Chen Jing-Chun, Dai Yan-Zhen, Tzeng Yew-Min, Liao Jiunn-Wang
Graduate Institute of Food Safety, National Chung Hsing University, Taichung, Taiwan.
Research Center for Animal Medicine, National Chung Hsing University, Taichung, Taiwan.
Toxicol Rep. 2021 Oct 11;8:1783-1791. doi: 10.1016/j.toxrep.2021.10.010. eCollection 2021.
Ovatodiolide is a bioactive cembrane-type diterpenoid isolated from (L.) Kuntze. It has been proven that ovatodiolide is anti-inflammatory, anti-tumorigenic, anti-melanogenic and attenuates asthma by regulating signaling pathways. The aim of this study was to evaluate the safety of ovatodiolide by conducting genotoxicity tests and 28-day oral toxicity tests in rats. Genotoxicity assays were conducted by using a bacterial reverse mutation test and mammalian chromosomal aberration test to assess whether ovatodiolide causes reverse mutations and mutagenicity with or without metabolism activation. For the mammalian erythrocyte micronucleus test, mice were administered a single dose of 0, 250, 500 or 1000 mg/kg b.w. ovatodiolide by single gavage. In the acute oral toxicity test, rats were given a single dose of ovatodiolide 1000 mg/kg b.w. by single gavage. In the 28-day oral toxicity test, groups were divided into a control, ovatodiolide 10, 25 and 50 mg/kg b.w. The results showed that there was no mutagenicity in the bacterial reverse mutation test or the mammalian chromosomal aberration test with or without S9 fraction. Ovatodiolide did not produce an increase in micronucleated reticulocytes in the micronucleus test. The results revealed that the acute oral toxicity of ovatodiolide is over 1000 mg/kg b.w. in rats. Moreover, 10, 25 and 50 mg/kg b.w. of ovatodiolide did not cause a significant effect in rats. According to the results of the genotoxicity and oral toxicity studies in rats, ovatodiolide did not produce any adverse effects, and the tested doses can serve as clinical references.
卵叶二内酯是一种从（L.）Kuntze中分离出的具有生物活性的贝壳杉烯型二萜类化合物。已证实卵叶二内酯具有抗炎、抗肿瘤、抗黑色素生成作用，并通过调节信号通路减轻哮喘。本研究的目的是通过在大鼠中进行遗传毒性试验和28天口服毒性试验来评估卵叶二内酯的安全性。遗传毒性试验采用细菌回复突变试验和哺乳动物染色体畸变试验，以评估卵叶二内酯在有无代谢活化的情况下是否会引起回复突变和致突变性。对于哺乳动物红细胞微核试验，小鼠通过单次灌胃给予0、250、500或1000mg/kg体重的卵叶二内酯单剂量。在急性口服毒性试验中，大鼠通过单次灌胃给予1000mg/kg体重的卵叶二内酯单剂量。在28天口服毒性试验中，将各组分为对照组、10、25和50mg/kg体重的卵叶二内酯组。结果表明，在有无S9组分的情况下，细菌回复突变试验或哺乳动物染色体畸变试验中均无致突变性。卵叶二内酯在微核试验中未导致微核网织红细胞增加。结果显示，卵叶二内酯对大鼠的急性口服毒性超过1000mg/kg体重。此外，10、25和50mg/kg体重的卵叶二内酯对大鼠未产生显著影响。根据大鼠遗传毒性和口服毒性研究结果，卵叶二内酯未产生任何不良反应，所测试的剂量可作为临床参考。
