Yang Chan, Liu Hanyu, Li Xinqiong, Peng Xi, Rao Guocheng, Xie Ziyan, Yang Qiangfei, Du Lian, Xie Chunguang
Division of Endocrinology and Metabolism, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu 610041, Sichuan, China.
Hospital of Chengdu University of Traditional Chinese Medicine, TCM regulating metabolic diseases key Laboratory of Sichuan province, 610075, Sichuan, Chengdu, China.
Heliyon. 2023 Sep 16;9(9):e20106. doi: 10.1016/j.heliyon.2023.e20106. eCollection 2023 Sep.
Type 2 diabetes (T2D) has emerged as a global epidemic, and conventional treatment approaches often face limitations in achieving long-term glycemic control and preventing complications. Traditional Chinese Medicine (TCM) offers a valuable alternative for managing T2D, with a long history of effectively using herbal formulations in clinical practice. However, the modular characteristics of these herbs and their specific mechanisms of action remain poorly understood. To comprehensively investigate the modular characteristics and mechanisms of Chinese herbs in treating T2D, as well as explore the synergistic interactions among different herbs and their modular components, we employed data mining, systematic pharmacology, and molecular docking. Our aim was to gain a comprehensive understanding of the potential therapeutic targets and pathways involved in herbal T2D treatment. In this study, a total of 1114 studies investigating the effects of TCM interventions in the treatment of T2D in adults were included. The analysis revealed 170 distinct types of Chinese herbs, 118 active components, and 238 common targets shared between the medicine and T2D. Additionally, this study identified six hub proteins (TNF, MMP2, PTGS, CASP3, CASP8, and CASP9) and two key chemicals (Diosgenin and Formononetin) found in TCM-mediated T2D suppression. It was observed that these proteins could bind with the ingredients. The MMP2-Diosgenin interaction exhibited the lowest binding free energy (-13.05 kJ/mol) and was primarily driven by hydrogen bonds with ALA-165. TNF-Diosgenin (-10.5 kcal/mol) showed three hydrogen bonds with LEU-37, ARG-82, and ASN-30. PTGS2 and Diosgenin (-8.71 kJ/mol) demonstrated a hydrogen bond with HIS-214. Furthermore, CASP9-Formononetin (-6.53 kcal/mol) exhibited the lowest binding free energy and hydrogen bonds with GLU-261 and SER-339 as the primary forces involved. CASP3-Formononetin (-6.07 kcal/mol) displayed three hydrogen bonds with ASN-342, TRP-348, and GLU-379. Lastly, CASP8 and Formononetin (-6.06 kJ/mol) formed a hydrogen bond with THR-390, TYR-392, and TYR-334. Moreover, critical therapeutic pathways, such as the immune inflammatory response, AGE-RAGE, and IL-17 signaling pathway, were found to be associated with T2D Chinese herb therapy. In conclusion, this study sheded light on the modular characteristics and mechanism of action of herbs used in Chinese Medicine for the treatment of T2D, which provided valuable insights for both researchers and practitioners in the field of Chinese Medicine, offering potential avenues for improved treatment strategies and personalized approaches to address the complex nature of T2D.
2型糖尿病（T2D）已成为一种全球流行病，传统治疗方法在实现长期血糖控制和预防并发症方面常常面临局限性。中医为T2D的管理提供了一种有价值的替代方法，在临床实践中有效使用草药配方有着悠久的历史。然而，这些草药的模块化特征及其具体作用机制仍知之甚少。为了全面研究中药治疗T2D的模块化特征和机制，并探索不同草药及其模块化成分之间的协同相互作用，我们采用了数据挖掘、系统药理学和分子对接方法。我们的目的是全面了解草药治疗T2D所涉及的潜在治疗靶点和途径。在本研究中，共纳入了1114项调查中医干预对成人T2D治疗效果的研究。分析揭示了170种不同类型的中药、118种活性成分以及药物与T2D之间共有的238个常见靶点。此外，本研究确定了在中医介导的T2D抑制中发现的六种枢纽蛋白（TNF、MMP2、PTGS、CASP3、CASP8和CASP9）和两种关键化学物质（薯蓣皂苷元和芒柄花素）。观察到这些蛋白质可以与这些成分结合。MMP2 - 薯蓣皂苷元相互作用表现出最低的结合自由能（-13.05 kJ/mol），主要由与ALA - 165的氢键驱动。TNF - 薯蓣皂苷元（-10.5 kcal/mol）与LEU - 37、ARG - 82和ASN - 30形成了三个氢键。PTGS2和薯蓣皂苷元（-8.71 kJ/mol）与HIS - 214形成了一个氢键。此外，CASP9 - 芒柄花素（-6.53 kcal/mol）表现出最低的结合自由能，与GLU - 261和SER - 339的氢键是主要作用力。CASP3 - 芒柄花素（-6.07 kcal/mol）与ASN - 342、TRP - 348和GLU - 379形成了三个氢键。最后，CASP8和芒柄花素（-6.06 kJ/mol）与THR - 390、TYR - 392和TYR - 334形成了一个氢键。此外，还发现关键治疗途径，如免疫炎症反应、AGE - RAGE和IL - 17信号通路与中医治疗T2D有关。总之，本研究揭示了用于治疗T2D的中药的模块化特征和作用机制，为中医领域的研究人员和从业者提供了有价值的见解，为改进治疗策略和个性化方法以应对T2D的复杂性提供了潜在途径。
