title: Potential gastroprotective effect of novel cyperenoic acid/quinone derivatives in human cell cultures.
abstract: The stem bark of Tabebuia species and the rhizomes of Jatropha isabelii are used in Paraguayan traditional medicine to treat gastric lesions and as anti-inflammatory agents. The sesquiterpene cyperenoic acid obtained from J. isabelii has been shown to display a gastroprotective effect in animal models of induced gastric ulcers while the quinone lapachol shows several biological effects associated with the use of the crude drug. The aim of this work was to prepare hybrid molecules presenting a terpene and a quinone moiety and to obtain an assessment of the gastroprotective activity of the new compounds using human cell cultures (MRC-5 fibroblasts and AGS epithelial gastric cells). Eight compounds, including the natural products and semisynthetic derivatives were assessed for proliferation of MRC-5 fibroblasts, protection against sodium taurocholate-induced damage, prostaglandin E2 content, and stimulation of cellular-reduced glutathione synthesis in AGS cells. The following antioxidant assays were performed: DPPH discoloration, scavenging of the superoxide anion, and inhibition of induced lipoperoxidation in erythrocyte membranes. 3-Hydroxy-β-lapachone (3) and cyperenoic acid (4) stimulated fibroblast proliferation. Lapachol (1), dihydroprenyl lapachol (2), 3-hydroxy-β-lapachone (3), and lapachoyl cyperenate (6) protected against sodium taurocholate-induced damage in AGS cells. Lapachol (1) and dihydroprenyl lapachoyl cyperenate (7) significantly stimulated prostaglandin E2 synthesis in AGS cells. Compounds 3, 4, and 7 raised reduced glutathione levels in AGS cells. The hybrid compounds presented activities different than those of the starting sesquiterpene or quinones.
authors.affiliation: Laboratorio de Cultivo Celular, Facultad de Ciencias de la Salud, Universidad de Talca, Talca, Chile. ctheodul@utalca.cl
authors.forename: Cristina
authors.initials: C
authors.lastname: Theoduloz
authors.forename: Ivanna Bravo
authors.initials: IB
authors.lastname: Carrión
authors.forename: Mariano Walter
authors.initials: MW
authors.lastname: Pertino
authors.forename: Daniela
authors.initials: D
authors.lastname: Valenzuela
authors.forename: Guillermo
authors.initials: G
authors.lastname: Schmeda-Hirschmann
mesh_terms: D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D002478:Cells, Cultured / Q000187:drug effects; D004847:Epithelial Cells / Q000187:drug effects; D005347:Fibroblasts / Q000187:drug effects; D005753:Gastric Mucosa / Q000187:drug effects; D006801:Humans; D031286:Jatropha / Q000737:chemistry*; D009285:Naphthoquinones / Q000494:pharmacology* / Q000627:therapeutic use*; D010239:Paraguay; D024301:Plant Bark / Q000737:chemistry; D010936:Plant Extracts / Q000494:pharmacology; D018547:Plant Stems / Q000737:chemistry; D020011:Protective Agents / Q000494:pharmacology; D027343:Rhizome / Q000737:chemistry; D012717:Sesquiterpenes / Q000302:isolation & purification / Q000494:pharmacology*; D013276:Stomach Ulcer / Q000188:drug therapy*; D029663:Tabebuia / Q000737:chemistry*
chemical_list: D000897:Anti-Ulcer Agents; D009285:Naphthoquinones; D010936:Plant Extracts; D020011:Protective Agents; D012717:Sesquiterpenes; C519558:cyperenoic acid; C008252:lapachol