Sánchez Marianela, Theoduloz Cristina, Schmeda-Hirschmann Guillermo, Razmilic Iván, Yáñez Tania, Rodríguez Jaime A
Laboratorio de Química de Productos Naturales, Instituto de Química de Recursos Naturales, Universidad de Talca, Casilla 747, Talca, Chile.
Life Sci. 2006 Aug 29;79(14):1349-56. doi: 10.1016/j.lfs.2006.03.044. Epub 2006 Apr 26.
The triterpene oleanolic acid 1 and its semisynthetic derivatives 2-7 were assessed for gastroprotective and ulcer-healing effect using human epithelial gastric cells (AGS) and human lung fibroblasts (MRC-5). The ability of the compounds to protect the AGS cells against the damage induced by sodium taurocholate (NaT), to stimulate the cellular reduced glutathione (GSH) and prostaglandin E(2) content, to enhance AGS and MRC-5 cell proliferation and to scavenge superoxide anion in vitro was studied. The cytotoxicity of the compounds was assessed towards MRC-5 and AGS cells. In addition, the gastroprotective activity of the compounds was assessed in vivo using the HCl/EtOH-induced ulcer model in mice. All the assayed compounds displayed a significant reduction of AGS cells damage after incubation with NaT. None of the studied compounds was active as a superoxide anion scavenger nor stimulated the GSH content in AGS cell cultures. Compounds 1, 2, 4 and 6 were able to increase the prostaglandin content in AGS cell cultures. Concerning the proliferation assays, a significant stimulating effect was observed for compounds 3 and 7 on AGS cells and for 1 and 7 on MRC-5 fibroblasts. Regarding cytotoxicity, derivatives 2, 4, 6 and 7 were less toxic than the parent compound oleanolic acid. Our results strongly support the predictive capacity of the in vitro assessment of gastroprotective activity allowing the reduction of experimental animals.
使用人胃上皮细胞（AGS）和人肺成纤维细胞（MRC-5）评估了三萜类齐墩果酸1及其半合成衍生物2-7的胃保护和溃疡愈合作用。研究了这些化合物保护AGS细胞免受牛磺胆酸钠（NaT）诱导的损伤、刺激细胞内还原型谷胱甘肽（GSH）和前列腺素E2含量、增强AGS和MRC-5细胞增殖以及在体外清除超氧阴离子的能力。评估了这些化合物对MRC-5和AGS细胞的细胞毒性。此外，使用盐酸/乙醇诱导的小鼠溃疡模型在体内评估了这些化合物的胃保护活性。所有测定的化合物在与NaT孵育后均显示出AGS细胞损伤的显著降低。所研究的化合物均无作为超氧阴离子清除剂的活性，也未刺激AGS细胞培养物中的GSH含量。化合物1、2、4和6能够增加AGS细胞培养物中的前列腺素含量。关于增殖试验，观察到化合物3和7对AGS细胞以及化合物1和7对MRC-5成纤维细胞具有显著的刺激作用。关于细胞毒性，衍生物2、4、6和7的毒性低于母体化合物齐墩果酸。我们的结果有力地支持了胃保护活性体外评估的预测能力，从而减少了实验动物的使用。
