Discovery of potential asthma targets based on the clinical efficacy of Traditional Chinese Medicine formulas

• Published in: Journal of ethnopharmacology 2020-04, Vol.252, p.112635, Article 112635
• Main Authors: Wang, Yu, Chen, Yan-Jiao, Xiang, Cheng, Jiang, Guang-Wei, Xu, Yu-Dong, Yin, Lei-Miao, Zhou, Dong-Dong, Liu, Yan-Yan, Yang, Yong-Qing
• Format: Article
• Language: English
• Subjects: Asthma; Bioinformatics analysis; Herbs; Signaling pathway; Targets
• ISSN: 0378-8741; 1872-7573
• DOI: 10.1016/j.jep.2020.112635

Standard therapy for asthma, a highly heterogeneous disease, is primarily based on bronchodilators and immunosuppressive drugs, which confer short-term symptomatic relief but not a cure. It is difficult to discover novel bronchodilators, although potential new targets are emerging. Traditional Chinese Medicine (TCM) formulas have been used to treat asthma for more than 2000 years, forming the basis for representative asthma treatments. Based on the efficacy of TCM formulas, anti-asthmatic herbal compounds bind proteins are potential targets for asthma therapy. This analysis will provide new drug targets and discovery strategies for asthma therapy. A list of candidate herbs for asthma was selected from the classical formulas (CFs) of TCM for the treatment of wheezing or dyspnea recorded in Treatise on Cold Damage and Miscellaneous Diseases (TCDMD) and from modern herbal formulas identified in the SAPHRON TCM Database using the keywords “wheezing” or “dyspnea”. Compounds in the selected herbs and compounds that directly bind target proteins were acquired by searching the Herbal Ingredients' Targets Database (HITD), TCM Data Bank (TCMDB) and TCM Integrated Database (TCMID). Therapeutic targets of conventional medicine (CM) for asthma were collected by searching Therapeutic Target Database (TTD), DrugBank and PubMed as supplements. Finally, the enriched gene ontology (GO) terms of the targets were obtained using the Database for Annotation Visualization and Integrated Discovery (DAVID) and protein-protein interactions (PPI) networks were constructed using Search Tool for the Retrieval of Interacting Genes/Proteins (STRING). The effects of two selected TCM compounds, kaempferol and ginkgolide A, on cellular resistance in human airway smooth muscle cells (ASMCs) and pulmonary resistance in a mouse model were investigated. The list of 32 candidate herbs for asthma was selected from 10 CFs for the treatment of wheezing or dyspnea recorded in TCDMD and 1037 modern herbal formulas obtained from the SAPHRON TCM Database. A total of 130 compounds from the 32 selected herbs and 68 herbal compounds directly bind target proteins were acquired from HITD and TCMDB. Eighty-eight therapeutic targets of CM for asthma were collected by searching TTD and PubMed as supplements. DAVID and STRING analyses showed targets of TCM formulas are primarily related to cytochrome P450 (CYP) family, transient receptor potential (TRP) channels, matrix metalloproteinases (MMPs) and ribosomal