Yunnan University of Chinese Medicine

This study aimed to investigate the mechanism of Xuanhong Dingchuan Tang (XHDCT) in delaying bronchial asthma inflammation via the microRNA (miR)-107-3p/prostaglandin endoperoxide synthase 2 (PTGS2)/mitogen-activated protein kinase (MAPK) axis. Based on the network pharmacological analysis, XHDCT chemical constituents and targets of each chemical constituent were screened through the TCMSP database, and differential-expressed genes of bronchial asthma were obtained from the GEO database, which were intersected to get XHDCT potential anti-inflammatory targets. The key anti-inflammatory targets of XHDCT were acquired by protein-protein interaction (PPI) analysis of the candidate targets. Bronchial asthma mouse models were established and the pathological changes of lung tissues were observed. Serum IgE levels were tested. Total cells and eosinophils in bronchoalveolar lavage fluid (BALF) were counted. The expression of Th2-associated cytokines (interleukin (IL)-4, IL-5, and IL-13) and chemokines (monocyte chemoattractant protein-1 (MCP-1) and eotaxin) in BALF were measured. The targeting relationship between miR-107-3p and PTGS2 was tested. XHDCT delayed bronchial asthma inflammation in in-vivo asthma mouse models. A total of 155 active ingredients and their 341 targets were intersected with bronchial asthma-relevant genes, obtaining 20 potential targets of XHDCT for bronchial asthma treatment. Based on the PPI and "drug-component-target" network diagram, PTGS2 was found to be in a central position. PTGS2 was downregulated and miR-107-3p was upregulated in bronchial asthma mice after XHDCT treatment. PTGS2 overexpression activated the MAPK signaling pathway to promote inflammation in bronchial asthma mice, whereas inflammatory symptoms were reduced and the MAPK signaling pathway was inhibited after XHDCT treatment. miR-107-3p was an upstream regulatory miRNA for PTGS2. After miR-107-3p interference, the activation of the PTGS2/MAPK axis promoted inflammation in bronchial asthma mice, whereas the inflammatory symptoms were reduced after XHDCT treatment. XHDCT promotes anti-inflammatory effects in bronchial asthma via the miR-107-3p/PTGS2/MAPK axis.

Psoriasis is a common clin. skin inflammatory disease.Haitang-Xiaoyin Mixture (HXM) represents a traditional Chinese medicine formulation utilized clin. for the management of psoriasis, which can reduce the psoriasis area and severity index (PASI) score, IL-23 and IL-23 levels in patients with psoriasis.However, the main active components and specific targets of HXM in the treatment of psoriasis and the relevant mechanisms of action are not clear.Therefore, in the study we aimed to elucidate the mechanistic basis of HXM′s therapeutic action in psoriasis treatment through the application of bioinformatics, network pharmacol., machine learning and mol. docking methodologies.The psoriasis-related genes were obtained from the Gene Expression Omnibus (GEO) dataset, which psoriasis-associated disease genes were identified utilizing the GeneCard and DisGeNEt databases.The active ingredients of HXM were retrieved from HERB and TCMSP databases.Protein-Protein Interactions (PPI), Gene Ontol. (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were conducted to identify potential targets and signaling pathways.Psoriasis key targets were determined using LASSO, SVM-RFE, and Boruta algorithms, followed by Receiver Operating Characteristic (ROC) anal.Key targets were GESA enriched and analyzed for transcription factors and immune cell infiltration.Finally mol. docking and mol. dynamics simulations were performed to validate the binding of active compounds to core targets, elucidating their mechanism of action.A total of 233 psoriasis-related targets and 290 drug targets were identified.After data set crossover, 37 pharmacodynamic targets were obtained.PPI network topol. anal. revealed 12 core targets.GO and KEGG enrichment anal. suggested that HXM may regulate angiogenesis, chemokine receptor binding process, as well as IL-17 and TNF related signaling pathways.Machine algorithm screening identified two psoriasis characteristic genes: CXCL2 and CXCR4.Immune infiltration results demonstrated a significant pos. correlation between the characteristic genes and M1 macrophages, along with identification of the top 20 transcription factors involved.Quercetin and triptolide were recognized as potential core components of HXM for treating psoriasis based on their mol. docking and mol. dynamics simulation results confirming strong binding abilities with CXCL2 and CXCR4 resp.This study elucidates the active constituents, potential targets, and underlying pathways involved in the therapeutic effects of HXM for psoriasis.Specifically, CXCL2 and CXCR4 are identified as key targets, with quercetin and triptolide representing crucial compounds exerting their effects on these targets.