Abstract：
BACKGROUND: Dendrobium officinale Kimura et Migo (DO), a valuable Chinese herbal medicine, has been reported to exhibit potential effects in the prevention and treatment of lung cancer. However, its material basis and mechanism of action have not been comprehensively analyzed.
OBJECTIVE: The objective of this study was to preliminarily elucidate the active components and pharmacological mechanisms of DO in treating lung cancer, according to UPLC-Q/TOF-MS, HPAEC-PAD, network pharmacology, molecular docking, and experimental verification.
METHODS: The chemical components of DO were identified via UPLC-Q/TOF-MS, while the monosaccharide composition of Dendrobium officinale polysaccharide (DOP) was determined by HPAEC-PAD. The prospective active constituents of DO as well as their respective targets were predicted in the combined database of Swiss ADME and Swiss Target Prediction. Relevant disease targets for lung cancer were searched in OMIM, TTD, and Genecards databases. Further, the active compounds and potential core targets of DO against lung cancer were found by the C-T-D network and the PPI network, respectively. The core targets were then subjected to enrichment analysis in the Metascape database. The main active compounds were molecularly docked to the core targets and visualized. Finally, the viability of A549 cells and the relative quantity of associated proteins within the major signaling pathway were detected.
RESULTS: 249 ingredients were identified from DO, including 39 flavonoids, 39 bibenzyls, 50 organic acids, 8 phenanthrenes, 27 phenylpropanoids, 17 alkaloids, 17 amino acids and their derivatives, 7 monosaccharides, and 45 others. Here, 50 main active compounds with high degree values were attained through the C-T-D network, mainly consisting of bibenzyls and monosaccharides. Based on the PPI network analysis, 10 core targets were further predicted, including HSP90AA1, SRC, ESR1, CREBBP, MAPK3, AKT1, PIK3R1, PIK3CA, HIF1A, and HDAC1. The results of the enrichment analysis and molecular docking indicated a close association between the therapeutic mechanism of DO and the PI3K-Akt signaling pathway. It was confirmed that the bibenzyl extract and erianin could inhibit the multiplication of A549 cells in vitro. Furthermore, erianin was found to down-regulate the relative expressions of p-AKT and p-PI3K proteins within the PI3K-Akt signaling pathway.
CONCLUSIONS: This study predicted that DO could treat lung cancer through various components, multiple targets, and diverse pathways. Bibenzyls from DO might exert anti-lung cancer activity by inhibiting cancer cell proliferation and modulating the PI3K-Akt signaling pathway. A fundamental reference for further studies and clinical therapy was given by the above data.
OBJECTIVE: The objective of this study was to preliminarily elucidate the active components and pharmacological mechanisms of DO in treating lung cancer, according to UPLC-Q/TOF-MS, HPAEC-PAD, network pharmacology, molecular docking, and experimental verification.
METHODS: The chemical components of DO were identified via UPLC-Q/TOF-MS, while the monosaccharide composition of Dendrobium officinale polysaccharide (DOP) was determined by HPAEC-PAD. The prospective active constituents of DO as well as their respective targets were predicted in the combined database of Swiss ADME and Swiss Target Prediction. Relevant disease targets for lung cancer were searched in OMIM, TTD, and Genecards databases. Further, the active compounds and potential core targets of DO against lung cancer were found by the C-T-D network and the PPI network, respectively. The core targets were then subjected to enrichment analysis in the Metascape database. The main active compounds were molecularly docked to the core targets and visualized. Finally, the viability of A549 cells and the relative quantity of associated proteins within the major signaling pathway were detected.
RESULTS: 249 ingredients were identified from DO, including 39 flavonoids, 39 bibenzyls, 50 organic acids, 8 phenanthrenes, 27 phenylpropanoids, 17 alkaloids, 17 amino acids and their derivatives, 7 monosaccharides, and 45 others. Here, 50 main active compounds with high degree values were attained through the C-T-D network, mainly consisting of bibenzyls and monosaccharides. Based on the PPI network analysis, 10 core targets were further predicted, including HSP90AA1, SRC, ESR1, CREBBP, MAPK3, AKT1, PIK3R1, PIK3CA, HIF1A, and HDAC1. The results of the enrichment analysis and molecular docking indicated a close association between the therapeutic mechanism of DO and the PI3K-Akt signaling pathway. It was confirmed that the bibenzyl extract and erianin could inhibit the multiplication of A549 cells in vitro. Furthermore, erianin was found to down-regulate the relative expressions of p-AKT and p-PI3K proteins within the PI3K-Akt signaling pathway.
CONCLUSIONS: This study predicted that DO could treat lung cancer through various components, multiple targets, and diverse pathways. Bibenzyls from DO might exert anti-lung cancer activity by inhibiting cancer cell proliferation and modulating the PI3K-Akt signaling pathway. A fundamental reference for further studies and clinical therapy was given by the above data.
摘要：
背景：金村石斛和Migo（DO），一种有价值的中草药，据报道，在预防和治疗肺癌方面具有潜在的作用。然而,其物质基础和作用机理尚未得到全面分析。
目的：本研究的目的是初步阐明DO治疗肺癌的活性成分和药理机制。根据UPLC-Q/TOF-MS，HPAEC-PAD,网络药理学，分子对接,和实验验证。
方法：通过UPLC-Q/TOF-MS鉴定DO的化学成分，用HPAEC-PAD测定铁皮石斛多糖(DOP)的单糖组成。在瑞士ADME和瑞士目标预测的组合数据库中预测了DO的预期活性成分及其各自的目标。在OMIM中搜索了肺癌的相关疾病靶标，TTD,和Genecards数据库。Further,通过C-T-D网络和PPI网络发现了DO抗肺癌的活性化合物和潜在的核心靶标，分别。然后在Metascape数据库中对核心靶标进行富集分析。将主要活性化合物分子对接至核心靶标并可视化。最后,检测A549细胞的活力和主要信号通路内相关蛋白的相对数量。
结果：从DO中鉴定出249种成分，包括39种类黄酮,39双苄基，50种有机酸,8菲烯，27种苯丙素类化合物，17生物碱，17个氨基酸及其衍生物，7个单糖，45个其他人。这里,通过C-T-D网络获得了50个具有高度值的主要活性化合物，主要由二苄基和单糖组成。基于PPI网络分析，进一步预测了10个核心目标，包括HSP90AA1，SRC，ESR1,CREBBP,MAPK3,AKT1,PIK3R1,PIK3CA,HIF1A,和HDAC1。富集分析和分子对接的结果表明DO的治疗机制与PI3K-Akt信号通路密切相关。证实了双苄基提取物和erianin可以在体外抑制A549细胞的增殖。此外，发现erianin下调PI3K-Akt信号通路中p-AKT和p-PI3K蛋白的相对表达。
结论：这项研究预测DO可以通过多种成分治疗肺癌，多个目标,和不同的途径。来自DO的联苄基可能通过抑制癌细胞增殖和调节PI3K-Akt信号通路发挥抗肺癌活性。以上数据为进一步研究和临床治疗提供了基本参考。
目的：本研究的目的是初步阐明DO治疗肺癌的活性成分和药理机制。根据UPLC-Q/TOF-MS，HPAEC-PAD,网络药理学，分子对接,和实验验证。
方法：通过UPLC-Q/TOF-MS鉴定DO的化学成分，用HPAEC-PAD测定铁皮石斛多糖(DOP)的单糖组成。在瑞士ADME和瑞士目标预测的组合数据库中预测了DO的预期活性成分及其各自的目标。在OMIM中搜索了肺癌的相关疾病靶标，TTD,和Genecards数据库。Further,通过C-T-D网络和PPI网络发现了DO抗肺癌的活性化合物和潜在的核心靶标，分别。然后在Metascape数据库中对核心靶标进行富集分析。将主要活性化合物分子对接至核心靶标并可视化。最后,检测A549细胞的活力和主要信号通路内相关蛋白的相对数量。
结果：从DO中鉴定出249种成分，包括39种类黄酮,39双苄基，50种有机酸,8菲烯，27种苯丙素类化合物，17生物碱，17个氨基酸及其衍生物，7个单糖，45个其他人。这里,通过C-T-D网络获得了50个具有高度值的主要活性化合物，主要由二苄基和单糖组成。基于PPI网络分析，进一步预测了10个核心目标，包括HSP90AA1，SRC，ESR1,CREBBP,MAPK3,AKT1,PIK3R1,PIK3CA,HIF1A,和HDAC1。富集分析和分子对接的结果表明DO的治疗机制与PI3K-Akt信号通路密切相关。证实了双苄基提取物和erianin可以在体外抑制A549细胞的增殖。此外，发现erianin下调PI3K-Akt信号通路中p-AKT和p-PI3K蛋白的相对表达。
结论：这项研究预测DO可以通过多种成分治疗肺癌，多个目标,和不同的途径。来自DO的联苄基可能通过抑制癌细胞增殖和调节PI3K-Akt信号通路发挥抗肺癌活性。以上数据为进一步研究和临床治疗提供了基本参考。
