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

Molecules. 2019 Apr 23;24(8):1595. 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.

Keywords: RNA sequencing; connective tissue growth factor; ginsenoside; glucocorticoid receptor; gypenoside LXXV; wound healing.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / chemistry
  • Anti-Inflammatory Agents / isolation & purification
  • Anti-Inflammatory Agents / pharmacology*
  • Cell Line
  • Cell Movement / drug effects
  • Cell Nucleus / drug effects
  • Cell Nucleus / metabolism
  • Cell Proliferation / drug effects
  • Connective Tissue Growth Factor / genetics*
  • Connective Tissue Growth Factor / metabolism
  • Dermatologic Agents / chemistry
  • Dermatologic Agents / isolation & purification
  • Dermatologic Agents / pharmacology*
  • Fibroblasts / cytology
  • Fibroblasts / drug effects
  • Fibroblasts / metabolism
  • Gene Expression Regulation
  • Ginsenosides / chemistry
  • Ginsenosides / isolation & purification
  • Ginsenosides / pharmacology
  • Gynostemma / chemistry
  • Humans
  • Keratinocytes / cytology
  • Keratinocytes / drug effects
  • Keratinocytes / metabolism
  • Male
  • Mice
  • Mice, Inbred ICR
  • Panax / chemistry
  • Plant Extracts / chemistry
  • Plant Extracts / isolation & purification
  • Plant Extracts / pharmacology
  • Protein Transport
  • Receptors, Glucocorticoid / genetics*
  • Receptors, Glucocorticoid / metabolism
  • Signal Transduction
  • Skin / drug effects
  • Skin / injuries
  • Skin / metabolism
  • Surgical Wound / drug therapy*
  • Surgical Wound / genetics
  • Surgical Wound / metabolism
  • Surgical Wound / pathology
  • Wound Healing / drug effects*
  • Wound Healing / physiology

Substances

  • Anti-Inflammatory Agents
  • CCN2 protein, mouse
  • Dermatologic Agents
  • Ginsenosides
  • Plant Extracts
  • Receptors, Glucocorticoid
  • gypenoside
  • Connective Tissue Growth Factor