interleukin-8 and 3-methylquercetin

Dry eye disease is one of the most common diseases, with increasing prevalence in many countries, but treatment options are limited. Cystic fibrosis transmembrane conductance regulator (CFTR) is a major ion channel that facilitates fluid secretion in ocular surface epithelium and is a potential target of therapeutic agent for the treatment of dry eye disease. In this study, we performed a cell-based, high-throughput screening for the identification of novel natural products that activate CFTR and restore the aqueous deficiency in dry eye. Screening of 1000 natural products revealed isorhamnetin, a flavonol aglycone, as a novel CFTR activator. Electrophysiological studies showed that isorhamnetin significantly increased CFTR chloride current, both wild type and ∆F508-CFTR. Isorhamnetin did not alter intracellular cAMP levels and the activity of other ion channels, including ANO1, ENaC, and hERG. Notably, application of isorhamnetin on mouse ocular surface induced CFTR activation and increased tear volume. In addition, isorhamnetin significantly reduced ocular surface damage and expression of interleukin (IL)-1β, IL-8, and tumor necrosis factor (TNF)-α in an experimental mouse model of dry eye. These data suggest that isorhamnetin may be used to treat dry eye disease.

Topics: Animals; Cystic Fibrosis Transmembrane Conductance Regulator; Disease Models, Animal; Dry Eye Syndromes; Epithelial Cells; Gene Expression Regulation; Humans; Interleukin-1beta; Interleukin-8; Mice; Quercetin; Tumor Necrosis Factor-alpha

Periodontitis is a highly prevalent infective and inflammatory disease with an adverse impact on systemic health. Isorhamnetin, a flavonoid mainly isolated from Hippophae fhamnoides L. fruit, has been reported to have anti-inflammatory effect. This study aimed to investigate the anti-inflammatory effects and mechanism of isorhamnetin on lipopolysaccharide (LPS)-induced inflammatory response in human gingival fibroblasts (HGFs). The production of inflammatory mediators and the expression of proteins were measured by ELISA and western blot analysis. The results demonstrated that isorhamnetin attenuated LPS-induced release of PGE

Topics: Anti-Inflammatory Agents; Cell Survival; Dinoprostone; Fibroblasts; Gingiva; Heme Oxygenase-1; Humans; Inflammation; Interleukin-6; Interleukin-8; Lipopolysaccharides; NF-E2-Related Factor 2; NF-kappa B; Periodontitis; Quercetin; Signal Transduction