He Dongye, Xu Yongping
Department of Endocrinology, Genetics and Metabolism, Affiliated Hospital of Jining Medical University, Jining 272029, China.
Medical Research Center, Affiliated Hospital of Jining Medical University, Jining 272029, China.
Evid Based Complement Alternat Med. 2022 Feb 15;2022:7889199. doi: 10.1155/2022/7889199. eCollection 2022.
is a novel food source and Chinese folk medicine with multiple pharmacological properties. Our previous exploration has demonstrated the antidepressant-like activity of leaves aqueous extract by reliable animal models of depression; however, a lack of toxicological information limits its pharmacological application. The present study aimed to evaluate the preliminary safety of extract by determining acute/subacute toxicity in mice and / genotoxicity. The oral-medium lethal dose of the extract in mice was found to be higher than 5000 mg/kg body weight in the acute toxicity study. In a 14-days subacute toxicity study, extract at doses of 400, 800, and 1600 mg/kg did not result in significant changes in food intake, water intake, body weight, relative organ weight, aspartate aminotransferase activity, alanine aminotransferase activity, creatinine level, and number of white blood cells and red blood cells. However, histopathology observation of organs taken from all mice showed that 1600 mg/kg extract caused slight hydropic degeneration in the cytoplasm of hepatocytes. In a 28-days subacute toxicity study, 600 mg/kg extract significantly increased the level of red blood cells but produced no negative side effects on other pathological parameters. Mice treated with the extract at doses of 200, 400, and 600 mg/kg for 28 days did not manifest any histopathological alterations of the liver, kidney, and spleen. Additionally, the extract showed no chromosomal aberrations in the micronucleus test and chromosomal aberration test. The results revealed that the extract showed no significant toxic effects and no potential genotoxicity but with the likelihood of transient erythrocytosis and slight hepatotoxicity. Further chronic toxicological evaluation involved in more physiological parameters, especially associated with liver toxicity and erythropoietin level, would be needed to determine its safety and application value.
是一种具有多种药理特性的新型食物来源和中国民间药物。我们之前的研究已通过可靠的抑郁症动物模型证明了其叶水提取物的抗抑郁样活性；然而，缺乏毒理学信息限制了其药理应用。本研究旨在通过测定小鼠的急性/亚急性毒性和/基因毒性来评估提取物的初步安全性。在急性毒性研究中，发现该提取物对小鼠的经口半数致死剂量高于5000毫克/千克体重。在为期14天的亚急性毒性研究中，400、800和1600毫克/千克剂量的提取物在食物摄入量、饮水量、体重、相对器官重量、天冬氨酸转氨酶活性、丙氨酸转氨酶活性、肌酐水平以及白细胞和红细胞数量方面未导致显著变化。然而，对所有小鼠的器官进行组织病理学观察表明，1600毫克/千克的提取物导致肝细胞胞质出现轻微水样变性。在为期28天的亚急性毒性研究中，600毫克/千克的提取物显著提高了红细胞水平，但对其他病理参数未产生负面副作用。用200、400和600毫克/千克剂量的提取物处理28天的小鼠，其肝脏、肾脏和脾脏未表现出任何组织病理学改变。此外，该提取物在微核试验和染色体畸变试验中未显示染色体畸变。结果表明，该提取物未显示出明显的毒性作用和潜在的基因毒性，但有可能出现短暂的红细胞增多症和轻微的肝毒性。需要进一步进行涉及更多生理参数，尤其是与肝毒性和促红细胞生成素水平相关的慢性毒理学评估，以确定其安全性和应用价值。
