Hydroxysafflor Yellow A Attenuates Small Airway Remodeling in a Rat Model of Chronic Obstructive Pulmonary Disease

Abstract

Our previous studies found that hydroxysafflor yellow A (HSYA), an active ingredient in Carthamus tinctorius L., has anti-inflammatory and anti-fibrosis properties. In this study, we investigated the effect of HSYA on small airway remodeling (SAR) in a chronic obstructive pulmonary disease (COPD) rat model induced by cigarette smoke and lipopolysaccharide (LPS). SAR is a common lesion in COPD characterized by thickening of the airway wall, mainly by subepithelial fibrosis. In this study the thickness of the small airway was determined by total wall area/basement membrane perimeter (WAt/Pbm). Collagen deposition of the small airway was assessed by Masson's trichrome staining. HSYA significantly attenuated the thickening and collagen deposition of the small airway and inhibited transforming growth factor β1 (TGF-β1) mRNA and protein expression in COPD rat. In addition, HSYA inhibited the phosphorylation of p38 mitogen-activated protein kinases (MAPK) in the lung tissue of rat. HSYA can attenuate experimentally induced airway remodeling and this attenuation may be attributed to suppression of TGF-β1 expression.Key words hydroxysafflor yellow A; airway remodeling; transforming growth factor-β1; p38 mitogen-activated protein kinase (MAPK); chronic obstructive pulmonary disease (COPD)Chronic obstructive pulmonary disease (COPD), characterized by airflow limitation that is progressive and persistent, is a leading cause of death worldwide.1) Cigarette smoking and bacterial infection have been widely recognized as the main causes of COPD.2,3) The main pathological changes of the lung from COPD are emphysema and small airway remodeling (SAR).4) SAR, characterized by subepithelial fibrosis, goblet cell metaplasia and excessive mucus production, is now accepted as an important cause of airflow obstruction in COPD.5) No ideal medication has been able to effectively reverse the airway remodeling. Therefore the development of novel medications for the prevention of airway remodeling in COPD is urgently needed.More recently, the role of transforming growth factor β1 (TGF-β1) in the pathogenesis of SAR in COPD has attracted more interests, particularly since genetic studies have demonstrated gene polymorphisms of the TGF-β superfamily is associated with COPD. TGF-β1 is ubiquitously expressed and is secreted by many lung cell types including airway epithelial cells, vascular endothelial cells, smooth muscle cells, fibroblasts and inflammatory cells. 6)TGF-β1 can increase deposition of extracellular matrix in the airways and can stimulate lung fibroblast differentiating into myofibroblast.7) It has been reported that intratracheal instillation of TGF-β1 in mice leads to airway remodeling with peribronchiolar collagen deposition and basal membrane thickening. 8) Thus, it seems reasonable to hypothesize that targeting the TGF-β1 expression may provide a novel therapeutic method for attenuating SAR in COPD.Safflower is the dry flower of Carthamus tinctorius L. and naturally distributed around the world.9) It has been used extensively...

Curcumin ameliorates alveolar epithelial injury in a rat model of chronic obstructive pulmonary disease

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Hydroxysafflor yellow A inhibits TGF-β1-induced activation of human fetal lung fibroblastsin vitro

“…The high-pressure liquid chromatography (HPLC) chromatographic system was used for HSYA analysis. [26] The purity of HSYA was 95.2% by the area normalization method ( Figure 2).…”

Hydroxysafflor Yellow A Suppresses MRC-5 Cell Activation Induced by TGF-β1 by Blocking TGF-β1 Binding to TβRII

“…HSYA was diluted with aseptic 0.9% NaCl for experimental use. HSYA analysis was performed using a high-performance liquid chromatography system (Wang Y. et al, 2014). The purity of the HSYA was previously determined by the area normalization method to be 95.2% (Pan et al, 2016).…”