迷迭香及其成分鼠尾草酸和熊果酸对皮肤肿瘤发生的抑制作用。

Inhibition of skin tumorigenesis by rosemary and its constituents carnosol and ursolic acid.

作者信息

Huang M T, Ho C T, Wang Z Y, Ferraro T, Lou Y R, Stauber K, Ma W, Georgiadis C, Laskin J D, Conney A H

机构信息

Department of Chemical Biology and Pharmacognosy, College of Pharmacy, Rutgers, State University of New Jersey, Piscataway 08855-0789.

出版信息

Cancer Res. 1994 Feb 1;54(3):701-8.

PMID:8306331

Abstract

A methanol extract of the leaves of the plant Rosmarinus officinalis L. (rosemary) was evaluated for its effects on tumor initiation and promotion in mouse skin. Application of rosemary to mouse skin inhibited the covalent binding of benzo(a)pyrene [B(a)P] to epidermal DNA and inhibited tumor initiation by B(a)P and 7,12-dimethylbenz[a]anthracene (DMBA). Topical application of 20 nmol B(a)P to the backs of mice once weekly for 10 weeks, followed 1 week later by promotion with 15 nmol 12-O-tetradecanoylphorbol-13-acetate (TPA) twice weekly for 21 weeks, resulted in the formation of 7.1 tumors per mouse. In a parallel group of animals that were treated topically with 1.2 or 3.6 mg of rosemary 5 min prior to each application of B(a)P, the number of tumors per mouse was decreased by 54 or 64%, respectively. Application of rosemary to mouse skin also inhibited TPA-induced ornithine decarboxylase activity, TPA-induced inflammation, arachidonic acid-induced inflammation, TPA-induced hyperplasia, and TPA-induced tumor promotion. Mice initiated with 200 nmol DMBA and promoted with 5 nmol TPA twice weekly for 19 weeks developed an average of 17.2 skin tumors per mouse. Treatment of the DMBA-initiated mice with 0.4, 1.2, or 3.6 mg of rosemary together with 5 nmol TPA twice weekly for 19 weeks inhibited the number of TPA-induced skin tumors per mouse by 40, 68, or 99%, respectively. Topical application of carnosol or ursolic acid isolated from rosemary inhibited TPA-induced ear inflammation, ornithine decarboxylase activity, and tumor promotion. Topical application of 1, 3, or 10 mumol carnosol together with 5 nmol TPA twice weekly for 20 weeks to the backs of mice previously initiated with DMBA inhibited the number of skin tumors per mouse by 38, 63, or 78%, respectively. Topical application of 0.1, 0.3, 1, or 2 mumol ursolic acid together with 5 nmol TPA twice weekly for 20 weeks to DMBA-initiated mice inhibited the number of tumors per mouse by 45-61%.

摘要

对迷迭香叶的甲醇提取物进行了评估，以研究其对小鼠皮肤肿瘤起始和促进作用的影响。将迷迭香涂抹于小鼠皮肤可抑制苯并(a)芘[B(a)P]与表皮DNA的共价结合，并抑制B(a)P和7,12-二甲基苯并[a]蒽(DMBA)引发的肿瘤。每周一次给小鼠背部局部涂抹20 nmol B(a)P，持续10周，1周后每周两次用15 nmol 12-O-十四烷酰佛波醇-13-乙酸酯(TPA)促进21周，每只小鼠形成7.1个肿瘤。在另一组平行动物中，在每次涂抹B(a)P前5分钟局部涂抹1.2或3.6 mg迷迭香，每只小鼠的肿瘤数量分别减少了54%或64%。将迷迭香涂抹于小鼠皮肤还可抑制TPA诱导的鸟氨酸脱羧酶活性、TPA诱导的炎症、花生四烯酸诱导的炎症、TPA诱导的增生以及TPA诱导的肿瘤促进作用。用200 nmol DMBA启动并每周两次用5 nmol TPA促进19周的小鼠，每只小鼠平均发生17.2个皮肤肿瘤。用0.4、1.2或3.6 mg迷迭香与5 nmol TPA每周两次共同处理DMBA启动的小鼠19周，每只小鼠TPA诱导的皮肤肿瘤数量分别减少40%、68%或99%。局部涂抹从迷迭香中分离出的鼠尾草酸或熊果酸可抑制TPA诱导的耳部炎症、鸟氨酸脱羧酶活性以及肿瘤促进作用。每周两次给先前用DMBA启动的小鼠背部局部涂抹1、3或10 μmol鼠尾草酸与5 nmol TPA，持续20周，每只小鼠的皮肤肿瘤数量分别减少38%、63%或78%。每周两次给DMBA启动的小鼠局部涂抹0.1、0.3、1或2 μmol熊果酸与5 nmol TPA，持续20周，每只小鼠的肿瘤数量减少45%-61%。