School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 100029, China.
Institution of Basic Theory, China Academy of Chinese Medical Sciences, Beijing 100700, China.
Phytomedicine. 2018 Nov 15;50:61-72. doi: 10.1016/j.phymed.2018.09.184. Epub 2018 Sep 18.
The inflammatory response has a complex pathogenesis; thus, it is a critical contributor to the development and complication of many diseases. Zhishi and Zhiqiao are famous Citrus herbal medicines that are rich in bioactive phenolic constituents with multiple anti-inflammatory activities.
Establishment of a multi-component-target-pathway network strategy to investigate the usage of Zhishi and Zhiqiao on inflammatory diseases can provide a reference for mechanisms of traditional Chinese medicine (TCM).
A multi-component-target-pathway network strategy was constructed to elucidate the various antiinflammatory effects of Zhishi and Zhiqiao by integrating multi-constituent determination, network pharmacology, molecular mechanisms in cells and integrated metabolomics in animals.
Based on the quantitatively determined global and characteristic chemical profiles of Zhishi and Zhiqiao, the component-target-pathway network was predicted by network pharmacology coupled with text mining and docking. The potential antiinflammatory mechanism of the various components in Zhishi and Zhiqiao were verified using LPS-induced inflammatory responses in RAW 264.7 cells. The different metabolic regulating effects of Zhishi and Zhiqiao against an LPS-induced inflammation model were investigated using a plasma metabolomics strategy.
The molecular mechanism of Zhishi mainly suppressed the MAPK signaling pathway, whereas Zhiqiao emphasized the PPAR-AKT signaling pathways simultaneously to block the inflammatory process. Meanwhile, Zhishi and Zhiqiao both exhibited an anti-inflammatory effect by inhibiting the NF-κB signaling pathway to reduce the production of inflammatory mediators. In the metabolomics study, Zhishi and Zhiqiao exhibited variant corrections of the disordered metabolic pathways through amino acid metabolism, glycometabolism and lipid metabolism.
All of these results indicate that Zhishi and Zhiqiao, in a diversified mixture, exert their anti-inflammatory effect through variant pathways. These findings can assist in developing the use of Zhishi and Zhiqiao for inflammatory diseases.
炎症反应的发病机制复杂，是许多疾病发生和并发症的关键因素。枳实和枳壳是两种著名的柑橘类草药，富含具有多种抗炎活性的生物活性酚类成分。
建立一个多成分-靶点-通路网络策略，研究枳实和枳壳对炎症性疾病的应用，可以为中药（TCM）的机制提供参考。
通过整合多成分测定、网络药理学、细胞内分子机制和动物整体代谢组学，构建多成分-靶点-通路网络策略，阐明枳实和枳壳的各种抗炎作用。
基于枳实和枳壳的全球和特征化学图谱的定量测定，通过网络药理学结合文本挖掘和对接预测成分-靶点-通路网络。利用 LPS 诱导 RAW 264.7 细胞炎症反应，验证枳实和枳壳中各种成分的潜在抗炎机制。采用血浆代谢组学策略研究枳实和枳壳对 LPS 诱导炎症模型的不同代谢调节作用。
枳实的分子机制主要抑制 MAPK 信号通路，而枳壳则同时强调 PPAR-AKT 信号通路，以阻断炎症过程。同时，枳实和枳壳均通过抑制 NF-κB 信号通路减少炎症介质的产生，发挥抗炎作用。在代谢组学研究中，枳实和枳壳通过氨基酸代谢、糖代谢和脂代谢，对失调的代谢途径表现出不同的纠正作用。
这些结果表明，枳实和枳壳在多样化的混合物中，通过不同的途径发挥抗炎作用。这些发现有助于开发枳实和枳壳在炎症性疾病中的应用。
