Mechanisms Underlying the Therapeutic Effects of Yiqi Wenyang Huwei Decoction in Treating Asthma Based on GEO Datasets, Network Pharmacology, Experimental Validation, and Molecular Docking.

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The Yiqi Wenyang Huwei Decoction (YWHD) is an herbal formula frequently utilized to treat asthma. Despite its wide usage, the specific mechanism of action remains unknown. Through an in-depth investigation utilizing network pharmacology, molecular docking techniques, and experimental validation, this study aims to uncover the molecular mechanism and material basis of YWHD in the treatment of asthma. The compounds and targets of YWHD were gathered from various databases such as TCMSP, PubMed, and CNKI. Additionally, asthma-related targets were obtained by combining the GEO dataset with GeneCards and OMIM databases. The STRING platform was employed to establish protein-protein interactions. GO and KEGG pathway enrichment analyses were conducted using DAVID. Molecular docking was utilized to assess the binding affinity between potential targets and active compounds. The asthma rat model was established through OVA induction, and a lung function meter was used to detect Mch-induced Max Rrs. HE staining was conducted to observe pathological changes, while ELISA was used to detect levels of inflammatory factors IL4, IL6, IL13, and IgE in BLAF. Furthermore, qPCR was used to detect levels of IL-1β, IL-6, JUN, and PTGS2 mRNA, while Western blot assay was employed to measure phosphorylation levels of NF-κB and IKKα. A comprehensive study revealed that YWHD has 188 active compounds and 250 corresponding targets. After conducting a topological analysis of the PPI network, the study identified 14 high-activity targets, including JUN, PTGS2, IL6, IL1B, CXCL8, MMP9, IL10, ALB, TGFB1, CCL2, IFNG, IL4, MAPK3, and STAT3. Further, GO and KEGG pathway enrichment analysis indicated that YWHD targets inflammation-related genes and regulates IL- 17 and NF-kappa B signaling pathways. Animal studies have shown that YWHD can effectively minimize airway Max Rrs, reduce the levels of inflammatory factors IL4, IL13, IL6, and IgE in BLAF, and improve airway inflammation in rats with asthma. Molecular experiments have also demonstrated that YWHD achieves this by down-regulating the expression levels of IL-1β, IL-6, JUN, and PTGS2 mRNA, inhibiting the phosphorylation modification levels of NF-κB and IKKα, and reducing the levels of inflammatory cytokines IL4, IL13, IL6, and IgE in BALF of rats. Interestingly, molecular docking has revealed that the active compounds in YWHD have a strong binding ability to the screening targets. This research endeavor systematically explicated the active constituents, prospective targets, and signaling pathways of YWHD for asthmatic intervention. The study provides an innovative notion and dependable resource for comprehending the molecular mechanism and pharmaceutical screening of YWHD in the context of asthma treatment.