Acute and sub-chronic oral toxicity studies of hesperidin isolated from orange peel extract in Sprague Dawley rats
Acute and sub-chronic oral toxicity studies of hesperidin isolated from orange peel extract in Sprague Dawley rats
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DOI：
10.1016/j.yrtph.2019.04.001
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发表时间：
2019-07-01
影响因子：
3.4
通讯作者：
Bodhankar, Subhash L.
中科院分区：
文献类型：
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作者：
Li, Yongsheng;Kandhare, Amit D.;Bodhankar, Subhash L.
柑橘含有苷橙皮素-7-鼠李糖苷（橙皮苷），具有抗氧化、抗癌和抗炎等一系列治疗潜力。然而，在使用之前需要对其安全性进行系统的检查。因此，本研究旨在评价从柑橘果实中分离的橙皮苷的急性和亚慢性毒性。橙皮苷（73%）是从柑橘类水果的干燥果皮的甲醇提取物中分离出来的，其特征在于使用FTIR，并通过HPLC标准化。在Sprague-Dawley大鼠中进行了其急性经口毒性（AOT）和亚慢性毒性研究。橙皮苷（5000 mg/kg）在AOT中显示10%的死亡率。在亚慢性毒性研究中，橙皮苷（250和500 mg/kg）未诱导体重、摄食量、临床体征、眼科和神经学观察结果、尿液分析、血液学、临床化学、器官重量和大体病理学的任何异常。然而，橙皮苷（1000 mg/kg）在体重和器官重量、血液学、临床化学和组织组织病理学方面显示出显著（p < 0.05）变化。综上所述，橙皮苷对雄性和雌性Sprague-Dawley大鼠的半数致死剂量（LD 50）为4837.5 mg/kg，低可见不良作用水平（LOAEL）为1000 mg/kg。因此，从柑橘类水果中分离的橙皮苷在动物研究中显示出良好的安全性。
Citrus sinensis contains glycoside hesperetin-7-rhamnoglucoside (hesperidin) which harbor an array of therapeutic potentials including antioxidant, anticancer, and anti-inflammatory. However, a systematic examination of safety is needed before its utilization. Hence, the present investigation is aimed to evaluate acute and sub chronic toxicity of hesperidin isolated from the citrus fruit. Hesperidin (73%) was isolated from a methanolic extract of dried peel of the citrus fruit, characterized using FTIR, and standardized by HPLC. Its acute oral toxicity (AOT) and sub-chronic toxicity studies were carried out in Sprague-Dawley rats. Hesperidin (5000 mg/kg) showed 10% mortality in AOT. In sub-chronic toxicity study, hesperidin (250 and 500 mg/kg) did not induce any abnormalities in body weight, food consumption, clinical signs, ophthalmological and neurological observations, urine analysis, hematology, clinical chemistry, organ weights, and gross pathology. However, hesperidin (1000 mg/kg) showed significant (p < 0.05) alterations in body and organ weights, hematology, clinical chemistry, and tissue histopathology. To conclude, hesperidin has median lethal dose (LD50) of 4837.5 mg/kg, and Low Observed Adverse Effect Level (LOAEL) at 1000 mg/kg for both male and female Sprague-Dawley rats. Thus, hesperidin isolated from citrus fruit showed a good safety profile in animal study.