Amygdalin alleviated TGF-β-induced epithelial-mesenchymal transition in bronchial epithelial cells

Asthma is one of the most common chronic respiratory diseases in the world, characterized by recurrent wheezing, coughing, chest tightness, and shortness of breath [1,2]. Statistically speaking, it afflicts over 30 million people in China, with the prevalence of asthma in adolescents and adults climbing to 1.24% [3]. Studies have shown that molecules with anti-inflammatory effects are necessary to improve lung function in patients with asthma [[4], [5], [6], [7]]. Due to its persistence and recurrence, asthma has become a modern clinical challenge. The discovery and development of effective therapeutic drugs for treating asthma are urgently needed.

A crucial pathology phenomenon in the progression of asthma is airway wall remodeling, which has been described as changes to the composition, thickness, and volume of the airway wall [8]. Epithelial-mesenchymal transition (EMT) is a biological process in which epithelial cells lose polarity and cell adhesion and gain migratory and invasive characteristics to become mesenchymal cells [9,10]. As reported, airway inflammation during asthma promotes the occurrence of EMT through the increase of transforming growth factor-beta (TGF-β) secretion, thereby initiating airway wall remodeling and exacerbating the development of asthma [11]. An increasing number of studies have confirmed the effectiveness of retarding asthma development by reversing the EMT phenotype. For example, icariin relieves airway responsiveness and inflammation in chronic asthma model mice by suppressing TGF-β-induced EMT in bronchial epithelial cells [12]. Also, bone marrow-derived mesenchymal stem cells reduce EMT in the airway epithelium, thereby alleviating allergic inflammation in the airways and decreasing airway wall remodeling in asthmatic rats [13]. Thus, EMT has been proposed as a promising target for the treatment of asthma.

Amygdalin is a main active ingredient in Chinese raw bitter almonds and has a wide range of pharmacological properties, such as being anti-oxidative and anti-inflammatory [14]. Recently, emerging evidence has indicated a regulatory effect of amygdalin on EMT progression. Wang et al. reported that amygdalin strikingly decreased vimentin and alpha-smooth muscle actin (α-SMA)—two mesenchymal cell markers—contents while increasing E-cadherin—a core protein of the epithelial adherens junction—content in the renal tissue of diabetic nephropathy rats [15]. Wang et al. revealed the protective effect of amygdalin on EMT in a mouse model of chronic obstructive pulmonary disease [16]. Mahuang decoction (MHD) is a Chinese prescription that has been used for asthma relief [17]. Among its seven main active ingredients, amygdalin has been confirmed to play the most prominent role in regulating asthma-involved cytokine contents in asthmatic rats [18]. However, it remains unclear whether amygdalin exhibits a therapeutic effect on asthma by suppressing EMT.

In the present study, the effect of amygdalin on EMT was evaluated in a successfully constructed asthmatic mouse model. The molecular mechanisms by which amygdalin affects EMT were explored in TGF-β-stimulated bronchial epithelial cells. It is hoped that our data will provide the experimental and theoretical basis for the clinical application of amygdalin in the treatment of asthma.

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