15-Day subchronic developmental toxicity studies of ursolic acid in rats.

Ursolic acid (UA) is a pentacyclic triterpenoid and has the characteristics to serve as a potential therapeutic agent for a range of disorders. However, detailed studies of the toxicity of UA, especially developmental toxicity of UA, are non-existing. The objective of this study was to determine the potential effects of UA on fetal development, adult reproductive system, and major organs. UA was dissolved in a 0.5% hydroxypropyl methylcellulose, 0.1% Tween 80 in Milli-Q Water solution. A 100, 300 or 1000 mg/kg/day dose of UA or a control vehicle was administered orally for 15 days to adults (Han Wistar) and pregnant females (Sprague-Dawley). The administration of UA in adults did not cause deaths or resulted in abnormal (reproductive) organ or body weights at the dose up to 1000 mg/kg/day. The administration of UA resulted in no significant toxicological changes in either maternal nor fetal subjects in terms of body weight, organ weights, food consumption, gross pathology, sex organs, maternal performances, and fetal performances. Together, this study indicates that oral dosing with UA is safe for adult rats and their offspring and the no observed adverse effect level for UA is likely higher than 1000 mg/kg/day.

Repeated dose (90 days) oral toxicity study of ursolic acid in Han-Wistar rats.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.