%0 Journal Article
%T Suppression of SLC7A11-Mediated Inhibition of Dendritic Cell Efferocytosis Underlies the Wound-Healing Effects of Ginsenoside Rg5
%A Peter Nilsson
%A Eva Johansson
%A Lars Andersson
%J Specialty Journal of Pharmacognosy, Phytochemistry, and Biotechnology
%@ 3062-441X
%D 2025
%V 5
%N 2
%R 10.51847/RY2VDp6lBq
%P 161-176
%X Ginsenoside Rg5 represents a scarce ginsenoside recognized for its ability to lower blood glucose levels in diabetic mice. The present investigation aimed to examine the influence of ginsenoside Rg5 on cutaneous wound repair in Leprdb/db mutant (db/db) mice on a C57BL/KsJ genetic background and to clarify the associated molecular pathways. Experiments were conducted using seven-week-old male C57BL/6J mice, SLC7A11-knockout (KO) animals, their corresponding littermate wild-type (WT) controls, and db/db mice in both in vivo and ex vivo settings. Oral delivery of ginsenoside Rg5 by gavage to db/db mice substantially lowered the quantity of apoptotic cells within the wound bed and promoted faster skin wound closure. Exposure to 50 μM ginsenoside Rg5 roughly doubled the efferocytic capacity of bone marrow-derived dendritic cells (BMDCs) isolated from db/db mice. The compound also decreased NF-κB p65 and SLC7A11 levels in the injured skin of db/db mice in a concentration-dependent fashion. Ginsenoside Rg5 bound directly to SLC7A11, thereby inhibiting cystine import and glutamate export in BMDCs from both db/db and SLC7A11-WT mice, whereas no such inhibition occurred in cells from SLC7A11-KO mice. Within BMDCs and conventional type 1 dendritic cells (cDC1s), ginsenoside Rg5 decreased intracellular glycogen reserves while stimulating anaerobic glycolysis. Pretreatment with the glycogen phosphorylase inhibitor CP-91149 largely prevented ginsenoside Rg5 from enhancing efferocytosis. Ginsenoside Rg5 downregulates SLC7A11 expression and directly interferes with its transporter activity through physical interaction. Together, these actions counteract the suppressive influence of SLC7A11 on anaerobic glycolysis, a metabolic pathway that powers dendritic cell efferocytosis. Thus, ginsenoside Rg5 emerges as a potential supportive therapeutic option for managing impaired wound repair in conditions such as diabetic foot ulcers.
%U https://galaxypub.co/article/suppression-of-slc7a11-mediated-inhibition-of-dendritic-cell-efferocytosis-underlies-the-wound-heali-houpni4ia2sc9zq