Discipline of Pharmacy, Graduate School of Health, University of Technology Sydney, Sydney, NSW 2007, Australia; Faculty of Health, Australian Research Centre in Complementary and Integrative Medicine, University of Technology Sydney, Ultimo, NSW 2007, Australia.
Centre for Inflammation, Centenary Institute and University of Technology Sydney, Faculty of Science, School of Life Sciences, Sydney, NSW 2007, Australia.
Toxicol In Vitro. 2023 Oct;92:105660. doi: 10.1016/j.tiv.2023.105660. Epub 2023 Aug 15.
Airway remodelling occurs in chronic respiratory diseases (CRDs) such as asthma and chronic obstructive pulmonary disease (COPD). It is characterized by aberrant activation of epithelial reparation, excessive extracellular matrix (ECM) deposition, epithelial-to-mesenchymal transition (EMT), and airway obstruction. The master regulator is Transforming Growth Factor-β (TGF-β), which activates tissue repair, release of growth factors, EMT, increased cell proliferation, and reduced nitric oxide (NO) secretion. Due to its fundamental role in remodelling, TGF-β is an emerging target in the treatment of CRDs. Berberine is a benzylisoquinoline alkaloid with antioxidant, anti-inflammatory, and anti-fibrotic activities whose clinical application is hampered by poor permeability. To overcome these limitations, in this study, berberine was encapsulated in monoolein-based liquid crystalline nanoparticles (BM-LCNs). The potential of BM-LCNs in inhibiting TGF-β-induced remodelling features in human bronchial epithelial cells (BEAS-2B) was tested. BM-LCNs significantly inhibited TGF-β-induced migration, reducing the levels of proteins upregulated by TGF-β including endoglin, thrombospondin-1, basic fibroblast growth factor, vascular-endothelial growth factor, and myeloperoxidase, and increasing the levels of cystatin C, a protein whose expression was downregulated by TGF-β. Furthermore, BM-LCNs restored baseline NO levels downregulated by TGF-β. The results prove the in vitro therapeutic efficacy of BM-LCNs in counteracting TGF-β-induced remodelling features. This study supports the suitability of berberine-loaded drug delivery systems to counteract airway remodelling, with potential application as a treatment strategy against CRDs.
气道重塑发生在慢性呼吸道疾病（CRD）中，如哮喘和慢性阻塞性肺疾病（COPD）。其特征为上皮修复的异常激活、细胞外基质（ECM）过度沉积、上皮-间充质转化（EMT）和气道阻塞。主调控因子是转化生长因子-β（TGF-β），它激活组织修复、生长因子释放、EMT、细胞增殖增加和一氧化氮（NO）分泌减少。由于其在重塑中的基本作用，TGF-β是治疗 CRD 的新兴靶点。小檗碱是一种苯并异喹啉生物碱，具有抗氧化、抗炎和抗纤维化作用，但其临床应用受到通透性差的限制。为了克服这些局限性，本研究将小檗碱包封在单油酸甘油酯基液晶纳米粒（BM-LCNs）中。测试了 BM-LCNs 在抑制人支气管上皮细胞（BEAS-2B）中 TGF-β诱导的重塑特征方面的潜力。BM-LCNs 显著抑制 TGF-β诱导的迁移，降低 TGF-β上调的蛋白水平，包括内皮糖蛋白、血小板反应蛋白-1、碱性成纤维细胞生长因子、血管内皮生长因子和髓过氧化物酶，并增加胱抑素 C 的水平，TGF-β下调其表达。此外，BM-LCNs 恢复了被 TGF-β下调的基础 NO 水平。结果证明了 BM-LCNs 在对抗 TGF-β诱导的重塑特征方面的体外治疗功效。这项研究支持载有小檗碱的药物传递系统对抗气道重塑的适用性，具有作为治疗 CRD 的潜在应用策略的潜力。
