Zhu De-Wei, Yu Qun, Sun Ji-Jia, Shen Yun-Hui
School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Front Pharmacol. 2021 Sep 30;12:733618. doi: 10.3389/fphar.2021.733618. eCollection 2021.
Pulmonary fibrosis, a common outcome of pulmonary interstitial disease of various different etiologies, is one of the most important causes of respiratory failure. Thunb. (family: Saururaceae) (), as has been reported, is a Chinese herbal medicine commonly used to treat upper respiratory tract infection and bronchitis. Our previous study has proven that sodium houttuyfonate (an additional compound from sodium bisulfite and houttuynin) had beneficial effects in the prevention of pulmonary fibrosis (PF) induced by bleomycin (BLM) in mice. In the present study, network pharmacology was used to investigate the efficiency and potential mechanisms of in PF treatment. Upon manual collection from the literature and databases such as TCMSP and TCM-ID, 10 known representative ingredients of species were screened. Then, the prediction of the potential active ingredients, action targets, and signaling pathways were conducted through the Gene Ontology (GO), protein-protein interaction (PPI),and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. The results of network pharmacology prediction suggested that may act through multiple signaling pathways to alleviate PF, including the phosphatidylinositol 3-kinase-protein kinase B (PI3K/AKT) pathways, mitogen-activated protein kinase (MAPK) pathways, the tumor necrosis factor (TNF) pathways, and interleukin-17 (IL-17) signaling pathways Molecular docking experiments showed that the chemical constituents of had good affinity with TNF, MAPK1, and AKT1, and using lipopolysaccharide (LPS)-induced A549 cells, a model was established to verify the anti-pulmonary fibrosis effects and related mechanisms of -relevant constituents. Finally, these evidences collectively suggest may alleviate PF progression PI3K/Akt, MAPK, and TNF signaling pathways and provide novel insights to verify the mechanism of in the treatment of PF.
肺纤维化是各种不同病因的肺间质性疾病的常见结局,是呼吸衰竭的最重要原因之一。据报道,蕺菜(三白草科)是一种常用于治疗上呼吸道感染和支气管炎的中药。我们之前的研究已证明,鱼腥草素钠(亚硫酸氢钠与鱼腥草素的加成化合物)对预防博来霉素(BLM)诱导的小鼠肺纤维化(PF)具有有益作用。在本研究中,采用网络药理学来研究其治疗PF的有效性和潜在机制。通过手动从诸如中药系统药理学数据库(TCMSP)和中药鉴定数据库(TCM-ID)等文献和数据库中收集信息,筛选出该物种的10种已知代表性成分。然后,通过基因本体论(GO)、蛋白质-蛋白质相互作用(PPI)和京都基因与基因组百科全书(KEGG)富集分析对潜在活性成分、作用靶点和信号通路进行预测。网络药理学预测结果表明,其可能通过多种信号通路发挥作用以减轻PF,包括磷脂酰肌醇3-激酶-蛋白激酶B(PI3K/AKT)通路、丝裂原活化蛋白激酶(MAPK)通路、肿瘤坏死因子(TNF)通路和白细胞介素-17(IL-17)信号通路。分子对接实验表明,该物种的化学成分与TNF、MAPK1和AKT1具有良好的亲和力,并利用脂多糖(LPS)诱导的A549细胞建立模型,以验证其相关成分的抗肺纤维化作用及相关机制。最后,这些证据共同表明其可能通过PI3K/Akt、MAPK和TNF信号通路减轻PF进展,并为验证其治疗PF的机制提供了新的见解。