Liang Jian, Chen Shu-Xian, Huang Song, Wu Ya-Yun, Zhou Cai-Jie, Jiang Dong-Xu, Liang Chu-Yan, Yuan Hui-Qi, Hou Shao-Zhen, Lai Xiao-Ping
Guangdong Provincial Key Laboratory of New Chinese Medicinals Development and Research, Guangzhou University of Chinese Medicine, Guangzhou Higher Education Mega Center, Guangzhou 510006, China.
Department of Hepatobiliary Surgery, The Third Affiliated Hospital of Sun Yat-sen University, No.600, Tianhe Road, Guangzhou 510630, China.
Regul Toxicol Pharmacol. 2017 Aug;88:283-290. doi: 10.1016/j.yrtph.2017.07.006. Epub 2017 Jul 8.
The aim of the study was to evaluate the safety of flavonoid fraction of Lithocarpus polystachyus Rehd (Sweet Tea-F, ST-F) in mice and rats through acute and sub-chronic toxicity studies respectively. For acute toxicity study, a single dose of 5000 mg/kg of ST-F was given orally to healthy KM mice. The mice were observed mortality and toxic symptoms for 24 h, then once a day up to 14 days. In the sub-chronic toxicity study, ST-F was administered orally at doses of 0, 70, 140, 560 mg/kg/day to rats for 26 weeks. Body weight and food intake were recorded weekly. Hematological, biochemical, coagulation and organ parameters were analyzed at the end of 26 weeks administration. Vital organs were evaluated by histopathology. In the acute toxicity study, ST-F caused neither significant toxic symptoms, nor mortality in mice. In sub-chronic toxicity study, daily oral administration of ST-F at the dose of 70 mg/kg resulted in a significant increase (P < 0.05) in the relative body weight at the 10-week, and the same situation brought at the dose of 140 mg/kg/day at the 22-week. Hematological and biochemical showed significant changes (P < 0.01 or P < 0.05) in WBC, GLU, ALP, AST and serum electrolytes levels at the dose of 560 mg/kg/day. The amount of RBC decreased significantly (P < 0.05) while the content of PLT slightly increased (P < 0.05) at the dose of 140 mg/kg/day. In additional, no obvious histological changes were observed in vital organs of ST-F treated animals compared to control group. The ST-F may be exit slight side effects at the dose of 560 mg/kg/day in rats. Thus, the overall results show that the no-observed adverse effect level (NOAEL) of ST-F was considered to be 140 mg/kg for male SD rats.
本研究旨在分别通过急性和亚慢性毒性研究，评估多穗柯（甜茶提取物-F，ST-F）黄酮类成分在小鼠和大鼠中的安全性。在急性毒性研究中，给健康的KM小鼠口服单次剂量5000mg/kg的ST-F。观察小鼠24小时的死亡率和中毒症状，然后每天观察一次，持续14天。在亚慢性毒性研究中，以0、70、140、560mg/kg/天的剂量给大鼠口服ST-F，持续26周。每周记录体重和食物摄入量。在给药26周结束时分析血液学、生化、凝血和器官参数。通过组织病理学评估重要器官。在急性毒性研究中，ST-F在小鼠中既未引起明显的中毒症状，也未导致死亡。在亚慢性毒性研究中，每天口服70mg/kg剂量的ST-F在第10周时导致相对体重显著增加（P<0.05），在第22周时，每天口服140mg/kg剂量时也出现同样情况。在560mg/kg/天的剂量下，血液学和生化指标显示白细胞、血糖、碱性磷酸酶、天冬氨酸转氨酶和血清电解质水平有显著变化（P<0.01或P<0.05）。在140mg/kg/天的剂量下，红细胞数量显著减少（P<0.05），而血小板含量略有增加（P<0.05）。此外，与对照组相比，ST-F处理动物的重要器官未观察到明显的组织学变化。在大鼠中，ST-F在560mg/kg/天的剂量下可能存在轻微副作用。因此，总体结果表明，雄性SD大鼠中ST-F的未观察到不良反应水平（NOAEL）被认为是140mg/kg。
