as an alternatives to synthetic drugs.
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