Abstract：
BACKGROUND: Ginseng Radix and Astragali Radix are commonly combined to tonify Qi and alleviate fatigue. Previous studies have employed biological networks to investigate the mechanisms of herb pairs in treating different diseases. However, these studies have only elucidated a single network for each herb pair, without emphasizing the superiority of the herb combination over individual herbs.
OBJECTIVE: This study proposes an approach of comparing biological networks to highlight the synergistic effect of the pair in treating cancer-related fatigue (CRF).
METHODS: The compounds and targets of Ginseng Radix, Astragali Radix, and CRF diseases were collected and predicted using different databases. Subsequently, the overlapping targets between herbs and disease were imported into the STRING and DAVID tools to build protein-protein interaction (PPI) networks and analyze enriched KEGG pathways. The biological networks of Ginseng Radix and Astragali Radix were compared separately or together using the DyNet application. Molecular docking was used to verify the predicted results. Further, in vitro experiments were conducted to validate the synergistic pathways identified in in silico studies.
RESULTS: In the PPI network comparison, the combination created 89 new interactions and an increased average degree (11.260) when compared to single herbs (10.296 and 9.394). The new interactions concentrated on HRAS, STAT3, JUN, and IL6. The topological analysis identified 20 core targets of the combination, including three Ginseng Radix-specific targets, three Astragali Radix-specific targets, and 14 shared targets. In KEGG enrichment analysis, the combination regulated additional signaling pathways (152) more than Ginseng Radix (146) and Astragali Radix (134) alone. The targets of the herb pair synergistically regulated cancer pathways, specifically hypoxia-inducible factor 1 (HIF-1) signaling pathway. In vitro experiments including enzyme-linked immunosorbent assay and Western blot demonstrated that two herbs combination could up-regulate HIF-1α signaling pathway at different combined concentrations compared to either single herb alone.
CONCLUSIONS: The herb pair increased protein interactions and adjusted metabolic pathways more than single herbs. This study provides insights into the combination of Ginseng Radix and Astragali Radix in clinical practice.
OBJECTIVE: This study proposes an approach of comparing biological networks to highlight the synergistic effect of the pair in treating cancer-related fatigue (CRF).
METHODS: The compounds and targets of Ginseng Radix, Astragali Radix, and CRF diseases were collected and predicted using different databases. Subsequently, the overlapping targets between herbs and disease were imported into the STRING and DAVID tools to build protein-protein interaction (PPI) networks and analyze enriched KEGG pathways. The biological networks of Ginseng Radix and Astragali Radix were compared separately or together using the DyNet application. Molecular docking was used to verify the predicted results. Further, in vitro experiments were conducted to validate the synergistic pathways identified in in silico studies.
RESULTS: In the PPI network comparison, the combination created 89 new interactions and an increased average degree (11.260) when compared to single herbs (10.296 and 9.394). The new interactions concentrated on HRAS, STAT3, JUN, and IL6. The topological analysis identified 20 core targets of the combination, including three Ginseng Radix-specific targets, three Astragali Radix-specific targets, and 14 shared targets. In KEGG enrichment analysis, the combination regulated additional signaling pathways (152) more than Ginseng Radix (146) and Astragali Radix (134) alone. The targets of the herb pair synergistically regulated cancer pathways, specifically hypoxia-inducible factor 1 (HIF-1) signaling pathway. In vitro experiments including enzyme-linked immunosorbent assay and Western blot demonstrated that two herbs combination could up-regulate HIF-1α signaling pathway at different combined concentrations compared to either single herb alone.
CONCLUSIONS: The herb pair increased protein interactions and adjusted metabolic pathways more than single herbs. This study provides insights into the combination of Ginseng Radix and Astragali Radix in clinical practice.
摘要：
背景：人参和黄芪通常合用以补气和缓解疲劳。以前的研究已经使用生物网络来研究草药对治疗不同疾病的机制。然而,这些研究仅阐明了每个草药对的单个网络，不强调草药组合优于个别草药。
目的：本研究提出了一种比较生物网络的方法，以突出该对在治疗癌症相关性疲劳（CRF）中的协同作用。
方法：人参的化合物和目标，黄芪,使用不同的数据库收集和预测CRF疾病。随后，将草药与疾病之间的重叠靶标导入STRING和DAVID工具,以构建蛋白质-蛋白质相互作用(PPI)网络并分析富集的KEGG途径.使用DyNet应用分别或一起比较了人参和黄芪的生物网络。使用分子对接来验证预测结果。Further,进行了体外实验以验证在计算机模拟研究中确定的协同途径。
结果：在PPI网络比较中，与单一草药(10.296和9.394)相比，该组合产生了89个新的相互作用，并且平均程度增加(11.260)。新的相互作用集中在HRAS上，STAT3,JUN,IL6拓扑分析确定了该组合的20个核心目标，包括三个人参特异性目标，三个黄芪特异性靶标，14个共同目标在KEGG富集分析中，与单独的人参（146）和黄芪（134）相比，该组合调节了额外的信号通路（152）。草药对的靶标协同调节癌症途径，缺氧诱导因子1(HIF-1)信号通路。包括酶联免疫吸附测定和蛋白质印迹在内的体外实验表明，与单独的任一草药相比，两种草药组合可以在不同的组合浓度上调HIF-1α信号通路。
结论：与单一草药相比，草药对增加了蛋白质相互作用并调节了代谢途径。本研究为人参和黄芪在临床实践中的结合提供了见解。
目的：本研究提出了一种比较生物网络的方法，以突出该对在治疗癌症相关性疲劳（CRF）中的协同作用。
方法：人参的化合物和目标，黄芪,使用不同的数据库收集和预测CRF疾病。随后，将草药与疾病之间的重叠靶标导入STRING和DAVID工具,以构建蛋白质-蛋白质相互作用(PPI)网络并分析富集的KEGG途径.使用DyNet应用分别或一起比较了人参和黄芪的生物网络。使用分子对接来验证预测结果。Further,进行了体外实验以验证在计算机模拟研究中确定的协同途径。
结果：在PPI网络比较中，与单一草药(10.296和9.394)相比，该组合产生了89个新的相互作用，并且平均程度增加(11.260)。新的相互作用集中在HRAS上，STAT3,JUN,IL6拓扑分析确定了该组合的20个核心目标，包括三个人参特异性目标，三个黄芪特异性靶标，14个共同目标在KEGG富集分析中，与单独的人参（146）和黄芪（134）相比，该组合调节了额外的信号通路（152）。草药对的靶标协同调节癌症途径，缺氧诱导因子1(HIF-1)信号通路。包括酶联免疫吸附测定和蛋白质印迹在内的体外实验表明，与单独的任一草药相比，两种草药组合可以在不同的组合浓度上调HIF-1α信号通路。
结论：与单一草药相比，草药对增加了蛋白质相互作用并调节了代谢途径。本研究为人参和黄芪在临床实践中的结合提供了见解。
