PDF(Pubmed)
Abstract：
Plantaginis semen is the dried ripe seed of Plantago asiatica L. or Plantago depressa Willd., which has a long history in alleviating hyperuricemia (HUA) and chronic kidney diseases. While the major chemical ingredients and mechanism remained to be illustrated. Therefore, this work aimed to elucidate the chemicals and working mechanisms of PS for HUA. UPLC-QE-Orbitrap-MS was applied to identify the main components of PS in vitro and in vivo. RNA sequencing (RNA-seq) was conducted to explore the gene expression profile, and the genes involved were further confirmed by real-time quantitative PCR (RT-qPCR). A total of 39 components were identified from PS, and 13 of them were detected in the rat serum after treating the rat with PS. The kidney tissue injury and serum uric acid (UA), xanthine oxidase (XOD), and cytokine levels were reversed by PS. Meanwhile, renal urate anion transporter 1 (Urat1) and glucose transporter 9 (Glut9) levels were reversed with PS treatment. RNA-seq analysis showed that the PPAR signaling pathway; glycine, serine, and threonine metabolism signaling pathway; and fatty acid metabolism signaling pathway were significantly modified by PS treatment. Further, the gene expression of Slc7a8, Pck1, Mgll, and Bhmt were significantly elevated, and Fkbp5 was downregulated, consistent with RNA-seq results. The PPAR signaling pathway involved Pparα, Pparγ, Lpl, Plin5, Atgl, and Hsl were elevated by PS treatment. URAT1 and PPARα proteins levels were confirmed by Western blotting. In conclusion, this study elucidates the chemical profile and working mechanisms of PS for prevention and therapy of HUA and provides a promising traditional Chinese medicine agency for HUA prophylaxis.
摘要：
车前草精液是车前草的干燥成熟种子。,在缓解高尿酸血症（HUA）和慢性肾脏疾病方面有着悠久的历史。而主要的化学成分和机理还有待说明。因此,这项工作旨在阐明PS用于HUA的化学物质和工作机制。应用UPLC-QE-Orbitrap-MS在体外和体内鉴定PS的主要成分。进行RNA测序（RNA-seq）以探索基因表达谱，并通过实时定量PCR（RT-qPCR）进一步确认所涉及的基因。从PS中总共鉴定出39种成分，用PS处理后，在大鼠血清中检测到13种。肾组织损伤与血清尿酸(UA)、黄嘌呤氧化酶(XOD),和细胞因子水平被PS逆转。同时,PS治疗可逆转肾尿酸阴离子转运蛋白1(Urat1)和葡萄糖转运蛋白9(Glut9)水平.RNA-seq分析表明PPAR信号通路;甘氨酸,丝氨酸,和苏氨酸代谢信号通路；脂肪酸代谢信号通路被PS处理显著修饰。Further,Slc7a8、Pck1、Mgll、Bhmt显著升高，Fkbp5下调，与RNA-seq结果一致。PPARα信号通路涉及PPARα，pparγ,Lpl,Plin5Atgl,PS治疗使Hsl升高。通过蛋白质印迹确认URAT1和PPARα蛋白水平。总之,本研究阐明了PS预防和治疗HUA的化学概况和工作机制，并为HUA预防提供了有前途的中药机构。
