Mengping Guo,1 Bo Sun,2 Xiaochen Ding,2 Jingxiang Su,2 Xiuzhen Wang,1 Xiangjun Qiu2 

1Department of Pharmacy, Luoyang Orthopedic-Traumatological Hospital of Henan Province, Henan Provincial Orthopedic Hospital Zhengzhou Campus, Zhengzhou, Henan, 450016, People’s Republic of China; 2College of Basic Medicine and Forensic Medicine, Henan University of Science and Technology, Luoyang, Henan, 471023, People’s Republic of China

Correspondence: Xiuzhen Wang, Department of Pharmacy, Luoyang Orthopedic-Traumatological Hospital of Henan Province, Henan Provincial Orthopedic Hospital Zhengzhou Campus, Zhengzhou, Henan, 450016, People’s Republic of China, Email wangxiuzhen86@163.com Xiangjun Qiu, College of Basic Medicine and Forensic Medicine, Henan University of Science and Technology, Luoyang, Henan, 471023, People’s Republic of China, Email lyxiangjun@126.com

Background: SiMiaoWan (SMW) can clear heat, expel dampness, tonify the kidney, strengthen the muscles, and treat damp heat in the spleen, stomach, and Lower Jiao. SMW is a formula commonly used for the clinical treatment of gout and hyperuricemia (HUA), especially asymptomatic HUA, and has shown remarkable therapeutic effects. This study aimed to investigate the therapeutic effect and mechanisms of SMW in a rat model of HUA using serum metabolomics.
Methods: Rats were administered high levels of uric acid (UA) to establish a model of hyperuricemia and subsequently treated with SMW. Then, the levels of the biochemical indicators serum uric acid (SUA), alanine aminotransferase (ALT), aspartate transaminase (AST), urea nitrogen (BUN), and creatinine (CRE) were measured, and histological analysis of stained liver and kidney tissue sections was performed. Furthermore, blood samples were collected after the animal experiment for serum untargeted metabolomics analysis via ultra-performance liquid chromatography–tandem mass spectrometry (UPLC‒MS/MS) and subsequent Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment pathway analysis.
Results: The levels of the biochemical indicators were significantly lower in rats treated with SMW than in control rats. Additionally, metabolomics and KEGG enrichment pathway analyses indicated that central carbon metabolism, protein digestion and absorption, and amino acid biosynthesis pathways may play important regulatory roles in the SMW-mediated lowering of the SUA level in hyperuricemic rats.
Conclusion: SMW effectively reduced the SUA level in hyperuricemic rat models and alleviated the renal impairment induced by hyperuricemia. The mechanism of SMW is closely associated with pathways related to central carbon metabolism in cancer, protein digestion and absorption, and amino acid biosynthesis.

Keywords: SiMiaoWan, hyperuricemia, liver and kidney function, metabolomics, Kyoto Encyclopedia of Genes and Genomes