代谢组学
汤剂
中医药
药理学
化学
代谢物
肾
医学
传统医学
生物化学
内科学
色谱法
病理
替代医学
作者
Wenya Gao,Mingliang Tian,Mingli Li,Shuangrong Gao,Xiaolu Wei,Chunqing Gao,Yanmin Zhou,Tao Li,Hongjie Wang,Baolin Bian,Nan Si,Wenpeng Zhao,Haiyu Zhao
出处
期刊:Phytomedicine
[Elsevier]
日期:2024-04-01
卷期号:126: 155222-155222
标识
DOI:10.1016/j.phymed.2023.155222
摘要
Diabetic nephropathy (DN) is one of the most popular and most significant microvascular complications of diabetes mellitus. Qingxin Lianzi Yin Decoction (QXLZY) was a traditional Chinese classical formula, suitable for chronic urinary system diseases. QXLZY had good clinical efficacy in early DN, but the underlying molecular mechanism remains unrevealed. This study aimed to establish the index component content determination method of QXLZY and explore the mechanism of QXLZY on DN by network pharmacology and metabolomics studies. Firstly, the content determination methods of QXLZY were established with calycosin-7-O-β-D-glucoside, acteoside, baicalin and glycyrrhizic acid as index components. Secondly, pharmacological experiments of QXLZY were evaluated using db/db mice. UHPLC-LTQ-Orbitrap MS was used to carry out untargeted urine metabolomics, serum metabolomics, and kidney metabolomics studies. Thirdly, employing network pharmacology, key components and targets were analyzed. Finally, targeted metabolomics was performed of the endogenous constituents in biological samples for validation based on untargeted metabolomics results. A method of the simultaneous determination of multiple index components in QXLZY was established, which passed the comprehensive methodological verification. It was simple, feasible, and scientific. QXLZY treatment alleviated kidney injury of db/db mice, as the degree of histopathological damage and the level of urinary microalbumin/creatinine ratio. Untargeted metabolomics studies have identified metabolic dysfunction in pathways associated with amino acid metabolism in db/db mice. Treatment with QXLZY could reverse metabolite abnormalities and influence the pathways related to energy metabolism and amino acid metabolism. It has been found that pathways with a high degree were involved in signal transduction, prominently on amino acids metabolism and lipid metabolism, analyzed by network pharmacology. Disorders of amino acid metabolism did occur in db/db mice. QXLZY could revert the levels of metabolites, such as quinolinic acid, arginine, and asparagine. This study demonstrated for the first time that QXLZY alleviated diabetes-induced pathological changes in the kidneys of db/db mice by correcting disturbances in amino acid metabolism. This work could provide a new experimental basis and theoretical guidance for the rational application of QXLZY on DN, exploring the new pharmacological effect of traditional Chinese medicine, and promoting in-depth research and development.
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