title: In Vivo and In Vitro Toxicity Evaluation of Polyprenols Extracted from Ginkgo biloba L. Leaves.
abstract: Polyprenols of Ginkgo biloba L. leaves (GBP) are a new type of lipid with 14-24 isoprenyl units, which in humans have strong bioactivity like the dolichols. A large amount of work showed that GBP had good antibacterial activity and powerful protective effects against acute hepatic injury induced by carbon tetrachloride and alcohol, as well as antitumor activity, but the safety of GBP was not considered. The current study was designed to evaluate the toxicity of these polyprenols. Acute toxicity in mice was observed for 14 days after GBP oral dosing with 5, 7.5, 10, 15 and 21.5 g/kg body weight (b. wt.) Further, an Ames toxicity assessment was carried out by plate incorporation assay on spontaneous revertant colonies of TA97, TA98, TA100 and TA102, with GBP doses designed as 8, 40, 200, 1000 and 5000 μg/dish, and subchronic toxicity was evaluated in rats for 91 days at GBP doses of 500, 1000 and 2000 mg/kg b. wt./day. The weight, food intake, hematological and biochemical indexes, the ratio of viscera/body weight, and histopathological examinations of tissue slices of organs were all investigated. The results showed that no animal behavior and appearance changes and mortality were seen during the observation period with 21.5 g/kg GBP dose in the acute toxicity test. Also, no mutagenicity effects were produced by GBP (mutation rate < 2) on the four standard Salmonella strains (p > 0.05) in the Ames toxicity test. Furthermore, the no observed adverse effect level (NOAEL) of GBP was 2000 mg/kg for 91 days feeding of rats in the subchronic toxicity tests. Results also showed the hematological and biochemical indexes as well as histopathological examination changed within a small range, and all clinical observation indexes were normal. No other distinct impacts on cumulative growth of body weight, food intake and food utilization rate were discovered with GBP. No significant difference was discovered for the rats' organ weight and the ratio of viscera to body weight (p > 0.05). Reversible pathological changes in the histopathological examinations of tissue slices of organs were not observed. GBP could therefore be considered as a safe material with minor side effects.
authors.affiliation: Institute of Chemical Industry of Forest Products, Chinese Academy of Forestry, Nanjing 210042, Jiangsu, China. wangczlhs@sina.com.|Key and Open Laboratory on Forest Chemical Engineering, State Forestry Administration, Nanjing 210042, China. wangczlhs@sina.com.|Key Laboratory of Biomass Energy and Material, Institute of Chemical Industry of Forest Products, Nanjing 210042, China. wangczlhs@sina.com.|Institute of New Technology of Forestry, Chinese Academy of Forestry, Beijing 100091, China. wangczlhs@sina.com.
authors.forename: Cheng-Zhang
authors.initials: CZ
authors.lastname: Wang
authors.affiliation: Institute of Chemical Industry of Forest Products, Chinese Academy of Forestry, Nanjing 210042, Jiangsu, China. yuanjj88lhs@163.com.|Key and Open Laboratory on Forest Chemical Engineering, State Forestry Administration, Nanjing 210042, China. yuanjj88lhs@163.com.|Key Laboratory of Biomass Energy and Material, Institute of Chemical Industry of Forest Products, Nanjing 210042, China. yuanjj88lhs@163.com.|Institute of New Technology of Forestry, Chinese Academy of Forestry, Beijing 100091, China. yuanjj88lhs@163.com.
authors.forename: Jiao-Jiao
authors.initials: JJ
authors.lastname: Yuan
authors.affiliation: Institute of Chemical Industry of Forest Products, Chinese Academy of Forestry, Nanjing 210042, Jiangsu, China. liwenjun611@163.com.|Key and Open Laboratory on Forest Chemical Engineering, State Forestry Administration, Nanjing 210042, China. liwenjun611@163.com.|Key Laboratory of Biomass Energy and Material, Institute of Chemical Industry of Forest Products, Nanjing 210042, China. liwenjun611@163.com.|Institute of New Technology of Forestry, Chinese Academy of Forestry, Beijing 100091, China. liwenjun611@163.com.
authors.forename: Wen-Jun
authors.initials: WJ
authors.lastname: Li
authors.affiliation: Institute of Chemical Industry of Forest Products, Chinese Academy of Forestry, Nanjing 210042, Jiangsu, China. chemicalzhy@163.com.|Key and Open Laboratory on Forest Chemical Engineering, State Forestry Administration, Nanjing 210042, China. chemicalzhy@163.com.|Key Laboratory of Biomass Energy and Material, Institute of Chemical Industry of Forest Products, Nanjing 210042, China. chemicalzhy@163.com.|Institute of New Technology of Forestry, Chinese Academy of Forestry, Beijing 100091, China. chemicalzhy@163.com.
authors.forename: Hong-Yu
authors.initials: HY
authors.lastname: Zhang
authors.affiliation: Institute of Chemical Industry of Forest Products, Chinese Academy of Forestry, Nanjing 210042, Jiangsu, China. yejianzhong1984@163.com.|Key and Open Laboratory on Forest Chemical Engineering, State Forestry Administration, Nanjing 210042, China. yejianzhong1984@163.com.|Key Laboratory of Biomass Energy and Material, Institute of Chemical Industry of Forest Products, Nanjing 210042, China. yejianzhong1984@163.com.|Institute of New Technology of Forestry, Chinese Academy of Forestry, Beijing 100091, China. yejianzhong1984@163.com.
authors.forename: Jian-Zhong
authors.initials: JZ
authors.lastname: Ye
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects*; D004435:Eating / Q000187:drug effects*; D005260:Female; D020441:Ginkgo biloba / Q000737:chemistry*; D006801:Humans; D007668:Kidney / Q000187:drug effects; D008099:Liver / Q000187:drug effects; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009152:Mutagenicity Tests; D009929:Organ Size / Q000187:drug effects; D010936:Plant Extracts / Q000737:chemistry; D018515:Plant Leaves / Q000737:chemistry*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013154:Spleen / Q000187:drug effects; D013729:Terpenes / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D013737:Testis / Q000187:drug effects; D023382:Toxicity Tests, Acute
chemical_list: D010936:Plant Extracts; D013729:Terpenes
keywords: Ginkgo biloba leaves; acute toxicity; polyprenols; subchronic toxicity; toxicity