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长柄钩吻标准化二氢查尔酮提取物对 Sprague-Dawley 大鼠的急性生殖毒性和两代致畸学研究。

Acute, reproductive toxicity and two-generation teratology studies of a standardized quassinoid-rich extract of Eurycoma longifolia Jack in Sprague-Dawley rats.

机构信息

School of Pharmaceutical Sciences, Universiti Sains Malaysia, 11800, Penang, Malaysia; School of Medicine, Taylor's University, 47500, Subang Jaya, Selangor, Malaysia.

出版信息

Phytother Res. 2014 Jul;28(7):1022-9. doi: 10.1002/ptr.5094. Epub 2013 Dec 6.

DOI:10.1002/ptr.5094
PMID:24318772
Abstract

The roots of Eurycoma longifolia Jack are popularly sought as herbal medicinal supplements to improve libido and general health amongst the local ethnic population. The major quassinoids of E. longifolia improved spermatogenesis and fertility but toxicity studies have not been well documented. The reproductive toxicity, two generation of foetus teratology and the up-and-down acute toxicity were investigated in Sprague-Dawley rats orally treated with quassinoid-rich E. longifolia extract (TAF273). The results showed that the median lethal dose (LD50 ) of TAF273 for female and male rats was 1293 and >2000 mg/kg, respectively. Fertility index and litter size of the TAF273 treated were significantly increased when compared with those of the non-treated animals. The TAF273-treated dams decreased in percentage of pre-implantation loss, post-implantation loss and late resorption. No toxic symptoms were observed on the TAF273-treated pregnant female rats and their foetuses were normal. The no-observed adverse effect level (NOAEL) obtained from reproductive toxicity and teratology studies of TAF273 in rats was 100 mg/kg body weight/day, being more than 10-fold lower than the LD50 value. Thus, any human dose derived from converting the rat doses of 100 mg/kg and below may be considered as safe for further clinical studies.

摘要

长柄钩藤根是当地民族常用的草药补充剂,可提高性欲和整体健康。长柄钩藤中的主要奎诺酮可改善精子发生和生育能力,但毒性研究尚未得到很好的记录。本研究采用富奎诺酮的长柄钩藤提取物(TAF273)对 Sprague-Dawley 大鼠进行了生殖毒性、两代胚胎致畸和上下急性毒性研究。结果表明,TAF273 对雌性和雄性大鼠的中位致死剂量(LD50)分别为 1293 和>2000mg/kg。与未处理的动物相比,TAF273 处理的生育指数和产仔数显著增加。TAF273 处理的孕鼠着床前损失、着床后损失和晚期吸收百分比降低。在 TAF273 处理的怀孕雌性大鼠及其胎儿中未观察到任何毒性症状,且胎儿正常。TAF273 在大鼠中的生殖毒性和致畸研究中获得的无观察不良效应水平(NOAEL)为 100mg/kg 体重/天,比 LD50 值低 10 倍以上。因此,从将 100mg/kg 及以下的大鼠剂量转换而来的任何人类剂量都可被认为是安全的,可进一步进行临床研究。

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