Department of Physiology and Pharmacology, "Sapienza" University , P.le Aldo Moro 5, 00185 Rome, Italy.
J Nat Prod. 2012 Jul 27;75(7):1294-8. doi: 10.1021/np3001893. Epub 2012 Jun 14.
The ability of the sodium salt of 3,4-secoisopimar-4(18),7,15-trien-3-oic acid (1), a diterpenoid obtained from Salvia cinnabarina, to inhibit the genotoxic effect of ethyl methanesulfonate (a clastogenic agent) and colcemid (an aneugenic agent), was studied using a micronucleus assay on cultured human lymphocytes. Cells were treated with 1 before (pretreatment), during (co-treatment), and after (post-treatment) treatment with the mutagens, in order to investigate the type of antimutagenic activity (desmutagenic or bioantimutagenic) manifested. In the range of concentrations tested (0.3-330 μM) 1 reduced significantly the frequency of micronuclei induced by ethyl methanesulfonate, in both pre- and co-treatment protocols (up to 74% and 70% of reduction, respectively), showing an anticlastogenic activity. Conversely, 1 did not inhibit the effect of colcemid in all treatments. The nuclear division index value of lymphocytes was not affected by treatment with 1, thus demonstrating that the anticlastogenic effect of 1 was not due to a cytotoxic effect. On the basis of the results obtained, it can be hypothesized that 1 exerts its anticlastogenic activity against ethyl methanesulfonate by a desmutagenic mechanism, possibly by chemical inactivation of the mutagen.
从丹参中提取的一种二萜 3,4-裂环异海松-4(18),7,15-三烯-3-酸的钠盐（1），能够抑制乙基甲磺酸（一种断裂剂）和秋水仙素（一种致畸剂）的遗传毒性作用。采用培养的人淋巴细胞微核试验，研究了这种二萜的这种作用。在处理诱变剂之前（预处理）、同时（共同处理）和之后（后处理）用 1 处理细胞，以研究所表现出的抗突变类型（去突变或生物抗突变）。在所测试的浓度范围内（0.3-330 μM），1 显著降低了乙基甲磺酸诱导的微核频率，在预处理和共同处理方案中分别降低了 74%和 70%，表现出抗断裂作用。相反，1 并没有抑制秋水仙素的作用，在所有处理中均如此。用 1 处理不会影响淋巴细胞的核分裂指数值，因此表明 1 的抗断裂作用不是由于细胞毒性作用。根据所获得的结果，可以假设 1 通过去突变机制发挥其对乙基甲磺酸的抗断裂作用，可能是通过化学失活使诱变剂失活。
