原人参二醇型皂苷活性代谢物Compound K药理活性的研究进展

人参皂苷Compound K〔20-O-β-D-葡萄糖基-20(S)-原人参二醇,CK〕是原人参二醇型人参皂苷在人体内主要吸收形式和药效实体。近年来,CK的药理活性研究又有了新进展:①CK可通过活化胱天蛋白酶8直接或通过线粒体途径间接地激活胱天蛋白酶3,诱导肿瘤细胞凋亡;下调基质金属蛋白酶9基因的表达,抑制肿瘤细胞的转移;②可通过下调多种炎症因子如白细胞介素-4(IL-4),IL-6,肿瘤坏死因子α等及环氧合酶2与一氧化氮合酶的表达而发挥抗炎、抗过敏和神经保护作用;③可阻断ATP敏感性K+离子通道,促进胰岛素分泌,增强组织胰岛素敏感性,抑制糖异生,促进糖酵解,对胰岛素依赖性糖尿病表现出良好的疗效;④可上调核苷切除修复相关蛋白基因的表达,减少紫外线引起的DNA损伤,防止皮肤老化等。本文重点对近几年有关CK的药理活性及其作用机制研究新进展进行综述。

Progress in pharmacological actions of ginsenoside compound K,an active metabolite of protopanaxadiol type saponins

Ginsenoside compound K (CK), 20-O-β-(D-glucopyranosyl)-20(S)- protopanaxadiol, is the major form of protopanaxadiol type saponins absorbed by bodies after oral administration, and the real component that mediates the pharmacologic actions. Recently, new progress have been made on study on pharmacological actions: ① CK can activate caspase 8, which plays a key role in CK -stimulated apoptosis via activation of caspase 3 directly or indirectly through mitochondria pathway and regulate the metastasis and invasiveness of tumor cells by down- regulating metalloproteinase 9 gene expression; ② CK can reduce expression levels of NO synthase and cyclooxygenase-2, and inhibit secretion of some pro-inflammatory cytokines like interleukin 4(IL- 4), IL-6 or tumor necrosis factor-α, which are responsible for its anti- inflammatory, anti-allergic, and neuro- protective activities; ③ CK can enhance the insulin secretion by blocking the ATP sensitive K⁺ channel, improve insulin sensitivity, shift glucose metabolisim from hepatic glucose production to hepatic glucose utilization in liver, which suggest CK could be a therapeutic reagent in type 2 diabetic patients; ④ CK can prevent the ultraviolet radiation induced skin damage through up-regulating nucleotide excision repair gene expression.