School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang 110016, PR China; Beijing Shijitan Hospital, Capital Medical University, Beijing Key Laboratory of Bio-characteristic Profiling for Evaluation of Rational Drug Use, Beijing 100038, PR China.
School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang 110016, PR China.
Bioorg Chem. 2019 Oct;91:103118. doi: 10.1016/j.bioorg.2019.103118. Epub 2019 Jul 12.
Stauntonia brachyanthera Hand.-Mazz. (SB), reported as a traditional Chinese medicine, displays a wide spectrum of interesting bioactivities, such as anti-inflammatory and analgesia. It is noteworthy that anti-gout effects of the components in SB have been reported. Hence, this study contributes to the prediction of promising active compounds and mechanisms for the treatment of gout. The active compounds with better oral bioavailability, and drug-likeness of SB were selected for further investigation by the approach of network pharmacology, molecular docking, gene ontology (GO) analysis, and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis, respectively. A total of 34 predicted targets and 98 compounds in SB were obtained. Sorted by structure types of compounds, phenylethanoid glycosides exhibited the best anti-gout activity, followed by phenolics and flavonoids. What's more, it was shown in the network analysis that Serine/threonine-protein kinase mTOR (mTOR), Mitogen-activated protein kinase 12 (MAPK12), tumor necrosis factor (TNF-α), Integrin alpha-4 (ITGA4) and Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma (PIK3CG) were the key targets with intensely interaction, which should be attached more attention for further study. The functional enrichment analysis indicated that SB probably produced the anti-gout effects by synergistically regulating many biological pathways, such as MAPK signaling pathway, PI3K-Akt signaling pathway, Toll-like receptor signaling pathway and NOD-like receptor signaling pathway, etc. In addition, C61, C67, C68 and C81 might be promising leading compounds with good molecular docking score. As a consequence, the active constituents and mechanisms based on data analysis were holistically illuminated, which was of vital importance to the development of new drugs for gout.
三叶崖爬藤（SB）是一种传统的中药，具有广泛的生物活性，如抗炎和镇痛作用。值得注意的是，已经报道了 SB 成分的抗痛风作用。因此，本研究有助于预测治疗痛风的有前途的活性化合物和机制。通过网络药理学、分子对接、基因本体（GO）分析和京都基因与基因组百科全书（KEGG）通路富集分析，分别选择具有更好口服生物利用度和类药性的 SB 活性化合物进行进一步研究。共获得 34 个 SB 预测靶点和 98 种化合物。按化合物的结构类型排序，苯乙醇苷类表现出最好的抗痛风活性，其次是酚类和黄酮类。此外，网络分析表明，丝氨酸/苏氨酸蛋白激酶 mTOR（mTOR）、丝裂原活化蛋白激酶 12（MAPK12）、肿瘤坏死因子（TNF-α）、整合素 alpha-4（ITGA4）和磷脂酰肌醇 4,5-二磷酸 3-激酶催化亚基 gamma（PIK3CG）是相互作用强烈的关键靶点，应进一步研究。功能富集分析表明，SB 可能通过协同调节多种生物学途径，如 MAPK 信号通路、PI3K-Akt 信号通路、Toll 样受体信号通路和 NOD 样受体信号通路等，产生抗痛风作用。此外，C61、C67、C68 和 C81 可能是具有良好分子对接评分的有前途的先导化合物。因此，基于数据分析的活性成分和机制得到了全面阐明，这对开发痛风新药具有重要意义。
