Acute and Sub-Chronic Toxicity Evaluation of the Crude Methanolic Bark Extract of <i>Bridelia micrantha</i> (Hochst.) Baill. (Phyllanthaceae) and Its Fraction

Colette Elysée Aboudi Etono, Landry Lienou Lienou, Fabrice Fabien Dongho Dongmo, Aristide Laurel Mokale Kognou, Raphael Tchientcheu, Rebecca Madeleine Ebelle Etame, Rosalie Anne Ngono Ngane
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Abstract

Bridelia micrantha, commonly known as coastal golden leaf, is a member of the family Phyllanthaceae. In preliminary studies nine fractions, named F1 - F9, were obtained by fractionating the crude methanol extract of the stem bark of Bridelia micrantha using column chromatographic techniques. The fraction F6 was the most active when tested for antibacterial activity. Thus, toxicity of this fraction was investigated for further use. The present study evaluated the acute and sub-chronic toxicity of the crude methanolic bark extract of Bridelia micrantha and its fraction. The acute toxicity was carried out according to the experimental protocol of Organization for Economic Co-operation and Development (OECD). The plant extract or the fraction F6 was administered orally to female mice at a single dose of 2000 mg/kg and the animals were observed for any behavioral changes or mortality for 14 days. In the sub-chronic toxicity study, the extract and fraction were administered orally at 200, 400 and 800 mg/kg bw/day for 28 days to healthy Wistar rats. The general behavior and body weight of the rats were recorded daily. At the end of the experimental period, hematological and biochemical analyses, changes in vital organ weight (liver, lung, heart, spleen and kidney), and histopathological examination of the liver and kidney were performed. No mortality or adverse effects were noted at the 2000 mg/kg dose during the oral acute toxicity test. In the sub-chronic study, the crude methanolic bark extract of Bridelia micrantha and the fraction F6 induced no mortality or treatment-related adverse effects on body weight, general behavior, relative organ weights, hematological and biochemical parameters. Histopathological examination of the liver and kidney showed normal architecture suggesting no morphological alterations. In conclusion, the oral administration of the crude methanolic bark extract of Bridelia micrantha and the fraction F6 for 28 days at a dosage of up to 800 mg/kg did not induce toxicological damage in rats. From acute toxicity study, the median lethal dose (LD50) of the crude methanolic bark extract of Bridelia micrantha and the fraction F6 was estimated to be more than 2000 mg/kg.
微花杜鹃粗甲醇树皮提取物的急性和亚慢性毒性评价(Hochst)。Baill。(Phyllanthaceae)及其组分
薇甘菊,俗称海岸金叶,是千叶科的一员。初步研究采用柱层析技术对薇甘菊茎皮粗甲醇提取物进行分离,得到9个组分,分别命名为F1 - F9。F6的抑菌活性最高。因此,对该组分的毒性进行了进一步的研究。本研究评价了薇甘菊树皮粗甲醇提取物及其组分的急性和亚慢性毒性。急性毒性试验按照经济合作与发展组织(OECD)的实验方案进行。将植物提取物或F6组分以2000 mg/kg的单次剂量口服雌性小鼠,观察14天内动物的行为变化和死亡情况。在亚慢性毒性研究中,以200、400和800 mg/kg体重/天的剂量口服健康Wistar大鼠28天。每天记录大鼠的一般行为和体重。实验结束时进行血液学、生化分析、重要脏器(肝、肺、心、脾、肾)重量变化及肝、肾组织病理学检查。口服急性毒性试验中,2000mg /kg剂量组未见死亡或不良反应。在亚慢性研究中,薇甘菊粗甲醇树皮提取物和F6部分未引起死亡,也未对体重、一般行为、相对器官重量、血液学和生化参数产生与治疗相关的不良影响。肝、肾组织病理学检查显示结构正常,未见形态学改变。综上所述,以800 mg/kg的剂量给药28 d后,薇甘菊粗甲醇皮提取物和F6部分未引起大鼠的毒理学损伤。从急性毒性研究中,估计薇甘菊粗甲醇树皮提取物及其F6部位的中位致死剂量(LD50)大于2000 mg/kg。
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