Polysaccharide extracted from Phellinus igniarius attenuated hyperuricemia by modulating bile acid metabolism and inhibiting uric acid synthesis in adenine/potassium oxonate-treated mice

Yuhan Gan; Yuting Zeng; Jingyi Huang; Yuxi Li; Qing Zhu; Lei Wang

doi:10.1016/j.jep.2025.119365

Polysaccharide extracted from Phellinus igniarius attenuated hyperuricemia by modulating bile acid metabolism and inhibiting uric acid synthesis in adenine/potassium oxonate-treated mice

J Ethnopharmacol. 2025 Jan 19:119365. doi: 10.1016/j.jep.2025.119365. Online ahead of print.

Authors

Yuhan Gan¹, Yuting Zeng², Jingyi Huang³, Yuxi Li³, Qing Zhu⁴, Lei Wang⁵

Affiliations

¹ School of Traditional Chinese Medicine, Guangdong Pharmaceutical University, Guangzhou, China; Key Laboratory of Glucolipid Metabolic Disorder, Ministry of Education of China, Guangdong Pharmaceutical University, Guangzhou, China.
² School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, China.
³ Key Laboratory of Glucolipid Metabolic Disorder, Ministry of Education of China, Guangdong Pharmaceutical University, Guangzhou, China.
⁴ Key Laboratory of Glucolipid Metabolic Disorder, Ministry of Education of China, Guangdong Pharmaceutical University, Guangzhou, China. Electronic address: [email protected].
⁵ School of Traditional Chinese Medicine, Guangdong Pharmaceutical University, Guangzhou, China. Electronic address: [email protected].

PMID: 39837359
DOI: 10.1016/j.jep.2025.119365

Abstract

Ethnopharmacological relevance: Phellinus igniarius (Linnearus: Fries) Quelet (Phellinus igniarius) is an edible and medicinal fungi and has been used in China for centuries. It is found to improve organs function and metabolic homeostasis including ameliorating hyperuricemia (HUA). Polysaccharide is a predominant component in P. igniarius.

Aims of this study: This study aimed to investigate the anti-HUA effects and underlying mechanism of the polysaccharide extracted from P. igniarius (PPI).

Materials and methods: PPI was extracted and characterized by molecular weight, monosaccharide composition and FT-IR spectroscopy. HUA was induced in C57BL/6 male mice by gavage of adenine/potassium oxonate for 14 days. PPI (2.2, 4.4 or 8.8 mg/kg) was orally given to HUA mice and its effects on HUA were determined.

Results: Compared to HUA group, PPI significantly reduced the serum levels of uric acid (UA), creatinine, blood urea nitrogen (BUN), AST, ALT, and total cholesterol. In the liver of HUA mice, PPI notably inhibited the activity of xanthine oxidase (XOD) and its expression mediated by peroxisome proliferator-activated receptor α (PPARα), suggesting a decrease in UA synthesis. Furthermore, PPI was found to modulate enterohepatic bile acid (BA) metabolism. The profile of BAs showed that PPI significantly elevated the TUDCA+THDCA levels in the liver of HUA mice. In the hepatocytes HepG2, TUDCA decreased the expression of PPARα/XOD and reduced UA production, whereas THDCA did not present similar effects. The anti-HUA effects of TUDCA was further confirmed in HUA mice, where it lowered serum UA level and inhibited XOD expression and activity.

Conclusion: This study demonstrates that PPI ameliorates HUA in vivo, and this effect may be mediated by the regulation of bile acid metabolism, particularly through the function of TUDCA in suppressing UA production in the liver.

Keywords: Phellinus igniarius; TUDCA; XOD; bile acid metabolism; hyperuricemia; polysaccharide.