BackgroundIdiopathic Pulmonary Fibrosis (IPF) is a fatal lung disease of unknown etiology with only two federally approved drug options. Given the complex molecular pathogenesis of IPF involving multiple cell types and multiple pathways, we explore the effects of a potential antifibrotic and antioxidant drug combination. Curcumin is a polyphenolic compound derived from turmeric with significant biological activity including a potential antifibrotic capacity. N-acetylcysteine (NAC) is a precursor to the antioxidant glutathione. To advance our understanding of these molecules, and to identify a clinical application, we present a small number of focused experiments that interrogates the effect of curcumin and NAC on pathways relevant to IPF in both fibroblasts and epithelial cells.MethodsPrimary epithelial cell and fibroblasts isolated from patients with IPF were challenged with a combination treatment of NAC and curcumin. Evaluation of the antifibrotic potential and effect on oxidative stress was performed through QPCR gene expression analysis and functional assays including scratch tests, viability assays, and measurement of induced reactive oxygen species.ResultsWe demonstrate that curcumin alone does have antifibrotic potential, but that effect is accompanied by proapoptotic increases in oxidative stress. Coupled with this, we find that NAC alone can reduce oxidative stress, but that epithelial cell viability is decreased through this treatment. However, co-administration of these two molecules decreases oxidative stress and maintains high cell viability in both cell types. In addition, this co-treatment maintains an antifibrotic potential.ConclusionsThese findings suggest a novel application for these molecules in IPF and encourage further exploration of this potential therapeutic approach.

中文翻译：

---

姜黄素通过 N-乙酰半胱氨酸联合治疗诱导氧化应激减弱：特发性肺纤维化的成纤维细胞和上皮细胞体外研究

背景特发性肺纤维化 (IPF) 是一种病因不明的致命肺部疾病，只有两种联邦批准的药物选择。鉴于 IPF 涉及多种细胞类型和多种途径的复杂分子发病机制，我们探索了潜在的抗纤维化和抗氧化药物组合的作用。姜黄素是一种源自姜黄的多酚化合物，具有显着的生物活性，包括潜在的抗纤维化能力。N-乙酰半胱氨酸 (NAC) 是抗氧化剂谷胱甘肽的前体。为了加深我们对这些分子的理解，并确定临床应用，我们提出了少量重点实验，这些实验询问姜黄素和 NAC 对成纤维细胞和上皮细胞中 IPF 相关通路的影响。方法从 IPF 患者中分离出的初级上皮细胞和成纤维细胞用 NAC 和姜黄素的联合治疗进行攻击。通过 QPCR 基因表达分析和功能测定（包括划痕试验、活力测定和诱导活性氧的测量）评估抗纤维化潜力和对氧化应激的影响。 结果我们证明单独的姜黄素确实具有抗纤维化潜力，但这种作用伴随着通过氧化应激的促凋亡增加。再加上，我们发现单独的 NAC 可以减少氧化应激，但通过这种处理降低了上皮细胞的活力。然而，这两种分子的共同给药可降低氧化应激并在两种细胞类型中保持高细胞活力。此外，