Geerlofs Lotte, He Zhiyong, Xiao Sa, Xiao Zhi-Cheng
Department of Anatomy and Developmental Biology, Monash University, Melbourne, 3168, Australia.
iRiccorgpharm Health Pty Ltd, Melbourne, 3168, Australia.
Toxicol Rep. 2020 May 8;7:610-623. doi: 10.1016/j.toxrep.2020.04.005. eCollection 2020.
Ursolic acid (UA) has been used in alternative medicine for decades, and there has been a great interest in its medicinal properties. Despite this increased interest, a detailed long-term toxicity study has not been performed. The objective of this study was to determine the long-term toxic effect of UA on clinical chemistry, haematology, coagulation, pathology/morphology, behaviour and motor skills in rats.
A solution was made by dissolving UA in a mixture of 0.1% Tween 80 and 0.5% hydroxypropyl methylcellulose in Milli-Q Water. The control group received the vehicle, and the test groups received a dose up to 1000 mg/kg/day via oral gavage. The solution was administered to both male and female (Han-Wistar) rats for 90 consecutive days.
UA did not cause any deaths, abnormal body weights or abnormal pathology at all test doses. In addition to that, no toxicological changes were observed in behaviour, neurotoxicity, coagulation, haematology or clinical chemistry that are related to the administration of UA.
This study indicates that oral dosing of UA for 90 consecutive days does not lead to toxic effects at any of the doses. Therefore, the NOAEL for UA is likely to be higher than 1000 mg/kg/day.
熊果酸(UA)已在替代医学中使用了数十年,人们对其药用特性一直非常感兴趣。尽管关注度有所提高,但尚未进行详细的长期毒性研究。本研究的目的是确定UA对大鼠临床化学、血液学、凝血、病理学/形态学、行为和运动技能的长期毒性作用。
将UA溶解于含有0.1%吐温80和0.5%羟丙基甲基纤维素的超纯水中制成溶液。对照组给予赋形剂,试验组通过灌胃给予高达1000mg/kg/天的剂量。该溶液连续90天给予雄性和雌性(Han-Wistar)大鼠。
在所有试验剂量下,UA均未导致任何死亡、体重异常或病理异常。此外,未观察到与UA给药相关的行为、神经毒性、凝血、血液学或临床化学方面的毒理学变化。
本研究表明,连续90天口服UA在任何剂量下均不会导致毒性作用。因此,UA的无观察到有害作用水平可能高于1000mg/kg/天。