Curcumin induced oxidative stress attenuation by N-acetylcysteine co-treatment: a fibroblast and epithelial cell in-vitro study in idiopathic pulmonary fibrosis

Abstract

Background Idiopathic 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. Methods Primary 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. Results We 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. Conclusions These findings suggest a novel application for these molecules in IPF and encourage further exploration of this potential therapeutic approach.

The Potential Effects of Curcumin on Pulmonary Fibroblasts of Idiopathic Pulmonary Fibrosis (IPF)—Approaching with Next-Generation Sequencing and Bioinformatics

“…In addition to proliferation inhibition, curcumin also inhibited TGF-β-dependent myofibroblast differentiation via inhibition of TGF-β-induced phosphorylation of Smad2/3 and ERK1/2, as well as inhibited collagen secretion from IPF fibroblasts [ 33 ]. Another study showed that curcumin inhibited the activation of genes associated with myofibroblast activation and proliferation, inhibited migration, induced apoptosis, and induced oxidative stress in pulmonary fibroblasts [ 50 ]. The antifibrotic effects of curcumin in pulmonary fibroblasts were also attributed to overexpression of cathepsins K and L [ 51 ], whereas another study showed that curcumin inhibited TGF-β1-dependent myofibroblast differentiation of pulmonary fibroblasts via peroxisome proliferator-activated receptor γ (PPARγ)-driven upregulation of cathepsins B and L [ 25 ].…”

Traditional Chinese medicine combined with pulmonary drug delivery system and idiopathic pulmonary fibrosis: Rationale and therapeutic potential

“…Single herbs used in IPF treatment are shown in Table 2 [ [54] , [55] , [56] , [57] , [58] , [59] , [60] , [61] , [62] , [63] ]. Under the guidance of the theory of TCM, compound preparations and single TCM act on all aspects of lung disease treatment through multiple channels and multiple targets, especially show the unique advantages in the treatment of IPF.…”

“… [ 54 ] Curcuma longa L. It can inhibit type I collagen synthesis and deposition, and TGF-β1 expression. [ 55 ] Salvia miltiorrhiza Bunge It can inhibit Smad-dependent signalling and Smad-dependent MAPK pathway, and restore the balance of Nrf2-NOX4. [ 56 ] Angelica sinensis (Oliv.)…”

Combined Treatment with Low Cytotoxic Ethyl Acetate Nepenthes Extract and Ultraviolet-C Improves Antiproliferation to Oral Cancer Cells via Oxidative Stress

“…The 1 H NMR spectrum of EANA has been previously reported [16] and shows that plumbagin is the major bioactive component. N-acetylcysteine (NAC) (Sigma-Aldrich; St. Louis, MO, USA) was selected to be a oxidative stress scavenger for validating the influence of oxidative stress [17][18][19] by 1 h pretreatment of 10 mM [20].…”