AB0053 BERGENIN, ACTING AS AN AGONIST OF SIRT1, REDUCE SERUM URATE IN MICE THROUGH THE UPREGULATION OF ABCG2

Background: About 20% of individuals in the USA have asymptomatic hyperuricaemia [1] . However, Urate-lowering therapy in asymptomatic hyperuricaemia condition is still controversial considering the benefit and side effects [2] . Therefore, safe and effective anti-hyperuricemia therapies are necessary. Objectives: Bergenin, the major bioactive ingredient isolated from Saxifraga stolonifera, could activate SIRT1. In this study, we identify the effect of bergenin on hyperuricemia, and explored the related mechanisms. Methods: Significant hyperuricemia was established in C57BL/6N mice treated with oxonate and yeast polysaccharide. Bergenin was administered to the mice at the same time. The serum uric acid and creatinine levels, clearance of uric acid and creatinine, the intestinal uric acid excretion, and renal pathological lesions were determined were used to evaluate the anti-hyperuricemic effects. The location and expression levels of ABCG2 in the kidney and intestine were analyzed. HK-2 and Caco-2 cell lines were exposed to soluble uric acid with or without the treatment of Bergenin. Then the expression of ABCG2 and underlying mechanisms were explored. Results: The administration of bergenin decreased serum uric acid in hyperuricemic mice by the promotion of uric acid excretion both in kidney and intestine. Bergenin recued the downregulation of ABCG2 in the kidney of hyperuricemic mice and upregulated the expression of ABCG2 in the jejunum and ileum. In vitro, Bergenin significantly increased the expression of ABCG2 as well as activated SIRT1, which was reversed by addition of PPARg antagonist GW9662 and siPPARg. Conclusion: These findings suggest bergenin increases uric acid excretion both in the kidney and intestines, which may be related to the upregulation of ABCG2 via SIRT1- PPARg pathway. References: [1]Zhu, Y., Pandya, B. J. & Choi, H. K. Prevalence of gout and hyperuricemia in the US general population: the National Health and Nutrition Examination Survey 2007–2008. Arthritis Rheum. 63, 3136–3141 (2011). [2]Joosten LAB, Crisan TO, Bjornstad P, Johnson RJ: Asymptomatic hyperuricaemia: a silent activator of the innate immune system. Nature reviews Rheumatology 2020, 16(2):75-86. Disclosure of Interests: None declared