Department of Biomedical Sciences, School of Medicine, Debre Markos University, Debre Markos, Ethiopia.
Department of Pathology, School of Medicine, Debre Markos University, Debre Markos, Ethiopia.
BMC Complement Med Ther. 2023 Feb 2;23(1):30. doi: 10.1186/s12906-023-03863-7.
The aerial part of Ocimum lamiifolium is commonly used in Ethiopian traditional medicine. Although this plant is mostly used in traditional medicine, its safety profile has not been documented yet. The aim of this study was to assess the sub-chronic toxicity of O. lamiifolium aqueous extract in rats and to determine the toxicity profile of GC-MS identified bioactive compounds obtained from essential oil of O. lamiifolium using in silico toxicity methods.
Eighty rats (40 male and 40 female) were randomly assigned to four groups of ten rats per sex/group. For 90 days, Groups I-III received 200, 400, and 600 mg/kg bw of aqueous extract of O. lamiifolium, respectively. Distilled water was given to Group IV (control). Clinical observations, food intake, and rat weight were all recorded during the experiment. In addition, several biochemical parameters, organ weight, and histology of the liver and kidney were all evaluated. For the in-silico toxicity study, GC-MS identified bioactive compounds in O. lamiifolium essential oil were obtained from published articles. The compounds two-dimensional structures were constructed using Chemdraw. The two-dimensional structures were converted into a simplified molecular input line entry system (SMILES) using the Swiss ADMET web tool. Furthermore, the toxicity parameters were predicted using the ProTox II server.
The administration of an aqueous extract of O. lamiifolium leaves significantly (p < 0.05) reduced the test animals' food intake and body weight gain. In the high dose (600 mg/kg bw) treated group, the serum alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase levels were significantly increased (p < 0.05). In female rats given 600 mg/kg bw of O. lamiifolium, the levels of serum urea were also increased. In addition, rats given 600 mg/kg bw had significantly lower blood glucose levels than the control group (p < 0.05). Doses up to 400 mg/kg bw didn't bring a significant change to the histology of the liver. However, in the high dose (600 mg/kg bw) treated group, some female rats' livers showed mild sinusoidal and central vein dilatation, as well as parenchymal necrosis. our findings showed that all compounds derived from the essential oil of O. lamiifolium showed no mutagenicity or cytotoxicity. However, 30% of the compounds tested were hepatotoxic, 20% carcinogenic, and 20% immunotoxin.
Our findings showed that oral administration of O. lamiifoliums aqueous extract up to a dose of 400 mg/kg bw is not toxic. However, high-dose (600 mg/kg bw) significantly affected the food consumption and weight gain of the experimental rats and the serum concentration of some liver and kidney enzymes were also significantly increased. Additionally, a considerable proportion of the tested compounds were predicted to be hepatotoxic, carcinogenic and immunotoxin. Furthermore, before employing O. lamiifolium preparations as drugs, a chronic toxicity research on the essential oil as well as its components that exhibited toxicity in the in-silico toxicity study is needed. Finally, use high doses of O. lamiifolium leaves with caution.
奥罗莫香叶的地上部分常用于埃塞俄比亚传统医学。尽管这种植物主要用于传统医学，但它的安全性尚未得到记录。本研究旨在评估奥罗莫香叶水提物在大鼠中的亚慢性毒性，并使用基于计算机的毒性方法确定从奥罗莫香叶精油中鉴定出的生物活性化合物的毒性特征。
80 只大鼠（40 只雄性和 40 只雌性）被随机分为四组，每组 10 只大鼠。90 天内，第 I-III 组分别给予 200、400 和 600mg/kg bw 的奥罗莫香叶水提物。第 IV 组（对照组）给予蒸馏水。在实验过程中，记录临床观察、食物摄入量以及大鼠体重。此外，还评估了生化参数、器官重量以及肝和肾的组织学。对于基于计算机的毒性研究，从已发表的文章中获得了奥罗莫香叶精油中鉴定出的生物活性化合物。使用 Chemdraw 构建化合物的二维结构。使用 Swiss ADMET 网络工具将二维结构转换为简化分子输入线条目系统（SMILES）。此外，使用 ProTox II 服务器预测毒性参数。
奥罗莫香叶水提物的给药显著（p<0.05）降低了实验动物的食物摄入量和体重增加。在高剂量（600mg/kg bw）处理组中，血清丙氨酸氨基转移酶、天冬氨酸氨基转移酶和碱性磷酸酶水平显著升高（p<0.05）。在给予奥罗莫香叶 600mg/kg bw 的雌性大鼠中，血清尿素水平也升高。此外，给予 600mg/kg bw 的大鼠血糖水平明显低于对照组（p<0.05）。高达 400mg/kg bw 的剂量对肝脏的组织学没有显著影响。然而，在高剂量（600mg/kg bw）处理组中，一些雌性大鼠的肝脏显示出轻微的窦状隙和中央静脉扩张以及实质坏死。我们的研究结果表明，所有从奥罗莫香叶精油中衍生的化合物均未显示出致突变性或细胞毒性。然而，30%的测试化合物具有肝毒性，20%具有致癌性，20%具有免疫毒素性。
我们的研究结果表明，口服奥罗莫香叶水提物的剂量高达 400mg/kg bw 是无毒的。然而，高剂量（600mg/kg bw）显著影响实验大鼠的食物摄入和体重增加，血清中一些肝和肾酶的浓度也显著升高。此外，测试的化合物中有相当一部分被预测具有肝毒性、致癌性和免疫毒素性。此外，在将奥罗莫香叶制剂用作药物之前，需要对其精油以及在基于计算机的毒性研究中显示出毒性的成分进行慢性毒性研究。最后，谨慎使用奥罗莫香叶的高剂量。
