Gastroprotective effect and cytotoxicity of terpenes from the Paraguayan crude drug “yagua rova” (Jatropha isabelli)

Mariano Pertinoa and Guillermo Schmeda-Hirschmann. Laboratorio de Química de Productos Naturales, Instituto de Química de Recursos Naturales, Universidad de Talca, Casilla 747, Talca, Chile Jaime A. Rodríguez and Cristina Theoduloz. Departamento de Ciencias Básicas Biomédicas, Facultad de Ciencias de la Salud, Universidad de Talca, Casilla 747, Talca, ChileA new jatrophone derivative (6), jatrophone (3), jatropholone A (4) and jatropholone B (5), acetyl aleuritolic acid (1), cyperenoic acid (2) and a monoterpene were isolated from the rhizomes of the Paraguayan crude drug Jatropha isabelli. The compounds were characterized by spectroscopic means. The gastroprotective effect of jatrophone, jatropholone A and B as well as 9β,13-dihydroxyisabellione 6 and the triterpene 1 was assessed in the HCl/EtOH-induced gastric lesions model in mice. Jatrophone elicited a strong gastroprotective effect with no significant differences between 25, 50 or 100 mg/kg and reducing lesions from 88 to 93%. The jatropholones A and B showed remarkable differences in the gastroprotective assay. Jatropholone A presented a dose-related response, with maximum effect (54% lesion reduction) at the highest dose (100 mg/kg), jatropholone B showed a strong action at all the doses, reducing lesions by 83–91%. The cytotoxicity of the compounds was assessed towards fibroblasts and AGS cells. Jatrophone was toxic against both cell lines (IC50 values: 2.8 and 2.5 μM, respectively). Jatropholone B (5) was not cytotoxic while jatropholone A (4) displayed a selective effect against AGS cells (IC50: 49 μM). The relevance of stereochemistry in the biological effects is clear comparing the effect of jatropholone A and B against AGS cells, with IC50 values of 49 and >1000 μM for the β and C-16 isomers, respectively. The results provide scientific support for the use of “yagua rova” as a gastroprotective crude drug in Paraguayan traditional medicine

Biotransformation of jatrophone by Aspergillus niger ATCC 16404

Schmeda-Hirschmann,G. (reprint author). Laboratorio de Química de Productos Naturales, Instituto de Química de Recursos Naturales, Universidad de Talca, Casilla 747, Talca, Chile

Gastroprotective activity and cytotoxic effect of cyperenoic acid derivatives

Pertino, Mariano; Razmilic, Iván; Schmeda-Hirschmann, Guillermo. Laboratorio de Química de Productos Naturales, Instituto de Química de Recursos Naturales, Universidad de Talca, Casilla 747, Talca, Chile. Rodríguez, Jaime A.; Theoduloz, Cristina. Depto de Ciencias Básicas Biomédicas, Facultad de Ciencias de la Salud, Universidad de Talca, Casilla 747, Talca, Chile.The gastroprotective effect of the sesquiterpene cyperenoic acid and seven semi-synthetic derivatives was assessed in the HCl/ethanol-induced gastric ulcer model in mice. At doses of 25, 50 and 100 mg kg−1, cyperenoic acid showed a dose-dependent gastroprotective effect reducing the lesions by 45 and 75% at 50 and 100 mg kg−1, respectively. Seven derivatives of the sesquiterpene were prepared and their gastroprotective activity compared at 50 mg kg−1. The cytotoxicity of the compounds was evaluated in fibroblasts and AGS cells. At 50 mg kg−1, patchoulan-15-oic acid (compound 8) presented the best gastroprotective effect, reducing the gastric lesions by 86%, with a similar effect to lansoprazole at 20 mg kg−1. The gastroprotective effect of cyperenol, cyperenoic acid methyl ester and the ethylamide and butylamide from cyperenoic acid were in the same range, reducing the gastric lesions by 72-77%. Cyperenol and cyperenoic acid methyl ester, however, were more cytotoxic with IC50 (concentration that produces a 50% inhibitory effect) values of 44 and 75, 48 and 75 μM against AGS cells and fibroblasts, respectively. The best gastroprotective effect with lower cytotoxicity was found for the compound 8, cyperenoic acid and the p-anisidyl derivative 7