阿魏酸降低黄独素B肝毒性并提高其抗肿瘤活性

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。

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

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.