Abstract

Ethnopharmacological relevance: The seeds of Hovenia acerba water extract (HAW) are used as an edible traditional Chinese medicine to treat diseases related to hyperuricemia (HUA).

Aim of the study: To evaluate HAW for its anti-HUA effect and to figure out their underlying mechanisms.

Materials and methods: The anti-HUA effects were evaluated on a mouse model by testing HAW's effects on the levels of serum uric acid (SUA), the biochemical indicators of liver and kidney function, and the histology of liver and kidney. Body weight and organ coefficients were determined for safety evaluation. RT-qPCR, Western blot and transcriptomic analysis was applied to investigate key mRNAs, proteins and signaling pathways.

Results: HAW significantly reduced the serum levels of UA, ALT, AST, and xanthine oxidase (XOD) and histologically alleviated the liver damage in HUA mice with no negative effect on body weight and organ coefficients. HAW markedly inhibited hepatic XOD activity and protein expression, significantly down-regulated mRNA and protein expressions of urate transporter 1 (URAT1) and glucose transporter 9 (GLUT9), and up-regulated those of ATP transporter G2 (ABCG2) and renal organic anion transporter 1 (OAT1). RNA-seq analysis showed that 248 HUA-induced differential expression genes (DEGs) were reversed by HAW in the kidney. qRT-PCR analysis showed that regulation of the expressions of HUA-related inflammatory genes were involved.

Conclusion: HAW possessed remarkable anti-HUA effect. The mechanism involved XOD inhibition to reduce uric acid production, up-regulation of ABCG2 and OAT1 to increase uric acid excretion, and down-regulation of GLUT9 and URAT1 to inhibit uric acid reabsorption, and regulation of HUA-related inflammatory genes.