The Affiliated Hospital of Guizhou Medical University, Guizhou Provincial Engineering Research Center of Ecological Food Innovation, The Key Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education, School of Public Health, Guizhou Medical University, Guiyang, 561113, China; Chongqing Medical and Pharmaceutical College, Chongqing, 400030, China.
The Affiliated Hospital of Guizhou Medical University, Guizhou Provincial Engineering Research Center of Ecological Food Innovation, The Key Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education, School of Public Health, Guizhou Medical University, Guiyang, 561113, China; College of Food and Biological Engineering, Chengdu University, Chengdu, 610106, China.
J Ethnopharmacol. 2024 Dec 5;335:118703. doi: 10.1016/j.jep.2024.118703. Epub 2024 Aug 16.
Pueraria lobata (Willd.) Ohwi is a traditional medicinal and edible homologous plant rich in flavonoids, triterpenes, saponins, polysaccharides and other chemical components. At present, studies have shown that Pueraria lobata radix (PR) has the effect of lowering blood sugar, improving insulin sensitivity and inhibiting obesity. However, the specific mechanism of PR inhibits obesity is still unclear, and there are few researches on the anti-obesity effect of PR through the combination of network pharmacology and experiment.
Pharmacology, molecular docking technology and experimental verification through the network, revealing the PR the material basis of obesity and the potential mechanism.
The present study used network pharmacology techniques to investigate the therapeutic effect and mechanism of action of PR. Through relevant databases, a total of 6 main chemical components and 257 potential targets were screened. Protein interaction analysis shows that AKT1, AKR1B1, PPARG, MMP9, TNF, TP53, BAD, and BCL2 are core targets. Enrichment analysis shows that the pathway of PR in preventing obesity involves the cancer signaling pathway and the PI3K-Akt signaling pathway, which may be the main pathways of action. Further molecular docking verification indicates that its core target exhibits good binding activity with 4 compounds: formononectin, purerin, 7,8,4 '- trihydroxide and daidzein. Using the ultra-high performance liquid chromatography-mass spectrometry (UPLC-MS) technology to detected and confirmed these main compounds. Cell experiment results revealed that puerarin inhibits cell proliferation and differentiation in a concentration dependent manner, significantly promoting cell apoptosis and affecting cell migration. Animal experiments have shown that puerarin reduces food intake and weight gain in mice. It was found that puerarin can upregulate HDL and downregulate TC, TG, and LDL blood biochemical indicators. Western blot results showed that puerarin significantly inhibited the expression of AKT1, AKR1B1, MMP9, TNF, TP53, BCL2, PPARG, and significantly increased the expression of BAD protein at both cellular and animal levels.
The present study established a method for measuring PR content and predicted its active ingredients and their mechanisms of action in the treatment of obesity, providing a theoretical basis for further research.
野葛(Willd.)Ohwi 是一种传统的药用和食用同源植物,富含黄酮类、三萜类、皂苷、多糖等化学成分。目前的研究表明,野葛根(PR)具有降血糖、提高胰岛素敏感性和抑制肥胖的作用。然而,PR 抑制肥胖的具体机制尚不清楚,且通过网络药理学与实验相结合研究 PR 抗肥胖作用的研究较少。
运用网络药理学、分子对接技术及实验验证,揭示 PR 治疗肥胖的物质基础及潜在作用机制。
本研究采用网络药理学技术,探讨 PR 的治疗作用及作用机制。通过相关数据库,共筛选出 6 种主要化学成分和 257 个潜在靶点。蛋白质相互作用分析显示,AKT1、AKR1B1、PPARG、MMP9、TNF、TP53、BAD 和 BCL2 是核心靶点。富集分析表明,PR 预防肥胖的途径涉及癌症信号通路和 PI3K-Akt 信号通路,这可能是其主要作用途径。进一步的分子对接验证表明,其核心靶点与 4 种化合物:芒柄花苷、葛根素、7,8,4'-三羟基二氢黄酮和大豆苷元均具有良好的结合活性。采用超高效液相色谱-质谱联用(UPLC-MS)技术对这些主要化合物进行检测和确认。细胞实验结果表明,葛根素呈浓度依赖性抑制细胞增殖和分化,显著促进细胞凋亡,影响细胞迁移。动物实验表明,葛根素可减少小鼠的食物摄入量和体重增加。发现葛根素可上调 HDL 并下调 TC、TG 和 LDL 血液生化指标。Western blot 结果表明,葛根素可显著抑制 AKT1、AKR1B1、MMP9、TNF、TP53、BCL2、PPARG 蛋白的表达,并在细胞和动物水平上显著增加 BAD 蛋白的表达。
本研究建立了一种测定 PR 含量的方法,并预测了其治疗肥胖的活性成分及其作用机制,为进一步研究提供了理论依据。