Abstract
Gintonin, a novel compound of ginseng, is a ligand of the lysophosphatidic acid (LPA) receptor. The in vitro and in vivo skin wound healing effects of gintonin remain unknown. Therefore, the objective of this study was to investigate the effects of gintonin on wound healing-linked responses, especially migration and proliferation, in skin keratinocytes HaCaT. In this study, 2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide assay, Boyden chamber migration assay, scratch wound healing assay, and Western blot assay were performed. A tail wound mouse model was used for the in vivo test. Gintonin increased proliferation, migration, and scratch closure in HaCaT cells. It also increased the release of vascular endothelial growth factor (VEGF) in HaCaT cells. However, these increases, induced by gintonin, were markedly blocked by treatment with Ki16425, an LPA inhibitor, PD98059, an ERK inhibitor, 1,2-Bis(2-aminophenoxy)ethane-N,N,N′,N′-tetraacetic acid tetrakis (acetoxymethyl ester), a calcium chelator, and U73122, a PLC inhibitor. The VEGF receptor inhibitor axitinib also attenuated gintonin-enhanced HaCaT cell proliferation. Gintonin increased the phosphorylation of AKT and ERK1/2 in HaCaT cells. In addition, gintonin improved tail wound healing in mice. These results indicate that gintonin may promote wound healing through LPA receptor activation and/or VEGF release-mediated downstream signaling pathways. Thus, gintonin could be a beneficial substance to facilitate skin wound healing.
Highlights
Ginseng is a traditional herbal medicine that has been used as a tonic for thousands of years
We have shown that a gintonin-enriched fraction (GEF) of ginseng can enhance hyaluronic acid and collagen release from human skin fibroblasts via lysophosphatidic acid (LPA) receptor activation [20]
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Summary
Ginseng is a traditional herbal medicine that has been used as a tonic for thousands of years. Substantial scientific research has shown that ginseng and its components exert various pharmacological activities, including anti-cancer, anti-diabetes, anti-oxidant, anti-inflammatory, immune system-improving, and central nervous system-improving effects [1,2,3,4,5,6,7,8]. A root of Panax ginseng C.A. Meyer, contains various biologically active components such as ginsenosides, polysaccharides, and glycolipoproteins [1,9,10]. We isolated a glycolipoprotein called gintonin from ginseng and found that gintonin has a variety of components including ginseng major latex-like protein151 (GLP151), ginseng ribonuclease-like storage protein, phosphatidic acids, and lysophosphatidic acid (LPA) [11]. We found that it is a ligand of LPA receptor subtypes [11]
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