Gastroprotective effect and cytotoxicity of terpenes from the Paraguayan crude drug "yagua rova" (Jatropha isabelli).
A 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 9beta,13alpha-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 microM, respectively). Jatropholone B (5) was not cytotoxic while jatropholone A (4) displayed a selective effect against AGS cells (IC50: 49 microM). 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 microM for the beta and alpha C-16 isomers, respectively. The results provide scientific support for the use of "yagua rova" as a gastroprotective crude drug in Paraguayan traditional medicine.
Pertino
Mariano
M
Laboratorio de Química de Productos Naturales, Instituto de Química de Recursos Naturales, Universidad de Talca, Casilla 747, Talca, Chile.
Schmeda-Hirschmann
Guillermo
G
Rodríguez
Jaime A
JA
Theoduloz
Cristina
C
D053799:2-Pyridinylmethylsulfinylbenzimidazoles / Q000494:pharmacology; D000284:Administration, Oral; D000818:Animals; D000897:Anti-Ulcer Agents / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology*; D002460:Cell Line / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005753:Gastric Mucosa / Q000187:drug effects; D020128:Inhibitory Concentration 50; D031286:Jatropha / Q000737:chemistry*; D064747:Lansoprazole; D008519:Medicine, Traditional; D051379:Mice; D010239:Paraguay; D020011:Protective Agents / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology*; D027343:Rhizome; D013057:Spectrum Analysis; D013272:Stomach Diseases / Q000188:drug therapy*; D013729:Terpenes / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology*
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000897:Anti-Ulcer Agents; D020011:Protective Agents; D013729:Terpenes; D064747:Lansoprazole