Toxicity and antitumor potential of Mesosphaerum sidifolium (Lamiaceae) oil and fenchone, its major component.

BACKGROUND: The essential oil from Mesosphaerum sidifolium (L'Hérit.) Harley & J.F.B.Pastore (syn. Hyptis umbrosa), Lamiaceae (EOM), and its major component, have been tested for toxicity and antitumor activity. METHODS: EOM was obtained from aerial parts of M. sidifolium subjected to hydro distillation, and gas chromatography-mass spectrometry was used to characterize the EOM chemical composition. The toxicity was evaluated using haemolysis assay, and acute toxicity and micronucleus tests. Ehrlich ascites carcinoma model was used to evaluate the in vivo antitumor activity and toxicity of EOM (50, 100 and 150 mg/kg), and fenchone (30 and 60 mg/kg) after 9 d of treatment. RESULTS: The EOM major components were fenchone (24.8%), cubebol (6.9%), limonene (5.4%), spathulenol (4.5%), ß-caryophyllene (4.6%) and α-cadinol (4.7%). The HC50 (concentration producing 50% haemolysis) was 494.9 µg/mL for EOM and higher than 3000 µg/mL for fenchone. The LD50 for EOM was approximately 500 mg/kg in mice. The essential oil induced increase of micronucleated erythrocytes only at 300 mg/kg, suggesting moderate genotoxicity. EOM (100 or 150 mg/kg) and fenchone (60 mg/kg) reduced all analyzed parameters (tumor volume and mass, and total viable cancer cells). Survival also increased for the treated animals with EOM and fenchone. For EOM 150 mg/kg and 5-FU treatment, most cells were arrested in the G0/G1 phase, whereas for fenchone, cells arrested in the S phase, which represents a blockage in cell cycle progression. Regarding the toxicological evaluation, EOM induced weight loss, but did not induce hematological, biochemical or histological (liver and kidneys) toxicity. Fenchone induced decrease of AST and ALT, suggesting liver damage. CONCLUSIONS: The data showed EOM caused in vivo cell growth inhibition on Ehrlich ascites carcinoma model by inducing cell cycle arrest, without major changes in the toxicity parameters evaluated. In addition, this activity was associated with the presence of fenchone, its major component.

Main ion channels and receptors associated with visceral hypersensitivity in irritable bowel syndrome.

Irritable bowel syndrome (IBS) is a very frequent functional gastrointestinal disorder characterized by recurrent abdominal pain or discomfort and alteration of bowel habits. The IBS physiopathology is extremely complex. Visceral hypersensitivity plays an important role in the pathogenesis of abdominal pain in both in vitro and in vivo models of this functional disorder. In order to obtain a general view of the participation of the main ion channels and receptors regarding the visceral hypersensitivity in the IBS and to describe their chemical structure, a literature review was carried out. A bibliographical research in the following electronic databases: Pubmed and Virtual Library in Health (BVS) was fulfilled by using the search terms "ion channels" "or" "receptors" "and" "visceral hypersensitivity" "or" "visceral nociception" "and" "irritable bowel syndrome". Original and review articles were considered for data acquisition. The activation of the ATP ion-gated channels, voltage-gated sodium (Nav) and calcium (Cav) channels, as well as the activation of protease-activated receptors (PAR2), transient receptor potential vanilloide-1, serotonin, cannabinoids and cholecystokinin are involved in the genesis of visceral hypersensitivity in IBS. The involvement of ion channels and receptors concerning visceral hypersensitivity is noteworthy in IBS models.