Molecular Mechanism Underlying Effects of Wumeiwan on Steroid-Dependent Asthma: A Network Pharmacology, Molecular Docking, and Experimental Verification Study

Abstract

Background 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.

Tuo-Min-Ding-Chuan Decoction Alleviates Airway Inflammations in the Allergic Asthmatic Mice Model by Regulating TLR4-NLRP3 Pathway-Mediated Pyroptosis: A Network Pharmacology and Experimental Verification Study

“…Based on previous studies, the criteria of oral bioavailability (OB) ≥30% and drug likeness (DL) ≥0.18 were used to screen bioactive ingredients from the TCMSP database, 13 OB and DL reflected the CHM absorption in the gastrointestinal tract. For those components obtained from other databases, Swiss ADME web service performed the screening with the method of computing the physicochemistry and estimating the pharmacokinetics, druglikeness, and medicinal chemistry friendliness of small molecules.…”

“…To optimize the complex PPI network, the topology analysis method of the PPI network was conducted to get HUB genes as previously reported. 13 Specifically, HUB genes were defined as nodes with DC over twofold the median degree of all the nodes, as well as “betweenness centrality (BC)”, “closeness centrality (CC)”, and “stress” were higher than the corresponding median values of their own. Furthermore, the molecular complex detection (MCODE) plug-in performed the topology analysis based on HUB genes, the following parameters were set: DC was set to 2, cut-off score was set to 0.2, K core score was set to 2, and the mix distance was set to 100.…”

“…With the therapeutic properties of multi-target and few side effects, TCM has developed over 2000 years in China and has exerted medical influences to 183 countries and regions. 13 TMDCD is an effective TCM formula granule in Phase 2 clinical trial for treating AA created by Professor Wang Qi from Beijing University of Chinese Medicine (BUCM), who is also known as the national Chinese medical science master and the academician of the Chinese Academy of Engineering. TMDCD is composed of 12 Chinese herbal medicine (CHM) including Ephedrae Herba, Armeniacae Semen Amarum, Gypsum, Glycyrrhizae Radix Et Rhizoma , etc.…”

Understanding global changes of the mouse brain proteome after vaginal infection with HSV-2 using a label-free shotgun approach

“…To test the plausibility and accuracy of differentially expressed molecules the detected proteins were aggregated together based on the trend of expression levels using cluster analysis. To establish the functional characteristics of differentially expressed proteins, Gene Ontology (GO) analysis ( Lyu et al., 2022 ) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis ( Kanehisa and Goto, 2000 ) were performed using the Metascape database. The GO and KEGG analysis parameter p-value cutoff was set to 0.05 with a minimum number of matches of 3 and a minimum enrichment score of 1.5 Results were presented using the ImageGP platform.…”

Determination of six core components from Mahuang Xuanfei Zhike syrup in rat plasma and tissues by UPLC–MS/MS: Application to a pharmacokinetics and tissue distribution study

“…In addition, molecular docking has the advantage of high throughput, and thus the binding affinities of multiple components in TCMs can be quickly predicted. Then the molecular mechanisms and pharmacological actions of these active components can be further investigated by experiments on molecular biology and pharmacology (Chen et al, 2021;Lyu et al, 2022). In this paper, network pharmacology and molecular docking were conducted to predict the main active components of MXZ syrup and explore its molecular mechanism against cough, phlegm and asthma.…”