Astragaloside VI and cycloastragenol-6-O-beta-D-glucoside promote wound healing in vitro and in vivo

  • Phytomedicine. 2018 Jan 1;38:183-191. doi: 10.1016/j.phymed.2017.12.003.
Shih-Yu Lee  1 ,  Wen-Liang Chang  2 ,  Zhi-Xiang Li  3 ,  Nicholas S Kirkby  4 ,  Wei-Cheng Tsai  3 ,  Shu-Fen Huang  3 ,  Ching-Huei Ou  5 ,  Tsu-Chung Chang  6
Affiliations
  • 1. Graduate Institute of Aerospace and Undersea Medicine, National Defense Medical Center, Taipei, Taiwan. Electronic address: [email protected].
  • 2. School of Pharmacy, National Defense Medical Center, Taipei, Taiwan. Electronic address: [email protected].
  • 3. Department of Biochemistry, National Defense Medical Center, Taipei, Taiwan.
  • 4. National Heart & Lung Institute, Imperial College London, London, United Kingdom. Electronic address: [email protected].
  • 5. Department of Anesthesiology, Cheng-Hsin General Hospital, Taipei, Taiwan.
  • 6. Department of Biochemistry, National Defense Medical Center, Taipei, Taiwan; Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan; Department of Biotechnology, Asia University, Taichung, Taiwan. Electronic address: [email protected].
PMID: 29425651 DOI: 10.1016/j.phymed.2017.12.003
Abstract

Background: Astragalus genus includes most of the common, historical herbal medicines that have various applications in Asian countries. However, clinical data and mechanistic insights into their actions are still lacking.

Purpose: In this study, we aimed to examine the effects of astragalosides on wound healing in vitro and in vivo, as well as the underlying mechanisms of these actions.

Methods: The wound healing activity of astragalosides was investigated in human HaCaT keratinocytes, human dermal fibroblast (HDF) cells, and murine models of wound healing.

Results: All eight astragalosides studied enhanced epidermal growth factor receptor (EGFR) activity in HaCaT cells. Among them, astragaloside VI (AS-VI) showed the strongest EGFR activation. Consistently, AS-VI and cycloastragenol-6-O-beta-D-glucoside (CMG), which is the major metabolite of astragalosides, enhanced extracellular signal-regulated kinase (ERK) activity in a concentration-dependent manner. In agreement, both compounds induced EGFR-dependent cell proliferation and migration in HaCaT and HDF cells. In addition, we showed that AS-VI and CMG accelerated the healing of both sterile and infected wounds in vivo. These effects were associated with increased angiogenesis in the scar tissue.

Conclusion: AS-VI and CMG increased the proliferation and migration of skin cells via activation of the EGFR/ERK signalling pathway, resulting in the improvement of wound healing in vitro and in vivo. These findings indicate the therapeutic potential of AS-VI and CMG to accelerate wound healing; additionally, they suggest the mechanistic basis of this activity.

Keywords
Astragaloside VI; Cycloastragenol-6-O-beta-D glucoside; EGFR; ERK; Wound healing.
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