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.