Identification And Characterization Of 19 Essential Oil CFTR Activators

In this paper, it studies the molecular pharmacology system of CFTR chloride channel activation by essential oil compounds. CFTR is the center of salt transport onto the skin, fluid flow and ion concentration, so it plays an important role of the body physiological functions. CFTR mutations affect a single organ or multi-organ pathological changes of the small intestine, pancreas, tracheal epithelial cells and the liver, salivary gland, male reproductive implications .Impaired function of CFTR Cl- channels in CF disrupts transepithelial ion transport, thus leads to the wide-ranging manifestations of the disease such as idiopathic chronic pancreatitis (ICP), kerato conjunctivitis sicca (KCS), habitual constipation, and therefore able to study the activation of wild-type and mutant CFTR function in small molecule modulator is very important.In this study, we use stable expression of human CFTR and halogen element iodine ions which highly sensitive to the green fluorescent protein mutant EYFP-H148Q of Fischer rat thyroid epithelial cells as a model to measure CFTR-mediated I-flow speed. The results showed that: essential oil compounds in the 14 kinds of small molecule compounds on wild-type andΔF508 mutant CFTR Cl-channels are activated, Butyl p-hydroxybenzoate, camphor and paeonol have activatedΔF508-CFTR Cl-channel affection , and butyl p-hydroxybenzoate, paeonol activated wt-CFTR Cl-channel effectively. The oxalic acid, salicylic acid, camphor, menthol of CFTR Cl-channels has a low activity, and 19 kinds of essential oil of G551D mutant CFTR Cl-channel activation did not. And study the activation that essential oil compounds dependent on the compounds of the 3,5 - cyclic adenosine monophosphate (cAMP) of the cystic fibrosis transmembrane conductance regulator (CFTR) Cl-channel. Essential oil compounds in the activation of the role played 5 minutes to reach half maximum activation in the drug-eluting disappear within 15 minutes. Essential oil compounds activation is reversible and dependent on the adenylate cyclase agonist Forskolin existence. As natural CFTR activators, essential oil may be useful for probing CFTR channel gating mechanisms and as a lead compound to develop pharmacological therapy of CFTR-related disease.