Integrated network pharmacology and antioxidant activity-guided screen system to exploring antioxidants and quality markers of Shunaoxin pills against chronic cerebral ischemia
Integrated network pharmacology and antioxidant activity-guided screen system to exploring antioxidants and quality markers of Shunaoxin pills against chronic cerebral ischemia
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DOI：
10.4103/wjtcm.wjtcm_5_19
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发表时间：
2019-01-01
影响因子：
4.4
通讯作者：
Bai, Gang
中科院分区：
文献类型：
--
作者：
Chang, Nian-Wei;Cheng, Dan-Dan;Bai, Gang
目的：本研究的主要目的是筛选舒脑心丸（SNX）中缓解氧化应激损伤和抗慢性脑缺血的质量标志物（Q标志物）。方法：通过大鼠慢性脑缺血模型评价SNX的疗效。通过超高效液相色谱-四极杆飞行时间鉴定了 SNX 的主要成分，而通过 PharmMapper 和京都基因和基因组百科全书 (KEGG) 分析预测了其抗氧化应激的核心靶点和途径。此外，通过柱后衍生系统高效液相色谱筛选抗氧化剂，并通过细胞实验验证代表性成分。结果：SNX可以增加过氧化氢酶和超氧化物歧化酶（SOD）的表达，并对抗大脑的氧化损伤。其作用可能与三类抗氧化途径有关，包括氮代谢、花生四烯酸代谢以及环鸟苷单磷酸依赖性蛋白激酶（cGMP-PKG）信号通路受多种活性成分调控靶点。其中，阿魏酸和藁本内酯显示出对活性氧自由基的关键清除能力，并显着提高一氧化氮（NO）、NO合酶和SOD的含量，并降低丙二醛。结论：通过综合网络药理学和抗氧化活性引导筛选系统，初步揭示了SNX中生物和化学过程的氧化抗性，以预防脑氧化应激损伤。阿魏酸和藁本内酯发挥了主要的抗氧化作用，可以作为 Q 标记来控制 SNX 的质量。
Objective: The main objective of the study is to screen the quality markers (Q-markers) for relieving oxidative stress damage and against chronic cerebral ischemia in Shunaoxin pills (SNX). Methods: The benefit effect of SNX was evaluated by a rat chronic cerebral ischemia model. The main ingredients of SNX were identified by ultra-performance liquid chromatography-quadrupole time-of-flight, whereas its core targets and pathways around antioxidative stress were predicted by PharmMapper and kyoto encyclopedia of genes and genomes (KEGG) analysis. Moreover, the antioxidants were screened by high-performance liquid chromatography with postcolumn derivatization system and then representative ingredients were verified by cell experiments. Results: SNX could increase expression of catalase and superoxide dismutase (SOD) as well as antagonize oxidative damage in the brain. The effects may be related to three types of antioxidant pathways, including nitrogen metabolism, arachidonic acid metabolism, and the cyclic guanosine monophosphate-dependent protein kinase (cGMP-PKG) signaling pathway by multiple active components regulate targets. Among them, ferulic acid and ligustilide were shown the key scavenging ability for reactive oxygen free radicals and significantly increased the contents of nitric oxide (NO), NO synthase, and SOD as well as decreased malonaldehyde. Conclusion: The oxidation resistances of biological and chemical processes in SNX to protect against cerebral oxidative stress injury were preliminary revealed by an integrated network pharmacology and antioxidant activity-guided screen system. Ferulic acid and ligustilide played a major antioxidant role that could be used as Q-markers to control the quality of SNX.