Department of Pediatrics, the Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250033, China.
School of Nursing, Cheeloo College of Medicine, Shandong University, Jinan 250012, China.
J Tradit Chin Med. 2022 Apr;42(2):296-303. doi: 10.19852/j.cnki.jtcm.20220225.003.
To predict the anti-inflammatory targets and related pathways of rhein in the treatment of asthma by using network pharmacology, and to further explore its potential mechanism in asthma.
The corresponding targets of rhein were obtained from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), and the rhein-target network was constructed with Cytoscape 3.7.1 software. The Genbank and Drugbank databases were used to collect and screen asthma targets, and the rhein-target-disease interaction network was constructed. A target protein-protein interaction (PPI) network was constructed using the STRING database to screen key targets. Finally, Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis was used to identify biological processes and signaling pathways. The anti-asthmatic effects of rhein were tested in vitro, and the expression levels of proteins in the mitogen-activated protein kinase/nuclear factor kappa-B (MAPK/ NF-κB) signaling pathway were assessed by western blot analysis.
Altogether, 83 targets of rhein were screened in the relevant databases, 989 targets of asthma were obtained in the National Center for Biotechnology Information (NCBI) GENE Database. PPI network analysis and KEGG pathway enrichment analysis predicted that rhein could regulate the epidermal active growth factor receptor (EGFR), mitogen-activated protein kinase 14 (MAPK14), tumour necrosis factor receptor superfamily member 1A (TNFRSF1A), receptor tyrosine-protein kinase erbB-2 (ERBB2), and other signaling pathways. Furthermore, we selected the MAPK signaling pathway to determine the anti-inflammatory effects of rhein. Consistently, further experiments demonstrated that rhein was shown to inhibit HBE cells inflammation.
The anti-inflammatory mechanism of rhein in the treatment of asthma may be related to EGFR, MAPK14, TNFRSF1A and ERBB2 as well as their signaling pathways. To prevent the exacerbation of asthma, instead of targeting a single pathway or a single target, all these targets and their signaling pathways should be controlled holistically. Rhein may alleviate the inflammation of asthma by inhibiting the MAPK/NF-κB pathway.
运用网络药理学预测大黄酸治疗哮喘的抗炎靶点及相关通路，进一步探讨其治疗哮喘的潜在机制。
从中药系统药理学数据库和分析平台（TCMSP）中获取大黄酸的相应靶点，并用 Cytoscape 3.7.1 软件构建大黄酸-靶标网络。利用 Genbank 和 Drugbank 数据库收集和筛选哮喘靶点，构建大黄酸-靶标-疾病相互作用网络。利用 STRING 数据库构建靶蛋白-蛋白相互作用（PPI）网络，筛选关键靶点。最后，通过京都基因与基因组百科全书（KEGG）富集分析，识别生物过程和信号通路。体外检测大黄酸的抗哮喘作用，通过蛋白质印迹分析检测丝裂原活化蛋白激酶/核因子κB（MAPK/NF-κB）信号通路中蛋白的表达水平。
从相关数据库中共筛选出 83 个大黄酸作用靶点，从美国国立生物技术信息中心（NCBI）GENE 数据库中获得 989 个哮喘靶点。PPI 网络分析和 KEGG 通路富集分析预测，大黄酸可能通过调节表皮生长因子受体（EGFR）、丝裂原活化蛋白激酶 14（MAPK14）、肿瘤坏死因子受体超家族成员 1A（TNFRSF1A）、受体酪氨酸蛋白激酶 erbB-2（ERBB2）等信号通路发挥作用。此外，我们选择 MAPK 信号通路来确定大黄酸的抗炎作用。进一步的实验结果表明，大黄酸能抑制 HBE 细胞炎症。
大黄酸治疗哮喘的抗炎机制可能与 EGFR、MAPK14、TNFRSF1A、ERBB2 及其信号通路有关。为了防止哮喘恶化，不能仅针对单一通路或单一靶点，而应全面控制所有这些靶点及其信号通路。大黄酸可能通过抑制 MAPK/NF-κB 通路缓解哮喘炎症。
