Evaluation of anti-apoptotic, anti-injury and anti- hepatitis B virus effects of isochlorogenic acid C in vitro
Evaluation of anti-apoptotic, anti-injury and anti- hepatitis B virus effects of isochlorogenic acid C in vitro
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DOI：
10.5897/jmpr11.1766
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发表时间：
2012-04
影响因子：
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通讯作者：
Shao-Qing Hu;Yi-Hang Wu;Bing-Jie Hao;Jingqiu Lou;Hua-jun Hu;Yong-yong Zhang;Yu Zhao
中科院分区：
文献类型：
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作者：
Shao-Qing Hu;Yi-Hang Wu;Bing-Jie Hao;Jingqiu Lou;Hua-jun Hu;Yong-yong Zhang;Yu Zhao
为了研究来自臭阿拉塔的异绿原酸C的抗肝炎作用，使用d-半乳糖胺（d-GalN）诱导的人肝细胞系HL-7702细胞凋亡/损伤模型来评价测试化合物的抗凋亡和抗损伤性质。DNA梯状条带分析和caspase-3激活显示肝细胞凋亡改变。通过细胞活力评估肝细胞损伤。同时，通过HBV转染的HepG2.2.15细胞中的HBsAg、HBeAg、HBV DNA、HBV共价闭合环状DNA（HBV cccDNA）和血红素加氧酶-1（HO-1）表达来评价测试化合物的抗B肝炎病毒（抗HBV）作用。结果显示，浓度为10至100 µg/ml的供试化合物显著降低了d-GalN激发的肝细胞的半胱天冬酶-3和转化生长因子β1（TGFβ1）水平。此外，受试化合物显著改善了d-GalN损伤的肝细胞的细胞活力，并在100 μg/ml的浓度下产生了47.28%的最大保护率。此外，测试化合物显著抑制HBsAg和HBeAg的产生。对HBsAg和HBeAg表达的最大抑制率分别为86.93%和59.79%。此外，测试化合物显著诱导HepG2.2.15细胞的HO-1表达。本研究证实异绿原酸C具有有效的保肝和抗HBV作用。受试化合物的抗凋亡和抗损伤作用可通过其抗氧化特性和干扰caspase-3和TGF-β1表达来实现。受试化合物的抗HBV作用靶点可能主要在HBV复制过程的下游环节，可能与阻断翻译步骤有关。此外，HO-1诱导可能有助于供试化合物的抗B型肝炎作用。关键词：臭灵丹阿拉塔，异绿原酸C，d-半乳糖胺，抗B型肝炎，共价闭合环状DNA，血红素加氧酶-1。
To study anti-hepatitis effect of isochlorogenic acid C from Laggera alata, anti-apoptotic and anti-injury properties of test compound were evaluated using the d-galactosamine (d-GalN)-induced apoptosis/injury model in human hepatocyte line HL-7702 cells. Hepatocyte apoptotic changes were demonstrated by DNA ladder analysis and caspase-3 activation. Hepatocyte injury was assessed by cell viability. Meanwhile, anti-hepatitis B virus (anti-HBV) effect of test compound was evaluated by the HBsAg, HBeAg, HBV DNA, HBV covalently closed circular DNA (HBV cccDNA) and heme oxygenase-1 (HO-1) expressions in HBV-transfected HepG2.2.15 cells. The results showed that test compound at concentrations of 10 to 100 µg/ml significantly reduced the caspase-3 and transformed growth factor β1 (TGFβ1) levels of the d-GalN-challenged hepatocytes. Also, test compound improved markedly cell viability of the d-GalN-injured hepatocytes and produced a maximum protection rate of 47.28% at a concentration of 100 μg/ml. Furthermore, test compound significantly inhibited productions of HBsAg and HBeAg. Its maximum inhibitory rates on the HBsAg and HBeAg expressions were 86.93 and 59.79%, respectively. In addition, test compound significantly induced the HO-1 expression of HepG2.2.15 cells. This study verifies that isochlorogenic acid C possesses potent hepatoprotective and anti-HBV effects. The anti-apoptotic and anti-injury effects of test compound could be achieved by its anti-oxidative properties and interfering the caspase-3 and TGF-β1 expressions. The anti-HBV target of test compound may mainly be at the downstream links of HBV replication process and is probably associated with blocking translation step. Furthermore, HO-1 induction may contribute to anti-hepatitis B effect of test compound. Key words: Laggera alata, isochlorogenic acid C, d-Galactosamine, anti-hepatitis B, covalently closed circular DNA, heme oxygenase-1.