scholarly journals Network Pharmacology-Based Strategy for Predicting Therapy Targets of Tripterygium wilfordii on Acute Myeloid Leukemia

2020 ◽  
Author(s):  
Tingting Fang ◽  
Lanqin Liu ◽  
wenjun liu
Keyword(s):  
Acute Myeloid Leukemia ◽  
Chinese Medicine ◽  
Signaling Pathway ◽  
Myeloid Leukemia ◽  
Enrichment Analysis ◽  
Network Pharmacology ◽  
Overlapping Genes ◽  
Tripterygium Wilfordii ◽  
Active Ingredients ◽  
Acute Myeloid

Abstract Background. Acute myeloid leukemia (AML) is a common malignant tumor of the hematopoietic system. How to extend the survival time of AML patients and improve their prognosis is still a major medical problem. Chinese medicine has a long history in treating AML. Tripterygium wilfordii (TW) is a traditional Chinese medicine. With the deepening of pharmacological research of traditional Chinese medicine, triptolide, one of its active ingredients, has been proven to have a positive effect on the treatment of AML. Therefore，this study aimed on studying the potential therapeutic targets and pharmacological mechanism of TW in Acute myeloid leukemia (AML) based on network pharmacology.Methods. The active components of TW were obtained by network pharmacology through oral bioavailability, drug-likeness filtration. Comparative analysis was used to study the overlapping genes between active ingredient’s targets and AML treatment-related targets. Using STRING database to analyze interactions between overlapping genes. KEGG pathway analysis and Gene Ontology enrichment analysis were conducted in DAVID. These genes were analyzed for survival in OncoLnc database.Key findings. We screened 53 active ingredients, the results of comparative analysis showed that 8 active ingredients had an effect on AML treatment. Based on the active ingredients and overlapping genes, we constructed the Drug-Compounds-Genes-Disease Network. Survival analysis of overlapping genes indicated that some targets possess a significant influence on patients’ survival and prognosis. The enrichment analysis showed that the main pathways of targets are Toll-like receptor signaling pathway, NF-kappa B signaling pathway and HIF-1 signaling pathway.Conclusion. This study, using a network pharmacologic approach, provides another strategy that can help us to understand the mechanisms by which TW treats AML comprehensively.

scholarly journals Network Pharmacology-Based Strategy for Predicting Therapy Targets of Tripterygium wilfordii on Acute Myeloid Leukemia

2020 ◽  
Author(s):  
Tingting Fang ◽  
Lanqin Liu ◽  
wenjun liu
Keyword(s):  
Acute Myeloid Leukemia ◽  
Chinese Medicine ◽  
Signaling Pathway ◽  
Myeloid Leukemia ◽  
Enrichment Analysis ◽  
Network Pharmacology ◽  
Overlapping Genes ◽  
Tripterygium Wilfordii ◽  
Active Ingredients ◽  
Acute Myeloid

Abstract Background. Acute myeloid leukemia (AML) is a common malignant tumor of the hematopoietic system. How to extend the survival time of AML patients and improve their prognosis is still a major medical problem. Chinese medicine has a long history in treating AML. Tripterygium wilfordii (TW) is a traditional Chinese medicine. With the deepening of pharmacological research of traditional Chinese medicine, triptolide, one of its active ingredients, has been proven to have a positive effect on the treatment of AML. Therefore,this study aimed on studying the potential therapeutic targets and pharmacological mechanism of TW in Acute myeloid leukemia (AML) based on network pharmacology. Methods. The active components of TW were obtained by network pharmacology through oral bioavailability, drug-likeness filtration. Comparative analysis was used to study the overlapping genes between active ingredient’s targets and AML treatment-related targets. Using STRING database to analyze interactions between overlapping genes. KEGG pathway analysis and Gene Ontology enrichment analysis were conducted in DAVID. These genes were analyzed for survival in OncoLnc database. Results. We screened 53 active ingredients, the results of comparative analysis showed that 8 active ingredients had an effect on AML treatment. Based on the active ingredients and overlapping genes, we constructed the Drug-Compounds-Genes-Disease Network. Survival analysis of overlapping genes indicated that some targets possess a significant influence on patients’ survival and prognosis. The enrichment analysis showed that the main pathways of targets are Toll-like receptor signaling pathway, NF-kappa B signaling pathway and HIF-1 signaling pathway. Conclusion. This study, using a network pharmacologic approach, provides another strategy that can help us to understand the mechanisms by which TW treats AML comprehensively.

scholarly journals Genetic Chinese Medicine Network Pharmacology Research, Quercetin Improves Drug Resistance in Acute Myeloid Leukemia by Targeting CXCL10

2021 ◽  
Author(s):  
Hu Linjun ◽  
QILIANG LU ◽  
YANG LIU ◽  
JUNJUN ZHAO ◽  
ZHI ZENG ◽  
...  
Keyword(s):  
Gene Expression ◽  
Drug Resistance ◽  
Acute Myeloid Leukemia ◽  
Chinese Medicine ◽  
Active Ingredient ◽  
Myeloid Leukemia ◽  
Network Pharmacology ◽  
Overlapping Genes ◽  
Acute Myeloid ◽  
Geo Database

Abstract Background: Acute myeloid leukemia (AML) is the most common acute leukemia in adults and is a highly heterogeneous and fatal disease. At present, the main method of treatment of AML is chemotherapy, but patients who relapse often develop resistance and are not sensitive to chemotherapy. Chinese medicine network pharmacology can provide new ideas about improving AML resistance.Methods: The gene expression data of relapsed drug-resistant AML and primary AML are from Gene Expression Omnibus (GEO) database. Based on the network pharmacology of traditional Chinese medicine, the effective components and target genes of Jiedu Huayu Decoction were analyzed. we performed Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene Ontology (GO) analyses, Protein-protein interaction (PPI) network and construction on overlapping genes. We will perform prognostic analysis and gene correlation analysis of overlapping genes in GEPIA. The binding energy between the differential gene and the active ingredient of the drug was studied by molecular docking.Results: We found that quercetin, the active ingredient in Jiedu Huayu Decoction, can target CXCL10, thereby improving AML resistance.Conclusions: In this study, we found that quercetin improves drug resistance in acute myeloid leukemia by targeting CXCL10 based on the GEO database and the network pharmacology study of Chinese medicine.

scholarly journals Exploration of the Molecular Targets and Mechanisms of Suxiao Xintong Dropping Pills for Myocardial Infarction by Network Pharmacology Method

2021 ◽  
Author(s):  
Daqiu Chen ◽  
Yanqing Wu ◽  
Yixing Chen ◽  
Qiaoxing Chen ◽  
Xianhua Ye ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Molecular Docking ◽  
Chinese Medicine ◽  
Traditional Chinese Medicine ◽  
Signaling Pathway ◽  
Network Pharmacology ◽  
Pathway Enrichment Analysis ◽  
Overlapping Genes ◽  
Active Ingredients ◽  
Hub Genes

Background: Suxiao Xintong dropping pills (SXXTDP), a traditional Chinese medicine, is widely applied for treating myocardial infarction (MI). However, its therapy mechanisms are still unclear. Therefore, this research is designed to explore the molecular mechanisms of SXXTDP in treating MI. Methods: The active ingredients of SXXTDP and their corresponding genes of the active ingredients were retrieved from the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database. MI-related genes were identified via analyzing the expression profiling data (accession number: GSE97320). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed to study the shared genes of drug and disease. Through protein-protein interaction (PPI) network and the Cytoscape plugin cytoHubba, the hub genes were screened out. The compounds and hub targets binding were simulated through molecular docking method. Results: We obtained 21 active compounds and 253 corresponding target genes from TCMSP database. 1833 MI-related genes were identified according to P＜0.05 and |log2FC| ≥ 0.5. 27 overlapping genes between drug and disease were acquired. GO analysis indicated that overlapping genes were mainly enriched in MAP kinase activity and antioxidant activity. KEGG analysis indicated that overlapping genes were mainly enriched in IL-17 signaling pathway and TNF signaling pathway. We obtained 10 hub genes via cytoHubba plugin. Six of the 10 hub genes, including PTGS2, MAPK14, MMP9, MAPK1, NFKBIA, and CASP8, were acted on molecular docking verification with their corresponding compounds of SXXTDP. Conclusion: SXXTDP may exert cardioprotection effect through regulating multiple targets and multiple pathways in MI.

scholarly journals Chidamide increases the sensitivity of refractory or relapsed acute myeloid leukemia cells to anthracyclines via regulation of the HDAC3 -AKT-P21-CDK2 signaling pathway

2020 ◽  
Vol 39 (1) ◽  
Author(s):  
Hao Wang ◽  
Yu-chen Liu ◽  
Cheng-ying Zhu ◽  
Fei Yan ◽  
Meng-zhen Wang ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Signaling Pathway ◽  
Salvage Therapy ◽  
Myeloid Leukemia ◽  
Complete Response ◽  
Dependent Manner ◽  
Induce Cell Cycle Arrest ◽  
Anthracycline Resistance ◽  
Acute Myeloid ◽  
Resistant Cells

Abstract Background Induction therapy for acute myeloid leukemia (AML) is an anthracycline-based chemotherapy regimen. However, many patients experience a relapse or exhibit refractory disease (R/R). There is an urgent need for more effective regimens to reverse anthracycline resistance in these patients. Methods In this paper, Twenty-seven R/R AML patients with anthracycline resistance consecutively received chidamide in combination with anthracycline-based regimen as salvage therapy at the Chinese PLA General Hospital. Results Of the 27 patients who had received one course of salvage therapy, 13 achieved a complete response and 1 achieved a partial response. We found that the HDAC3-AKT-P21-CDK2 signaling pathway was significantly upregulated in anthracycline-resistant AML cells compared to non-resistant cells. AML patients with higher levels of HDAC3 had lower event-free survival (EFS) and overall survival (OS) rates. Moreover, anthracycline-resistant AML cells are susceptible to chidamide, a histone deacetylase inhibitor which can inhibit cell proliferation, increase cell apoptosis and induce cell-cycle arrest in a time- and dose-dependent manner. Chidamide increases the sensitivity of anthracycline-resistant cells to anthracycline drugs, and these effects are associated with the inhibition of the HDAC3-AKT-P21-CDK2 signaling pathway. Conclusion Chidamide can increase anthracycline drug sensitivity by inhibiting HDAC3-AKT-P21-CDK2 signaling pathway, thus demonstrating the potential for application.

scholarly journals The Underlying Mechanism of Chinese Herb of Regulating Marrow in the Treatment of  Osteonecrosis of the Femoral Head Based on Network Pharmacology and Molecular Docking

2021 ◽  
Author(s):  
Xiaojian Wang ◽  
Rui Wang ◽  
Ting Xu ◽  
Hongting Jin ◽  
Peijian Tong ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Chinese Medicine ◽  
Signaling Pathway ◽  
Kegg Pathway ◽  
Enrichment Analysis ◽  
Underlying Mechanism ◽  
Chinese Herbs ◽  
Network Pharmacology ◽  
Active Components ◽  
Pathway Enrichment

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.

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