Department of Physiology and Pharmacology "V. Erspamer", Sapienza University of Rome, P.le Aldo Moro 5, 00185 Rome, Italy.
Department of Biochemical Science "A. Rossi Fanelli", Sapienza University of Rome, P.le Aldo Moro 5, 00185 Rome, Italy.
Food Chem Toxicol. 2018 Jan;111:393-404. doi: 10.1016/j.fct.2017.11.018. Epub 2017 Nov 14.
In the present study, the ability of the natural sesquiterpene β-caryophyllene (CRY) and its metabolite β-caryophyllene oxide (CRYO) to inhibit the genotoxicity of a condensate of cigarette smoke (CSC) was evaluated both in bacterial and mammalian cells. Also, the inhibition of the CSC-mediated STAT3 phosphorylation and intracellular oxidative stress was evaluated as potential chemopreventive mechanism. Under our experimental conditions, both the sesquiterpenes exhibited antimutagenic properties, being CRY the most potent compound. The antimutagenicity was highlighted in all experimental protocols, being particularly strong in the co- and post-treatments. The test substances also reduced the micronuclei frequency induced by CSC, with a major effectiveness of CRY. CRY was also able to reduce the CSC-mediated increase of the Y705- pSTAT3 levels, in spite of a lacking effect of CRYO. Furthermore, the sesquiterpenes CRY and CRYO displayed a moderate antioxidant activity, with a 25 % and 40 % inhibition of the ROS-levels increased by CSC, respectively. On the basis of these results, CRY seems to be a multi-target chemopreventive agent, although the genoprotective and antioxidant effects of CRYO suggest that both compounds deserve to be deeply investigated for a possible application in the prevention and treatment of different smoke-related ailments.
在本研究中，评估了天然倍半萜 β-石竹烯（CRY）及其代谢物 β-石竹烯氧化物（CRYO）抑制香烟烟雾冷凝物（CSC）遗传毒性的能力。此外，还评估了抑制 CSC 介导的 STAT3 磷酸化和细胞内氧化应激作为潜在的化学预防机制的能力。在我们的实验条件下，两种倍半萜类化合物均表现出抗突变特性，CRY 是最有效的化合物。在所有实验方案中都突出了抗突变性，特别是在共同和后续处理中更为强烈。测试物质还降低了 CSC 诱导的微核频率，CRY 的效果更为显著。CRY 还能够降低 CSC 介导的 Y705-pSTAT3 水平升高，尽管 CRYO 没有这种作用。此外，倍半萜类化合物 CRY 和 CRYO 显示出适度的抗氧化活性，分别抑制 CSC 增加的 ROS 水平的 25%和 40%。基于这些结果，CRY 似乎是一种多靶点化学预防剂，尽管 CRYO 的基因保护和抗氧化作用表明这两种化合物都值得深入研究，以可能应用于预防和治疗与吸烟有关的各种疾病。
