使用生物测定法和替代模型对茎皮水醇提取物的毒理学特征进行研究。
Toxicological profile of the stem bark hydroalcoholic extract using bioassays and an alternative model.
机构信息
Laboratory of Neuropharmacology and Preclinical Toxicology, Federal University of Rio Grande Do Sul, Porto Alegre, RS - Brazil.
Laboratory of Genetic Toxicology, Postgraduate Program in Molecular and Cell Biology Applied to Health, Lutheran University of Brazil (ULBRA), Canoas, RS, Brazil.
出版信息
J Toxicol Environ Health A. 2023 Sep 17;86(18):678-695. doi: 10.1080/15287394.2023.2237069. Epub 2023 Jul 24.
genus has been used in folk medicine in Brazil, but few studies investigated its toxicity profile. Thus, the aim of this study was to determine toxicological parameters of stem bark hydroalcoholic extract by utilizing three cell lines including murine macrophages (RAW 264.7), mouse fibroblast cells (L929) and human lung fibroblast (MRC-5), as well as microsome assay, and model. The predominant detected phytoconstituents in the extract were coumarins, flavonoids, phenolics, tannins and saponins and by HPLC analysis, astilbin (AST) was found to be the main component. The DPPH assay demonstrated that hydroalcoholic extract exhibited potent antioxidant activity, with an IC of 3.12 μg/ml. The extract at concentrations of 400 and 800 μg/ml decreased cell viability 48 hr after treatment in L929 and MRC-5 cell lines. In the Raw 264.7 strain, just the highest concentration (800 μg/ml) lowered cell viability within 48 hr following exposure. The concentration of 100 μg/ml did not markedly affect cell viability in the trypan blue assay. In the alkaline comet assay the extract was found to be non-genotoxic. In the Ames test, the extract exhibited low mutagenic potential without metabolic activation, since only the highest concentrations produced an effect. extract only affected the survival of at concentrations of 800 and 1600 μl/ml. These findings demonstrate that extract appears to exert low toxicity as evidenced and mutagenicity assays; however, the biological relevance of the response of survival to safety assessments needs further studies.
该属植物在巴西民间医学中被使用,但很少有研究调查其毒性概况。因此,本研究的目的是利用包括鼠巨噬细胞(RAW 264.7)、小鼠成纤维细胞(L929)和人肺成纤维细胞(MRC-5)在内的三种细胞系以及微粒体测定和模型来确定茎皮水醇提取物的毒理学参数。提取物中检测到的主要植物成分是香豆素、类黄酮、酚类、单宁和皂苷,通过 HPLC 分析,发现主要成分是 astilbin (AST)。DPPH 测定表明,水醇提取物具有很强的抗氧化活性,IC 为 3.12μg/ml。提取物在 400 和 800μg/ml 的浓度下,在 L929 和 MRC-5 细胞系中处理 48 小时后,降低了细胞活力。在 Raw 264.7 株中,只有最高浓度(800μg/ml)在暴露后 48 小时内降低了细胞活力。100μg/ml 的浓度在台盼蓝测定中对细胞活力没有明显影响。在碱性彗星试验中,提取物被发现是非遗传毒性的。在 Ames 试验中,提取物在没有代谢活化的情况下表现出低诱变潜力,因为只有最高浓度才有作用。提取物仅在 800 和 1600μl/ml 的浓度下影响 的存活。这些发现表明,提取物似乎表现出低毒性,如遗传毒性和诱变性试验所示;然而,对 存活反应的生物学相关性进行安全评估需要进一步的研究。