Ginseng Gintonin Enhances Hyaluronic Acid and Collagen Release from Human Dermal Fibroblasts Through Lysophosphatidic Acid Receptor Interaction

Rami Lee,Hongik Hwang,Ik-Hyun Cho,Na-Eun Lee,Hyewhon Rhim,Seung-Yeol Nah

doi:10.3390/molecules24244438

Abstract

Gintonin is a newly discovered component of ginseng and acts as a ligand for G protein-coupled lysophosphatidic acid (LPA) receptors. It is currently unclear whether gintonin has skin-related effects. Here, we examined the effects of a gintonin-enriched fraction (GEF) on [Ca2+]i transient induction in human dermal fibroblasts (HDFs). We found that GEF treatment transiently induced [Ca2+]i in a dose-dependent manner. GEF also increased cell viability and proliferation, which could be blocked by Ki16425, an LPA1/3 receptor antagonist, or 1,2-Bis(2-aminophenoxy)ethane-N,N,N′,N′-tetraacetic acid tetrakis(acetoxymethyl ester) (BAPTA-AM), a calcium chelator. We further found that GEF stimulated hyaluronic acid (HA) release from HDFs in a dose- and time-dependent manner, which could be attenuated by Ki16425, U73122, a phospholipase C inhibitor, 2-Aminoethoxydiphenyl borate (2-APB), an IP3 receptor antagonist, and BAPTA-AM. Moreover, we found that GEF increased HA synthase 1 (HAS1) expression in a time-dependent manner. We also found that GEF stimulates collagen release and the expression of collagen 1, 3, and 7 synthases in a time-dependent manner. GEF-mediated collagen synthesis could be blocked by Ki16425, U73122, 2-APB, and BAPTA-AM. GEF treatment also increased the mRNA levels of LPA1-6 receptor subtypes at 8 h and increased the protein levels of LPA1-6 receptor subtypes at 8 h. Overall, these results indicate that the GEF-mediated transient induction of [Ca2+]i is coupled to HA and collagen release from HDFs via LPA receptor regulations. We can, thus, conclude that GEF might exert a beneficial effect on human skin physiology via LPA receptors.

Highlights

Ginseng is a well-known traditional herbal medicine that has been used for its pharmacological and therapeutic effects in Korea, China, and Japan for thousands of years [1,2]
Ginsenoside Rb1, Rg1, and compound K had no effect on the transient induction of [Ca2+ ]i by gintonin-enriched fraction (GEF) in human dermal fibroblasts (HDFs), indicating that GEF, but not ginsenosides, are the main cause of the transient induction of [Ca2+ ]i via lysophosphatidic acid (LPA) receptor activation in non-neuronal
We found that GEF treatment caused a significant increase in collagen synthase expression (COL1A1, COL3A1, and COL7A1) in a time-dependent manner and caused significant overexpression at 24 h compared to the control (0 h)

Summary

Introduction

Ginseng is a well-known traditional herbal medicine that has been used for its pharmacological and therapeutic effects in Korea, China, and Japan for thousands of years [1,2]. It has been studied extensively and has been shown to have effects on neurological disorders, such as Alzheimer’s disease (AD), stroke, Parkinson’s disease, and multiple sclerosis [3,4,5,6,7]. GEF transiently induces [Ca2+ ]i and stimulates diverse Ca2+ -dependent cellular effects, ranging from neurotransmitter release to neuronal cell proliferation, through G protein-coupled LPA receptors [11,13]. The relationship between gintonin and the nervous system has been well-investigated, relatively little is known about the effects of gintonin on skin, on fibroblasts that are closely related to skin biology

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Results

Conclusion