Modular characteristics and mechanism of action of herbs for type 2 diabetes treatment in Chinese medicine

Chan Yang; Hanyu Liu; Xinqiong Li; Xi Peng; Guocheng Rao; Ziyan Xie; Qiangfei Yang; Lian Du; Chunguang Xie

doi:10.1016/j.heliyon.2023.e20106

Modular characteristics and mechanism of action of herbs for type 2 diabetes treatment in Chinese medicine

Heliyon. 2023 Sep 16;9(9):e20106. doi: 10.1016/j.heliyon.2023.e20106. eCollection 2023 Sep.

Authors

Chan Yang¹, Hanyu Liu², Xinqiong Li¹, Xi Peng¹, Guocheng Rao¹, Ziyan Xie², Qiangfei Yang³, Lian Du⁴, Chunguang Xie²

Affiliations

¹ 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.
² Hospital of Chengdu University of Traditional Chinese Medicine, TCM regulating metabolic diseases key Laboratory of Sichuan province, 610075, Sichuan, Chengdu, China.
³ Jianyang City People's Hospital, 610040,Sichuan, China.
⁴ Chengdu University of Traditional Chinese Medicine, China.

Abstract

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.

Keywords: Chinese herbs; Network pharmacology, molecular docking; Pharmacological mechanism, herbal characteristic; Type 2 diabetes; traditional Chinese medicine.