Journal of Ginseng Research

The Korean Society of Ginseng (고려인삼학회)
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Ginsenoside Rg5 promotes wound healing in diabetes by reducing the negative regulation of SLC7A11 on the efferocytosis of dendritic cells

  • Wei Xia (Department of Endocrinology, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China) ;
  • Zongdong Zhu (Department of Orthopedics, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China) ;
  • Song Xiang (Department of Endocrinology, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China) ;
  • Yi Yang (Department of Endocrinology, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China)
  • Received : 2023.04.06
  • Accepted : 2023.06.19
  • Published : 2023.11.01
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Abstract

Background: ginsenoside Rg5 is a rare ginsenoside with known hypoglycemic effects in diabetic mice. This study aimed to explore the effects of ginsenoside Rg5 on skin wound-healing in the Leprdb/db mutant (db/db) mice (C57BL/KsJ background) model and the underlying mechanisms. Methods: Seven-week-old male C57BL/6J, SLC7A11-knockout (KO), the littermate wild-type (WT), and db/db mice were used for in vivo and ex vivo studies. Results: Ginsenoside Rg5 provided through oral gavage in db/db mice significantly alleviated the abundance of apoptotic cells in the wound areas and facilitated skin wound healing. 50 μM ginsenoside Rg5 treatment nearly doubled the efferocytotic capability of bone marrow-derived dendritic cells (BMDCs) from db/db mice. It also reduced NF-κB p65 and SLC7A11 expression in the wounded areas of db/db mice dose-dependently. Ginsenoside Rg5 physically interacted with SLC7A11 and suppressed the cystine uptake and glutamate secretion of BMDCs from db/db and SLC7A11-WT mice but not in BMDCs from SLC7A11-KO mice. In BMDCs and conventional type 1 dendritic cells (cDC1s), ginsenoside Rg5 reduced their glycose storage and enhanced anaerobic glycolysis. Glycogen phosphorylase inhibitor CP-91149 almost abolished the effect of ginsenoside Rg5 on promoting efferocytosis. Conclusion: ginsenoside Rg5 can suppress the expression of SLC7A11 and inhibit its activity via physical binding. These effects collectively alleviate the negative regulations of SLC7A11 on anaerobic glycolysis, which fuels the efferocytosis of dendritic cells. Therefore, ginsenoside Rg5 has a potential adjuvant therapeutic reagent to support patients with wound-healing problems, such as diabetic foot ulcers.

Keywords

Acknowledgement

All persons who have made substantial contributions to the work reported in the manuscript (e.g., technical help, writing and editing assistance, general support), but who do not meet the criteria for authorship, are named in the Acknowledgements and have given us their written permission to be named. If we have not included an Acknowledgements, then that indicates that we have not received substantial contributions from non-authors.

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