6'‑O‑Caffeoylarbutin attenuates experimental hyperuricemia by regulating renal and intestinal urate transport, intestinal barrier integrity, and gut microbiota

Résumé fourni par la source

Hyperuricemia (HUA) is primarily attributed to insufficient uric acid (UA) excretion.6'-O-Caffeoylarbutin (CA), the primary bioactive constituent of anti-gout herbal tea (Que Zui tea), has demonstrated potential urate-lowering effects; however, its underlying mechanisms require further elucidation.In the present study, a hypoxanthine (HX) and potassium oxonate (PO) induced hyperuricemia (HUA) mouse model was established to assess the effects of different doses of CA. Biochemical analyses, histopathological examination, western blotting and 16S rRNA gene sequencing were conducted to explore the underlying mechanisms.Notably, CA markedly reduced serum uric acid (SUA), serum creatinine (SCr) and blood urea nitrogen (BUN) levels and alleviated renal and intestinal histopathological damage.In the kidney, CA upregulated ATP-binding cassette sub-family G member 2 (ABCG2), and downregulated glucose transporter 9 (GLUT9) and urate transporter 1 expression (URAT1).In the intestine, CA increased ABCG2, PDZ domain containing 1 (PDZK1) and tight junction protein expression, while decreasing GLUT9, suggesting improved urate excretion and barrier integrity.16S ribosomal RNA sequencing revealed that CA was associated with increased gut microbial diversity and reduced abundance of potentially harmful bacteria, including Desulfovibrio.Phylogenetic Investigation of Communities by Reconstruction of Unobserved States-based prediction suggested accompanying shifts in microbial functions related to transport and metabolism.In conclusion, these findings suggested that CA may exert beneficial effects on HUA involving regulation of renal and intestinal urate transport, improvement of intestinal barrier function and favorable modulation of gut microbiota.CA may therefore serve as a potential candidate for functional food development or therapeutic strategies against HUA.

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