The Publication:

Safety of natural anthraquinone emodin: an assessment in mice

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Publication Summary:

Literature has shown that emodin, a natural anthraquinone, may be used in the treatment of various diseases including cancer. However, its clinical development is hindered by uncertainties about its potential toxicity. We aimed to examine if emodin causes any toxicity in mice at doses that have been shown to be effectively in treating cancer (toxicity study) and to assess the time course of emodin clearance when it is administered intraperitoneally or orally (pharmacokinetic study). We first performed a 12-week subchronic toxicity study using 3 different doses of emodin (~20 mg/kg, 40 mg/kg, and 80 mg/kg body weight). In this study, emodin was infused into the diet. Body weight and composition were assessed after the 12-week period. Tissues were harvested and assessed for gross pathological changes and blood was collected for a complete blood count and evaluation of liver and kidney functions (alanine transaminase and aspartate transaminase activities and creatinine content). For the pharmacokinetic study, emodin was given to mice intraperitoneally or orally at 20 mg/kg or 40 mg/kg doses and circulating levels of emodin were determined at 1, 4 and 12 h following administration. We found that 12 weeks of low (20 mg/kg), medium (40 mg/kg), or high (80 mg/kg) dose of emodin feeding did not cause pathophysiological perturbations in major organs. We showed that glucuronidated emodin peaks at 1 h for either intraperitoneally or orally administered emodin and is eliminated by 12 h. In summary, this study demonstrated that emodin is safe for use in mice when given at 20, 40, and 80 mg/kg doses, which are equivalent to the doses of 1.6, 3.3, and 6.5 mg/kg in humans, respectively, once a days for as long as 12 weeks.