title: Gintonin, an exogenous ginseng-derived LPA receptor ligand, promotes corneal wound healing.
abstract: 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+]iin concentration-dependent and reversible manners. Gintonin-mediated mobilization of [Ca2+]iwas 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 facilitatedin vitrowound 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 toin vitroandin vivotherapeutic effects against corneal damage. Gintonin can be applied as a clinical agent for the rapid healing of corneal damage.
authors: Ginsentology Research Laboratory and Department of Physiology, College of Veterinary Medicine, Konkuk University, Seoul 05029, Korea.
authors: Hyeon-Joong
authors: HJ
authors: Kim
authors: Veterinary Medical Teaching Hospital, Konkuk University, Seoul 05029, Korea.
authors: Joon Young
authors: JY
authors: Kim
authors: Ginsentology Research Laboratory and Department of Physiology, College of Veterinary Medicine, Konkuk University, Seoul 05029, Korea.
authors: Byung-Hwan
authors: BH
authors: Lee
authors: Ginsentology Research Laboratory and Department of Physiology, College of Veterinary Medicine, Konkuk University, Seoul 05029, Korea.
authors: Sun-Hye
authors: SH
authors: Choi
authors: Center for Neuroscience, Korea Institute of Science and Technology, Seoul 02792, Korea.
authors: Hyewon
authors: H
authors: Rhim
authors: Neuropsychopharmacology and toxicology program, College of Pharmacy, Kangwon National University, Chuncheon 24341, Korea.
authors: Hyoung-Chun
authors: HC
authors: Kim
authors: Veterinary Medical Teaching Hospital, Konkuk University, Seoul 05029, Korea.
authors: Seoung-Yob
authors: SY
authors: Ahn
authors: Veterinary Medical Teaching Hospital, Konkuk University, Seoul 05029, Korea.
authors: Soon-Wuk
authors: SW
authors: Jeong
authors: Department of Convergence Medical Science, College of Oriental Medicine, Kyung Hee University, Seoul 02447, Korea.
authors: Minhee
authors: M
authors: Jang
authors: Department of Convergence Medical Science, College of Oriental Medicine, Kyung Hee University, Seoul 02447, Korea.
authors: Ik-Hyun
authors: IH
authors: Cho
authors: Ginsentology Research Laboratory and Department of Physiology, College of Veterinary Medicine, Konkuk University, Seoul 05029, Korea.
authors: Seung-Yeol
authors: SY
authors: Nah
mesh_terms: D000818:Animals; D015153:Blotting, Western / Q000662:veterinary; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D003315:Cornea / Q000187:drug effects / Q000473:pathology; D065306:Corneal Injuries / Q000188:drug therapy* / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008297:Male; D010936:Plant Extracts / Q000627:therapeutic use*; D011817:Rabbits; D049368:Receptors, Lysophosphatidic Acid / Q000187:drug effects; D014945:Wound Healing / Q000187:drug effects*
chemical_list: D010936:Plant Extracts; D049368:Receptors, Lysophosphatidic Acid; C000603040:gintonin; D002118:Calcium
keywords: corneal injuries; ginseng; gintonin; human corneal epithelium cells; lysophosphatidic acid receptor