Therapeutic basis of glycyrrhizin on chronic hepatitis B
Therapeutic basis of glycyrrhizin on chronic hepatitis B
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DOI：
10.1016/0166-3542(96)00942-4
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发表时间：
1996-05-01
影响因子：
7.6
通讯作者：
Shiraki, K
中科院分区：
文献类型：
--
作者：
Sato, H;Goto, W;Shiraki, K
甘草酸是一种草药（甘草）的主要成分，在日本已被静脉注射用于治疗慢性乙型肝炎，并可改善肝功能，偶尔可使肝炎完全康复。该物质在体外修饰细胞内转运并抑制乙型肝炎病毒（HBV）表面抗原（HBsAg）的唾液化。本研究旨在阐明其有效性的药理学基础。测定了甘草酸、甘草酸3- o -单脲醛酸和甘草酸的结构-生物活性关系，发现甘草酸的活性最高。在豚鼠静脉注射甘草酸后，对三种物质与肝脏的结合量进行了评估。肝脏中甘草酸和甘草酸3- o -单脲酸浓度为31.8 ~ 1.3 μ g/g，甘草酸未检出。当甘草酸在PLC/PRF/5细胞培养的细胞部分达到这些浓度时，它抑制HBsAg的分泌。这些结果表明，甘草酸可能与肝细胞结合，在一定浓度下，甘草酸可以改变肝细胞上hbv相关抗原的表达，抑制HBsAg的唾液化。
Glycyrrhizin, a major component of a herb (licorice), has been intravenously used for the treatment of chronic hepatitis B in Japan and improves liver function with occasional complete recovery from hepatitis. This substance modifies the intracellular transport and suppresses sialylation of hepatitis B virus (HBV) surface antigen (HBsAg) in vitro. This study was designed to clarify the pharmacological basis for its effectiveness. The structure-bioactivity relationship of glycyrrhizin, glycyrrhetic acid 3-O-monoglucuronide and glycyrrhetic acid was determined, and glycyrrhetic acid was found to be the most active of them. The amounts of three substances bound to the liver were evaluated in guinea pigs after intravenous administration of glycyrrhizin. Glycyrrhizin and glycyrrhetic acid 3-O-monoglucuronide were detected at concentrations of 31.8-1.3 mu g/g of liver, but glycyrrhetic acid was not detected. When glycyrrhizin attained these concentrations in the cellular fraction of the PLC/PRF/5 cell culture, it suppressed the secretion of HBsAg as reported previously. These results indicated that glycyrrhizin administered intravenously might bind to hepatocytes at the concentration at which glycyrrhizin could modify the expression of HBV-related antigens on the hepatocytes and suppress sialylation of HBsAg.