Drug Design, Development and Therapy (Mar 2022)
Molecular Mechanism Underlying Effects of Wumeiwan on Steroid-Dependent Asthma: A Network Pharmacology, Molecular Docking, and Experimental Verification Study
Abstract
Mingsheng Lyu,1,* Yahui Wang,2,* Qiuyi Chen,1,* Jingbo Qin,3 Dan Hou,1 Shuaiyang Huang,1 Dongmei Shao,1 Xuefeng Gong,4 Guirui Huang,1 Shiyu Zhang,1 Zhijie Zhang,1 Hongsheng Cui1 1Department of Respiratory, The Third Affiliated Hospital, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 2Department of Neurology and Stroke Center, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 3National Institute of TCM Constitution and Preventive Medicine, School of Chinese Medicine, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 4Department of Traditional Chinese Medicine, Beijing Chaoyang Hospital, Capital Medical University, Beijing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Hongsheng Cui, Department of Respiratory, The Third Affiliated Hospital, Beijing University of Chinese Medicine, Beijing, People’s Republic of China, Tel +8613901101359, Email [email protected]: Steroid-dependent asthma (SDA) is characterized by oral corticosteroid (OCS) resistance and dependence. Wumeiwan (WMW) showed potentials in reducing the dose of OCS of SDA patients based on our previous studies.Methods: Network pharmacology was conducted to explore the molecular mechanism of WMW against SDA with the databases of TCMSP, STRING, etcetera. GO annotation and KEGG functional enrichment analysis were conducted by metascape database. Pymol performed the molecular docking. In the experiment, the OVA-induced plus descending dexamethasone intervention chronic asthmatic rat model was conducted. Lung pathological changes were analyzed by H&E, Masson, and IHC staining. Relative expressions of the gene were performed by real-time PCR.Results: A total of 102 bioactive ingredients in WMW were identified, as well as 191 common targets were found from 241 predicted targets in WMW and 3539 SDA-related targets. The top five bioactive ingredients were identified as pivotal ingredients, which included quercetin, candletoxin A, palmidin A, kaempferol, and beta-sitosterol. Besides, 35 HUB genes were obtained from the PPI network, namely, TP53, AKT1, MAPK1, JUN, HSP90AA1, TNF, RELA, IL6, CXCL8, EGFR, etcetera. GO biological process analysis indicated that HUB genes were related to bacteria, transferase, cell differentiation, and steroid. KEGG pathway enrichment analysis indicated that the potential mechanism might be associated with IL-17 and MAPK signaling pathways. Molecular docking results supported these findings. H&E and Masson staining proved that WMW could reduce airway inflammation and remodeling of model rats, which might be related to the downward expression of IL-8 proved by IHC staining and real-time PCR.Conclusion: WMW could be a complementary and alternative therapy for SDA by reducing airway inflammation.Keywords: steroid-dependent asthma, Wumeiwan, Chinese herbal medicine, IL-8, network pharmacology, molecular docking
