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J Vet Sci 2017; 18(3): 387-397  https://doi.org/10.4142/jvs.2017.18.3.387
Gintonin, an exogenous ginseng-derived LPA receptor ligand, promotes corneal wound healing
Hyeon-Joong Kim1,†, Joon Young Kim2,†, Byung-Hwan Lee1, Sun-Hye Choi1, Hyewon Rhim3, Hyoung-Chun Kim4, Seoung-Yob Ahn2, Soon-Wuk Jeong2, Minhee Jang5, Ik-Hyun Cho5, Seung-Yeol Nah1,*
1Ginsentology Research Laboratory and Department of Physiology, College of Veterinary Medicine, and 2Veterinary Medical Teaching Hospital, Konkuk University, Seoul 05029, Korea
3Center for Neuroscience, Korea Institute of Science and Technology, Seoul 02792, Korea
4Neuropsychopharmacology and toxicology program, College of Pharmacy, Kangwon National University, Chuncheon 24341, Korea
5Department of Convergence Medical Science, College of Oriental Medicine, Kyung Hee University, Seoul 02447, Korea
Correspondence to: Seung-Yeol Nah
Tel: +82-2-450-4154; Fax: +82-2-450-3037; E-mail: synah@konkuk.ac.kr
The first two authors contributed equally to this work.
Received: April 4, 2016; Revised: July 3, 2016; Accepted: August 26, 2016; Published online: September 30, 2017.
Ginseng gintonin is an exogenous ligand of lysophosphatidic acid (LPA) receptors. Accumulating evidence shows LPA helps in rapid recovery of corneal damage. The aim of this study was to evaluate the therapeutic efficacy of gintonin in a rabbit model of corneal damage. We investigated the signal transduction pathway of gintonin in human corneal epithelium (HCE) cells to elucidate the underlying molecular mechanism. We next evaluated the therapeutic effects of gintonin, using a rabbit model of corneal damage, by undertaking histochemical analysis. Treatment of gintonin to HCE cells induced transient increases of [Ca2+]i in concentration-dependent and reversible manners. Gintonin-mediated mobilization of [Ca2+]i was attenuated by LPA1/3 receptor antagonist Ki16425, phospholipase C inhibitor U73122, inositol 1,4,5-triphosphate receptor antagonist 2-APB, and intracellular Ca2+ chelator BAPTA-AM. Gintonin facilitated in vitro wound healing in a concentration-dependent manner. When applied as an eye-drop to rabbits with corneal damage, gintonin rapidly promoted recovery. Histochemical analysis showed gintonin decreased corneal apoptosis and increased corneal cell proliferation. We demonstrated that LPA receptor activation by gintonin is linked to in vitro and in vivo therapeutic effects against corneal damage. Gintonin can be applied as a clinical agent for the rapid healing of corneal damage.
Keywords: corneal injuries, ginseng, gintonin, human corneal epithelium cells, lysophosphatidic acid receptor

© 2017 The Korean Society of Veterinary Science.

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.