Ferulic acid prevents liver injury and increases the anti-tumor effect of diosbulbin B in vivo  

阿魏酸降低黄独素B肝毒性并提高其抗肿瘤活性(英文)

作　　者：Jun-ming WANG Yu-chen SHENG Li-li JI Zheng-tao WANG 

机构地区：[1]MOE Key Laboratory for Standardization of Chinese Medicines and Shanghai Key Laboratory of Complex Prescription,Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine [2]School of Pharmacy, Henan University of Traditional Chinese Medicine [3]Center for Drug Safety Evaluation and Research, Shanghai University of Traditional Chinese Medicine

出　　处：《Journal of Zhejiang University-Science B(Biomedicine & Biotechnology)》2014年第6期540-547,共8页浙江大学学报（英文版）B辑（生物医学与生物技术）

基　　金：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);the Program for Changjiang Scholars and Innovative Research Team in University(No.PCSIRTIRT1071),China

摘　　要：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.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。

关 键 词：Ferulic acid Diosbulbin B HEPATOTOXICITY Oxidative stress injury Anti-tumor activity 

分 类 号：R96[医药卫生—药理学]