Ginsenoside Rh1 potentiates dexamethasone’s anti-inflammatory effects for chronic inflammatory disease by reversing dexamethasone-induced resistance

作者：Jun Li, Juan Du, Dong Liu, Binbin Cheng, Fanfu Fang, Li Weng, Chen Wang, Changquan Ling · 发表于：Arthritis Research & Therapy · 年份：2014 · DOI：10.1186/ar4556 · 被引用次数：42 · 研究领域：Ginseng Biological Effects and Applications、Natural product bioactivities and synthesis、Sphingolipid Metabolism and Signaling

INTRODUCTION: Acquired resistance to glucocorticoids constitutes a major clinical challenge, often overlooked in the search for compounds to improve the effect of classic steroids. We sought to unravel how a plant-original compound, ginsenoside Rh1, potentiates dexmethasone (DEX)'s potential anti-inflammation properties. METHODS: Ginsenoside Rh1 combined with DEX was applied in a short-term and long-term treatment protocol for inflammation. Its potential mechanism on anti-inflammation was explored. In addition, the effect of Rh1 on the side-effect induced by DEX was studied. Furthermore, the in vivo anti-inflammatory effects of Rh1 combined with DEX were evaluated in a collagen-induced arthritis (CIA) mice model. RESULTS: Ginsenoside Rh1 potentiates DEX's anti-inflammatory effects even after prolonged DEX treatment. Rh1 could improve the glucocorticoid receptor (GR)'s transrepression on nuclear factor kappa B (NF-κB) and transactivation on dual specificity protein phosphatase 1 (DUSP1), which is responsible for DEX's anti-inflammatory effects. Parallel Western blot assay and radioligand binding analysis revealed that Rh1 could increase the expression and binding of GR. This is in sharp contrast to DEX alone, showing a direct link among prolonged treatment, decreasing GR and the abolishment of anti-inflammation. Interestingly, Rh1 does not enhance the transactivation of glucocorticoid-responsive elements (GRE) driven genes - gluconeogenic enzyme glucose-6-phosphatase (G6P) and...