Network pharmacology-based identification of key pharmacological pathways of Yin–Huang–Qing–Fei capsule acting on chronic bronchitis

Guohua Yu,1,2,* Yanqiong Zhang,2,* Weiqiong Ren,3 Ling Dong,1 Junfang Li,2,4 Ya Geng,2,5 Yi Zhang,2 Defeng Li,2 Haiyu Xu,2 Hongjun Yang2 1School of Chinese Materia Medica, Beijing University of Chinese Medicine, 2Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, 3The First Affiliated Hospital of Hunan University of Traditional Chinese Medicine, Changsha, 4School of Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, Tianjin, 5School of Basic Medicine, Shandong University of Chinese Medicine, Jinan, China *These authors contributed equally to this work Abstract: For decades in China, the Yin–Huang–Qing–Fei capsule (YHQFC) has been widely used in the treatment of chronic bronchitis, with good curative effects. Owing to the complexity of traditional Chinese herbal formulas, the pharmacological mechanism of YHQFC remains unclear. To address this problem, a network pharmacology-based strategy was proposed in this study. At first, the putative target profile of YHQFC was predicted using MedChem Studio, based on structural and functional similarities of all available YHQFC components to the known drugs obtained from the DrugBank database. Then, an interaction network was constructed using links between putative YHQFC targets and known therapeutic targets of chronic bronchitis. Following the calculation of four topological features (degree, betweenness, closeness, and coreness) of each node in the network, 475 major putative targets of YHQFC and their topological importance were identified. In addition, a pathway enrichment analysis based on the Kyoto Encyclopedia of Genes and Genomes pathway database indicated that the major putative targets of YHQFC are significantly associated with various pathways involved in anti-inflammation processes, immune responses, and pathological changes caused by asthma. More interestingly, eight major putative targets of YHQFC (interleukin [IL]-3, IL-4, IL-5, IL-10, IL-13, FCER1G, CCL11, and EPX) were demonstrated to be associated with the inflammatory process that occurs during the progression of asthma. Finally, a molecular docking simulation was performed and the results exhibited that 17 pairs of chemical components and candidate YHQFC targets involved in asthma pathway had strong binding efficiencies. In conclusion, this network pharmacology-based investigation revealed that YHQFC may attenuate the inflammatory reaction of chronic bronchitis by regulating its candidate targets, which may be implicated in the major pathological processes of the asthma pathway. Keywords: traditional Chinese medicine, Yin–Huang–Qing–Fei capsule, chronic bronchitis, network pharmacology, asthma pathwa