探讨葛根调节肥胖的机制。
Exploring the mechanism of Pueraria lobata (Willd.) Ohwi in the regulation of obesity.
发表日期:2024 Aug 16
作者:
Jingxin Mao, Maolin Li, Xiaodong Wang, Binbin Wang, Peng Luo, Guoze Wang, Xiulan Guo
来源:
JOURNAL OF ETHNOPHARMACOLOGY
摘要:
葛根(Pueraria lobata (Wild.) Ohwi)是一种传统的药食同源植物,富含黄酮类、三萜类、皂苷类、多糖类等化学成分。目前研究表明PR具有降低血糖、提高胰岛素敏感性、抑制肥胖等作用。然而,PR抑制肥胖的具体机制尚不清楚,通过网络药理学与实验相结合的方式研究PR的抗肥胖作用的研究还很少。通过网络药理、分子对接技术和实验验证,揭示了葛根的抗肥胖作用。洛贝塔根(PR)肥胖的物质基础及其潜在机制。本研究采用网络药理学技术探讨PR的治疗效果和作用机制。通过相关数据库,共筛选出6种主要化学成分和257个潜在靶标。蛋白质相互作用分析显示 AKT1、AKR1B1、PPARG、MMP9、TNF、TP53、BAD 和 BCL2 是核心靶标。富集分析显示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通路。进一步的分子对接验证表明,其核心靶标与福芒菌素、纯菌素、7,8,4'-三氢氧化物和黄豆苷元4种化合物均表现出良好的结合活性。利用超高效液相色谱-质谱(UPLC-MS)技术对这些主要化合物进行了检测和确证。细胞实验结果表明,葛根素以浓度依赖性方式抑制细胞增殖和分化,显着促进细胞凋亡并影响细胞迁移。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。研究发现,葛根素能上调HDL,下调TC、TG、LDL血液生化指标。 Western blot结果显示,葛根素在细胞和动物水平上均显着抑制AKT1、AKR1B1、MMP9、TNF、TP53、BCL2、PPARG的表达,并显着增加BAD蛋白的表达。本研究建立了测定PR含量的方法并预测其治疗肥胖的活性成分及其作用机制,为进一步研究提供理论基础。版权所有©2024。出版者:Elsevier B.V.
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.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.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.Copyright © 2024. Published by Elsevier B.V.