British journal of pharmacology · 2026
Ginsenoside compound K up-regulates β-subunits of long-chain L-3-hydroxyacyl-CoA (HADHB) to promote fatty acid oxidation recovery and improve the balance of macrophage polarization in mice with ulcerative colitis.
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Liu Lili, Liu Mengxue, Zhang Yanqiu, Zeng Xuran, Wang Qiao, Chen Jingyu
Аннотация
BACKGROUND AND PURPOSE: Ulcerative colitis (UC) is characterized by mucosal inflammation and a range of clinical symptoms, including abdominal pain, diarrhoea and bloody stools. Evidence indicates that UC is associated with an imbalance M1/M2 polarization of macrophages. Ginsenoside compound K (GCK) has anti-inflammatory potential the mechanism of action remains unclear. Whether GCK regulates macrophage polarization via β-subunits of long-chain L-3-hydroxyacyl-CoA (HADHB)-mediated fatty acid oxidation (FAO)b was investigated.
EXPERIMENTAL APPROACH: The expression of HADHB and macrophage polarization were analysed in both UC patients and dextran sodium sulfate (DSS)-induced UC mice. The effects of GCK on macrophage polarization and FAO-related indicators were evaluated using a DSS-induced UC mouse model and LPS-stimulated RAW264.7 cells, via flow cytometry, western blot, RT-qPCR, dual-luciferase reporter assay and metabolite detection.
KEY RESULTS: In both UC patients and DSS-induced UC mice, HADHB expression in macrophages was decreased, a finding significantly correlated with the imbalance between M1 and M2 macrophage polarization. GCK activated the glucocorticoid receptor (GR/NR3C1), up-regulated HADHB expression, promoted FAO in macrophages and modulated M1/M2 polarization in RAW264.7 cells. GCK treatment up-regulated HADHB expression, restored M1/M2 macrophage polarization balance and ameliorated colonic inflammation in DSS-induced UC mice; these effects of GCK were mediated via GR activation.
CONCLUSIONS AND IMPLICATIONS: GCK regulates the M1/M2 balance of macrophages through the GR-HADHB-FAO axis, thereby alleviating UC. This study reveals for the first time a novel mechanism by which GCK regulates macrophage polarization through metabolic reprogramming, offering a new potential therapeutic target and candidate drug for the clinical treatment of UC.
EXPERIMENTAL APPROACH: The expression of HADHB and macrophage polarization were analysed in both UC patients and dextran sodium sulfate (DSS)-induced UC mice. The effects of GCK on macrophage polarization and FAO-related indicators were evaluated using a DSS-induced UC mouse model and LPS-stimulated RAW264.7 cells, via flow cytometry, western blot, RT-qPCR, dual-luciferase reporter assay and metabolite detection.
KEY RESULTS: In both UC patients and DSS-induced UC mice, HADHB expression in macrophages was decreased, a finding significantly correlated with the imbalance between M1 and M2 macrophage polarization. GCK activated the glucocorticoid receptor (GR/NR3C1), up-regulated HADHB expression, promoted FAO in macrophages and modulated M1/M2 polarization in RAW264.7 cells. GCK treatment up-regulated HADHB expression, restored M1/M2 macrophage polarization balance and ameliorated colonic inflammation in DSS-induced UC mice; these effects of GCK were mediated via GR activation.
CONCLUSIONS AND IMPLICATIONS: GCK regulates the M1/M2 balance of macrophages through the GR-HADHB-FAO axis, thereby alleviating UC. This study reveals for the first time a novel mechanism by which GCK regulates macrophage polarization through metabolic reprogramming, offering a new potential therapeutic target and candidate drug for the clinical treatment of UC.