Ming Xi, Lu Yingzhu, Huang Huihui, Zheng Jialin, Wang Tianzi, Li Zhuoqun, Yu Xingzhu, Xiong Lei
Department of Pediatrics and Department of Integrative Medicine on Pediatric, The First Hospital Affiliated Yunnan University of Chinese Medicine, 120 Guanghua Road, Kunming, Yunnan, 650021, China.
No.1 Clinical Medical College of Yunnan, University of Chinese Medicine, Kunming, Yunnan, 650051, China.
Funct Integr Genomics. 2024 Dec 20;25(1):1. doi: 10.1007/s10142-024-01506-9.
This study aimed to investigate the mechanism of Xuanhong Dingchuan Tang (XHDCT) in delaying bronchial asthma inflammation via the microRNA (miR)-107-3p/prostaglandin endoperoxide synthase 2 (PTGS2)/mitogen-activated protein kinase (MAPK) axis. Based on the network pharmacological analysis, XHDCT chemical constituents and targets of each chemical constituent were screened through the TCMSP database, and differential-expressed genes of bronchial asthma were obtained from the GEO database, which were intersected to get XHDCT potential anti-inflammatory targets. The key anti-inflammatory targets of XHDCT were acquired by protein-protein interaction (PPI) analysis of the candidate targets. Bronchial asthma mouse models were established and the pathological changes of lung tissues were observed. Serum IgE levels were tested. Total cells and eosinophils in bronchoalveolar lavage fluid (BALF) were counted. The expression of Th2-associated cytokines (interleukin (IL)-4, IL-5, and IL-13) and chemokines (monocyte chemoattractant protein-1 (MCP-1) and eotaxin) in BALF were measured. The targeting relationship between miR-107-3p and PTGS2 was tested. XHDCT delayed bronchial asthma inflammation in in-vivo asthma mouse models. A total of 155 active ingredients and their 341 targets were intersected with bronchial asthma-relevant genes, obtaining 20 potential targets of XHDCT for bronchial asthma treatment. Based on the PPI and "drug-component-target" network diagram, PTGS2 was found to be in a central position. PTGS2 was downregulated and miR-107-3p was upregulated in bronchial asthma mice after XHDCT treatment. PTGS2 overexpression activated the MAPK signaling pathway to promote inflammation in bronchial asthma mice, whereas inflammatory symptoms were reduced and the MAPK signaling pathway was inhibited after XHDCT treatment. miR-107-3p was an upstream regulatory miRNA for PTGS2. After miR-107-3p interference, the activation of the PTGS2/MAPK axis promoted inflammation in bronchial asthma mice, whereas the inflammatory symptoms were reduced after XHDCT treatment. XHDCT promotes anti-inflammatory effects in bronchial asthma via the miR-107-3p/PTGS2/MAPK axis.
本研究旨在探讨宣红定喘汤（XHDCT）通过微小RNA（miR）-107-3p/前列腺素内过氧化物合酶2（PTGS2）/丝裂原活化蛋白激酶（MAPK）轴延缓支气管哮喘炎症的机制。基于网络药理学分析，通过中药系统药理学数据库（TCMSP）筛选XHDCT的化学成分及其各化学成分的靶点，并从基因表达综合数据库（GEO）获取支气管哮喘的差异表达基因，将两者进行交集分析以获得XHDCT潜在的抗炎靶点。通过对候选靶点进行蛋白质-蛋白质相互作用（PPI）分析，获得XHDCT关键的抗炎靶点。建立支气管哮喘小鼠模型，观察肺组织的病理变化，检测血清免疫球蛋白E（IgE）水平，计数支气管肺泡灌洗液（BALF）中的总细胞数和嗜酸性粒细胞数，测定BALF中Th2相关细胞因子（白细胞介素（IL）-4、IL-5和IL-13）和趋化因子（单核细胞趋化蛋白-1（MCP-1）和嗜酸性粒细胞趋化因子）的表达，检测miR-107-3p与PTGS2之间的靶向关系。XHDCT在体内哮喘小鼠模型中可延缓支气管哮喘炎症。共155种活性成分及其341个靶点与支气管哮喘相关基因进行交集分析，获得20个XHDCT治疗支气管哮喘的潜在靶点。基于PPI和“药物-成分-靶点”网络图，发现PTGS2处于中心位置。XHDCT治疗后，支气管哮喘小鼠中PTGS2表达下调，miR-107-3p表达上调。PTGS2过表达激活MAPK信号通路，促进支气管哮喘小鼠的炎症反应，而XHDCT治疗后炎症症状减轻，MAPK信号通路受到抑制。miR-107-3p是PTGS2的上游调控微小RNA。miR-107-3p干扰后，PTGS2/MAPK轴的激活促进支气管哮喘小鼠的炎症反应，而XHDCT治疗后炎症症状减轻。XHDCT通过miR-107-3p/PTGS2/MAPK轴促进支气管哮喘的抗炎作用。
