Department of Chinese Medicine Literature and Culture, Shandong University of Traditional Chinese Medicine, Jinan, Shandong, 250355, China.
Department of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan, Shandong, 250355, China.
J Ethnopharmacol. 2021 Jan 10;264:113390. doi: 10.1016/j.jep.2020.113390. Epub 2020 Sep 12.
Jiangzhuo Formula (JZF) is a traditional Chinese herbal prescription that is clinically applied to treat dyslipidemia. However, the mechanism underlying its efficacy remains unexplored.
This study aims to elucidate the underlying mechanisms, explore potential pathways, and identify the key proteins of JZF for the treatment of dyslipidemia.
In this work, Q-Orbitrap high-resolution liquid chromatography mass spectrometry was used to identify the natural ingredients in JZF, rats with dyslipidemia were established via a high-fat diet for four weeks, then the dyslipidemia rats were treated with high-dose JZF (9 g/d) and low-dose JZF (4.5 g/d) for four weeks. After treatment, serum lipid detection and Oil-red-O staining were conducted to assess the efficacy of JZF in ameliorating dyslipidemia. Tandem mass tag (TMT) -based quantitative proteomics technology was then used to evaluate the roles and importance of proteins from the extracted hepatic tissue. The differentially expressed proteins were assessed by Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, Gene Ontology (GO), and protein-protein interaction (PPI) networks. Western blot and PCR analysis were used to validate the potential targets regulated by JZF.
JZF could significantly improve the blood lipid profiles of serum and fat deposits of the liver. A total of 123 differentially expressed proteins were detected after JZF intervention, comprising 65 up-regulated proteins and 58 down-regulated proteins. The KEGG pathway analysis revealed that cholesterol metabolism, the PPAR signaling pathway, and bile secretion were the principal pathways involved in the disordered lipid metabolism, while GO analysis suggested that proteins that are located in the cell, regulate cellular processes, and show binding activity contribute to reductions in lipids. The combination of proteomics, Western blot, and PCR suggested that Apolipoprotein B (APOB), Apolipoprotein E (APOE), cholesterol 7 alpha-hydroxylase A1 (CYP7A1), and Hydroxymethylglutaryl-CoA synthase 1 (HMGCS1) might play critical roles in JZF's lipid-lowering network.
JZF can effectively improve lipid profiles via multiple pathways involved in cholesterol metabolism, the PPAR signaling pathway, and bile secretion. Generally, the proteomics techniques used in this research show that JZF could be a promising drug for the treatment of dyslipidemia.
降脂方（JZF）是一种临床应用于治疗血脂异常的中药方剂。然而，其疗效的机制尚不清楚。
本研究旨在阐明 JZF 治疗血脂异常的潜在机制、探索潜在途径和鉴定关键蛋白。
在这项工作中，使用 Q-Orbitrap 高分辨率液相色谱质谱法鉴定 JZF 中的天然成分，通过高脂饮食喂养大鼠 4 周建立血脂异常大鼠模型，然后用高剂量 JZF（9g/d）和低剂量 JZF（4.5g/d）治疗 4 周。治疗后，通过血清脂质检测和油红 O 染色评估 JZF 改善血脂异常的功效。然后，使用串联质量标签（TMT）-基于定量蛋白质组学技术评估从提取的肝组织中蛋白质的作用和重要性。通过京都基因与基因组百科全书（KEGG）途径、基因本体论（GO）和蛋白质-蛋白质相互作用（PPI）网络评估差异表达蛋白。Western blot 和 PCR 分析用于验证 JZF 调节的潜在靶标。
JZF 可显著改善血清血脂谱和肝脏脂肪沉积。JZF 干预后共检测到 123 个差异表达蛋白，包括 65 个上调蛋白和 58 个下调蛋白。KEGG 途径分析表明，胆固醇代谢、PPAR 信号通路和胆汁分泌是参与脂质代谢紊乱的主要途径，GO 分析表明，位于细胞内、调节细胞过程和显示结合活性的蛋白有助于降低脂质。蛋白质组学、Western blot 和 PCR 的组合表明，载脂蛋白 B（APOB）、载脂蛋白 E（APOE）、胆固醇 7α-羟化酶 A1（CYP7A1）和羟甲基戊二酰辅酶 A 合酶 1（HMGCS1）可能在 JZF 的降脂网络中发挥关键作用。
JZF 可通过参与胆固醇代谢、PPAR 信号通路和胆汁分泌的多条途径有效改善血脂谱。总的来说，本研究中使用的蛋白质组学技术表明，JZF 可能是治疗血脂异常的一种有前途的药物。
