Cucurbitacin E ameliorates airway remodelling by inhibiting nerve growth factor expression in nicotine‐treated bronchial epithelial cells and mice: The key role of let‐7c‐5p up‐regulated expression

Abstract

Cucurbitacin E (CuE) shows potential to handle airway remodelling. In the current study, the effects of CuE on nicotine-induced airway remodelling were explored by focussing on its interaction with let-7c-5p/NGF axis. The potential microRNA (miR) as the therapeutic target for CuE treatment was determined using a microarray assay. Changes in viability, inflammation and let-7c-5p/ NGF pathway in nicotine-treated bronchial epithelial cells (BECs) were detected under CuE treatment (5 μM). The pathways were manipulated with let-7c-5p inhibitor. Mice were subjected to nicotine treatment and handled with CuE. Changes in pulmonary function and structure were detected. Based on the microarray data, let-7c-5p was selected as the therapeutic target. Viability and inflammation of BECs were induced by nicotine and then restored by CuE. At molecular level, nicotine suppressed let-7c-5p while induced NGF, FN1 and COLIA levels. The effects of CuE were counteracted by let-7c-5p inhibition. In a mouse model, nicotine impaired the function and structure of lung, which was attenuated by CuE and then re-impaired by let-7c-5p antagomir. Collectively, CuE protected against nicotine-induced airway remodelling and partially depended on the induction of let-7c-5p; our future work would pay more attention to other downstream effectors of the miR to promote the treatment of nicotine-induced pulmonary disorders.bronchial epithelial cells, Cucurbitacin E, miRNA-let-7c-5p, nerve growth factor, nicotineairway remodelling | INTRODUCTIONAirway remodelling and associated inflammation are major contributors to the progression of bronchial asthma, which is one of the major life-threatening respiratory system disorders worldwide. 1 The progression of airway remodelling is characterized by hyperplasia and epithelial-mesenchymal transition (EMT) of airway epithelial cells 2,3 which are closely related to cigarette smoking. [4][5][6] A study by Amin et al. showed that the levels Huimin Liu and Lu Yu contribute equally to the work.

Cucurbitacin E Alleviates Colonic Barrier Function Impairment and Inflammation Response and Improves Microbial Composition on Experimental Colitis Models

“…Recently, the anti-inflammatory effects of cucurbitacin E have been reported in several in vitro cell models 10,16,17 and in vivo mouse models of neuroinflammatory injury. 18,19 However, its beneficial effects on intestinal inflammation have not been studied.…”