Anti-hyperuricemic effects of the seeds of Hovenia acerba in hyperuricemia mice.

J Ethnopharmacol

State Key Laboratory of Functions and Applications of Medicinal Plants & School of Pharmaceutical Sciences, Guizhou Medical University, 6 Ankang Avenue, Guian New District, 561113, Guizhou, China; University Engineering Research Center for the Prevention and Treatment of Chronic Diseases By Authentic Medicinal Materials in Guizhou Province, 6 Ankang Avenue, Guian New District, 561113, Guizhou, China; Guizhou Provincial Engineering Technology Research Center for Chemical Drug R&D, Guizhou Medical University, 6 Ankang Avenue, Guian New District, 561113, Guizhou, China. Electronic address:

Published: December 2024

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.

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Source
http://dx.doi.org/10.1016/j.jep.2024.119215DOI Listing

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