scholarly journals DMAG, a novel countermeasure for the treatment of thrombocytopenia

2021 ◽  
Vol 27 (1) ◽  
Author(s):  
Jing Lin ◽  
Jing Zeng ◽  
Sha Liu ◽  
Xin Shen ◽  
Nan Jiang ◽  
...  

Abstract Background Thrombocytopenia is one of the most common hematological disease that can be life-threatening caused by bleeding complications. However, the treatment options for thrombocytopenia remain limited. Methods In this study, giemsa staining, phalloidin staining, immunofluorescence and flow cytometry were used to identify the effects of 3,3ʹ-di-O-methylellagic acid 4ʹ-glucoside (DMAG), a natural ellagic acid derived from Sanguisorba officinalis L. (SOL) on megakaryocyte differentiation in HEL cells. Then, thrombocytopenia mice model was constructed by X-ray irradiation to evaluate the therapeutic action of DMAG on thrombocytopenia. Furthermore, the effects of DMAG on platelet function were evaluated by tail bleeding time, platelet aggregation and platelet adhesion assays. Next, network pharmacology approaches were carried out to identify the targets of DMAG. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed to elucidate the underling mechanism of DMAG against thrombocytopenia. Finally, molecular docking simulation, molecular dynamics simulation and western blot analysis were used to explore the relationship between DAMG with its targets. Results DMAG significantly promoted megakaryocyte differentiation of HEL cells. DMAG administration accelerated platelet recovery and megakaryopoiesis, shortened tail bleeding time, strengthened platelet aggregation and adhesion in thrombocytopenia mice. Network pharmacology revealed that ITGA2B, ITGB3, VWF, PLEK, TLR2, BCL2, BCL2L1 and TNF were the core targets of DMAG. GO and KEGG pathway enrichment analyses suggested that the core targets of DMAG were enriched in PI3K–Akt signaling pathway, hematopoietic cell lineage, ECM-receptor interaction and platelet activation. Molecular docking simulation and molecular dynamics simulation further indicated that ITGA2B, ITGB3, PLEK and TLR2 displayed strong binding ability with DMAG. Finally, western blot analysis evidenced that DMAG up-regulated the expression of ITGA2B, ITGB3, VWF, p-Akt and PLEK. Conclusion DMAG plays a critical role in promoting megakaryocytes differentiation and platelets production and might be a promising medicine for the treatment of thrombocytopenia. Graphical Abstract

2021 ◽  
Author(s):  
Jing Lin ◽  
Jing Zeng ◽  
Sha Liu ◽  
Xin Shen ◽  
Nan Jiang ◽  
...  

Abstract Background: Thrombocytopenia is one of the most common hematological disease that can be life-threatening caused by bleeding complications. However, the treatment options for thrombocytopenia remain limited. Methods: In this study, giemsa staining, phalloidin staining and flow cytometry were firstly used to identify the effects of 3,3'-Di-O-methylellagic acid 4'-glucoside (DMAG), a natural ellagic acid derived from Sanguisorba officinalis L. (SOL) on megakaryocyte differentiation in HEL cells. Then, thrombocytopenia mice model was constructed by X-ray irradiation to evaluate the therapeutic action of DMAG on thrombocytopenia. Next, network pharmacology approachs were carried out to identify the targets of DMAG. Moreover, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrich-ment analyses were performed to elucidate the underling mechanism of DMAG against thrombocytopenia. Finally, Molecular docking simulation, molecular dynamics simulation and western blot analysis were used to explore the relationship between DAMG with its targets.Results: DMAG significantly promoted megakaryocyte differentiation and maturation of HEL cells. DMAG administration accelerated platelet recovery and megakaryopoiesis in thrombocytopenia mice. Network pharmacology revealed that ITGA2B, ITGB3, VWF, PLEK, TLR2, BCL2, BCL2L1 and TNF were the core targets of DMAG. GO and KEGG pathway enrichment analyses suggested that the core targets of DMAG were enriched in PI3K-Akt signaling pathway, hematopoietic cell lineage, ECM-receptor interaction and platelet activation. Molecular docking simulation and molecular dynamics simulation further indicated that ITGA2B, ITGB3, PLEK and TLR2 displayed strong binding ability with DMAG. Finally, western blot analysis evidenced that DMAG up-regulated the expression of ITGA2B, ITGB3, VWF and PLEK. Conclusion: DMAG plays a critical role in promoting megakaryocytes differentiation and platelets production and might be a promising medicine for the treatment of thrombocytopenia.


2020 ◽  
Vol 19 (7) ◽  
pp. 1449-1457
Author(s):  
Chuan Liu ◽  
Fang-Fang Fan ◽  
Xuan-Hao Li ◽  
Wen-Xiang Wang ◽  
Ya Tu ◽  
...  

Purpose: To study the mechanism involved in the anti-cholecystitis effect the Tibetan medicine “Dida”, using network pharmacology-integrated molecular docking simulationsMethods: In this investigation, the bioactive compounds of Dida were collected, network pharmacology methods to predict their targets, and networks were constructed through GO and KEGG pathway analyses. The potential binding between the bioactive compounds and the targets were demonstrated using molecular docking simulations.Results: A total of 12 bioactive compounds and 50 key targets of Dida were identified. Two networks, namely, protein–protein interaction (PPI) network of cholecystitis targets, and compound–target– pathway network, were established. Network analysis showed that 10 targets (GAPDH, AKT1, CASP3, EGFR, TNF, MAPK3, MAPK1, HSP90AA1, STAT3, and BCL2L1) may be the therapeutic targets of Dida in cholecystitis. Analysis of the KEGG pathway indicated that the anti-cholecystitis effect of Dida may its regulation of a few crucial pathways, such as apoptosis, as well as toll-like  receptor, T cell receptor, NOD-like receptor, and MAPK signaling pathways. Furthermore, molecular docking simulation revealed that CASP3, CAPDH, HSP90AA1, MAPK3, MAPK1, and STAT3 had well-characterized interactions with the corresponding compounds.Conclusion: The mechanism underlying the anti-cholecystitis effect of Dida has been successfully predicted and verified using a combination of network pharmacology and molecular docking simulation. This provides a firm basis for the experimental verification of the use of Dida in the treatment of cholecystitis, and enhances its rational application in clinical practice. Keywords: Tibetan medicine, Dida, Cholecystitis, Mechanism, Network pharmacology, Molecular docking simulation


2020 ◽  
Vol 19 (9) ◽  
pp. 1953-1961
Author(s):  
Chuan Liu ◽  
Fang-Fang Fan ◽  
Xuan-Hao Li ◽  
Wen-Xiang Wang ◽  
Ya Tu ◽  
...  

Purpose: To study the mechanism involved in the anti-cholecystitis effect the Tibetan medicine “Dida”, using network pharmacology-integrated molecular docking simulationsMethods: In this investigation, the bioactive compounds of Dida were collected, network pharmacology methods to predict their targets, and networks were constructed through GO and KEGG pathway analyses. The potential binding between the bioactive compounds and the targets were demonstrated using molecular docking simulations.Results: A total of 12 bioactive compounds and 50 key targets of Dida were identified. Two networks, namely, protein-protein interaction (PPI) network of cholecystitis targets, and compound-target-pathway network, were established. Network analysis showed that 10 targets (GAPDH, AKT1, CASP3, EGFR, TNF, MAPK3, MAPK1, HSP90AA1, STAT3, and BCL2L1) may be the therapeutic targets of Dida in cholecystitis. Analysis of the KEGG pathway indicated that the anti-cholecystitis effect of Dida may its regulation of a few crucial pathways, such as apoptosis, as well as toll-like  receptor, T cell receptor, NOD-like receptor, and MAPK signaling pathways. Furthermore, molecular docking simulation revealed that CASP3, CAPDH, HSP90AA1, MAPK3, MAPK1, and STAT3 had well-characterized interactions with the corresponding compounds.Conclusion: The mechanism underlying the anti-cholecystitis effect of Dida was successfully predicted and verified using a combination of network pharmacology and molecular docking simulation. This provides a firm basis for the experimental verification of the use of Dida in the treatment of cholecystitis, and enhances its rational application in clinical medication. Keywords: Tibetan medicine, Dida, Cholecystitis, Mechanism of effect, Network pharmacology, Molecular docking simulation


2019 ◽  
Vol 22 (6) ◽  
pp. 411-420 ◽  
Author(s):  
Xian-Jun Wu ◽  
Xin-Bin Zhou ◽  
Chen Chen ◽  
Wei Mao

Aim and Objective: Cardiovascular disease is a serious threat to human health because of its high mortality and morbidity rates. At present, there is no effective treatment. In Southeast Asia, traditional Chinese medicine is widely used in the treatment of cardiovascular diseases. Quercetin is a flavonoid extract of Ginkgo biloba leaves. Basic experiments and clinical studies have shown that quercetin has a significant effect on the treatment of cardiovascular diseases. However, its precise mechanism is still unclear. Therefore, it is necessary to exploit the network pharmacological potential effects of quercetin on cardiovascular disease. Materials and Methods: In the present study, a novel network pharmacology strategy based on pharmacokinetic filtering, target fishing, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, compound-target-pathway network structured was performed to explore the anti- cardiovascular disease mechanism of quercetin. Results:: The outcomes showed that quercetin possesses favorable pharmacokinetic profiles, which have interactions with 47 cardiovascular disease-related targets and 12 KEGG signaling pathways to provide potential synergistic therapeutic effects. Following the construction of Compound-Target-Pathway (C-T-P) network, and the network topological feature calculation, we obtained top 10 core genes in this network which were AKT1, IL1B, TNF, IL6, JUN, CCL2, FOS, VEGFA, CXCL8, and ICAM1. KEGG pathway enrichment analysis. These indicated that quercetin produced the therapeutic effects against cardiovascular disease by systemically and holistically regulating many signaling pathways, including Fluid shear stress and atherosclerosis, AGE-RAGE signaling pathway in diabetic complications, TNF signaling pathway, MAPK signaling pathway, IL-17 signaling pathway and PI3K-Akt signaling pathway.


2021 ◽  
Vol 29 ◽  
pp. 239-256
Author(s):  
Qian Wang ◽  
Lijing Du ◽  
Jiana Hong ◽  
Zhenlin Chen ◽  
Huijian Liu ◽  
...  

BACKGROUND: Shanmei Capsule is a famous preparation in China. However, the related mechanism of Shanmei Capsule against hyperlipidemia has yet to be revealed. OBJECTIVE: To elucidate underlying mechanism of Shanmei Capsule against hyperlipidemia through network pharmacology approach and molecular docking. METHODS: Active ingredients, targets of Shanmei Capsule as well as targets for hyperlipidemia were screened based on database. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment were performed via Database for Annotation, Visualization, and Integrated Discovery (DAVID) 6.8 database. Ingredient-target-disease-pathway network was visualized utilizing Cytoscape software and molecular docking was performed by Autodock Vina. RESULTS: Seventeen active ingredients in Shanmei Capsule were screened out with a closely connection with 34 hyperlipidemia-related targets. GO analysis revealed 40 biological processes, 5 cellular components and 29 molecular functions. A total of 15 signal pathways were enriched by KEGG pathway enrichment analysis. The docking results indicated that the binding activities of key ingredients for PPAR-α are equivalent to that of the positive drug lifibrate. CONCLUSIONS: The possible molecular mechanism mainly involved PPAR signaling pathway, Bile secretion and TNF signaling pathway via acting on MAPK8, PPARγ, MMP9, PPARα, FABP4 and NOS2 targets.


2021 ◽  
Author(s):  
Xiaojian Wang ◽  
Rui Wang ◽  
Ting Xu ◽  
Hongting Jin ◽  
Peijian Tong ◽  
...  

Abstract Background The lesion of marrow is a crucial factor in orthopedic diseases, which is recognized by orthopedics-traumatology expert from "Zhe-School of Chinese Medicine". The Chinese herbs of regulating marrow has been widely used to treat osteonecrosis of the femoral head (ONFH) in China, while the interaction mechanisms were still elucidated. Thus, we conducted this study to explore the underlying mechanism of the five highest-frequency Chinese herbs of regulating marrow(HF-CHRM) in the treatment of ONFH with the aid of network pharmacology(NP) and molecular docking(MD). Methods The active components and potential targets of HF-CHRM were obtained through several online databases, such as Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP), UniProt database. The gene targets related to ONFH were collected with the help of the OMIM and GeneCards disease-related databases. The "drug- component-target-disease" network and protein-protein interaction(PPI) network of the drug and disease intersecting targets were constructed by using Cytoscape software and the STRING database. R software was used for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. The MD of critical components and targets was carried out using Autodock Vina and Pymol to validate the binding affinity. Results A total of 54 active components, 1074 drug targets and 195 gene targets were obtained. There were 1219 ONFH related targets. 39 drug and disease intersection targets(representative genes: IL6, TP53, VEGFA, ESR1, IL1B) were obtained and considered potential therapeutic targets. 1619 items were obtained by the GO enrichment analysis, including 1517 biological processes, 10 cellular components and 92 molecular functions, which is mainly related to angiogenesis, bone and lipid metabolism and inflammatory reaction. The KEGG pathway enrichment analysis revealed 119 pathways, including AGE-RAGE signaling pathway, PI3K-Akt signaling pathway and IL-17 signaling pathway. MD results showed that quercetin, wogonin, and kaempferol active components had good affinity with IL6, TP53, and VEGFA core proteins. Conclusion The HF-CHRM can treat ONFH by multi-component, multi-target, and multi-pathway comprehensive action.


2019 ◽  
Vol 2019 ◽  
pp. 1-15 ◽  
Author(s):  
Ziqi Meng ◽  
Xinkui Liu ◽  
Jiarui Wu ◽  
Wei Zhou ◽  
Kaihuan Wang ◽  
...  

Background. Compound Kushen Injection (CKI) is a Chinese patent drug that shows good efficacy in treating lung cancer (LC). However, its underlying mechanisms need to be further clarified.Methods. In this study, we adopted a network pharmacology method to gather compounds, predict targets, construct networks, and analyze biological functions and pathways. Moreover, molecular docking simulation was employed to assess the binding potential of selected target-compound pairs.Results. Four networks were established, including the compound-putative target network, protein-protein interaction (PPI) network of LC targets, compound-LC target network, and herb-compound-target-pathway network. Network analysis showed that 8 targets (CHRNA3, DRD2, PRKCA, CDK1, CDK2, CHRNA5, MMP1, and MMP9) may be the therapeutic targets of CKI in LC. In addition, molecular docking simulation indicated that CHRNA3, DRD2, PRKCA, CDK1, CDK2, MMP1, and MMP9 had good binding activity with the corresponding compounds. Furthermore, enrichment analysis indicated that CKI might exert a therapeutic role in LC by regulating some important pathways, namely, pathways in cancer, proteoglycans in cancer, PI3K-Akt signaling pathway, non-small-cell lung cancer, and small cell lung cancer.Conclusions. This study validated and predicted the mechanism of CKI in treating LC. Additionally, this study provides a good foundation for further experimental studies and promotes the reasonable application of CKI in the clinical treatment of LC.


2021 ◽  
Vol 2021 ◽  
pp. 1-16
Author(s):  
Xiaowen Zhou ◽  
Zhenqian Yan ◽  
Yaxin Wang ◽  
Qi Ren ◽  
Xiaoqi Liu ◽  
...  

Background. Hyperlipidemia, due to the practice of unhealthy lifestyles of modern people, has been a disturbance to a large portion of population worldwide. Recently, several scholars have turned their attention to Chinese medicine (CM) to seek out a lipid-lowering approach with high efficiency and low toxicity. This study aimed to explore the mechanism of Huatan Jiangzhuo decoction (HTJZD, a prescription of CM) in the treatment of hyperlipidemia and to determine the major regulation pathways and potential key targets involved in the treatment process. Methods. Data on the compounds of HTJZD, compound-related targets (C-T), and known disease-related targets (D-T) were collected from databases. The intersection targets (I-T) between C-T and D-T were filtered again to acquire the selected targets (S-T) according to the specific index. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment, as well as network construction, were applied to predict the putative mechanisms of HTJZD in treating hyperlipidemia. Thereafter, an animal experiment was conducted to validate the therapeutic effect of HTJZD. In addition, regulated differentially expressed genes (DEGs) were processed from the RNA sequencing analysis results. Common genes found between regulated DEGs and S-T were analyzed by KEGG pathway enrichment to select the key targets. Lastly, key targets were validated by real-time quantitative reverse transcription PCR (qRT-PCR) analysis. Results. A total of 210 S-T were filtered out for enrichment analysis and network construction. The enrichment results showed that HTJZD may exert an effect on hyperlipidemia through the regulation of lipid metabolism and insulin resistance. The networks predict that the therapeutic effect of HTJZD may be based on the composite pharmacological action of these active compounds. The animal experiment results verify that HTJZD can inhibit dyslipidemia in rats with hyperlipidemia, suppress lipid accumulation in the liver, and reverse the expression of 202 DEGs, which presented an opposite trend in the model and HTJZD groups. Six targets were selected from the common targets between 210 S-T and 202 regulated DEGs, and the qRT-PCR results showed that HTJZD could effectively reverse Srebp-1c, Cyp3a9, and Insr mRNA expression (P < 0.01). Conclusion. In brief, network pharmacology predicted that HTJZD exerts a therapeutic effect on hyperlipidemia. The animal experimental results confirmed that HTJZD suppressed the pathological process induced by hyperlipidemia by regulating the expression of targets involved in lipid metabolism and insulin resistance.


2020 ◽  
Author(s):  
Ling Zhang ◽  
Yunkai Dai ◽  
Yuping Li ◽  
Weijing Chen ◽  
Ruliu Li ◽  
...  

Abstract Background Chronic gastritis (CG) is an inflammatory disease which is one of the common diseases of the digestive system. To investigate the mechanisms of herbal pair Acoritataninowii Rhizoma(Shichangpu, AR) and Curcumae Radix༈Yujin, CR༉ in treatment of CG based on the network pharmacology. Methods The possible active ingredients and targets of AR-CR were obtained by the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). The UniProt database was used to query the human gene corresponding to each target protein. The genes related to CG were collected from the GeneCards database, the OMIM database, the DisGeNET database and the PharmGKB database. Intersected the target genes of AR-CR and CG, then protein-protein interaction(PPI) network was constructed by STRING website. The overlapped genes were subjected to gene ontology༈GO༉enrichment and Kyoto encyclopedia of genes and genomes༈KEGG༉pathway enrichment analyses by David. Results 45 intersection genes were obtained, and there were 40 targets in the PPI network for protein interaction, the kernel targets with Degree ≥ 10 included AKT1, TNF, JUN, MAPK3, MAPK8 and MAPK1. The Go enrichment analysis was mainly related to protein binding, enzyme binding, protein homodimerization activity, etc. The KEGG pathway enrichment analyses mainly involved the Pathways in cancer, TNF signaling pathway, Apoptosis, and VEGF signaling pathway. Conclusion AR-CR might delayed, blocked or reversed the atrophy, intestinal metaplasia, dysplasia and canceration of gastric mucosa by targeting key proteins and signal pathways,achieved the effect of the treatment of CG.


2020 ◽  
Vol 2020 ◽  
pp. 1-11 ◽  
Author(s):  
Xuejiao Xie ◽  
Xingyu Ma ◽  
Siyu Zeng ◽  
Wansi Tang ◽  
Liucheng Xiao ◽  
...  

Atherosclerosis is a common metabolic disease characterized by lipid metabolic disorder. The processes of atherosclerosis include endothelial dysfunction, new endothelial layer formation, lipid sediment, foam cell formation, plaque formation, and plaque burst. Owing to the adverse effects of first-line medications, it is urgent to discover new medications to deal with atherosclerosis. Berberine is one of the most promising natural products derived from traditional Chinese medicine. However, the panoramic mechanism of berberine against atherosclerosis has not been discovered clearly. In this study, we used network pharmacology to investigate the interaction between berberine and atherosclerosis. We identified potential targets related to berberine and atherosclerosis from several databases. A total of 31 and 331 putative targets for berberine and atherosclerosis were identified, respectively. Then, we constructed berberine and atherosclerosis targets with PPI data. Berberine targets network with PPI data had 3204 nodes and 79437 edges. Atherosclerosis targets network with PPI data had 5451 nodes and 130891 edges. Furthermore, we merged the two PPI networks and obtained the core PPI network from the merged PPI network. The core PPI network had 132 nodes and 3339 edges. At last, we performed functional enrichment analyses including GO and KEGG pathway analysis in David database. GO analysis indicated that the biological processes were correlated with G1/S transition of mitotic cells cycle. KEGG pathway analysis found that the pathways directly associated with berberine against atherosclerosis were cell cycle, ubiquitin mediated proteolysis, MAPK signaling pathway, and PI3K-Akt signaling pathway. After combining the results in context with the available treatments for atherosclerosis, we considered that berberine inhibited inflammation and cell proliferation in the treatment of atherosclerosis. Our study provided a valid theoretical foundation for future research.


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