Modular Characteristics and Mechanism of Action of Herbs for Type 2 Diabetes Treatment in Chinese Medicine

Type 2 diabetes (T2D) is a form of "thirst disease," or Xiaoke in Chinese, that was first referenced in Huangdi Neijing. The discovery of a Chinese herb delivers considerable benefits and has great potential for treating T2D. Despite the fact that a large number of publications have reported the role of TCM in the treatment of T2D, it is still unknown which Chinese herbs are the most commonly used drugs in the treatment of T2D, what the common characteristics of these Chinese herbs are, and what the main active ingredients and molecular mechanisms of these commonly used herbs are. In this study, data mining, systematic pharmacology, and molecular docking technology were utilized. There were 170 distinct types of Chinese herbs discovered, 118 active components, and 238 common targets across medicine and T2D. Moreover, we discovered six hub proteins (TNF, MMP2, PTGS, CASP3, CASP8, and CASP9) and two of the herbs' most basic chemicals (Diosgenin and Formononetin) in TCM-mediated T2D suppression, as well as critical therapeutic pathways (immune inflammatory response, AGE-RAGE, and IL-17 pathway) linked to T2D Chinese herb therapy. These findings lay a solid platform for future diabetic medication research and development.2型糖尿病（Type 2 diabetes, T2D）属于中医“消渴病”范畴，其相关记载最早见于《黄帝内经》。中药的发现为2型糖尿病的治疗带来了显著益处与巨大应用潜力。尽管已有大量文献报道中医药（Traditional Chinese Medicine, TCM）在2型糖尿病治疗中的作用，但目前仍存在诸多待解问题：临床治疗2型糖尿病最常用的中药有哪些、此类常用中药具备哪些共性特征，以及这些常用中药的核心活性成分与分子作用机制为何。本研究采用数据挖掘、系统药理学与分子对接技术开展研究，最终筛选得到170种不同的中药、118种活性成分，以及238个中药与2型糖尿病的共同作用靶点。此外，本研究明确了中医药调控2型糖尿病进程中的6个核心靶点蛋白（肿瘤坏死因子（TNF）、基质金属蛋白酶2（MMP2）、前列腺素内过氧化物合酶（PTGS）、半胱氨酸天冬氨酸蛋白酶3（CASP3）、半胱氨酸天冬氨酸蛋白酶8（CASP8）、半胱氨酸天冬氨酸蛋白酶9（CASP9））、2种中药核心活性成分（薯蓣皂苷元（Diosgenin）与芒柄花素（Formononetin）），以及与中药治疗2型糖尿病密切相关的关键信号通路：免疫炎症反应通路、AGE-RAGE（晚期糖基化终末产物-晚期糖基化终末产物受体）通路与IL-17（白介素-17）通路。本研究结果为未来糖尿病治疗药物的研发奠定了坚实的基础。