Therapeutic targets of vitamin C on liver injury and associated biological mechanisms: A study of network pharmacology
Therapeutic targets of vitamin C on liver injury and associated biological mechanisms: A study of network pharmacology
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维生素C对肝损伤的治疗靶点及相关生物学机制：网络药理学研究☉
DOI：
10.1016/j.intimp.2018.11.048
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发表时间：
2019-01-01
影响因子：
5.6
通讯作者：
Yang, Bin
中科院分区：
文献类型：
--
作者：
Su, Min;Guo, Chao;Yang, Bin
在我们以前的研究中，维生素C（VC）对肝损伤（LI）发挥了有效的药理活性。因此，本研究拟采用网络药理学策略预测VC抗LI的治疗靶点，并进一步探讨VC抗LI的药理分子机制。确定LI的病理靶点，然后获得VC的验证靶点。通过构建VC抗LI的靶点-功能蛋白相互作用网络，获得VC抗LI的核心治疗靶点。此外，对核心治疗靶点进行生物学功能和途径富集分析，以评估VC对LI的生物学过程和关键信号通路。如网络药理学试验所示，确定了VC抗LI的6个关键治疗靶点，显示肿瘤坏死因子（TNF）、核因子-κ-B p65（RELA）、核因子-κ-B p105（NFKB 1）、TNF受体相关因子2（TRAF 2）、白细胞介素6（IL-6）和白细胞介素1 β（IL 1 B）。基于大卫数据库和omicshare云平台的数据分析，生物功能富集实验表明VC对LI的治疗作用与调节炎症反应和细胞凋亡密切相关。此外，途径富集分析表明VC的抗LI益处主要涉及调节前20个信号通路，例如炎症相关的TNF信号通路、NF-κ B B信号通路。两者合计，生物信息学数据阐明，抗LI药理活性的VC可能主要与抑制炎症应激，有助于抑制LI的发展。这些结果突出了预测的治疗靶点可能是抗LI的潜在生物标志物。
In our previous studies, vitamin C (VC) exerts potent pharmacological activities against liver injury (LI). Therefore, this report was designed to use network pharmacology-based strategy to predict therapeutic targets of VC against LI, and further to investigate the pharmacological molecular mechanisms. Pathological targets of LI were identified, followed by acquisition of verified targets of VC. After constructing target-functional protein interaction network of VC against LI, the core therapeutic targets of VC against LI were obtained. Further, biological function and pathway enrichment analyses were performed on core therapeutic targets to evaluate the biological processes and key signaling pathways of VC against LI. As revealed in network pharmacology assays, 6 key therapeutic targets for VC against LI were identified, showing tumor necrosis factor (TNF), nuclear factorkappa-B p65 (RELA), nuclear factor-kappa-B p105 (NFKB1), TNF receptor-associated factor 2 (TRAF2), interleukin 6 (IL-6) and interleukin 1 beta (IL1B). On the basis of data analyses from DAVID database and omicshare cloud platform, bio-functional enrichment assays showed that the therapeutic effects of VC against LI were closely associated with regulating inflammatory reaction and apoptosis. Further, pathway enrichment analysis indicated the anti-LI benefits of VC were principally implicated in regulating the top 20 signaling pathways, such as inflammation-associated TNF signaling pathway, NF-kappa B signaling pathway. Taken together, the bioinformatics data elucidate that anti-LI pharmacological activities of VC may be predominantly related to inhibition of inflammatory stress, contributing to suppression of LI development. These resultant findings highlight the predicted therapeutic targets may be potential biomarkers for anti-LI.