阿魏酸降低黄独素B肝毒性并提高其抗肿瘤活性 |
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引用本文: | Jun-ming WANG,Yu-chen SHENG,Li-li JI,Zheng-tao WANG. 阿魏酸降低黄独素B肝毒性并提高其抗肿瘤活性[J]. 浙江大学学报(自然科学英文版), 2014, 0(6): 540-547 |
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作者姓名: | Jun-ming WANG Yu-chen SHENG Li-li JI Zheng-tao WANG |
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基金项目: | Project supported by the Program for New Century Excellent Talents in University (No. NCET-11-1054), the National Natural Science Foundation of China (No. 81322053), and the Program for Changjiang Scholars and Innovative Research Team in University (No. PCSIRT- IRT 1071 ), China |
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摘 要: | 研究目的:观察阿魏酸对黄独素B诱导肝毒性的抑制活性及其机理,同时探索阿魏酸对黄独素B抗肿瘤活性的增效作用。创新要点:黄独素B为中药黄药子抗肿瘤的主要药效活性成分,但同时又是其致肝毒性的主要毒性成分。本研究立足于中医药配伍减毒增效理论,试图通过试验考察配伍阿魏酸对黄独素B肝毒性/抗肿瘤活性的减毒增效作用,为黄独素B与阿魏酸联合应用于抗肿瘤提供了一定的临床前试验依据。研究方法:荷瘤小鼠(S180肉瘤)连续12天灌胃给药阿魏酸和黄独素B。通过对血清丙氨酸/天冬氨酸转氨酶活性(见图2)、肝脂质过氧化(见图3)和肝组织病理分析(见图4)考察阿魏酸对黄独素B肝毒性的抑制作用;通过对铜锌.超氧化物歧化酶和过氧化氢酶的活性(见图5a、5b)和基因表达分析(见图5c)探讨阿魏酸抑制黄独素B肝毒性的机理;通过对瘤重、抑瘤率的统计分析阿魏酸增加的黄独素B抗肿瘤活性。重要结论:阿魏酸可以通过改善黄独素B诱导的氧应激损伤从而抑制其肝毒性,同时还可以协同增加黄独素B的抗肿瘤活性。
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关 键 词: | 阿魏酸 黄独素B 肝毒性 氧应激损伤 抗肿瘤 |
Ferulic acid prevents liver injury and increases the anti-tumor effect of diosbulbin B in vivo |
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Abstract: | The present study is designed to investigate the protection by ferulic acid against the hepatotoxicity induced by diosbulbin B and its possible mechanism, and further observe whether ferulic acid augments diosbulbin B- induced anti-tumor activity. The results show that ferulic acid decreases diosbulbin B-increased serum alanine transaminase/aspartate transaminase (ALT/AST) levels. Ferulic acid also decreases lipid peroxide (LPO) levels which are elevated in diosbulbin B-treated mice. Histological evaluation of the liver demonstrates hydropic degeneration in diosbulbin B-treated mice, while ferulic acid reverses this injury. Moreover, the activities of copper- and zinc-containing superoxide dismutase (CuZn-SOD) and catalase (CAT) are decreased in the livers of diosbulbin B-treated mice, while ferulic acid reverses these decreases. Further results demonstrate that the mRNA expressions of CuZn-SOD and CAT in diosbulbin B-treated mouse liver are significantly decreased, while ferulic acid prevents this decrease. In addition, ferulic acid also augments diosbulbin B-induced tumor growth inhibition compared with diosbulbin B alone. Taken together, the present study shows that ferulic acid prevents diosbulbin B-induced liver injury via ameliorating diosbulbin B-induced liver oxidative stress injury and augments diosbulbin B-induced anti-tumor activity. |
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Keywords: | Ferulic acid Diosbulbin B Hepatotoxicity Oxidative stress injury Anti-tumor activity |
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