背景:葛根(威尔德。)Ohwi是一种富含类黄酮的传统药用和食用同源植物,三萜,皂苷,多糖和其他化学成分。目前,研究表明,PR具有降低血糖的作用,改善胰岛素敏感性和抑制肥胖。然而,PR抑制肥胖的具体机制尚不清楚,网络药理学与实验相结合对PR的抗肥胖作用研究较少。
目的:药理学,分子对接技术和实验验证,揭示葛根(PR)肥胖的物质基础和潜在机制。
结果:本研究利用网络药理学技术研究PR的治疗效果和作用机制。通过相关数据库,共筛选了6种主要化学成分和257种潜在靶标。蛋白相互作用分析表明AKT1、AKR1B1、PPARG、MMP9,TNF,TP53,坏,和BCL2是核心目标。富集分析表明,PR在预防肥胖中的作用通路涉及肿瘤信号通路和PI3K-Akt信号通路,这可能是主要的行动途径。进一步的分子对接验证表明,其核心靶标与4种化合物表现出良好的结合活性:purerin,7,8,4'-三氢氧化物和大豆苷元。采用超高效液相色谱-质谱(UPLC-MS)技术对这些主要化合物进行检测和确证。细胞实验结果表明,葛根素以浓度依赖的方式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,葛根素可以减少小鼠的食物摄入量和体重增加。发现葛根素可以上调HDL和下调TC,TG,和LDL血液生化指标。Westernblot结果显示葛根素显著抑制AKT1、AKR1B1、MMP9、TNF、TP53,BCL2,PPARG,并且在细胞和动物水平上均显着增加了BAD蛋白的表达。
结论:本研究建立了测量PR含量的方法,并预测了其有效成分及其在肥胖治疗中的作用机制,为进一步的研究提供了理论基础。
BACKGROUND: 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 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.
OBJECTIVE: Pharmacology, molecular docking technology and experimental verification through the network, revealing the Pueraria lobata radix (PR) the material basis of obesity and the potential mechanism.
RESULTS: 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.
CONCLUSIONS: 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.