scholarly journals Network Pharmacology Prediction and Molecular Docking-Based Strategy to Discover the Potential Pharmacological Mechanism of Wen-yu-jin Against Pulmonary Fibrosis in Mouse Model

2021 ◽  
Author(s):  
lu wang ◽  
Wenxiang Zhu ◽  
Rui Sun ◽  
Jing Liu ◽  
Qihong Ma ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Pulmonary Fibrosis ◽  
Signaling Pathway ◽  
Lung Fibrosis ◽  
Mapk Signaling ◽  
Mapk Signaling Pathway ◽  
Network Pharmacology ◽  
In Vitro Experiments

Abstract Background Pulmonary fibrosis (PF) is a devastating lung disease. The two drugs approved by the FDA, pirfenidone and nintedanib, can only delay the progression of the disease but cannot cure the disease. These drugs also present adverse effects. Wen-yu-jin (WYJ) obtained from steamed roots of Curcuma wenyujin showed a variety of pharmacological activities. In this study we investigated whether WYJ present anti-lung fibrosis effects. Methods Ultra-high pressure liquid chromatography combined with linear ion trap-orbital tandem mass spectrometry (UHPLC-LTQ-orbital trap) was used to identify chemical composition of WYJ. PF-related and WYJ-related targets were obtained from public databases. Network pharmacological was performed to acquire potential targets and major signaling pathways. The binding activity of composition with core targets was predicted by molecular docking. Based on the predicted results, the anti-lung fibrosis effect of WYJ was verified in vivo and in vitro experiments. Results 23 major compositions of WYJ were identified based on UHPLC-LTQ-Orbitrap. According to the results of network pharmacology, MAPK signaling pathway might play an important role in WYJ against lung fibrosis and STAT3 also could be the potential therapeutic targets. Molecular docking results indicated that most of the compositions have good binding activities with core targets. In vivo and in vitro experiments showed that WYJ alleviated process of fibrosis by inhibiting MAPK signaling pathway and the levels of phosphorylated STAT3 (p-STAT3). Conclusion According to the results of network pharmacology and molecular docking, in vivo and in vitro experiments further verified potential targets and molecular mechanism of WYJ against lung fibrosis. Our study provided a novel approach to explain the pharmacological basis of other herbs.

scholarly journals An Integration of Network Pharmacology and Experimental Verification to Investigate the Mechanism of Guizhi to Treat Nephrotic Syndrome

2021 ◽  
Vol 12 ◽  
Author(s):  
Dan He ◽  
Qiang Li ◽  
Guangli Du ◽  
Guofeng Meng ◽  
Jijia Sun ◽  
...  
Keyword(s):  
Nephrotic Syndrome ◽  
Molecular Docking ◽  
Protein Expression ◽  
Signaling Pathway ◽  
P38 Mapk ◽  
Experimental Verification ◽  
Active Component ◽  
Mapk Signaling

Background: Guizhi has the pharmacological activity of anti-inflammatory. However, the effect mechanism of Guizhi against nephrotic syndrome (NS) remains unclear. A network pharmacological approach with experimental verification in vitro and in vivo was performed to investigate the potential mechanisms of Guizhi to treat NS.Methods: Active compounds and potential targets of Guizhi, as well as the related targets of NS were obtained from the public databases. The intersecting targets of Guizhi and NS were obtained through Venny 2.1.0. The key targets and signaling pathways were determined by protein-protein interaction (PPI), genes ontology (GO) and kyoto encyclopedia of genes and genomes (KEGG) analysis. And the overall network was constructed with Cytoscape. Molecular docking verification was carried out by AutoDock Vina. Finally, in vitro and in vivo experiments were performed to verify the mechanism of Guizhi to treat NS.Results: 63 intersecting targets were obtained, and the top five key targets mainly involed in NF- Kappa B and MAPK signaling pathway. In the overall network, cinnamaldehyde (CA) was the top one active compound with the highest degree value. The molecular docking showed that the top five key targets were of good binding activity with the active components of Guizhi. To in vitro experiment, CA, the main active component of Guizhi, inhibited the secretion of IL-1β, IL-6, TNF-α in LPS challenged RAW264.7 cells, and down regulated the protein expression of p-NF-κB p65 and p-p38 MAPK in LPS challenged RAW264.7 cells. In vitro experiment showed that, 24 urinary protein and renal function were increased in ADR group. To western blot, CA down regulated the protein expression of p-p38 MAPK in rats of adriamycin-induced nephropathy.Conclusion: CA might be the main active component of Guizhi to treat NS, and the underlying mechanism might mainly be achieved by inhibiting MAPK signaling pathway.

scholarly journals Anti-Breast Cancer Effect of 2-Dodecyl-6-Methoxycyclohexa-2,5-Diene-1,4-Dione in vivo and in vitro Through MAPK Signaling Pathway

2020 ◽  
Vol Volume 14 ◽  
pp. 2667-2684 ◽  
Author(s):  
Xing Zhou ◽  
Xingchun Wu ◽  
Luhui Qin ◽  
Shunyu Lu ◽  
Hongliang Zhang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Signaling Pathway ◽  
Mapk Signaling ◽  
Mapk Signaling Pathway

scholarly journals Icariin Promotes the Migration of BMSCs In Vitro and In Vivo via the MAPK Signaling Pathway

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Feng Jiao ◽  
Wang Tang ◽  
He Huang ◽  
Zhaofei Zhang ◽  
Donghua Liu ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Mapk Signaling ◽  
Stress Fiber ◽  
Fiber Formation ◽  
Mapk Signaling Pathway ◽  
Actin Stress Fiber ◽  
Stress Fiber Formation ◽  
Actin Stress Fiber Formation

Bone marrow-derived mesenchymal stem cells (BMSCs) are widely used in tissue engineering for regenerative medicine due to their multipotent differentiation potential. However, their poor migration ability limits repair effects. Icariin (ICA), a major component of the Chinese medical herb Herba Epimedii, has been reported to accelerate the proliferation, osteogenic, and chondrogenic differentiation of BMSCs. However, it remains unknown whether ICA can enhance BMSC migration, and the possible underlying mechanisms need to be elucidated. In this study, we found that ICA significantly increased the migration capacity of BMSCs, with an optimal concentration of 1 μmol/L. Moreover, we found that ICA stimulated actin stress fiber formation in BMSCs. Our work revealed that activation of the MAPK signaling pathway was required for ICA-induced migration and actin stress fiber formation. In vivo, ICA promoted the recruitment of BMSCs to the cartilage defect region. Taken together, these results show that ICA promotes BMSC migration in vivo and in vitro by inducing actin stress fiber formation via the MAPK signaling pathway. Thus, combined administration of ICA with BMSCs has great potential in cartilage defect therapy.

scholarly journals Arctigenin Suppressed Epithelial-Mesenchymal Transition Through Wnt3a/β-Catenin Pathway in PQ-Induced Pulmonary Fibrosis

2020 ◽  
Vol 11 ◽  
Author(s):  
Fei Gao ◽  
Yun Zhang ◽  
Zhizhou Yang ◽  
Mengmeng Wang ◽  
Zhiyi Zhou ◽  
...  
Keyword(s):  
Pulmonary Fibrosis ◽  
Signaling Pathway ◽  
Lung Fibrosis ◽  
Epithelial Mesenchymal Transition ◽  
A549 Cells ◽  
Underlying Mechanism ◽  
Alveolar Type ◽  
Mesenchymal Transition

Arctigenin (ATG), a major bioactive substance of Fructus Arctii, counters renal fibrosis; however, whether it protects against paraquat (PQ)-induced lung fibrosis remains unknown. The present study was to determine the effect of ATG on PQ-induced lung fibrosis in a mouse model and the underlying mechanism. Firstly, we found that ATG suppressed PQ-induced pulmonary fibrosis by blocking the epithelial-mesenchymal transition (EMT). ATG reduced the expressions of Vimentin and α-SMA (lung fibrosis markers) induced by PQ and restored the expressions of E-cadherin and Occludin (two epithelial markers) in vivo and in vitro. Besides, the Wnt3a/β-catenin signaling pathway was significantly activated in PQ induced pulmonary fibrosis. Further analysis showed that pretreatment of ATG profoundly abrogated PQ-induced EMT-like phenotypes and behaviors in A549 cells. The Wnt3a/β-catenin signaling pathway was repressed by ATG treatment. The overexpression of Wnt3a could weaken the therapeutic effect of ATG in A549 cells. These findings suggested that ATG could serve as a new therapeutic candidate to inhibit or even reverse EMT-like changes in alveolar type II cells during PQ-induced lung fibrosis, and unraveled that the Wnt3a/β-catenin pathway might be a mechanistic tool for ATG to control pulmonary fibrosis.

scholarly journals Effect of Total Flavones from Cuscuta Chinensis on Anti-Abortion via the MAPK Signaling Pathway

2018 ◽  
Vol 2018 ◽  
pp. 1-12 ◽  
Author(s):  
Hai-wang Wu ◽  
Yi-hui Feng ◽  
Dong-ying Wang ◽  
Wei-yu Qiu ◽  
Qing-ying Yu ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Prolactin Receptor ◽  
Chinese Herb ◽  
Mapk Signaling ◽  
Mapk Signaling Pathway ◽  
Dependent Manner ◽  
Active Components ◽  
Cuscuta Chinensis

For centuries, the Chinese herb Cuscuta chinensis has been applied clinically for abortion prevention in traditional Chinese medicine (TCM). Total flavones extracted from Cuscuta chinensis (TFCC) are one of the active components in the herb and also display anti-abortion effect similar to the unprocessed material. However, how TFCC exerts the anti-abortion effect remains largely unknown. In this study, we aim at characterizing the anti-abortion effects of TFCC and its underlying molecular mechanism in vitro and in vivo using human primary decidua cells and a mifepristone-induced abortion model in rat, respectively. The damage to the decidua caused by mifepristone in vivo was reversed by TFCC treatment in a dosage-dependent manner. High dosage of TFCC significantly upregulated the expression of estrogen receptor (ER), progesterone receptor (PR), and prolactin receptor (PRLR) in decidua tissue but downregulated the expression of p-ERK. Furthermore, we detected higher level of p-ERK and p-p38 in primary decidua cells from spontaneous abortion while treatment by TFCC downregulated their expression. Our results suggest TFCC mediates its anti-abortion effect by interfering with MAPK signaling pathway.

scholarly journals Effects of Nervilia fordii Extract on Pulmonary Fibrosis Through TGF-β/Smad Signaling Pathway

2021 ◽  
Vol 12 ◽  
Author(s):  
Yufeng Yao ◽  
Yue Yuan ◽  
Zenghui Lu ◽  
Yunxia Ma ◽  
Yuanyuan Xie ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Pulmonary Fibrosis ◽  
Signaling Pathway ◽  
Therapeutic Effects ◽  
Collagen Deposition ◽  
Smad Signaling ◽  
Smad Signaling Pathway ◽  
Tgf Β1

Idiopathic pulmonary fibrosis (IPF) is a progressive and irreversible interstitial pulmonary disease with a poor prognosis. The extract of Nervilia fordii (NFE) has shown remarkable benefit in the treatment of acute lung injury, lung cancer, and severe acute respiratory syndrome (SARS). However, the potential mechanism and efficacy of NFE in the treatment of IPF remain unknown. In this study, a systematic network pharmacology analysis was used to predict the mechanism and efficacy of NFE in the treatment of IPF, based on the major components of NFE elucidated by UPLC-TOF-MS/MS. The potential molecular interactions between the compounds and potential targets were predicted using molecular docking. In vivo, rats with pulmonary fibrosis induced by a single intratracheal injection of bleomycin (BLM) were orally administered NFE for 14 days. Lung index and biochemical levels were determined, and histopathological analysis using hematoxylin and eosin (H&E) and Masson staining was performed. The effects of NFE on fibroblast proliferation in Lipopolysaccharide (LPS) and TGF-β1-induced mouse 3T6 fibroblasts were evaluated in vitro. In total, 20 components were identified in NFE, and 102 potential targets for IPF treatment were predicted. These targets potentially participate in processes regulated by transmembrane receptor protein tyrosine kinase, ERBB2, and et al. Molecular docking results predicted high affinity interactions between three components (rhamnazin, rhamnetin, and rhamnocitrin) and the potential targets, suggesting that TGF-β is the most important potential target of NFE in the treatment of pulmonary fibrosis. NFE significantly decreased the lung index and alleviated BLM-induced pulmonary fibrosis in rats. Histopathological observation of lung tissues showed that NFE alleviated inflammation and collagen deposition in BLM-induced rats. NFE inhibited the migration of LPS- and TGF-β1-induced 3T6 fibroblasts, reduced the contents of hydroxyproline and collagen, and contributed to anti-inflammation and anti-oxidation. With the intervention of NFE, the protein and RNA expression of TGF-β1, a-SMA, Smad3/4, p-Smad3/4, CTGF, and p-ERK1/2 were significantly downregulated, while Smad7 and ERK1/2 were upregulated significantly in vivo and in vitro. These findings indicated that NFE may exert therapeutic effects on pulmonary fibrosis by alleviating inflammation, oxidation, and collagen deposition. The mechanism related to the inhibition of the TGF-β/Smad signaling pathway.

scholarly journals Network Pharmacology-Based Prediction of the Active Ingredients and Potential Targets of Chinese Herbal Danyu Gukang Pills for Application to Osteonecrosis of the Femoral Head Disease

2021 ◽  
Author(s):  
Yongchang Guo ◽  
Dapeng Zhang ◽  
Yuju Cao ◽  
Xiaoyan Feng ◽  
Caihong Shen ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Femoral Head ◽  
Signaling Pathway ◽  
Molecular Mechanisms ◽  
Enrichment Analysis ◽  
Network Pharmacology ◽  
Pathway Enrichment Analysis ◽  
In Vitro Experiments ◽  
Active Components

Abstract Ethnopharmacological relevanceOsteonecrosis of the femoral head (ONFH) is still a challenge for orthopedists worldwide, which may lead to disability in patients without effective treatment. A newly developed formula of Chinese medicine, Danyu Gukang Pills (DGP), was recognized to be effective for ONFH. Nevertheless, its molecular mechanisms remain to be clarified. MethodsNetwork pharmacology was adopted to detect the mechanism of DGP on ONFH. The compounds of DGP were collected from the online databases, and active components were selected based on their OB and DL index. The potential proteins of DGP were acquired from TCMSP database, while the potential genes of ONFH were obtained from Gene Cards and Pubmed Gene databases. The function of Gene and potential pathways were researched by GO and KEGG pathway enrichment analysis. The compounds-targets and targets-pathways network were constructed in an R and Cytosacpe software. The mechanism was further investigated via molecular docking. Finally, in-vitro experiments were validated in the BMSCs. ResultsA total of 2305 compounds in DGP were gained, among which, 370 were selected as active components for which conforming to criteria. Combined the network analysis, molecular docking and in-vitro experiments, the results firstly demonstrated that the treatment effect of DGP on ONFH may be closely related to HIF-1α, VEGFA and HIF-1 signaling pathway. ConclusionThe current study firstly researched the molecular mechanism of DGP on ONFH based on network pharmacology. The results indicated that DGP may exert the effect on ONFH targeting on HIF-1α and VEGFA via HIF-1 signaling pathway.

scholarly journals tRNA-Derived Fragment tRF-Glu-TTC-027 Regulates the Progression of Gastric Carcinoma via MAPK Signaling Pathway

2021 ◽  
Vol 11 ◽  
Author(s):  
Weiguo Xu ◽  
Bin Zhou ◽  
Juan Wang ◽  
Li Tang ◽  
Qing Hu ◽  
...  
Keyword(s):  
Gastric Carcinoma ◽  
Signaling Pathway ◽  
Cell Lines ◽  
Mapk Pathway ◽  
Mapk Signaling ◽  
Mapk Signaling Pathway ◽  
Migration And Invasion ◽  
Underlying Mechanisms

Transfer RNA-derived RNA fragments (tRFs) belong to non-coding RNAs (ncRNAs) discovered in most carcinomas. Although some articles have demonstrated the characteristics of tRFs in gastric carcinoma (GC), the underlying mechanisms still need to be elucidated. Meanwhile, it was reported that the MAPK pathway was momentous in GC progression. Thus we focused on investigating whether tRF-Glu-TTC-027 could act as a key role in the progression of GC with the regulation of the MAPK pathway. We collected the data of the tRNA-derived fragments expression profile from six paired clinical GC tissues and corresponding adjacent normal samples in this study. Then we screened tRF-Glu-TTC-027 for analysis by using RT-PCR. We transfected GC cell lines with tRF-Glu-TTC-027 mimics or mimics control. Then the proliferation, migration, and invasion assays were performed to assess the influence of tRF-Glu-TTC-027 on GC cell lines. Fluorescence in situ hybridization assay was conducted to confirm the cell distribution of tRF-Glu-TTC-027. We confirmed the mechanism that tRF-Glu-TTC-027 influenced the MAPK signaling pathway and observed a strong downregulation of tRF-Glu-TTC-027 in clinical GC samples. Overexpression of tRF-Glu-TTC-027 suppressed the malignant activities of GC in vitro and in vivo. MAPK signaling pathway was confirmed to be a target pathway of tRF-Glu-TTC-027 in GC by western blot. This is the first study to show that tRF-Glu-TTC-027 was a new tumor-suppressor and could be a potential object for molecular targeted therapy in GC.

scholarly journals Anti-Breast Cancer Effect of 2-Dodecyl-6-Methoxycyclohexa-2,5-Diene-1,4-Dione in vivo and in vitro Through MAPK Signaling Pathway [Corrigendum]

2020 ◽  
Vol Volume 14 ◽  
pp. 4575-4577
Author(s):  
Xing Zhou ◽  
Xingchun Wu ◽  
Luhui Qin ◽  
Shunyu Lu ◽  
Hongliang Zhang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Signaling Pathway ◽  
Mapk Signaling ◽  
Mapk Signaling Pathway

scholarly journals Angelicin Shows Antitumor Effects On The Oral Squamous Cell Carcinoma By Negatively Regulating DUSP6-Mediated cMYC-MAPK Signaling Pathway

2021 ◽  
Author(s):  
Na Liu ◽  
Qianhui Shang ◽  
Jiajia Qi ◽  
Qionghua Li ◽  
Yutong Sun ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Signaling Pathway ◽  
Regulatory Mechanism ◽  
Mapk Signaling ◽  
Mapk Signaling Pathway ◽  
Antitumor Effects

Abstract Background: Angelicin has been reported to have antitumor effects on many cancers. However, few studies on angelicin in oral squamous cell carcinoma (OSCC) have been performed. Methods: In this study, we performed a cell cycle and apoptosis assay, wound healing assay, and transwell assay to assess the effects of angelicin on malignant phenotypes of OSCC in vitro. To determine the potential regulatory mechanism, we conducted differentially expressed genes analysis of OSCC cells. Subsequently, nude mouse xenograft models were used to evaluate the function of angelicin and validate the regulatory mechanism in vivo. Results: The results showed that angelicin inhibited the malignant phenotype of OSCC in vitro and reduced tumor formation in vivo. Mechanistically, angelicin induced the downregulation of the significantly different gene—dual-specificity phosphatase 6 (DUSP6) and the downstream transcription factor c-MYC in the mitogen-activated protein kinase (MAPK) signaling pathway. Conclusion: Our results indicate that angelicin has antitumor effects on OSCC by negatively regulating the DUSP6-mediated cMYC-MAPK signaling pathway and is a promising antitumor drug in OSCC therapy.

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