Chemical constituents and synergistic anti-gout studies on Eurycoma longifolia and potential mechanisms evaluation based on systemic analysis approach
Chemical constituents and synergistic anti-gout studies on Eurycoma longifolia and potential mechanisms evaluation based on systemic analysis approach
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东革阿里化学成分、协同抗痛风研究及基于系统分析方法的潜在机制评价
DOI：
10.1016/j.bioorg.2019.103302
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发表时间：
2019-11-01
影响因子：
5.1
通讯作者：
Meng, Dali
中科院分区：
文献类型：
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作者：
Liu, Ying;Lai, Lantao;Meng, Dali
东革阿里(Eurycoma longifolia Jack, EL)作为传统药物的使用历史悠久，从其根部分离得到37种化合物，主要包括具有苦木素骨架的三萜类化合物和对咔啉生物碱。结果表明，EL总提取物在中、高剂量下可显着抑制MSU诱导的急性痛风关节炎大鼠模型的关节肿胀（P < 0.05，P < 0.01），同时在10 g/kg剂量下表现优于阳性对照（P < 0.05，P < 0.01）。为了寻找潜在的化合物和可能的机制，采用网络药理学、分子对接和京都基因与基因组百科全书（KEGG）通路富集分析，提出了156个筛选化合物中与痛风不同发病机制相关的17个靶点和5个潜在化合物（C36、C107、C124、C125和C130）的假说，与多个靶点发挥协同作用。 EL不是以“一种基因、一种药物、一种疾病”为指导思想，而是通过多种途径、多靶点展现出整体性能，而非单一化合物。值得注意的是，黄嘌呤脱氢酶/氧化酶（XDH）、前列腺素G/H合酶2（PTGS2）、肝脏脂肪酸结合蛋白（FABP1）、嘌呤核苷磷酸化酶（PNP）和过氧化物酶体增殖物激活受体α（PPARA）是相互作用强烈的关键靶标。此外，功能富集分析表明，EL可能是通过协同调节Toll样受体信号通路、MAPK信号通路、NOD样受体信号通路等多个生物通路发挥痛风保护作用。
37 compounds mainly including triterpenoids with the quassinoid skeleton and p-carboline alkaloids have been isolated from the roots of Eurycoma longifolia Jack (EL), which has been used as traditional medicine for a long history. It has been demonstrated that the total extracts from EL could significantly inhibit the joint swelling in MSU-induced acute gout arthritis rat model at middle and high doses (P < 0.05, P < 0.01), as meanwhile, better performance than that of positive control (P < 0.05, P < 0.01) has been observed at the dose of 10 g/kg. Aiming to search potential compounds and probable mechanisms, network pharmacology, molecular docking and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis were adopted, leading to the hypothesis of 17 targets related to different pathogenesis of gout and 5 potential compounds (C36, C107, C124, C125 and C130) among 156 selected compounds, playing synergetic role with multiple targets. Instead of the guiding ideology of "a gene, a drug, a disease", varieties of compounds but not a single one from EL display holistic performance through multiple pathways with multi-targets. It was noteworthy that Xanthine dehydrogenase/oxidase (XDH), Prostaglandin G/H synthase 2 (PTGS2), Fatty acid-binding protein, liver (FABP1), Purine nucleoside phosphorylase (PNP), and Peroxisome proliferator activated receptor alpha (PPARA) were the key targets with intensely interaction. Furthermore, the functional enrichment analysis indicated that EL probably produced the gout protection effects by synergistic regulation in multiple biological pathways, including Toll-like receptor signaling pathway, MAPK signaling pathway, and NOD-like receptor signaling pathway, etc.