Gastroprotective effect and cytotoxicity of abietane diterpenes from the Chilean Lamiaceae Sphacele chamaedryoides (Balbis) Briq.
OBJECTIVE
The aim of this report was to isolate, identify and assess the gastroprotective effect and cytotoxicity of abietane diterpenes from the Chilean medicinal plant Sphacele chamaedryoides (Balbis) Briq. (Lamiaceae).


METHODS
The isolated compounds were identified by spectroscopic means. The gastroprotective effect of the compounds was studied on the HCl/EtOH-induced gastric lesions model in mice. The cytotoxicity of the compounds was assessed on human normal lung fibroblasts (MRC-5) and gastric adenocarcinoma cells (AGS).


RESULTS
From the aerial parts of the plant, five phenolic and five p-quinone abietanes, the sesquiterpene spathulenol and two flavonoids were obtained. The main diterpene from the plant was carnosol (7:). Lansoprazole at 20 mg/kg reduced gastric lesions by 64.7% (P < 0.01), being statistically similar to carnosol at doses of 10 and 20 mg/kg; the percent lesion reduction with 7: at 5 mg/kg was 49.3%. At a single oral dose of 5 mg/kg, the diterpenes bearing a p-quinone moiety - 6,7-dehydroroyleanone (1), royleanone (2), 7,20-epoxyroyleanone (3), taxoquinone (5) and horminone (6) - presented a gastroprotective effect of 54.4, 70.8, 65.0, 35.8 and 52.7%, respectively. Of the C-7 hydroxy derivatives, the activity was much lower for the 7beta-OH isomer. The phenolic diterpenes 7 and 7-oxo-11,12,14-trihydroxy-8,11,13-abietatrien-20-al (8) inhibited gastric lesions by 49.3 and 53.0%, respectively. Royleanone (2), 7,20-epoxyroyleanone (3), horminone (6), 8 and spathulenol proved to be cytotoxic with IC50 values in the range of 11-67 microm. The selective cytotoxicity of compounds 1 (IC50: 61 and 366 microm) and 5 (IC50: 310 and 27 microm) against AGS cells and fibroblasts, respectively, merit additional studies.


CONCLUSIONS
All the abietanes obtained from S. chamaedryoides present either one or two phenolic OH groups, a quinone system, or both. Several compounds present in the plant showed higher gastroprotective effect than lansoprazole. The cytotoxic effect of most compounds was found at fairly high concentrations and lacked cell specificity. Further studies are required using different tumour cell lines and viability/proliferation assays to assess the specificity of the isolated compounds. The selective cytotoxicity of compounds 1 and 5 against AGS cells and fibroblasts, respectively, merit additional studies.
Areche
Carlos
C
Laboratorio de Productos Naturales, Instituto de Química de Recursos Naturales, Universidad de Talca, Talca, Chile.
Schmeda-Hirschmann
Guillermo
G
Theoduloz
Cristina
C
Rodríguez
Jaime A
JA
D053799:2-Pyridinylmethylsulfinylbenzimidazoles / Q000494:pharmacology / Q000627:therapeutic use; D045784:Abietanes / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use*; D000230:Adenocarcinoma / Q000188:drug therapy*; D000818:Animals; D000897:Anti-Ulcer Agents / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use*; D000972:Antineoplastic Agents, Phytogenic / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use*; D002460:Cell Line; D045744:Cell Line, Tumor; D006801:Humans; D019686:Lamiaceae / Q000737:chemistry*; D064747:Lansoprazole; D008168:Lung; D008297:Male; D051379:Mice; D008517:Phytotherapy; D035261:Plant Components, Aerial; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D013270:Stomach / Q000187:drug effects* / Q000473:pathology; D013274:Stomach Neoplasms / Q000188:drug therapy*
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D045784:Abietanes; D000897:Anti-Ulcer Agents; D000972:Antineoplastic Agents, Phytogenic; D010936:Plant Extracts; D064747:Lansoprazole; C068623:carnosol