Naringenin Regulates CFTR Activation and Expression in Airway Epithelial Cells

• Main Authors: Rui Shi, Zi-Ting Xiao, Yi-Jun Zheng, Yi-Lin Zhang, Jia-Wen Xu, Jie-Hong Huang, Wen-Liang Zhou, Pei-Bo Li, Wei-Wei Su
• Format: Article
• Language: English
• Published: Cell Physiol Biochem Press GmbH & Co KG 2017-11-01
• Series: Cellular Physiology and Biochemistry
• Subjects: Naringenin; Airway epithelium; CFTR; Cl- secretion; Traditional Chinese medicine
• Online Access: https://www.karger.com/Article/FullText/485419
• ISSN: 1015-8987; 1421-9778

Background/Aims: Sputum symptoms are commonly seen in the elderly. This study aimed to identify an efficacious expectorant treatment stratagem through evaluating the secretion-promoting activation and cystic fibrosis transmembrane conductance regulator (CFTR) expression of the bioactive herbal monomer naringenin. Methods: Vectorial Cl- transport was determined by measuring short-circuit current (ISC) in rat airway epithelium. cAMP content was measured by ELISA in primary cultured epithelial cells and Calu-3 cells. CFTR expression in Calu-3 cells was determined by qPCR. Results: Addition of naringenin to the basolateral side of the rat airway led to a concentration-dependent sustained increase in ISC. The current was suppressed when exposed to Cl–-free solution or by bumetanide, BaCl2, and DPC but not by DIDS and IBMX. Forskolin-induced ISC increase and CFTRinh-172/MDL-12330A-induced ISC inhibition were not altered by naringenin. Intracellular cAMP content was significantly increased by naringenin. With lipopolysaccharide stimulation, CFTR expression was significantly reduced, and naringenin dose-dependently enhanced CFTR mRNA expression. Conclusion: These results demonstrate that naringenin has the ability to stimulate Cl- secretion, which is mediated by CFTR through a signaling pathway by increasing cAMP content. Moreover, naringenin can increase CFTR expression when organism CFTR expression is seriously hampered. Our data suggest a potentially effective treatment strategy for sputum.