Yuan Guozhen, Shi Shuai, Jia Qiulei, Shi Jingjing, Shi Shuqing, Zhang Xuesong, Shou Xintian, Zhu Xueping, Hu Yuanhui
Department of Cardiology, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China.
Evid Based Complement Alternat Med. 2021 Apr 16;2021:6633402. doi: 10.1155/2021/6633402. eCollection 2021.
Rapid increases in metabolic disorders, such as type 2 diabetes mellitus (T2DM) and hyperlipidemia, are becoming a substantial challenge to worldwide public health. Traditional Chinese medicine has a long history and abundant experience in the treatment of diabetes and hyperlipidemia, and Radix (known as Gegen in Chinese) is one of the most prevalent Chinese herbs applied to treat these diseases. The underlying mechanism by which Gegen simultaneously treats diabetes and hyperlipidemia, however, has not been clearly elucidated to date. Therefore, we systematically explored the potential mechanism of Gegen in the treatment of T2DM complicated with hyperlipidemia based on network pharmacology. We screened the potential targets of Gegen, T2DM, and hyperlipidemia in several online databases. Then, the hub targets were analyzed by performing protein-protein interaction, Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment assays, and finally, the complicated connections among compounds, targets, and pathways were visualized in Cytoscape. We found that isoflavones, including daidzein, genistein, and puerarin, as well as -sitosterol, are the key active ingredients of Gegen responsible for its antidiabetic and antihyperlipidemia effects, which mainly target AKR1B1, EGFR, ESR, TNF, NOS3, MAPK3, PPAR, CYP19A1, INS, IL6, and SORD and multiple pathways, such as the PI3K-Akt signaling pathway; the AGE-RAGE signaling pathway in diabetic complications, fluid shear stress, and atherosclerosis; the PPAR signaling pathway; insulin resistance; the HIF-1 signaling pathway; the TNF signaling pathway; and others. These active ingredients also target multiple biological processes, including the regulation of glucose and lipid metabolism, the maintenance of metabolic homeostasis, and anti-inflammatory and antioxidant pathways. In conclusion, Gegen is a promising therapeutic phytomedicine for T2DM with hyperlipidemia that targets multiple proteins, biological processes, and pathways.
代谢紊乱，如2型糖尿病（T2DM）和高脂血症的迅速增加，正成为全球公共卫生面临的重大挑战。中医在糖尿病和高脂血症的治疗方面有着悠久的历史和丰富的经验，葛根是治疗这些疾病最常用的中药材之一。然而，葛根同时治疗糖尿病和高脂血症的潜在机制至今尚未明确阐明。因此，我们基于网络药理学系统地探索了葛根治疗T2DM合并高脂血症的潜在机制。我们在几个在线数据库中筛选了葛根、T2DM和高脂血症的潜在靶点。然后，通过进行蛋白质-蛋白质相互作用、基因本体论（GO）和京都基因与基因组百科全书（KEGG）富集分析来分析枢纽靶点，最后，在Cytoscape中可视化化合物、靶点和通路之间的复杂联系。我们发现，包括大豆苷元、染料木黄酮和葛根素在内的异黄酮以及β-谷甾醇是葛根发挥抗糖尿病和抗高脂血症作用的关键活性成分，它们主要靶向AKR1B1、EGFR、ESR、TNF、NOS3、MAPK3、PPAR、CYP19A1、INS、IL6和SORD以及多个通路，如PI3K-Akt信号通路；糖尿病并发症、流体剪切应力和动脉粥样硬化中的AGE-RAGE信号通路；PPAR信号通路；胰岛素抵抗；HIF-1信号通路；TNF信号通路等。这些活性成分还靶向多个生物学过程，包括调节葡萄糖和脂质代谢、维持代谢稳态以及抗炎和抗氧化通路。总之，葛根是一种有前景的治疗T2DM合并高脂血症的植物药，它靶向多种蛋白质、生物学过程和通路。
