Abstract：
This study aims to explore the potential metabolic pathways and targets of Puerariae Thomsonii Radix in the clinical treatment of mild dyslipidemia. UPLC-Q-TOF-MS and EASY-nLC-timsTOF-Pro2 were employed to perform metabolomic and proteomic analyses of the plasma samples collected from the patients with mild dyslipidemia at baseline and after 12 weeks of treatment with Puerariae Thomsonii Radix. The multivariate statistical analysis was carried out for comparison between groups, and the correlation analysis was performed for the metabolites and proteins closely related to mild dyslipidemia with the blood lipid indexes. The possible pathways and targets for mitigating mild dyslipidemia were screened out by the Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analysis. The results showed that 56 differential metabolites and 78 differential proteins in the plasma of patients were associated with Puerariae Thomsonii Radix treatment. In addition, changes were detected for the proteins or metabolites(ApoB-100, 9,10-DHOME, GAPDH, PGK1, PGAM1, ENO1, etc.) involved in lipoprotein, lipid, and glucose metabolism and the proteins or metabolites(oxidized phospholipid, PLA2G7, LTA4H, etc.) related to inflammation and oxidative stress. Puerariae Thomsonii Radix may down-regulate the overexpression of ApoB-100, activate the peroxisome proliferator-activated receptor α/γ(PPARα/γ), promote the catabolism of fat and glycerol, and alleviate the oxidative stress mediated by oxidized phospholipids and leukotriene B4(LTB4) in the treatment of mild dyslipidemia.
摘要：
本研究旨在探讨葛根在临床治疗轻度血脂异常中的潜在代谢途径和作用靶点。采用UPLC-Q-TOF-MS和EASY-nLC-TimsTOF-Pro2对基线和用葛根治疗12周后从轻度血脂异常患者收集的血浆样品进行代谢组学和蛋白质组学分析。进行多变量统计分析，进行组间比较，并对与轻度血脂异常密切相关的代谢产物和蛋白与血脂指标进行相关性分析。通过基因本体论（GO）和京都基因和基因组百科全书（KEGG）富集分析筛选出缓解轻度血脂异常的可能途径和靶标。结果表明，患者血浆中56种差异代谢物和78种差异蛋白与葛根治疗有关。此外,检测到蛋白质或代谢物的变化(ApoB-100，9,10-DHOME，GAPDH,PGK1、PGAM1、ENO1等.)参与脂蛋白，脂质，和葡萄糖代谢和蛋白质或代谢物(氧化磷脂，PLA2G7,LTA4H,等。)与炎症和氧化应激有关。葛根可能下调ApoB-100的过表达,激活过氧化物酶体增殖物激活受体α/γ(PPARα/γ),促进脂肪和甘油的分解代谢，减轻氧化磷脂和白三烯B4（LTB4）介导的氧化应激，治疗轻度血脂异常。
