ABSTRACT
Naringin and its aglycone, naringenin, occur naturally in our regular diet and traditional Chinese medicines. This study aimed to detect an effective therapeutic approach for cough variant asthma (CVA) through evaluating the relaxant effect of these two bioactive herbal monomers as antitussive and antiasthmatic on rat tracheal smooth muscle. The relaxant effect was determined by measuring muscular tension with a mechanical recording system in rat tracheal rings. Cytosolic Ca2+ concentration was measured using a confocal imaging system in primary cultured tracheal smooth muscle cells. In rat tracheal rings, addition of both naringin and naringenin could concentration dependently relax carbachol (CCh)-evoked tonic contraction. This epithelium-independent relaxation could be suppressed by BaCl2, tetraethylammonium, and iberiotoxin (IbTX), but not by glibenclamide. After stimulating primary cultured tracheal smooth muscle cells by CCh or high KCl, the intracellular Ca2+ increase could be inhibited by both naringin and naringenin, respectively. This reaction was also suppressed by IbTX. These results demonstrate that both naringin and naringenin can relax tracheal smooth muscle through opening big conductance Ca2+-activated K+ channel, which mediates plasma membrane hyperpolarization and reduces Ca2+ influx. Our data indicate a potentially effective therapeutic approach of naringin and naringenin for CVA.
Subject(s)
Anti-Asthmatic Agents/administration & dosage , Antitussive Agents/administration & dosage , Asthma/drug therapy , Flavanones/administration & dosage , Large-Conductance Calcium-Activated Potassium Channel alpha Subunits/metabolism , Plant Extracts/administration & dosage , Trachea/drug effects , Animals , Asthma/genetics , Asthma/metabolism , Asthma/physiopathology , Calcium/metabolism , Citrus/chemistry , Humans , Large-Conductance Calcium-Activated Potassium Channel alpha Subunits/genetics , Male , Muscle Relaxation/drug effects , Rats , Rats, Sprague-Dawley , Trachea/physiopathologyABSTRACT
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.