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    In Silico Prediction of Molecular Targets of Astragaloside IV for Alleviation of COVID-19 Hyperinflammation by Systems Network Pharmacology and Bioinformatic Gene Expression Analysis. Ge Chenliang,He Yan Frontiers in pharmacology Introduction:The overproduction of cytokines and chemokines caused by excessive and uncontrolled inflammation contributes to the development of COVID-19. Astragaloside IV is considered as an anti-inflammatory and antioxidant agent. This study aimed at undertaking a network pharmacology approach and bioinformatics analysis to uncover the pharmacological mechanisms of Astragaloside IV on COVID-19. Methods:Potential targets of Astragaloside IV were screened from public databases. Differentially expressed genes (DEGs) in SARS-CoV-2 were screened using bioinformatics analysis on the Gene Expression Omnibus (GEO) datasets GSE147507. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were subsequently performed. The overlapping genes, GO terms and KEGG pathways between Astragaloside IV targets and SARS-CoV-2 DEGs were confirmed, and the location of overlapping targets in the key pathways was queried using KEGG Mapper. Results:A total of 425 potential targets of Astragaloside IV were screened. Besides, a total of 546 DEGs were identified between SARS-CoV-2 infected samples and control samples, including 380 up-regulated and 166 down-regulated genes. There was a significant overlap in GO terms and KEGG pathways between Astragaloside IV targets and SARS-CoV-2 DEGs. The shared genes included MMP13, NLRP3, TRIM21, GBP1, ADORA2A, PTAFR, TNF, MLNR, IL1B, NFKBIA, ADRB2, and IL6. Conclusions:This study is the first to propose Astragaloside IV as a new drug candidate for alleviating hyper-inflammation in COVID-19 patients. Besides, the key targets and pathways may reveal the main pharmacological mechanism of Astragaloside IV in the treatment of COVID-19. 10.3389/fphar.2020.556984
    Network pharmacology and molecular docking analyses on Lianhua Qingwen capsule indicate Akt1 is a potential target to treat and prevent COVID-19. Xia Qi-Dong,Xun Yang,Lu Jun-Lin,Lu Yu-Chao,Yang Yuan-Yuan,Zhou Peng,Hu Jia,Li Cong,Wang Shao-Gang Cell proliferation OBJECTIVES:Coronavirus disease 2019 (COVID-19) is rapidly spreading worldwide. Lianhua Qingwen capsule (LQC) has shown therapeutic effects in patients with COVID-19. This study is aimed to discover its molecular mechanism and provide potential drug targets. MATERIALS AND METHODS:An LQC target and COVID-19-related gene set was established using the Traditional Chinese Medicine Systems Pharmacology database and seven disease-gene databases. Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis and protein-protein interaction (PPI) network were performed to discover the potential mechanism. Molecular docking was performed to visualize the patterns of interactions between the effective molecule and targeted protein. RESULTS:A gene set of 65 genes was generated. We then constructed a compound-target network that contained 234 nodes of active compounds and 916 edges of compound-target pairs. The GO and KEGG indicated that LQC can act by regulating immune response, apoptosis and virus infection. PPI network and subnetworks identified nine hub genes. The molecular docking was conducted on the most significant gene Akt1, which is involved in lung injury, lung fibrogenesis and virus infection. Six active compounds of LQC can enter the active pocket of Akt1, namely beta-carotene, kaempferol, luteolin, naringenin, quercetin and wogonin, thereby exerting potential therapeutic effects in COVID-19. CONCLUSIONS:The network pharmacological strategy integrates molecular docking to unravel the molecular mechanism of LQC. Akt1 is a promising drug target to reduce tissue damage and help eliminate virus infection. 10.1111/cpr.12949
    An integrated network pharmacology and RNA-Seq approach for exploring the preventive effect of Lonicerae japonicae flos on LPS-induced acute lung injury. Liu Chang,Yin Zhigang,Feng Tingting,Zhang Min,Zhou Zhi,Zhou Ying Journal of ethnopharmacology ETHNOPHARMACOLOGICAL RELEVANCE:Lonicerae japonicae flos (LJF, the dried flower bud or newly bloomed flower of Lonicera japonica Thunb.), a typical herbal medicine, targets the lung, heart and stomach meridian with the function of clearing heat and detoxication. It ameliorated inflammatory responses and protected against acute lung inflammation in animal models. Acute lung injury (ALI) is a kind of inflammatory disease in which alveolar cells are damaged. However, a network pharmacology study to thoroughly investigate the mechanisms preventing ALI has not been performed. AIM OF THE STUDY:In this study, we examined the main active ingredients in LJF and the protective effects of LJF on LPS-induced ALI in rats. MATERIALS AND METHODS:First, the main active ingredients of LJF were screened in the TCMSP database, and the ALI-associated targets were collected from the GeneCards database. Then, we used compound-target and target-pathway networks to uncover the preventive mechanisms of LJF. Furthermore, we assessed the preventive effects of LJF in an LPS-induced rat model with the RNA-Seq technique to validate the possible molecular mechanisms of the effects of LJF in the treatment of ALI. RESULTS:The network pharmacology results identified 28 main active compounds in LJF, and eight chemical components highly related to the potential targets, which were potential active compounds in LJF. In all, 94 potential targets were recognized, including IL6, TNF, PTGS2, APP, F2, and GRM5. The pathways revealed that the possible targets of LJF involved in the regulation of the IL-17 signalling pathway. Then, in vivo experiments indicated that LJF decreased the levels of proinflammatory cytokines (TNF-, IL-1, and IL-6) in serum and bronchoalveolar lavage fluid, decreased the levels of oxidative stress factors (MDA and MPO) and increased the activities of SOD and GSH-Px in lung tissue. The RNA-Seq results revealed that 7811, 775 and 3654 differentially expressed genes (DEGs) in Ctrl (control group), ALI-LJF (Lonicerae japonicae flos group) and ALI-DXSM (dexamethasone group), respectively. KEGG pathway analysis showed that the DEGs associated with immune response and inflammation signalling pathways and the IL-17 signalling pathway were significantly enriched in LJF. Compared with those in ALI, the expression of CXCL2, CXCL1, CXCL6, NFKBIA, IFNG, IL6, IL17A, IL17F, IL17C, MMP9 and TNFAIP3, which are involved in the IL-17 signalling pathway, were significantly decreased in the LJF group according to the qRT-PCR analyses. CONCLUSIONS:In view of the network pharmacology and RNA-Seq results, the study identified the main active ingredient and potential targets of LJF involved in protecting against ALI, which suggests directions for further research on LJF. 10.1016/j.jep.2020.113364
    Therapeutic target and molecular mechanism of vitamin C-treated pneumonia: a systematic study of network pharmacology. Li Rong,Guo Chao,Li Yu,Liang Xiao,Yang Lu,Huang Wenjun Food & function Vitamin C (VC), a well-reported antioxidant, is found with beneficial actions of preventing and treating pneumonia. However, the detailed pharmacological target and mechanism of VC-treated pneumonia remain unclear. Thus, the present bioinformatics approach using systematic network pharmacology aimed to reveal primary predictive targets, cellular processes, and molecular pathways of VC-treated pneumonia. As shown in bioinformatics assays, the data included 90 primary presumptive targets of VC-treated pneumonia, and 5 other core targets of VC-treated pneumonia were identified as mitogen activated protein kinase 1 (MAPK1), c-c chemokine receptor type 5 (CCR5), mitogen activated protein kinase 3 (MAPK3), angiotensin II type 2 (AT-2) receptor (AGTR2), and signal transducer and activator of transcription 3 (STAT3). In addition, all biological processes (including top 20) and signaling pathways (including top 20) of VC-treated pneumonia were identified and illustrated through bioinformatics analyses. In conclusion, VC-achieved anti-pneumonia effects are mechanically implicated with the suppression of inflammation and enhancement of immunoregulation associated with functional processes and signaling pathways. More interestingly, the identified VC targets may act as biomarkers for the diagnosis and treatment of pneumonia. 10.1039/d0fo00421a
    Uncovering the mechanism of Maxing Ganshi Decoction on asthma from a systematic perspective: A network pharmacology study. Song Wenjie,Ni Shenglou,Fu Yanling,Wang Yun Scientific reports Maxing Ganshi Decoction (MXGSD) is used widely for asthma over thousands of years, but its underlying pharmacological mechanisms remain unclear. In this study, systematic and comprehensive network pharmacology was utilized for the first time to reveal the potential pharmacological mechanisms of MXGSD on asthma. Specifically, we collected 141 bioactive components from the 600 components in MXGSD, which shared 52 targets common to asthma-related ones. In-depth network analysis of these 52 common targets indicated that asthma might be a manifestation of systemic neuro-immuno-inflammatory dysfunction in the respiratory system, and MXGSD could treat asthma through relieving airway inflammation, improving airway remodeling, and increasing drug responsiveness. After further cluster and enrichment analysis of the protein-protein interaction network of MXGSD bioactive component targets and asthma-related targets, we found that the neurotrophin signaling pathway, estrogen signaling pathway, PI3K-Akt signaling pathway, and ErbB signaling pathway might serve as the key points and principal pathways of MXGSD gene therapy for asthma from a systemic and holistic perspective, and also provides a novel idea for the development of new drugs for asthma. 10.1038/s41598-018-35791-9
    Interleukin-11 is a therapeutic target in idiopathic pulmonary fibrosis. Ng Benjamin,Dong Jinrui,D'Agostino Giuseppe,Viswanathan Sivakumar,Widjaja Anissa A,Lim Wei-Wen,Ko Nicole S J,Tan Jessie,Chothani Sonia P,Huang Benjamin,Xie Chen,Pua Chee Jian,Chacko Ann-Marie,Guimarães-Camboa Nuno,Evans Sylvia M,Byrne Adam J,Maher Toby M,Liang Jiurong,Jiang Dianhua,Noble Paul W,Schafer Sebastian,Cook Stuart A Science translational medicine Idiopathic pulmonary fibrosis (IPF) is a progressive fibrotic lung disease where invasive pulmonary myofibroblasts secrete collagen and destroy lung integrity. Here, we show that interleukin-11 () is up-regulated in the lung of patients with IPF, associated with disease severity, and IL-11 is secreted from IPF fibroblasts. In vitro, IL-11 stimulates lung fibroblasts to become invasive actin alpha 2, smooth muscle-positive (ACTA2), collagen-secreting myofibroblasts in an extracellular signal-regulated kinase (ERK)-dependent, posttranscriptional manner. In mice, fibroblast-specific transgenic expression or administration of murine IL-11 induces lung myofibroblasts and causes lung fibrosis. IL-11 receptor subunit alpha-1 ()-deleted mice, whose lung fibroblasts are unresponsive to profibrotic stimulation, are protected from fibrosis in the bleomycin mouse model of pulmonary fibrosis. We generated an IL-11-neutralizing antibody that blocks lung fibroblast activation downstream of multiple stimuli and reverses myofibroblast activation. In therapeutic studies, anti-IL-11 treatment diminished lung inflammation and reversed lung fibrosis while inhibiting ERK and SMAD activation in mice. These data prioritize IL-11 as a drug target for lung fibrosis and IPF. 10.1126/scitranslmed.aaw1237