Abstract：
Ginsenoside compound K (GCK) possesses a glucocorticoid (GC)-like structure and functions as an agonist of the glucocorticoid receptor (GR), thereby exerting anti-inflammatory effects through GR activation. However, it remains unclear whether GCK leads to hyperglycemia, which is a known adverse reaction associated with classical GCs. In this study, we have successfully demonstrated that GCK exerts its anti-inflammatory effects in a rat model of adjuvant arthritis without impacting gluconeogenesis and pentose phosphate pathways, thus avoiding any glucose metabolism disorders. By employing the GR mutant plasmid, we have identified the binding site between GCK and GR as GRM560T, which differs from the binding site shared by dexamethasone (DEX) and GR. Notably, compared to DEX, GCK induces distinct levels of phosphorylation at S211 on GR upon binding to activate steroid receptor coactivator 1 (SRC1)-a co-factor responsible for mediating anti-inflammatory effects-while not engaging peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α)-an associated coactivator involved in gluconeogenesis.
摘要：
人参皂苷化合物K(GCK)具有糖皮质激素(GC)样结构,作为糖皮质激素受体(GR)的激动剂,从而通过GR激活发挥抗炎作用。然而,目前尚不清楚GCK是否会导致高血糖，这是与经典GCs相关的已知不良反应。在这项研究中,我们已成功证明GCK在佐剂性关节炎大鼠模型中发挥其抗炎作用，而不影响糖异生和磷酸戊糖途径。从而避免任何葡萄糖代谢紊乱。通过使用GR突变质粒，我们已经确定GCK和GR之间的结合位点为GRM560T，与地塞米松（DEX）和GR共有的结合位点不同。值得注意的是,与DEX相比，GCK在与激活类固醇受体共激活因子1（SRC1）-负责介导抗炎作用的辅助因子-同时不参与过氧化物酶体增殖物激活受体γ共激活因子-1α（PGC-1α）-参与糖异生的相关共激活因子时，在GR上S211处诱导不同水平的磷酸化。
