Safety evaluation of Eucommia ulmoides extract.

Eucommia ulmoides Oliver is native to China and frequently used in traditional Chinese medicine formulations. However, studies show that Eucommia ulmoides extract (EUE) are potentially genotoxic and nephrotoxic. To evaluate its safety, the Ames test, bone marrow micronucleus assay and chromosomal aberration assay, along with acute (24 h) and sub-chronic (13 weeks) toxicity were conducted. EUE was non-genotoxic within the dose ranges of 0.0352-22 mg/plate (raw plant equivalent as below), 22-88 g/kg body weight and 2-20 mg/mL. The maximum tolerated dose of EUE was not less than 168 g/kg, which is 1260 times that of clinical doses in human adults. Long-term (13 weeks) administration led to dose-dependent increase in nephrotoxicity-related indices, and pathological changes in renal tissues. These changes were alleviated 5 weeks after ceasing the low dosage of 11.2 g/kg but persisted at the high dosage of 56 g/kg. Conclusively, EUE is non-genotoxic, and do not result in acute toxicity. However, long-term and high-dose administration can lead to partly reversible nephrotoxicity.