recoflavone and Dry-Eye-Syndromes

To investigate the effect of DA-6034, 7-carboxymethyloxy-3',4',5-trimethoxy flavone, in experimentally-induced inflammatory dry eye in rabbit. In addition, to elucidate the mechanism of DA-6034, we evaluated the mitogen-activated protein kinase (MAPK) signaling pathway and transcriptional factor-kappa B (NF-kB) in corneal epithelial cells.. Rabbit lacrimal glands were injected with the T-cell mitogen concanavalin A (Con A). DA-6034 was then administered topically four times a day for six days starting 24 hr after Con A injection. Tear volume, tear function, MMP-9 and inflammatory cytokine levels in the lacrimal glands, and histological evaluation were subsequently assessed. In in vitro study, phosphorylated MAPKs (c-Jun NH2-terminal kinase (JNK) and p38 MAPK) and NF-kB were detected by enzyme-linked immunosorbent assay (ELISA) using human corneal epithelial cells.. A single injection of Con A into the lacrimal glands induced a pronounced inflammatory response, caused elevated levels of MMP-9 and cytokines IL-8 and TGF-beta(1), and induced a decrease in tear volume and shortening of tear breakup time (TBUT). In this inflammation model of dry eye, DA-6034 clearly showed therapeutic efficacy by restoring tear function and inhibiting inflammatory responses after topical ocular application. Furthermore, DA-6034 attenuated the phosphorylation of JNK and p38 MAPK and inhibited NF-kB activation in a concentration-dependent manner in corneal epithelial cells.. These results suggest that DA-6034 has the therapeutic effect in rabbit lacrimal gland inflammation model of dry eye and might be a potential treatment option for acute dry eye syndrome.

Topics: Administration, Topical; Animals; Blotting, Western; Cell Culture Techniques; Cytokines; Dacryocystitis; Disease Models, Animal; Dry Eye Syndromes; Enzyme Activation; Enzyme-Linked Immunosorbent Assay; Epithelium, Corneal; Flavonoids; MAP Kinase Signaling System; Matrix Metalloproteinase 9; Mitogen-Activated Protein Kinases; NF-kappa B; Phosphorylation; Rabbits; Tears

This study was conducted to evaluate the effect of DA-6034, a potent secretagogue, on aqueous tear fluid secretion and its quality in normal rabbit. We also evaluated, in animal models of experimentally induced dry eye disease, its effectiveness over time to stimulate aqueous tear production by ocular ferning test and goblet cell proliferation.. Aqueous tear production, total protein levels, and glycoprotein levels in normal rabbits were evaluated after topical application of DA-6034 (0.3, 1, and 3%). Moreover, time course aqueous tear volume measurement and ocular ferning test in tear fluid were performed in dry eyes of rabbits that had been given 1% atropine sulfate, topically. Altogether, tear fluid production and conjunctival goblet cell numbers were measured in dry eyes of mice that had been given topical scopolamine.. Topical application of DA-6034 (0.3, 1, and 3%) significantly increased (P < 0.05) aqueous tear production in a concentration-dependent manner in normal rabbits. There was no change in total protein levels while glycoprotein levels were significantly increased (P < 0.05) at 3% DA-6034. The increase in aqueous tear fluid was significant (P < 0.05) and lasted for 2 h post-instillation in dry eyes of rabbits that had been given 1% atropine sulfate; 10-day repeated instillation of the drug in this model resulted in large and homogeneous fern-like tear patterns. In a mouse model, DA-6034 given as a 3% eyedrop solution significantly increased (P < 0.05) tear fluid production and conjunctival goblet cell number.. These results suggest that DA-6034 accelerates not only tear secretion but also mucin production and may be a potential therapeutic agent for the treatment of dry eye disease.

Topics: Administration, Topical; Animals; Atropine; Cell Proliferation; Conjunctiva; Disease Models, Animal; Dry Eye Syndromes; Eye Proteins; Female; Flavonoids; Goblet Cells; Male; Mice; Mice, Inbred C57BL; Mucins; Ophthalmic Solutions; Rabbits; Scopolamine; Tears