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对具有抗炎潜力的叶提取物进行单次急性和重复亚急性毒性评估。

Single acute and repeated subacute toxicity evaluations of leaf extract with anti-inflammatory potential.

作者信息

Sohn Eunjin, Kim Yu Jin, Lim Hye-Sun, Jeong Soo-Jin

机构信息

Korean Medicine Convergence Research Division, Korea Institute of Oriental Medicine, Daejeon, South Korea.

Herbal Medicine Resources Research Center, Korea Institute of Oriental Medicine, Naju, South Korea.

出版信息

Drug Chem Toxicol. 2025 Jul;48(4):864-875. doi: 10.1080/01480545.2024.2407866. Epub 2024 Oct 3.

DOI:10.1080/01480545.2024.2407866
PMID:39360591
Abstract

The nutraceutical and biological potential of , a fruiting plant, has been reported. We and others have demonstrated that leaf extract (AAL) has various pharmacological properties, such as antioxidant, antimicrobial, and neuroprotective effects. However, knowledge about the safety and potential toxicity of AAL remains limited. We aimed to assess the potential toxicity of AAL using acute and repeated subacute oral toxicity tests in rats. In both acute and repeated subacute toxicity test, no AAL-related behavioral abnormalities or changes in mortality, food intake, body weight were observed up to a dosage of 2000 mg/kg, indicating that the median lethal dose of AAL is higher than 2000 mg/kg. In subacute toxicity tests, no significant changes in hematological and biochemical parameters, urinalysis results, and histopathological variables were observed. Therefore, the no-observed-adverse-effect level (NOAEL) of orally administered AAL was estimated to be 2000 mg/kg/day in male and female rats. We also examined the effect of AAL on the inflammatory reaction in lipopolysaccharide (LPS)-stimulated BV-2 cells. AAL treatment significantly inhibited the LPS-stimulated increases in the levels of nitric oxide (NO) and inflammatory cytokines, implying that AAL has an anti-inflammatory effect. Quality control analysis revealed that two marker compounds, rutin and isoquercitrin, were present at 27.570 and 4.322 mg/g, respectively, in a freeze-dried AAL sample and were completely eluted within 27 min. The extraction recovery was 99.47-103.80%, and the precision was ≤2.79%. Overall, these findings suggest the safety, anti-inflammatory activity, and standardization of AAL.

摘要

一种结果实植物的营养保健和生物学潜力已有报道。我们和其他人已证明该植物叶提取物(AAL)具有多种药理特性,如抗氧化、抗菌和神经保护作用。然而,关于AAL安全性和潜在毒性的知识仍然有限。我们旨在通过对大鼠进行急性和重复亚急性口服毒性试验来评估AAL的潜在毒性。在急性和重复亚急性毒性试验中,在剂量高达2000mg/kg时,均未观察到与AAL相关的行为异常或死亡率、食物摄入量、体重的变化,这表明AAL的半数致死剂量高于2000mg/kg。在亚急性毒性试验中,未观察到血液学和生化参数、尿液分析结果及组织病理学变量有显著变化。因此,估计雄性和雌性大鼠口服AAL的未观察到不良反应水平(NOAEL)为2000mg/kg/天。我们还研究了AAL对脂多糖(LPS)刺激的BV-2细胞炎症反应的影响。AAL处理显著抑制了LPS刺激引起的一氧化氮(NO)水平和炎性细胞因子的升高,这意味着AAL具有抗炎作用。质量控制分析表明,在冻干的AAL样品中,两种标记化合物芦丁和异槲皮苷的含量分别为27.570mg/g和4.322mg/g,且在27分钟内完全洗脱。提取回收率为99.47 - 103.80%,精密度≤2.79%。总体而言,这些发现表明AAL具有安全性、抗炎活性和标准化特征。

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