Liu Zhen, Sun Qi, Liu Xinyue, Song Zheying, Song Fei, Lu Congxian, Zhang Yu, Song Xicheng, Yang Yujuan, Li Yumei
Department of Otorhinolaryngology, Head and Neck Surgery, Yantai Yuhuangding Hospital, Qingdao University, Yantai, China.
Shandong Provincial Clinical Research Center for Otorhinolaryngologic Diseases, Yantai, China.
Front Plant Sci. 2022 Aug 9;13:934130. doi: 10.3389/fpls.2022.934130. eCollection 2022.
YU-Pingfeng San (YPFS) can regulate inflammatory response to alleviate the symptoms of nasal congestion and runny rose in allergic rhinitis (AR). However, the mechanism of action remains unclear. In this study, 30 active ingredients of three effective herbs included in YPFS and 140 AR/YPFS-related genes were identified by database analysis. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis showed that the targets were mainly enriched in immune inflammatory-related biological processes and pathways. Finally, three hub gene targeting epidermal growth factor receptor (EGFR), mitogen-activated protein kinase 1 (MAPK1), and protein kinase B1 (AKT1) related to YPFS and AR were identified by network pharmacology analysis. YPFS treatment decreased the expression of EGFR, MAPK1, and AKT1 in ovalbumin (OVA)-induced AR mice and impaired the production of inflammatory factors interleukin (IL)-4, IL-5, and IL-13, thus alleviating immunoglobulin E (IgE) production and the symptoms of scratching nose in AR. Through molecular docking analysis, we found that the active ingredients decursin, anomalin, and wogonin of YPFS could bind to EGFR, MAPK1, and AKT1 proteins. Moreover, decursin treatment impaired the expression of IL-4 and IL-5 in human PBMCs. These results suggested that YPFS could alleviate the AR inflammatory responses by targeting EGFR, MAPK1, and AKT1, showing the mechanism of action of YPFS in AR treatment.
玉屏风散(YPFS)可调节炎症反应,减轻过敏性鼻炎(AR)的鼻塞和流涕症状。然而,其作用机制尚不清楚。本研究通过数据库分析确定了YPFS中三种有效草药的30种活性成分以及140个AR/YPFS相关基因。基因本体论(GO)和京都基因与基因组百科全书(KEGG)富集分析表明,这些靶点主要富集于免疫炎症相关的生物学过程和通路。最后,通过网络药理学分析确定了三个与YPFS和AR相关的枢纽基因,分别靶向表皮生长因子受体(EGFR)、丝裂原活化蛋白激酶1(MAPK1)和蛋白激酶B1(AKT1)。YPFS治疗可降低卵清蛋白(OVA)诱导的AR小鼠中EGFR、MAPK1和AKT1的表达,并抑制炎症因子白细胞介素(IL)-4、IL-5和IL-13的产生,从而减轻AR中免疫球蛋白E(IgE)的产生和抓挠鼻子的症状。通过分子对接分析,我们发现YPFS的活性成分白花前胡素、山奈酚和汉黄芩素可与EGFR、MAPK1和AKT1蛋白结合。此外,白花前胡素治疗可抑制人外周血单个核细胞(PBMCs)中IL-4和IL-5的表达。这些结果表明,YPFS可通过靶向EGFR、MAPK1和AKT1减轻AR炎症反应,揭示了YPFS在AR治疗中的作用机制。