Network Pharmacology and Experimental Validation of Qingwen Baidu Decoction Therapeutic Potential in COVID-19-related Lung Injury.

Coronavirus disease 2019 (COVID-19) is a lifethreatening disease worldwide due to its high infection and serious outcomes resulting from acute lung injury. Qingwen Baidu decoction (QBD), a well-known herbal prescription, has shown significant efficacy in patients with Coronavirus disease 2019. Hence, this study aims to uncover the molecular mechanism of QBD in treating COVID-19-related lung injury. Traditional Chinese Medicine Systems Pharmacology database (TCMSP), DrugBanks database, and Chinese Knowledge Infrastructure Project (CNKI) were used to retrieve the active ingredients of QBD. Drug and disease targets were collected using UniProt and Online Mendelian Inheritance in Man databases (OMIM). The core targets of QBD for pneumonia were analyzed by the Protein-Protein Interaction Network (PPI), Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) to reveal the underlying molecular mechanisms. The analysis of key targets using molecular docking and animal experiments was also validated. A compound-direct-acting target network mainly containing 171 compounds and 110 corresponding direct targets was constructed. The key targets included STAT3, c-JUN, TNF-α, MAPK3, MAPK1, FOS, PPARG, MAPK8, IFNG, NFκB1, etc. Moreover, 117 signaling pathways mainly involved in cytokine storm, inflammatory response, immune stress, oxidative stress and glucose metabolism were found by KEGG. The molecular docking results showed that the quercetin, alanine, and kaempferol in QBD demonstrated the strongest affinity to STAT3, c- JUN, and TNF-α. Experimental results displayed that QBD could effectively reduce the pathological damage to lung tissue by LPS and significantly alleviate the expression levels of the three key targets, thus playing a potential therapeutic role in COVID-19. QBD might be a promising therapeutic agent for COVID-19 via ameliorating STAT3-related signals.

Yang J ，Zhang Z ，Liu H ，Wang J ，Xie S ，Li P ，Wen J ，Wei S ，Li R ，Ma X ，Zhao Y ... -  《-》

[Mechanism of Ganke Granules intervening acute lung injury based on network pharmacology and experimental verification].

Liang H ，Li XY ，Zhang XW ，Bao YW ，Ding ML ，Yuan QH ，He CS ，Zeng N ... -  《-》

Network pharmacology and molecular docking analysis on molecular targets and mechanisms of Huashi Baidu formula in the treatment of COVID-19.

Tao Q ，Du J ，Li X ，Zeng J ，Tan B ，Xu J ，Lin W ，Chen XL ... -  《-》

Exploring the mechanism of Corbrin capsules in the intervention of AKI-COVID-19 based on network pharmacology combined with GEO dataset.

of the study: This study used network pharmacology and the Gene Expression Omnibus (GEO) database to investigate the therapeutic effects of Corbrin capsules on acute kidney injury (AKI)-COVID-19 (coronavirus disease 2019). The active constituents and specific molecular targets of Corbrin capsules were obtained from the Traditional Chinese Medicine Systems Pharmacology (TCMSP) and Swiss Target Prediction databases. The targets related to AKI and COVID-19 disease were obtained from the Online Mendelian Inheritance in Man (OMIM), GeneCards, and GEO databases. A protein-protein interaction (PPI) network was constructed by utilizing Cytoscape. To enhance the analysis of pathways associated with the pathogenesis of AKI-COVID-19, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed. Furthermore, immune infiltration analysis was performed by using single-sample gene set enrichment analysis (ssGSEA) and CIBERSORT. Molecular docking was used to assess interactions between differentially expressed genes and active ingredients. Verification was performed by utilizing GEO databases and in vivo assays. This study revealed an overlap of 18 significantly differentially expressed genes between the Corbrin capsules group and the AKI-COVID-19 target group. Analysis of the PPI network identified TP53, JAK2, PIK3CA, PTGS2, KEAP1, and MCL1 as the top six core protein targets with the highest degrees. The results obtained from GO and KEGG analyses demonstrated that the target genes were primarily enriched in the apoptosis and JAK-STAT signaling pathways. Moreover, the analysis of immune infiltration revealed a notable disparity in the percentage of quiescent memory CD4 + T cells. Western blot analyses provided compelling evidence suggesting that the dysregulation of 6 core protein targets could be effectively reversed by Corbrin capsules. This study revealed the key components, targets, and pathways involved in treating AKI-related COVID-19 using Corbrin capsules. This study also provided a new understanding of the molecular mechanisms underlying this treatment.

Qin XJ ，Hu WJ ，Xu XJ 《-》

Jingfang granule alleviates Pseudomonas aeruginosa-induced acute lung inflammation through suppression of STAT3/IL-17/NF-κB pathway based on network pharmacology analysis and experimental validation.

Pseudomonas aeruginosa is an opportunistic bacterial pathogen which is the second leading cause of hospital-acquired pneumonia. Jingfang granule (JFG) is an herbal formula of Traditional Chinese medicine (TCM) widely used in treatment of acute respiratory tract infections in China. However, the molecular mechanisms of JFG in treatment of P. aeruginosa-induced acute pneumonia are not clear. This study aimed to investigate the mechanisms underlying the effects of JFG on P. aeruginosa-induced acute inflammation using a mouse model of bacterial acute pneumonia. The chemical components and targets of JFG were retrieved from Traditional Chinese Medicine Systems Pharmacology (TCMSP) database, and the P. aeruginosa pneumonia-related targets were obtained from the disease databases, including Online Mendelian Inheritance in Man (OMIM), GeneCards and DisGeNet. The protein-protein interaction (PPI) network was constructed using STRING database. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed using the Database for Annotation, Visualization and Integrated Discovery (DAVID). Molecular docking was performed using AutoDockTools 1.5.6. Further in vivo experiments employed a mouse model of P. aeruginosa acute pneumonia to verify the target proteins and signaling pathways affected by JFG, which were predicted by the network pharmacology analysis. A total of 218 active components and 257 targets of JFG were retrieved from TCMSP database. Moreover, 99 intersectant targets were obtained between the 257 JFG targets and 694 disease targets. Among the intersectant targets, STAT3, IL-6, AKT1, TNF, MAPK1, MAPK3 and EGFR were identified to be the key therapeutic targets through PPI network analysis, and STAT3 was in the center of the network, which is a key regulator of IL-17 expression. KEGG pathway enrichment analysis suggested that IL-17 signaling pathway was one of the crucial inflammatory pathways affected by JFG in treatment of P. aeruginosa pneumonia. Furthermore, the in vivo experiments demonstrated that the JFG-treated mice displayed reduced proinflammatory cytokine production (IL-17, IL-1β, IL-6 and TNF), diminished neutrophil infiltration and decreased mortality, compared with the non-drug-treated mice during P. aeruginosa lung infection. Moreover, the expression or phosphorylation levels of the key regulators in STAT3/IL-17/NF-κB axis including STAT3, ERK1/2 (MAPK3/1), AKT, NF-κB p65 and RORγt were significantly reduced in the lung tissues of the JFG-treated mice. JFG was effective in treatment of P. aeruginosa acute lung infection, which reduced inflammatory responses through suppressing STAT3/IL-17/NF-κB pathway.

Gu M ，Su W ，Dai J ，Wang J ，Jia X ，Yao J ，Zhang G ，Zhu Q ，Pang Z ... -  《-》