Gypenoside LXXV Promotes Cutaneous Wound Healing In Vivo by Enhancing Connective Tissue Growth Factor Levels Via the Glucocorticoid Receptor Pathway.

Sungjoo Park,Jun Hyoung Lee,Sun Chang Kim,Yoseb Song,Byeong Min Jeon,Eunsu Ko,Chang-Hao Cui,Jingang Hou,Hun Sik Kim

doi:10.3390/molecules24081595

Abstract

Cutaneous wound healing is a well-orchestrated event in which many types of cells and growth factors are involved in restoring the barrier function of skin. In order to identify whether ginsenosides, the main active components of Panax ginseng, promote wound healing, the proliferation and migration activities of 15 different ginsenosides were tested by MTT assay and scratched wound closure assay. Among ginsenosides, gypenoside LXXV (G75) showed the most potent wound healing effects. Thus, this study aimed to investigate the effects of G75 on wound healing in vivo and characterize associated molecular changes. G75 significantly increased proliferation and migration of keratinocytes and fibroblasts, and promoted wound closure in an excision wound mouse model compared with madecassoside (MA), which has been used to treat wounds. Additionally, RNA sequencing data revealed G75-mediated significant upregulation of connective tissue growth factor (CTGF), which is known to be produced via the glucocorticoid receptor (GR) pathway. Consistently, the increase in production of CTGF was confirmed by western blot and ELISA. In addition, GR-competitive binding assay and GR translocation assay results demonstrated that G75 can be bound to GR and translocated into the nucleus. These results demonstrated that G75 is a newly identified effective component in wound healing.

Highlights

The skin is the largest organ and mainly functions as a barrier between the outer and inner environments [1]
G75 showed the strongest effects on migration of HaCaT keratinocytes. These results suggested that G75 has most promising wound healing activity among different kinds of ginsenosides in terms of proliferation and migration of HaCaT keratinocytes
We found a clear enrichment of genes involved in wound healing such as a response to growth factor, We found a clear enrichment of genes involved in wound healing such as a response to growth factor, cell migration, positive regulation of cell motility, response to cytokine, regulation of cell adhesion, cell migration, positive regulation of cell motility, response to cytokine, regulation of cell adhesion, epithelium development, epithelial cell proliferation, cellular response to fibroblast growth factor epithelium development, epithelial cell proliferation, cellular response to fibroblast growth factor stimulus, cellular response to epidermal growth factor stimulus, ERK1 and ERK2 cascade, TOR

Summary

Introduction

The skin is the largest organ and mainly functions as a barrier between the outer and inner environments [1]. Cutaneous wound healing is an important process in that a loss of the skin’s barrier function following wounds is restored by interplay and crosstalk between various cells and mediators [2]. Wound healing occurs in three stages: inflammation, proliferation, and remodeling [3]. The proliferation stage occurs sequentially to restore the epithelial barrier function by stimulating the proliferation and migration of cells, such as keratinocytes and fibroblasts [4]. The proliferation and migration of both these cells are the most critical processes in wound healing because re-epithelization accounts for up to 80% of wound closure [2,5]. Since cutaneous wound healing is important for clinical problems, and for aesthetic reasons, the effects of various bioactive components on promoting wound healing have been studied [7,8,9]

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