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人参皂苷Rg1通过糖皮质激素受体相关核因子-κB途径对酒精性肝炎的抗炎作用

Anti-inflammatory function of ginsenoside Rg1 on alcoholic hepatitis through glucocorticoid receptor related nuclear factor-kappa B pathway.

作者信息

Gao Yan, Chu Shifeng, Li Jingwei, Li Jianping, Zhang Zhao, Xia Congyuan, Heng Yang, Zhang Meijin, Hu Jinfeng, Wei Guining, Li Yueting, Chen Naihong

机构信息

State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Department of Pharmacology, Institute of Materia Medica, Neuroscience Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.

Department of Pharmacology, Hunan University of Chinese Medicine, Changsha, Hunan 410208, China.

出版信息

J Ethnopharmacol. 2015 Sep 15;173:231-40. doi: 10.1016/j.jep.2015.07.020. Epub 2015 Jul 18.

Abstract

ETHNOPHARMACOLOGICAL RELEVANCE

Ginseng is the dried root of Panax ginseng C.A. Mayer. Since ancient times, ginseng has been used as one kind of treatment drug or tonic in China and even other eastern countries like Korea and Japan. Pharmacological active chemical ingredients and its extract of ginseng are a mixture of triterpenoid saponins, collectively called ginsenosides. Among them, ginsenoside Rg1 is the most pharmacological active one.

AIM OF THE STUDY

Based on prior experimental results and the understanding of alcoholic hepatitis, the major aim of this study is to investigate whether Rg1 is beneficial in a rodent model mimic alcoholic hepatic injury associated with binge drinking and explore the underlying possible mechanisms.

MATERIALS AND METHODS

C57BL/6 mice were given oral consumption of 6g/kg alcohol 1h after treated with Rg1 (10, 20 and 40mg/kg) or dexamethasone (1mg/kg) for 9 consecutive days. Biochemical analyses were performed and liver fragments were processed for microscopy, immunohistochemistry and western blot analysis.

RESULTS

According to our data, Rg1 treatment significantly reversed the high mortality rate induced by alcohol consumption and also alleviated liver impairment as evidenced by the decrease of serum parameters. Meanwhile, histological and ultrastructural analysis of alcoholic groups showed hepatocellular impairment but restored in Rg1-treated groups. Overproductive inflammatory cytokines were also suppressed by Rg1 in alcohol-intoxicated mouse livers. In addition, changes of GR related NF-κB pathway, including phospho-IκB-α, were also modulated to normal levels.

CONCLUSION

This study demonstrates that Rg1 might promote GR mediating the repression of NF-κB and inhibit the inflammatory reactions in alcoholic hepatitis.

摘要

民族药理学相关性

人参是五加科人参的干燥根。自古以来,人参在中国乃至韩国和日本等其他东方国家一直被用作一种治疗药物或滋补品。人参的药理活性化学成分及其提取物是三萜皂苷的混合物,统称为人参皂苷。其中,人参皂苷Rg1是药理活性最强的一种。

研究目的

基于先前的实验结果以及对酒精性肝炎的了解,本研究的主要目的是探究Rg1在模拟暴饮相关酒精性肝损伤的啮齿动物模型中是否有益,并探索其潜在的可能机制。

材料与方法

C57BL/6小鼠在连续9天接受Rg1(10、20和40mg/kg)或地塞米松(1mg/kg)治疗后1小时,口服6g/kg酒精。进行生化分析,并对肝脏组织切片进行显微镜检查、免疫组织化学和蛋白质印迹分析。

结果

根据我们的数据,Rg1治疗显著逆转了酒精摄入诱导的高死亡率,并减轻了肝脏损伤,血清参数的降低证明了这一点。同时,酒精组的组织学和超微结构分析显示肝细胞损伤,但在Rg1治疗组中恢复。Rg1还抑制了酒精中毒小鼠肝脏中过度产生的炎性细胞因子。此外,与GR相关的NF-κB途径的变化,包括磷酸化IκB-α,也被调节至正常水平。

结论

本研究表明,Rg1可能促进GR介导的NF-κB抑制,并抑制酒精性肝炎中的炎症反应。

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