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The therapeutic effect of DA-6034 on ocular inflammation via suppression of MMP-9 and inflammatory cytokines and activation of the MAPK signaling pathway in an experimental dry eye model.
Curr Eye Res. 2010 Feb; 35(2):165-75.CE

Abstract

PURPOSE

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.

METHODS

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.

RESULTS

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.

CONCLUSIONS

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.

Authors+Show Affiliations

Research Institutes, Dong-A Pharmaceutical Company, Yongin, Kyunggi, South Korea.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

20136427

Citation

Seo, Mi Jeong, et al. "The Therapeutic Effect of DA-6034 On Ocular Inflammation Via Suppression of MMP-9 and Inflammatory Cytokines and Activation of the MAPK Signaling Pathway in an Experimental Dry Eye Model." Current Eye Research, vol. 35, no. 2, 2010, pp. 165-75.
Seo MJ, Kim JM, Lee MJ, et al. The therapeutic effect of DA-6034 on ocular inflammation via suppression of MMP-9 and inflammatory cytokines and activation of the MAPK signaling pathway in an experimental dry eye model. Curr Eye Res. 2010;35(2):165-75.
Seo, M. J., Kim, J. M., Lee, M. J., Sohn, Y. S., Kang, K. K., & Yoo, M. (2010). The therapeutic effect of DA-6034 on ocular inflammation via suppression of MMP-9 and inflammatory cytokines and activation of the MAPK signaling pathway in an experimental dry eye model. Current Eye Research, 35(2), 165-75. https://doi.org/10.3109/02713680903453494
Seo MJ, et al. The Therapeutic Effect of DA-6034 On Ocular Inflammation Via Suppression of MMP-9 and Inflammatory Cytokines and Activation of the MAPK Signaling Pathway in an Experimental Dry Eye Model. Curr Eye Res. 2010;35(2):165-75. PubMed PMID: 20136427.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The therapeutic effect of DA-6034 on ocular inflammation via suppression of MMP-9 and inflammatory cytokines and activation of the MAPK signaling pathway in an experimental dry eye model. AU - Seo,Mi Jeong, AU - Kim,Ju Mi, AU - Lee,Min Jung, AU - Sohn,Yong Sung, AU - Kang,Kyung Koo, AU - Yoo,Moohi, PY - 2010/2/9/entrez PY - 2010/2/9/pubmed PY - 2010/4/17/medline SP - 165 EP - 75 JF - Current eye research JO - Curr Eye Res VL - 35 IS - 2 N2 - PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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. SN - 1460-2202 UR - https://www.unboundmedicine.com/medline/citation/20136427/The_therapeutic_effect_of_DA_6034_on_ocular_inflammation_via_suppression_of_MMP_9_and_inflammatory_cytokines_and_activation_of_the_MAPK_signaling_pathway_in_an_experimental_dry_eye_model_ L2 - https://www.tandfonline.com/doi/full/10.3109/02713680903453494 DB - PRIME DP - Unbound Medicine ER -