Rodeiro I, Donato M T, Martínez I, Hernández I, Garrido G, González-Lavaut J A, Menéndez R, Laguna A, Castell J V, Gómez-Lechón M J
Laboratorio de Farmacología, Departamento de Investigaciones Biomédicas, Centro de Química Farmacéutica, 200 y 21, Atabey, Playa, Ciudad de la Habana, Cuba.
Toxicol In Vitro. 2008 Aug;22(5):1242-9. doi: 10.1016/j.tiv.2008.04.006. Epub 2008 Apr 15.
The protective effects of five Cuban natural products (Mangifera indica L. (MSBE), Erythroxylum minutifolium, Erythroxylum confusum, Thalassia testudinum and Dictyota pinnatifida extracts and mangiferin) on the oxidative damage induced by model toxicants in rat hepatocyte cultures were studied. Cells were pre-incubated with the natural products (5-200 microg/mL) for 24 h. Then hepatotoxins (tert-butyl hydroperoxide, ethanol, carbon tetrachloride and lipopolysaccharide) were individually added and post-incubated for another 24 h. After treatments, cell viability was determined using the MTT assay. Mangiferin and MSBE exhibited the highest cytoprotective potential (EC50 between 50 and 125 microg/mL), followed by T. testudinum and Erythroxylum extracts, whereas no significant protective effects was produced by Dictyota extract treatment. Antioxidant properties of the natural products against lipid peroxidation and GSH depletion induced by tert-butyl hydroperoxide were then investigated. The results show that at 36 h pre-treatment of cells with mangiferin or MSBE, concentrations of T. testudinum and Erythroxylum extracts ranging from 25 to 100 microg/mL significantly inhibited lipid peroxidation induced by tert-butyl hydroperoxide (100 and 250 microM) and increased the GSH levels reduced by the toxicant. D. pinnatifida inhibited lipid peroxidation, but did not preserve GSH levels. In conclusion, MSBE, E. minutifolium, E. confusum and T. testudinum extracts and mangiferin showed hepatoprotective activity against induced damage in all the experimental series, where mangiferin and the extracts of MSBE and T. testudinum were the best candidates to inhibit "in vitro" damage to rat hepatocytes. This hepatoprotective effect found could be associated with the antioxidant properties observed for the products.
研究了五种古巴天然产物(芒果(MSBE)、小叶古柯、混生古柯、泰来藻和羽裂叉指藻提取物以及芒果苷)对大鼠肝细胞培养物中模型毒物诱导的氧化损伤的保护作用。将细胞与天然产物(5 - 200微克/毫升)预孵育24小时。然后分别加入肝毒素(叔丁基过氧化氢、乙醇、四氯化碳和脂多糖)并再孵育24小时。处理后,使用MTT法测定细胞活力。芒果苷和MSBE表现出最高的细胞保护潜力(半数有效浓度在50至125微克/毫升之间),其次是泰来藻和古柯提取物,而羽裂叉指藻提取物处理未产生显著的保护作用。接着研究了天然产物对叔丁基过氧化氢诱导的脂质过氧化和谷胱甘肽消耗的抗氧化特性。结果表明,在细胞用芒果苷或MSBE预处理36小时时,浓度范围为25至100微克/毫升的泰来藻和古柯提取物显著抑制了叔丁基过氧化氢(100和250微摩尔)诱导的脂质过氧化,并提高了被毒物降低的谷胱甘肽水平。羽裂叉指藻抑制了脂质过氧化,但未维持谷胱甘肽水平。总之,MSBE、小叶古柯、混生古柯和泰来藻提取物以及芒果苷在所有实验系列中均表现出对诱导损伤的肝保护活性,其中芒果苷以及MSBE和泰来藻的提取物是抑制大鼠肝细胞“体外”损伤的最佳候选物。所发现的这种肝保护作用可能与观察到的这些产物的抗氧化特性有关。