Artemisia selengensis Turcz. leaves extract ameliorates hyperuricemia in mice by inhibiting hepatic xanthine oxidase activity, modulating renal uric acid transporters, and improving metabolic disorders

Abstract

Artemisia selengensis Turcz. (AST) is a common edible and medicinal herb with multiple health benefits. Our previous research indicated that AST leaves, by-products of AST, possess strong in vitro xanthine oxidase (XOD) inhibitory activity, making them a potential treatment for hyperuricemia (HUA). In this study, we investigated the anti-HUA effect of AST leaves extract (ASTLE) in HUA mice and explore the underlying mechanisms. Chemical analysis showed that ASTLE is rich in caffeoylquinic acids (CQAs), including four mono-CQAs (1-CQA, 3-CQA, 5-CQA, and 4-CQA) and six di-CQAs (1,3-diCQA, 1,4-diCQA, 3,4-diCQA, 1,5-diCQA, 3,5-diCQA, and 4,5-diCQA). In HUA mice, ASTLE reduced serum uric acid level and increased urine uric acid level and fraction excretion of uric acid. ASTLE also protected against liver and kidney damage, as evidenced by decreased serum levels of glutamic oxaloacetic transaminase, glutamic-pyruvic transaminase, creatinine, and blood urea nitrogen. After ASTLE intervention, the hepatic XOD activity was inhibited. Additionally, the mRNA expression of mURAT1 and mGLUT9 was down-regulated, while the mRNA expression of mABCG2, mOAT1, and mOAT3 was up-regulated. Metabolomic analysis further suggested that ASTLE mainly regulated amino acids and their metabolites, which are associated with renal uric acid excretion function. These results demonstrate that ASTLE rich in CQAs, has beneficial effects against HUA in mice by inhibiting hepatic XOD activity, modulating the mRNA expression of renal uric acid transporters, and improving metabolic disorders in HUA mice. Our findings suggest that AST leaves may be a promising natural resource for ameliorating HUA.