Sub-chronic safety evaluation of the ethanol extract of Aralia elata leaves in Beagle dogs.

Regul Toxicol Pharmacol. 2016 Aug;79:1-11. doi: 10.1016/j.yrtph.2016.05.005. Epub 2016 May 6. Li F1, He X2, Niu W3, Feng Y3, Bian J3, Kuang H4, Xiao H5. Author information 1 Department of Basic Medicine, College of Pharmacy, Heilongjiang University of Chinese Medicine, Harbin 150040, China; Research Center for Pharmacology and Toxicology, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100193, China. 2 Research Center for Pharmacology and Toxicology, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100193, China. 3 Department of Basic Medicine, College of Pharmacy, Heilongjiang University of Chinese Medicine, Harbin 150040, China. 4 Department of Basic Medicine, College of Pharmacy, Heilongjiang University of Chinese Medicine, Harbin 150040, China. Electronic address: hxkuang@hotmail.com. 5 Department of Basic Medicine, College of Pharmacy, Heilongjiang University of Chinese Medicine, Harbin 150040, China. Electronic address: hrbxiaohongbin@126.com. Abstract Aralia elata Seem. (A. elata) is a traditional Chinese medicine to treat some diseases. This investigation aims to evaluate the pharmaceutical safety of the ethanol extract of A. elata leaves, namely ethanol leaves extract (ELE), in Beagle dogs. In sub-chronic oral toxicity study, dogs were treated with the ELE at doses of 50, 100 and 200 mg/kg for 12 weeks and followed by 4 weeks recovery period. During experimental period, clinical signs, mortality, body temperature, food consumption and body weight were recorded. Analysis of electrocardiogram, urinalysis, ophthalmoscopy, hematology, serum biochemistry, organ weights and histopathology were performed. The results showed that both food consumption and body weight significantly decreased in high-dose group. Treatment-related side effects and mortality were observed in high-dose female dogs. Some parameters showed significant alterations in electrocardiogram, urinalysis, serum biochemistry and relative organ weights. These alterations were not related to dose or consistent across gender, which were ascribed to incidental and biological variability. The findings in this study indicated that the no-observed adverse effect level (NOAEL) of the ELE was 100 mg/kg in dogs and provided a vital reference for selecting a safe application dosage for human consumption. KEYWORDS: Aralia elata Seem.; Beagle dogs; Sub-chronic toxicity PMID: 27156779 DOI: 10.1016/j.yrtph.2016.05.005