Department of Biological Sciences, Xinyang Normal University, Xinyang 464000, China; Institute for Conservation and Utilization of Agro-bioresources in Dabie Mountains, Xinyang, China, 464000.
Department of Biological Sciences, Xinyang Normal University, Xinyang 464000, China.
Life Sci. 2020 Jan 1;240:117063. doi: 10.1016/j.lfs.2019.117063. Epub 2019 Nov 14.
Network pharmacology uses bioinformatics to broaden our understanding of drug actions and thereby advance drug discovery. Here we apply network pharmacology to generate testable hypotheses about the multi-target mechanism of celastrol against systemic lupus erythematosus (SLE).
We reconstructed drug-target pathways and networks to predict the likely protein targets of celastrol and the main interactions between those targets and the drug. Then we validated our predictions of candidate targets by performing docking studies with celastrol.
The results suggest that celastrol acts against SLE by regulating the function of several signaling proteins, such as interleukin 10, tumor necrosis factor, and matrix metalloprotein 9, which regulate signaling pathways involving mitogen-activated protein kinase and tumor necrosis factor as well as apoptosis pathways. Celastrol is predicted to affect networks involved mainly in cytokine activity, cytokine receptor binding, receptor ligand activity, receptor regulator activity, and cofactor binding. Molecular docking analysis showed that hydrogen bonding and π-π stacking were the main forms of interaction.
This network pharmacology strategy may be useful for discovery of multi-target drugs against complex diseases, specifically, it provides protein targets associated with SLE that may be further tested for therapeutic potential by celastrol.
网络药理学利用生物信息学拓宽我们对药物作用的理解，从而推进药物研发。在此，我们将网络药理学应用于生成关于藜芦碱治疗系统性红斑狼疮（SLE）的多靶点机制的可测试假说。
我们重建了药物-靶标途径和网络，以预测藜芦碱的可能蛋白靶标以及这些靶标与药物之间的主要相互作用。然后，我们通过与藜芦碱进行对接研究来验证候选靶标的预测。
结果表明，藜芦碱通过调节几种信号蛋白（如白细胞介素 10、肿瘤坏死因子和基质金属蛋白酶 9）的功能来治疗 SLE，这些信号蛋白调节涉及丝裂原激活蛋白激酶和肿瘤坏死因子以及细胞凋亡途径的信号通路。藜芦碱被预测会影响主要涉及细胞因子活性、细胞因子受体结合、受体配体活性、受体调节剂活性和辅助因子结合的网络。分子对接分析表明，氢键和π-π堆积是主要的相互作用形式。
这种网络药理学策略可能有助于发现针对复杂疾病的多靶点药物，特别是它提供了与 SLE 相关的蛋白靶标，这些靶标可能进一步通过藜芦碱进行治疗潜力的测试。
