Anti-hypoxic activity of Biyang floral mushroom polyphenols: deep eutectic solvent-based ultrasound-assisted extraction versus ethanol extraction.

UNLABELLED: This study evaluated the anti-hypoxic activity of Biyang floral mushroom polyphenols (BFMPs) extracted using deep eutectic solvent (DES)-based ultrasound-assisted and ethanol methods. In vitro, BFMPs-DES (200 μg/mL) increased the viability of CoCl2-induced PC12 cells by 73.40% vs. the hypoxia group. In vivo, BFMPs-DES (200 mg/kg) prolonged the survival duration of mice under normobaric hypoxia by 54.24% vs. the hypoxia group. Chromatography analysis revealed a higher relative abundance of propyl gallate (PG, 22.58 ng/mg) in BFMPs-DES. PG pretreatment effectively increased cell viability, elevated GSH level, and reduced MDA production and LDH activity in CoCl2-induced PC12 cells. Integrated network pharmacology, bioinformatics, and immunohistochemistry validation indicated that PG pretreatment could regulate effectively the protein expression level of HIF-1α, EPO, and VEGF, thereby ameliorating hypoxia injury. These findings suggest that BFMPs-DES possess notable anti-hypoxic properties, with PG as the pivotal bioactive compound. This work expands the application potential of Biyang floral mushrooms against hypoxia. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10068-026-02230-9.