Yao Tie, Yan Jiankun, Li Yang, Wang Jiaxin, Qiao Miao, Hu Xintong, Shi Xuliu, Cao Shijie, Qiu Feng
School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University Shenyang 110016 China
School of Chinese Materia Medica, Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine Tianjin 301617 China.
RSC Adv. 2020 Nov 11;10(67):41154-41163. doi: 10.1039/d0ra06763f. eCollection 2020 Nov 9.
L. (XS) is a traditional Chinese medicine (TCM) that has been widely used in Chinese medicine prescription for allergic rhinitis (AR). However, the action mechanisms of XS on the therapeutic effects on AR remain elusive. Herein, an integrated approach of phytochemistry, network pharmacology and metabolomics was first applied to uncover the action mechanisms of XS for AR. The therapeutic effect of XS extract on AR was evaluated in rat models of ovalbumin (OVA)-induced AR. The cytokine levels in rat serum and histopathological changes of nasal mucosa were assessed after oral treatment with XS. Chemical compositions of XS were elucidated by phytochemical methods, and active ingredients were identified ADME-TOX screening . Network pharmacology was performed to establish and analyze the compound-target-disease network so as to find the possible mechanism of XS in treating AR. In addition, metabolomics analysis was applied to investigate the changes in the endogenous metabolite levels that result from XS treatments. As result, the XS extract significantly increased the serum concentrations of IL-2 and reduced the levels of serum IL-4, while XS could ameliorate inflammation in the nasal sub-mucosal area, indicating that XS has significant therapeutic effects on AR model rats. Furthermore, a total of 119 compounds were isolated from XS, and 59 of these compounds were identified as active ingredients through ADME-TOX screening . An in-depth analysis of the network pharmacology implied that the active ingredients of XS could regulate the inflammatory response "multi-component, multi-target" patterns. In combination with the results of metabolomics, we found that the active ingredients of XS have a beneficial effect on AR through regulating the metabolism of arachidonic acid, which was reflected by medicating the Fc epsilon RI signaling pathway, and the neuroactive ligand-receptor interaction pathway, as well as the key proteins in arachidonic acid metabolism, such as PTGS2, PTGS1, PTGES and ALOX5. Additionally, molecular docking showed that multiple compounds have better binding with PTGS2 and ALOX5, which might be two crucial targets. Overall, these results suggest that the treatment of XS for AR is realized by regulating the metabolism of arachidonic acid a combination form. This study provides the basis for clinical applications of XS.
辛夷（XS）是一种传统中药，已广泛应用于过敏性鼻炎（AR）的中药方剂中。然而，辛夷对AR治疗作用的作用机制仍不清楚。在此，首次应用植物化学、网络药理学和代谢组学的综合方法来揭示辛夷治疗AR的作用机制。在卵清蛋白（OVA）诱导的AR大鼠模型中评估了辛夷提取物对AR的治疗效果。口服辛夷后，评估大鼠血清中的细胞因子水平和鼻黏膜的组织病理学变化。通过植物化学方法阐明了辛夷的化学成分，并通过ADME-TOX筛选鉴定了活性成分。进行网络药理学以建立和分析化合物-靶点-疾病网络，从而找到辛夷治疗AR的可能机制。此外，应用代谢组学分析来研究辛夷处理导致的内源性代谢物水平的变化。结果，辛夷提取物显著提高了血清IL-2浓度并降低了血清IL-4水平，而辛夷可改善鼻黏膜下区域的炎症，表明辛夷对AR模型大鼠具有显著的治疗作用。此外，从辛夷中总共分离出119种化合物，其中59种化合物通过ADME-TOX筛选被鉴定为活性成分。对网络药理学的深入分析表明，辛夷的活性成分可以通过“多成分、多靶点”模式调节炎症反应。结合代谢组学结果，我们发现辛夷的活性成分通过调节花生四烯酸代谢对AR具有有益作用，这通过调节FcεRI信号通路、神经活性配体-受体相互作用通路以及花生四烯酸代谢中的关键蛋白如PTGS2、PTGS1、PTGES和ALOX5来体现。此外，分子对接表明多种化合物与PTGS2和ALOX5具有更好的结合，这可能是两个关键靶点。总体而言，这些结果表明辛夷对AR的治疗是通过调节花生四烯酸代谢以组合形式实现的。本研究为辛夷的临床应用提供了依据。
