scholarly journals Potential Mechanism Prediction of Herbal Medicine for Pulmonary Fibrosis Associated with SARS-CoV-2 Infection Based on Network Analysis and Molecular Docking

2021 ◽  
Vol 12 ◽  
Author(s):  
De Jin ◽  
Xuedong An ◽  
Yuqing Zhang ◽  
Shenghui Zhao ◽  
Liyun Duan ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Pulmonary Fibrosis ◽  
Signaling Pathways ◽  
Topological Analysis ◽  
Recovery Period ◽  
Treatment Protocol ◽  
Docking Simulation ◽  
Mapk Signaling ◽  
Tnf Α ◽  
Tgf Β1

Background: Coronavirus Disease 2019 (COVID-19) is still a relevant global problem. Although some patients have recovered from COVID-19, the sequalae to the SARS-CoV-2 infection may include pulmonary fibrosis, which may contribute to considerable economic burden and health-care challenges. Convalescent Chinese Prescription (CCP) has been widely used during the COVID-19 recovery period for patients who were at high risk of pulmonary fibrosis and is recommended by the Diagnosis and Treatment Protocol for COVID-19 (Trial Version sixth, seventh). However, its underlying mechanism is still unclear.Methods: In this study, an integrated pharmacology approach was implemented, which involved evaluation of absorption, distribution, metabolism and excretion of CCP, data mining of the disease targets, protein-protein interaction (PPI) network construction, and analysis, enrichment analysis, and molecular docking simulation, to predict the bioactive components, potential targets, and molecular mechanism of CCP for pulmonary fibrosis associated with SARS-CoV-2 infection.Results: The active compound of CCP and the candidate targets, including pulmonary fibrosis targets, were obtained through database mining. The Drug-Disease network was constructed. Sixty-five key targets were identified by topological analysis. The findings of Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway annotation suggested that the VEGF, Toll-like 4 receptor, MAPK signaling pathway, and TGF-β1 signaling pathways may be involved in pulmonary fibrosis. In the molecular docking analyses, VEGF, TNF-α, IL-6, MMP9 exhibited good binding activity. Findings from our study indicated that CCP could inhibit the expression of VEGF, TNF-α, IL-6, MMP9, TGF-β1 via the VEGF, Toll-like 4 receptor, MAPK, and TGF-β1 signaling pathways.Conclusion: Potential mechanisms involved in CCP treatment for COVID-19 pulmonary fibrosis associated with SARS-CoV-2 infection involves multiple components and multiple target points as well as multiple pathways. These findings may offer a profile for further investigations of the anti-fibrotic mechanism of CCP.

TGF-β1-induced EMT activation via both Smad-dependent and MAPK signaling pathways in Cu-induced pulmonary fibrosis

2021 ◽  
Vol 418 ◽  
pp. 115500
Author(s):  
Hongrui Guo ◽  
Zhijie Jian ◽  
Huan Liu ◽  
Hengmin Cui ◽  
Huidan Deng ◽  
...  
Keyword(s):  
Pulmonary Fibrosis ◽  
Signaling Pathways ◽  
Mapk Signaling ◽  
Mapk Signaling Pathways ◽  
Tgf Β1

scholarly journals Prediction of the Active Ingredients, Potential Targets, and Signaling Pathways in ZaoRenDiHuang Capsules for Treatment of Insomnia Based on Network Analysis and Molecular Docking

2020 ◽  
Author(s):  
De Jin ◽  
Jinghua Zhang ◽  
Yuqing Zhang ◽  
Xuedong AN ◽  
Shenghui Zhao ◽  
...  
Keyword(s):  
Data Mining ◽  
Molecular Docking ◽  
Network Analysis ◽  
Signaling Pathways ◽  
Signaling Pathway ◽  
Topological Analysis ◽  
Docking Simulation ◽  
Network Pharmacology ◽  
Receptor Interaction ◽  
Active Ingredients

Abstract Background：Insomnia is a major global public health issue with a high incidence, which presents a significant economic burden. Importantly, insomnia is often accompanied by a myriad of symptoms during the daytime, the most common being insomnia dizziness, headache, malaise, fatigue, anxiety, and even contribute to several diseases. However, the action mode of multi-component and multi-target for Chinese medicine could be a promising therapy for insomnia. According to the previous research, the ZaoRenDiHuang (ZRDH) Capsules showed the noteworthy anti-insomnia effect. Up to now, active ingredients, potential targets, and signaling pathways and mechanism of action are not yet clear. In this study, network pharmacology was employed to elucidate the potential anti-insomnia mechanism of ZRDH.Methods：In this study, an integrated pharmacology approach was implemented, which involved evaluation of absorption, distribution, metabolism and excretion of ZRDH, data mining of the insomnia targets, protein-protein interaction (PPI) network analysis, enrichment analysis, and molecular docking simulation, to predict the bioactive components, potential targets, and molecular mechanism of ZRDH for insomnia.Results：In this work, 44 anti-insomnia components of ZRDH and 65 anti-insomnia targets of insomnia were filtrated through database mining. The Drug-Disease network was constructed andfive key components Jujuboside A, Schizandrin A, Schizandrin C, Schizandrin B, and Spinosin, were further obtained. Sixty-five key targets were identified by topological analysis. Sequential studies turned out, NMURl, CAlCR, GABA, TAER2, ORDS, CYS1TR2, HTR1B, TLR4 were the common key targets. Docking studies indicated that the bioactive compounds could stably bind the pockets of target proteins. The findings of Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway annotation suggested that the Neuroactive ligand−receptor interaction, Serotonergic synapse CAMP signaling pathway, HIF−1a signaling pathway, Toll−like receptor signaling pathway, anti-insomnia through data mining and network analysis.Conclusion: In sunmmary, potential mechanisms involved in ZRDH treatment for insomnia involves multiple components and multiple target points as well as multiple pathways. These findings may offer a profile for further investigations of the anti-fibrotic mechanism of ZRDH.

scholarly journals Urolithin A attenuates renal fibrosis by inhibiting TGF-β1/Smad and MAPK signaling pathways

2021 ◽  
Vol 83 ◽  
pp. 104547
Author(s):  
Zhenzhen Cheng ◽  
Jingjing Tu ◽  
Hongpan Zhang ◽  
Yi zhang ◽  
Benhong Zhou
Keyword(s):  
Signaling Pathways ◽  
Renal Fibrosis ◽  
Mapk Signaling ◽  
Urolithin A ◽  
Mapk Signaling Pathways ◽  
Tgf Β1

Candida tropicalis induces pro-inflammatory cytokine production, NF-κB and MAPKs pathways regulation, and dectin-1 activation

2018 ◽  
Vol 64 (12) ◽  
pp. 937-944 ◽  
Author(s):  
Zhimin Duan ◽  
Qing Chen ◽  
Rong Zeng ◽  
Leilei Du ◽  
Caixia Liu ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Inflammatory Cytokine ◽  
Mononuclear Cells ◽  
Human Peripheral Blood ◽  
Mapk Signaling ◽  
Dependent Manner ◽  
Peripheral Blood Mononuclear ◽  
Downstream Signaling ◽  
Tnf Α ◽  
Mitogen Activated Protein

The prevalence of Candida infection induced by non-albicans Candida (NAC) species is increasing. However, as a common NAC species, C. tropicalis has received much less study in terms of host immunity than C. albicans has. In this study, we evaluated the pro-inflammatory cytokine responses evoked by C. tropicalis and determined whether dectin-1 and downstream NF-κB and mitogen-activated protein kinases (MAPKs) signaling pathways played roles in inflammation in human peripheral blood mononuclear cells (PBMCs) and THP-1 macrophage-like cells. Exposure of PBMCs and THP-1 macrophage-like cells to C. tropicalis led to the enhanced gene expression and secretion of TNF-α and IL-6 in a time- and dose-dependent manner. THP-1 macrophage-like cells being challenged by C. tropicalis resulted in the activation of the NF-κB, p38, and ERK1/2 MAPK signaling pathways. We also found that the expression of dectin-1 was increased with C. tropicalis treatment. These data reveal that dectin-1 may play a role in sensing the inflammation response induced by C. tropicalis and that NF-κB and MAPK are involved in the downstream signaling pathways in macrophages.

scholarly journals Potential role of senescent macrophages in radiation-induced pulmonary fibrosis

2021 ◽  
Vol 12 (6) ◽  
Author(s):  
Lulu Su ◽  
Yinping Dong ◽  
Yueying Wang ◽  
Yuquan Wang ◽  
Bowen Guan ◽  
...  
Keyword(s):  
Matrix Metalloproteinases ◽  
Pulmonary Fibrosis ◽  
Late Toxicity ◽  
Airway Epithelial ◽  
Tnf Α ◽  
Elevated Expression ◽  
Radiation Induced ◽  
Therapeutic Radiation ◽  
Tgf Β1

AbstractRadiation-induced pulmonary fibrosis (RIPF) is a late toxicity of therapeutic radiation in clinic with poor prognosis and limited therapeutic options. Previous results have shown that senescent cells, such as fibroblast and type II airway epithelial cell, are strongly implicated in pathology of RIPF. However, the role of senescent macrophages in the development RIPF is still unknown. In this study, we report that ionizing radiation (IR) increase cellular senescence with higher expression of senescence-associated β-galactosidase (SA-β-Gal) and senescence-specific genes (p16, p21, Bcl-2, and Bcl-xl) in irradiated bone marrow-derived monocytes/macrophages (BMMs). Besides, there’s a significant increase in the expression of pro-fibrogenic factors (TGF-β1 and Arg-1), senescence-associated secretory phenotype (SASP) proinflammatory factors (Il-1α, Il-6, and Tnf-α), SASP chemokines (Ccl2, Cxcl10, and Ccl17), and SASP matrix metalloproteinases (Mmp2, Mmp9 and Mmp12) in BMMs exposed to 10 Gy IR. In addition, the percentages of SA-β-Gal+ senescent macrophages are significantly increased in the macrophages of murine irradiated lung tissue. Moreover, robustly elevated expression of p16, SASP chemokines (Ccl2, Cxcl10, and Ccl17) and SASP matrix metalloproteinases (Mmp2, Mmp9, and Mmp12) is observed in the macrophages of irradiated lung, which might stimulate a fibrotic phenotype in pulmonary fibroblasts. In summary, irradiation can induce macrophage senescence, and increase the secretion of SASP in senescent macrophages. Our findings provide important evidence that senescent macrophages might be the target for prevention and treatment of RIPF.

scholarly journals Angelica Polysaccharide Attenuates LPS-Induced Inflammation Response of Primary Dairy Cow Claw Dermal Cells Via NF-κB and MAPK Signaling Pathways

2021 ◽  
Author(s):  
Mengyue Tian ◽  
Ke Li ◽  
Ruonan Liu ◽  
Jinliang Du ◽  
Dongmin Zou ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Dairy Cow ◽  
Colorimetric Method ◽  
Mapk Signaling ◽  
Economic Losses ◽  
Tnf Α ◽  
Inflammatory Chemokines ◽  
Anti Inflammatory ◽  
Dermal Cells ◽  
Mapk Signaling Pathways

Abstract Background: Laminitis, an inflammation of the claw laminae, is one of the major causes of bovine lameness, which can lead to enormous economic losses and animal welfare problems in dairy farms. Angelica polysaccharide (AP) is proved to possess anti-inflammatory properties. But the role of AP on inflammatory response of the claw dermal cells has not been reported. The aim of this study was to investigate the anti-inflammatory effects of AP on lipopolysaccharide (LPS)-induced primary claw dermal cells of dairy cow and clarify the potential mechanisms. In the current research, the primary claw dermal cells were exposed to gradient concentrations of AP (10, 50, 100 µg/mL) in the presence of 10 µg/mL LPS. The levels of cytokines and nitric oxide (NO) were detected with ELISA and Griess colorimetric method. The mRNA expressions of TLR4, MyD88 and chemokines were measured with qPCR. The activation of NF-κB and MAPK signaling pathways was detected with western blotting.Results: The results indicated that AP reduced the production of inflammatory mediators (TNF-α, IL-1β, IL-6 and NO), downregulated the mRNA expression of TLR4, MyD88 and some pro-inflammatory chemokines (CCL2, CCL20, CXCL2, CXCL8, CXCL10), and suppressed the NF-κB and MAPK signaling pathways evidenced by inhibition of the phosphorylation of IκBα, p65 and ERK, JNK, p38.Conclusions: Our results demonstrated that AP may exert its anti-inflammatory effects on claw dermal cells of dairy cow by regulating the NF-κB and MAPK signaling pathways.

scholarly journals Qiliqiangxin Attenuates Cardiac Remodeling via Inhibition of TGF-β1/Smad3 and NF-κB Signaling Pathways in a Rat Model of Myocardial Infarction

2018 ◽  
Vol 45 (5) ◽  
pp. 1797-1806 ◽  
Author(s):  
Anbang Han ◽  
Yingdong Lu ◽  
Qi Zheng ◽  
Jian Zhang ◽  
YiZhou Zhao ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Cardiac Function ◽  
Signaling Pathways ◽  
Rat Model ◽  
Cardiac Remodeling ◽  
Left Ventricular ◽  
Protective Effects ◽  
Tnf Α ◽  
Tgf Β1

Background/Aims: Qiliqiangxin (QL), a traditional Chinese medicine, has been demonstrated to be effective and safe for the treatment of chronic heart failure. Left ventricular (LV) remodeling causes depressed cardiac performance and is an independent determinant of morbidity and mortality after myocardial infarction (MI). Our previous studies have shown that QL exhibits cardiac protective effects against heart failure after MI. The objective of this study was to explore the effects of QL on myocardial fibrosis in rats with MI and to investigate the underlying mechanism of these effects. Methods: A rat model of acute myocardial infarction was induced by ligating the left anterior descending coronary artery. The rats were treated with QL (1.0 g/kg/day) for 4 weeks after surgery. Echocardiography and histology examination were performed to evaluate heart function and fibrosis, respectively. Protein levels of transforming growth factor-β1 (TGF-β1), phosphorylated Smad3 (p-Smad3), phosphorylated Smad7 (p-Smad7), collagen I (Col- I), alpha smooth muscle actin (a-SMA), tumor necrosis factor-α (TNF-α), interleukin 6 (IL-6), nuclear factor κB (NF-κB), and phosphorylated inhibitor of kappa B alpha (p-IκBα) were measured by western blot analysis. Results: QL treatment ameliorated adverse cardiac remodeling 8 weeks after AMI, including better preservation of cardiac function, decreased inflammation, and reduced fibrosis. In addition, QL treatment reduced Col-I, a-SMA, TGF-β1, and p-Smad3 expression levels but increased p-Smad7 levels in postmyocardial infarct rat hearts. QL administration also reduced the elevated levels of cardiac inflammation mediators, such as TNF-α and IL-6, as well as NF-κB and p-IκBα expression. Conclusions: QL therapy exerted protective effects against cardiac remodeling potentially by inhibiting TGF-β1/Smad3 and NF-κB signaling pathways, thereby preserving cardiac function, as well as reducing myocardial inflammation and fibrosis.

scholarly journals Asperuloside and Asperulosidic Acid Exert an Anti-Inflammatory Effect via Suppression of the NF-κB and MAPK Signaling Pathways in LPS-Induced RAW 264.7 Macrophages

2018 ◽  
Vol 19 (7) ◽  
pp. 2027 ◽  
Author(s):  
Jingyu He ◽  
Xianyuan Lu ◽  
Ting Wei ◽  
Yaqian Dong ◽  
Zheng Cai ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Methyl Ester ◽  
Signaling Pathways ◽  
Mapk Signaling ◽  
Raw 264.7 Cells ◽  
Raw 264.7 ◽  
Tnf Α ◽  
Anti Inflammatory ◽  
Mapk Signaling Pathways ◽  
Inflammatory Effect

Hedyotis diffusa is a folk herb that is used for treating inflammation-related diseases in Asia. Previous studies have found that iridoids in H. diffusa play an important role in its anti-inflammatory activity. This study aimed to investigate the anti-inflammatory effect and potential mechanism of five iridoids (asperuloside (ASP), asperulosidic acid (ASPA), desacetyl asperulosidic acid (DAA), scandoside methyl ester (SME), and E-6-O-p-coumaroyl scandoside methyl ester (CSME)) that are presented in H. diffusa using lipopolysaccharide (LPS)—induced RAW 264.7 cells. ASP and ASPA significantly decreased the production of nitric oxide (NO), prostaglandin E2 (PGE2), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) in parallel with the inhibition of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), TNF-α, and IL-6 mRNA expression in LPS-induced RAW 264.7 cells. ASP treatment suppressed the phosphorylation of the inhibitors of nuclear factor-kappaB alpha (IκB-α), p38, extracellular signal-regulated kinase (ERK), and c-Jun N-terminal kinase (JNK). The inhibitory effect of ASPA was similar to that of ASP, except for p38 phosphorylation. In summary, the anti-inflammatory effects of ASP and ASPA are related to the inhibition of inflammatory cytokines and mediators via suppression of the NF-κB and mitogen-activated protein kinase (MAPK) signaling pathways, which provides scientific evidence for the potential application of H. diffusa.

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