{"title":"解毒消肿方对弥漫性大 B 细胞淋巴瘤作用机制的网络药理学、分子对接和实验验证","authors":"Congmin Wei, Ming Hu, Qi Hu","doi":"10.2174/0113862073290877240604102022","DOIUrl":null,"url":null,"abstract":"<p><strong>Introduction: </strong>Diffuse Large B-Cell Lymphoma (DLBCL) is the most common Bcell lymphoma type. Detoxification and tumor elimination formula, a herbal compound, can potentially treat lymphoma. In this study, network pharmacology and molecular docking approaches were utilized to reveal the potential mechanism of the Jiedu Xiaoliu formula (JDXLF) against DLBCL.</p><p><strong>Methods: </strong>Active compounds and targets of JDXLF were obtained from the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database. Targets related to DLBCL were retrieved from GeneCards and Online Mendelian Inheritance in Man (OMIM) databases. Protein- Protein Interaction (PPI) networks were established to screen core targets. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed using R 4.2.2. Model interactions between potential disease targets and pharmacologically active compounds were determined by molecular docking.</p><p><strong>Results: </strong>Screening of 14 herbal active ingredients yielded 129 active compounds and 1414 disease targets for DLBCL. GO annotations showed that the effects of JDXLF were related to protein phosphorylation and reactive oxygen species response. KEGG pathway enrichment analysis indicated that the detoxification and elimination of tumors formula mainly regulated apoptosis pathways. Nobiletin showed good interaction with AKT1, TP53, and CASP3, and the cell counting kit-8 (CCK-8) assay confirmed that nobiletin inhibited the proliferation of SU-DHL-4 cells. Western blot analysis showed that nobiletin downregulated the expressions of p-PI3K, p- AKT, and BCL-2 proteins and upregulated those of cleaved-caspase3 and BAX.</p><p><strong>Conclusion: </strong>Our findings preliminarily suggested that the active ingredient of JDXLF, nobiletin, may induce apoptosis in Diffuse Large B-Cell Lymphoma SU-DHL-4 cells by regulating the PI3K/AKT signaling pathway.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.6000,"publicationDate":"2024-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Network Pharmacology, Molecular Docking, and Experimental Validation of the Mechanism of Jiedu Xiaoliu Formula against Diffuse Large B-Cell Lymphoma.\",\"authors\":\"Congmin Wei, Ming Hu, Qi Hu\",\"doi\":\"10.2174/0113862073290877240604102022\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Introduction: </strong>Diffuse Large B-Cell Lymphoma (DLBCL) is the most common Bcell lymphoma type. Detoxification and tumor elimination formula, a herbal compound, can potentially treat lymphoma. In this study, network pharmacology and molecular docking approaches were utilized to reveal the potential mechanism of the Jiedu Xiaoliu formula (JDXLF) against DLBCL.</p><p><strong>Methods: </strong>Active compounds and targets of JDXLF were obtained from the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database. Targets related to DLBCL were retrieved from GeneCards and Online Mendelian Inheritance in Man (OMIM) databases. Protein- Protein Interaction (PPI) networks were established to screen core targets. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed using R 4.2.2. Model interactions between potential disease targets and pharmacologically active compounds were determined by molecular docking.</p><p><strong>Results: </strong>Screening of 14 herbal active ingredients yielded 129 active compounds and 1414 disease targets for DLBCL. GO annotations showed that the effects of JDXLF were related to protein phosphorylation and reactive oxygen species response. KEGG pathway enrichment analysis indicated that the detoxification and elimination of tumors formula mainly regulated apoptosis pathways. Nobiletin showed good interaction with AKT1, TP53, and CASP3, and the cell counting kit-8 (CCK-8) assay confirmed that nobiletin inhibited the proliferation of SU-DHL-4 cells. 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引用次数: 0
摘要
简介弥漫大 B 细胞淋巴瘤(DLBCL)是最常见的 B 细胞淋巴瘤类型。解毒消瘤方是一种中药复方制剂,具有治疗淋巴瘤的潜在作用。本研究利用网络药理学和分子对接方法揭示了解毒消瘤方(JDXLF)治疗DLBCL的潜在机制:方法:从中药系统药理学(TCMSP)数据库中获取解毒消积方的活性化合物和靶点。与 DLBCL 相关的靶点来自 GeneCards 和 Online Mendelian Inheritance in Man (OMIM) 数据库。建立蛋白质-蛋白质相互作用(PPI)网络以筛选核心靶点。使用 R 4.2.2 进行了基因本体(GO)和京都基因组百科全书(KEGG)通路富集分析。通过分子对接确定了潜在疾病靶点与药理活性化合物之间的相互作用模型:结果:对 14 种草药活性成分的筛选得出了 129 种活性化合物和 1414 个 DLBCL 疾病靶点。GO注释显示,JDXLF的作用与蛋白质磷酸化和活性氧反应有关。KEGG 通路富集分析表明,解毒消瘤方主要调控细胞凋亡通路。金金钗素与AKT1、TP53和CASP3有良好的相互作用,细胞计数试剂盒-8(CCK-8)检测证实金金钗素能抑制SU-DHL-4细胞的增殖。Western印迹分析表明,金没药能下调p-PI3K、p- AKT和BCL-2蛋白的表达,上调裂解-caspase3和BAX蛋白的表达:结论:我们的研究结果初步表明,JDXLF 的有效成分金黄素可通过调节 PI3K/AKT 信号通路诱导弥漫性大 B 细胞淋巴瘤 SU-DHL-4 细胞凋亡。
Network Pharmacology, Molecular Docking, and Experimental Validation of the Mechanism of Jiedu Xiaoliu Formula against Diffuse Large B-Cell Lymphoma.
Introduction: Diffuse Large B-Cell Lymphoma (DLBCL) is the most common Bcell lymphoma type. Detoxification and tumor elimination formula, a herbal compound, can potentially treat lymphoma. In this study, network pharmacology and molecular docking approaches were utilized to reveal the potential mechanism of the Jiedu Xiaoliu formula (JDXLF) against DLBCL.
Methods: Active compounds and targets of JDXLF were obtained from the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database. Targets related to DLBCL were retrieved from GeneCards and Online Mendelian Inheritance in Man (OMIM) databases. Protein- Protein Interaction (PPI) networks were established to screen core targets. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed using R 4.2.2. Model interactions between potential disease targets and pharmacologically active compounds were determined by molecular docking.
Results: Screening of 14 herbal active ingredients yielded 129 active compounds and 1414 disease targets for DLBCL. GO annotations showed that the effects of JDXLF were related to protein phosphorylation and reactive oxygen species response. KEGG pathway enrichment analysis indicated that the detoxification and elimination of tumors formula mainly regulated apoptosis pathways. Nobiletin showed good interaction with AKT1, TP53, and CASP3, and the cell counting kit-8 (CCK-8) assay confirmed that nobiletin inhibited the proliferation of SU-DHL-4 cells. Western blot analysis showed that nobiletin downregulated the expressions of p-PI3K, p- AKT, and BCL-2 proteins and upregulated those of cleaved-caspase3 and BAX.
Conclusion: Our findings preliminarily suggested that the active ingredient of JDXLF, nobiletin, may induce apoptosis in Diffuse Large B-Cell Lymphoma SU-DHL-4 cells by regulating the PI3K/AKT signaling pathway.
期刊介绍:
Combinatorial Chemistry & High Throughput Screening (CCHTS) publishes full length original research articles and reviews/mini-reviews dealing with various topics related to chemical biology (High Throughput Screening, Combinatorial Chemistry, Chemoinformatics, Laboratory Automation and Compound management) in advancing drug discovery research. Original research articles and reviews in the following areas are of special interest to the readers of this journal:
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