Gastroprotective and ulcer-healing activity of oleanolic acid derivatives: In vitro–in vivo relationships

• Published in: Life sciences (1973) 2006-08, Vol.79 (14), p.1349-1356
• Main Authors: Sánchez, Marianela, Theoduloz, Cristina, Schmeda-Hirschmann, Guillermo, Razmilic, Iván, Yáñez, Tania, Rodríguez, Jaime A.
• Format: Article
• Language: English
• Subjects: 2-Pyridinylmethylsulfinylbenzimidazoles; AGS cells; Animals; Anti-Ulcer Agents - chemical synthesis; Anti-Ulcer Agents - therapeutic use; Cell Line; Cell Proliferation - drug effects; Cell Survival - drug effects; Central Nervous System Depressants; Chemical Phenomena; Chemistry, Physical; Cytotoxicity; Dinoprostone - metabolism; Epithelial Cells; Ethanol; Fibroblasts; Free Radical Scavengers - pharmacology; Gastric Mucosa - cytology; Gastric Mucosa - drug effects; Gastroprotective; Glutathione - metabolism; Humans; Hydrochloric Acid; Lansoprazole; Male; Mice; Oleanolic acid; Oleanolic Acid - analogs & derivatives; Oleanolic Acid - chemical synthesis; Oleanolic Acid - pharmacology; Omeprazole - analogs & derivatives; Omeprazole - pharmacology; Stomach Ulcer - chemically induced; Stomach Ulcer - pathology; Stomach Ulcer - prevention & control; Superoxides - metabolism; Taurocholic Acid - antagonists & inhibitors; Taurocholic Acid - toxicity; Triterpenes; Ulcer-healing
• ISSN: 0024-3205; 1879-0631
• DOI: 10.1016/j.lfs.2006.03.044

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.