Guo Mengping, Sun Bo, Ding Xiaochen, Su Jingxiang, Wang Xiuzhen, Qiu Xiangjun
Department of Pharmacy, Luoyang Orthopedic-Traumatological Hospital of Henan Province, Henan Provincial Orthopedic Hospital Zhengzhou Campus, Zhengzhou, Henan, 450016, People's Republic of China.
College of Basic Medicine and Forensic Medicine, Henan University of Science and Technology, Luoyang, Henan, 471023, People's Republic of China.
Drug Des Devel Ther. 2025 Jul 7;19:5761-5779. doi: 10.2147/DDDT.S533394. eCollection 2025.
(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.
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.
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.
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.
四妙丸能清热利湿、补肾壮骨,治疗脾胃及下焦湿热。四妙丸是临床治疗痛风和高尿酸血症(HUA),尤其是无症状HUA常用的方剂,已显示出显著的治疗效果。本研究旨在利用血清代谢组学研究四妙丸对HUA大鼠模型的治疗作用及其机制。
给大鼠投喂高剂量尿酸以建立高尿酸血症模型,随后用四妙丸进行治疗。然后,检测血清尿酸(SUA)、丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)、尿素氮(BUN)和肌酐(CRE)等生化指标水平,并对肝脏和肾脏组织切片进行染色后的组织学分析。此外,动物实验结束后采集血样,通过超高效液相色谱-串联质谱(UPLC-MS/MS)进行血清非靶向代谢组学分析,并随后进行京都基因与基因组百科全书(KEGG)富集通路分析。
四妙丸治疗的大鼠生化指标水平显著低于对照大鼠。此外,代谢组学和KEGG富集通路分析表明,中心碳代谢、蛋白质消化吸收和氨基酸生物合成途径可能在四妙丸介导的高尿酸血症大鼠SUA水平降低中发挥重要调节作用。
四妙丸有效降低了高尿酸血症大鼠模型的SUA水平,减轻了高尿酸血症所致的肾损伤。四妙丸的作用机制与癌症中与中心碳代谢、蛋白质消化吸收和氨基酸生物合成相关的途径密切相关。