Yao Yufeng, Yuan Yue, Lu Zenghui, Ma Yunxia, Xie Yuanyuan, Wang Meiqi, Liu Fangle, Zhu Chenchen, Lin Chaozhan
School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, China.
School of Basic Medical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, China.
Front Pharmacol. 2021 Apr 19;12:659627. doi: 10.3389/fphar.2021.659627. eCollection 2021.
Idiopathic pulmonary fibrosis (IPF) is a progressive and irreversible interstitial pulmonary disease with a poor prognosis. The extract of (NFE) has shown remarkable benefit in the treatment of acute lung injury, lung cancer, and severe acute respiratory syndrome (SARS). However, the potential mechanism and efficacy of NFE in the treatment of IPF remain unknown. In this study, a systematic network pharmacology analysis was used to predict the mechanism and efficacy of NFE in the treatment of IPF, based on the major components of NFE elucidated by UPLC-TOF-MS/MS. The potential molecular interactions between the compounds and potential targets were predicted using molecular docking. , rats with pulmonary fibrosis induced by a single intratracheal injection of bleomycin (BLM) were orally administered NFE for 14 days. Lung index and biochemical levels were determined, and histopathological analysis using hematoxylin and eosin (H&E) and Masson staining was performed. The effects of NFE on fibroblast proliferation in Lipopolysaccharide (LPS) and TGF-β1-induced mouse 3T6 fibroblasts were evaluated . In total, 20 components were identified in NFE, and 102 potential targets for IPF treatment were predicted. These targets potentially participate in processes regulated by transmembrane receptor protein tyrosine kinase, ERBB2, and et al. Molecular docking results predicted high affinity interactions between three components (rhamnazin, rhamnetin, and rhamnocitrin) and the potential targets, suggesting that TGF-β is the most important potential target of NFE in the treatment of pulmonary fibrosis. NFE significantly decreased the lung index and alleviated BLM-induced pulmonary fibrosis in rats. Histopathological observation of lung tissues showed that NFE alleviated inflammation and collagen deposition in BLM-induced rats. NFE inhibited the migration of LPS- and TGF-β1-induced 3T6 fibroblasts, reduced the contents of hydroxyproline and collagen, and contributed to anti-inflammation and anti-oxidation. With the intervention of NFE, the protein and RNA expression of TGF-β1, -SMA, Smad3/4, -Smad3/4, CTGF, and -ERK1/2 were significantly downregulated, while Smad7 and ERK1/2 were upregulated significantly and . These findings indicated that NFE may exert therapeutic effects on pulmonary fibrosis by alleviating inflammation, oxidation, and collagen deposition. The mechanism related to the inhibition of the TGF-β/Smad signaling pathway.
特发性肺纤维化（IPF）是一种进行性且不可逆的间质性肺疾病，预后较差。[具体提取物名称]提取物（NFE）在急性肺损伤、肺癌和严重急性呼吸综合征（SARS）的治疗中已显示出显著疗效。然而，NFE治疗IPF的潜在机制和疗效仍不清楚。在本研究中，基于超高效液相色谱-飞行时间质谱联用（UPLC-TOF-MS/MS）阐明的NFE主要成分，采用系统网络药理学分析来预测NFE治疗IPF的机制和疗效。使用分子对接预测化合物与潜在靶点之间的潜在分子相互作用。通过气管内单次注射博来霉素（BLM）诱导肺纤维化的大鼠口服NFE 14天。测定肺指数和生化水平，并进行苏木精-伊红（H&E）染色和Masson染色的组织病理学分析。评估NFE对脂多糖（LPS）和转化生长因子-β1（TGF-β1）诱导的小鼠3T6成纤维细胞增殖的影响。共鉴定出NFE中的20种成分，并预测了102个IPF治疗的潜在靶点。这些靶点可能参与由跨膜受体蛋白酪氨酸激酶、ERBB2等调节的过程。分子对接结果预测三种成分（鼠李素、鼠李亭和鼠李柠檬素）与潜在靶点之间具有高亲和力相互作用，表明TGF-β是NFE治疗肺纤维化最重要的潜在靶点。NFE显著降低大鼠肺指数并减轻BLM诱导的肺纤维化。肺组织的组织病理学观察表明，NFE减轻了BLM诱导大鼠的炎症和胶原沉积。NFE抑制LPS和TGF-β1诱导的3T6成纤维细胞迁移，降低羟脯氨酸和胶原含量，并有助于抗炎和抗氧化。在NFE干预下，TGF-β1、α-平滑肌肌动蛋白（α-SMA）、Smad3/4、p-Smad3/4、结缔组织生长因子（CTGF）和p-细胞外信号调节激酶1/2（p-ERK1/2）的蛋白质和RNA表达显著下调，而Smad7和ERK1/2显著上调。这些结果表明，NFE可能通过减轻炎症、氧化和胶原沉积对肺纤维化发挥治疗作用。其机制与抑制TGF-β/Smad信号通路有关。
