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Prediction of Targets of Curculigoside A in Osteoporosis and Rheumatoid Arthritis Using Network Pharmacology and Experimental Verification
Drug Design, Development and Therapy ( IF 4.7 ) Pub Date : 2020-11-26 , DOI: 10.2147/dddt.s282112 Jiawen Han 1, 2 , Minjie Wan 1, 3 , Zhanchuan Ma 1, 2 , Cong Hu 1, 2, 4 , Huanfa Yi 1, 2
Drug Design, Development and Therapy ( IF 4.7 ) Pub Date : 2020-11-26 , DOI: 10.2147/dddt.s282112 Jiawen Han 1, 2 , Minjie Wan 1, 3 , Zhanchuan Ma 1, 2 , Cong Hu 1, 2, 4 , Huanfa Yi 1, 2
Affiliation
Purpose: Network pharmacology is considered to be the next-generation drug development model that uses bioinformatics to predict and identify multiple drug targets and interactions in diseases. Here, network pharmacology was used to investigate the mechanism by which Curculigoside A (CA) acts in rheumatoid arthritis (RA) and osteoporosis.
Methods: First, TCMSP and SwissADME were applied to predict the druggability of CA. Then, potential targets were identified from overlapping data in SwissTarget and TargetNet, and targets were analyzed using Genemania and DAVID6.8 to obtain information about the GO and KEGG pathways. Ultimately, the drug-target-pathway network was identified after using Cytoscape 3.0 for visualization. Besides, qPCR was used to validate the predicted five major genes targets (EGFR, MAP2K1, MMP2, FGFR1, and MCL1).
Results: The results of TCMSP and SwissADME demonstrated that CA exhibits good druggability; 26 potential protein targets were classified by SwissTarget and TargetNet. The results of Genemania and DAVID6.8 indicated that CA probably caused anti-osteoporosis and anti-RA effects by regulating some biological pathways, especially nitrogen metabolism, estrogen signaling pathway, Rap1 signaling pathway, and PI3K/Akt signaling pathway. Besides, the result of Cytoscape 3.0 showed that the 26 targets participate in osteoporosis and RA-related pathways, metabolism, and other physiological processes. In vitro induced inflammation cell model experiments, the qPCR results showed that CA pretreatment significantly decreased the expression of EGFR, MAP2K1, MMP2, FGFR1, and MCL1 genes.
Conclusion: These results suggested that network pharmacology may provide possible mechanism of how CA exerts therapeutic effects in osteoporosis and RA.
Keywords: Curculigoside A, network pharmacology, target identity, osteoporosis, rheumatoid arthritis
中文翻译：
利用网络药理学和实验验证预测仙茅苷 A 在骨质疏松症和类风湿关节炎中的作用靶点
目的：网络药理学被认为是下一代药物开发模型，它利用生物信息学来预测和识别疾病中的多个药物靶点和相互作用。在这里，网络药理学被用来研究仙茅苷 A (CA) 在类风湿性关节炎 (RA) 和骨质疏松症中的作用机制。
方法：首先应用TCMSP和SwissADME预测CA的成药性。然后，从 SwissTarget 和 TargetNet 中的重叠数据中识别潜在目标，并使用 Genemania 和 DAVID6.8 分析目标以获得有关 GO 和 KEGG 通路的信息。最终，在使用 Cytoscape 3.0 进行可视化后，确定了药物-靶点-通路网络。此外，qPCR 用于验证预测的五个主要基因靶标（EGFR、MAP2K1、MMP2、FGFR1和MCL1 )。
结果：TCMSP和SwissADME的结果表明CA具有良好的成药性；SwissTarget 和 TargetNet 对 26 个潜在的蛋白质目标进行了分类。Genemania和DAVID6.8的结果表明，CA可能通过调节一些生物通路，特别是氮代谢、雌激素信号通路、Rap1信号通路和PI3K/Akt信号通路，引起抗骨质疏松和抗RA作用。此外，Cytoscape 3.0 的结果表明，这 26 个靶点参与了骨质疏松症和 RA 相关通路、代谢等生理过程。体外诱导炎症细胞模型实验，qPCR结果显示CA预处理显着降低EGFR、MAP2K1、MMP2、FGFR1的表达, 和MCL1基因。
结论：这些结果表明，网络药理学可能提供 CA 如何在骨质疏松症和 RA 中发挥治疗作用的可能机制。
关键词：仙茅苷A，网络药理学，靶点识别，骨质疏松症，类风湿性关节炎
更新日期：2020-11-25
Methods: First, TCMSP and SwissADME were applied to predict the druggability of CA. Then, potential targets were identified from overlapping data in SwissTarget and TargetNet, and targets were analyzed using Genemania and DAVID6.8 to obtain information about the GO and KEGG pathways. Ultimately, the drug-target-pathway network was identified after using Cytoscape 3.0 for visualization. Besides, qPCR was used to validate the predicted five major genes targets (EGFR, MAP2K1, MMP2, FGFR1, and MCL1).
Results: The results of TCMSP and SwissADME demonstrated that CA exhibits good druggability; 26 potential protein targets were classified by SwissTarget and TargetNet. The results of Genemania and DAVID6.8 indicated that CA probably caused anti-osteoporosis and anti-RA effects by regulating some biological pathways, especially nitrogen metabolism, estrogen signaling pathway, Rap1 signaling pathway, and PI3K/Akt signaling pathway. Besides, the result of Cytoscape 3.0 showed that the 26 targets participate in osteoporosis and RA-related pathways, metabolism, and other physiological processes. In vitro induced inflammation cell model experiments, the qPCR results showed that CA pretreatment significantly decreased the expression of EGFR, MAP2K1, MMP2, FGFR1, and MCL1 genes.
Conclusion: These results suggested that network pharmacology may provide possible mechanism of how CA exerts therapeutic effects in osteoporosis and RA.
Keywords: Curculigoside A, network pharmacology, target identity, osteoporosis, rheumatoid arthritis
中文翻译：
利用网络药理学和实验验证预测仙茅苷 A 在骨质疏松症和类风湿关节炎中的作用靶点
目的：网络药理学被认为是下一代药物开发模型，它利用生物信息学来预测和识别疾病中的多个药物靶点和相互作用。在这里，网络药理学被用来研究仙茅苷 A (CA) 在类风湿性关节炎 (RA) 和骨质疏松症中的作用机制。
方法：首先应用TCMSP和SwissADME预测CA的成药性。然后，从 SwissTarget 和 TargetNet 中的重叠数据中识别潜在目标，并使用 Genemania 和 DAVID6.8 分析目标以获得有关 GO 和 KEGG 通路的信息。最终，在使用 Cytoscape 3.0 进行可视化后，确定了药物-靶点-通路网络。此外，qPCR 用于验证预测的五个主要基因靶标（EGFR、MAP2K1、MMP2、FGFR1和MCL1 )。
结果：TCMSP和SwissADME的结果表明CA具有良好的成药性；SwissTarget 和 TargetNet 对 26 个潜在的蛋白质目标进行了分类。Genemania和DAVID6.8的结果表明，CA可能通过调节一些生物通路，特别是氮代谢、雌激素信号通路、Rap1信号通路和PI3K/Akt信号通路，引起抗骨质疏松和抗RA作用。此外，Cytoscape 3.0 的结果表明，这 26 个靶点参与了骨质疏松症和 RA 相关通路、代谢等生理过程。体外诱导炎症细胞模型实验，qPCR结果显示CA预处理显着降低EGFR、MAP2K1、MMP2、FGFR1的表达, 和MCL1基因。
结论：这些结果表明，网络药理学可能提供 CA 如何在骨质疏松症和 RA 中发挥治疗作用的可能机制。
关键词：仙茅苷A，网络药理学，靶点识别，骨质疏松症，类风湿性关节炎
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