The Active Fraction From Polyporus umbellatus Against Hyperuricemia.

OBJECTIVE: This study aimed to identify the active fraction of Polyporus umbellatus extract (PUE) for the treatment of hyperuricemia (HUA) and elucidate the associated mechanism of action. METHODS: HUA was induced in mice using hypoxanthine and potassium oxonate. Serum uric acid (UA), urinary UA, creatinine (CRE), blood urea nitrogen (BUN), xanthine oxidase (XOD) activity, inflammatory cytokines (Interleukin-6 (IL-6), Tumor necrosis factor-α (TNF-α)), and renal urate transporters (Uric acid transporter 1 (URAT1), Organic anion transporter 1 (OAT1)) were subsequently measured. The active fraction was identified by bioactivity-guided fractionation using D101 macroporous resin chromatography. Two major compounds were isolated and evaluated for anti-inflammatory (nitric oxide (NO) production, cytokine mRNA expression) and antioxidant (Malondialdehyde (MDA), Superoxide dismutase (SOD)) activities in monosodium urate (MSU)-induced RAW264.7 macrophages. RESULTS: PUE significantly ameliorated hyperuricemia in HUA mice, reducing serum UA, CRE, BUN, and renal URAT1 expression; increasing urinary UA excretion and OAT1 expression; inhibiting XOD activity; attenuating renal inflammation and histopathological damage. The 95% ethanol eluate was identified as the most active fraction and yielded ergosterol (A) and 5α,8α-epidioxy-(22E,24R)-ergosta-6,22-dien-3β-ol (B). Both compounds suppressed MSU-induced NO release, proinflammatory cytokine expression, and oxidative stress. CONCLUSION: The 95% ethanol eluate of P. umbellatus exerts anti-hyperuricemic effects through multiple mechanisms, possibly related to XOD inhibition, anti-inflammatory activity, antioxidant protection, and regulation of renal uric acid transport proteins. Ergosterol derivatives are proposed as the potential active components in this extract.