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, and Seung-Yeol Nah1,*
1Ginsentology Research Laboratory and Department of Physiology, College of Veterinary Medicine, Konkuk University, Seoul, 05029, Korea
2Veterinary Medical Teaching Hospital, Konkuk University, Seoul, 05029, Korea
3Center for Neuroscience, Korea Institute of Science and Technology Seoul, 139-791, Korea
4Neuropsychopharmacology and toxicology program, College of Pharmacy, Kangwon National University, Chuncheon, 200-701, Korea
5Department of Convergence Medical Science, College of Oriental Medicine, Kyung Hee University, Seoul 130-701, Korea
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The first two authors contributed equally to this work.
Received: April 4, 2016; Revised: July 3, 2016; Accepted: August 26, 2016; Published online: September 1, 2016.
Ginseng gintonin is an exogenous ligand of lysophosphatidic acid (LPA) receptor. Accumulating evidence shows LPA helps a 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 histochemical analysis. Treatment of gintonin to HCE cells induced transient increases of [Ca2+]i with concentration-dependent and reversible manners. The gintonin-mediated mobilizations of [Ca2+]i was attenuated by the LPA1/3 receptor antagonist Ki16425, a phospholipase C inhibitor U73122, an inositol 1,4,5-triphosphate receptor antagonist 2-APB, and an 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 the recovery. Histochemical analysis also showed gintonin decreased corneal apoptosis and increased corneal cell proliferation. We demonstrated 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: LPA receptor, corneal damage, ginseng, gintonin, human corneal epithelium cells

© 2016 The Korean Society of Veterinary Science.