Oleanolic Acid Alleviates Hyperuricemia via Gut Microbiota Control the Integrity of Gut Barrier and the Expressions of Urate Transporter in Mice

• DOI: 10.1021/acs.jafc.4c09270
• Publication Date: 2025-02-20T07:50:38Z
• Authors: Tingting Zhang; Siyan Liu; Shenlin Liu; Pengtao Zhao; Chaoqun Zhang; Xiaoyu Wang; Yonghong Meng; Yalong Lu
• Keywords: Abcg2

Hyperuricemia (HUA) is a globally prevalent metabolic disorder characterized by an imbalance in uric acid (UA) production and excretion. In this study, we found that oleanolic (OA), natural pentacyclic triterpene, effectively reduced HUA associated kidney injury C57BL/6J mice. A 12-week OA treatment significantly dose-dependently UA creatinine levels serum urine while suppressing hepatic xanthine oxidase activity Mechanistic analysis revealed modulates the expression of urate transporters including ABCG2, GLUT9, URAT1 small intestine. Furthermore, restored gut microbiota imbalances, increased short-chain fatty production, enhanced expressions intestinal tight junction proteins mice, thereby improving barrier integrity Consequently, fecal transplantation (FMT) was employed to illustrate major mediating role OA's alleviation Recipient mice transplanted with feces from OA-treated exhibited lower blood urinary levels, inflammation, improved balance compared those receiving untreated (p < 0.05). Additionally, FMT normalized transporter reinforced junctions recipient These findings underscore mitigates primarily modulating microbiota, regulating expression, reinforcing integrity, offering novel insights into its preventive potential for managing related complications.