Atividade antiinflamatória, antinociceptiva, e gastroprotetora do óleo essencial de croton sonderianus muell. arg.

Abstract

Croton sonderianus,locally know as “marmeleiro-preto” is a reputed popular remedy for the treatment of stomach ache, uterine bleeding, and in the control of vomitions and diarrhoea. The present study evaluated the essential oil obtained from leaves of Croton sonderianus (EOCS) in murine models of acute inflammation, nociception and against gastric lesions induced by ethanol and indomethacin, all of the experiments were accomplished in male mice. In models of acute inflammation, EOCS failed to inhibit carrageenan-induced paw edema in a manner similar to indomethacin; however, EOCS (200 mg/Kg, p.o.) was effective against dextran-induced paw edema, similar to cyproheptadine, an H1 and 5-HT receptor antagonist. Also, EOCS (100 and 200 mg/Kg, p.o.) could effectively suppress the ear edema induced by topical application of Croton oil. These results suggest that the anti-inflammatory activity of EOCS may be related mostly to the inhibition of histamine and serotonin than to inhibition of synthesis/liberation of prostaglandins. Similar to acetylsalicylic acid, EOCS demonstrated antinociceptive activity against acetic acid-induced writhing at the oral doses of 50, 100 and 200 mg/Kg. In formalin test, EOCS (100 and 200 mg/Kg, p.o.) similar to morphine (7,5 mg/Kg, i.p.) showed significant (p<0,01) antinociceptive activity at both neurogenic and inflammatory phases. The antinociception induced by EOCS (100 mg/Kg, p.o.) was found to be effectively antagonized by glibenclamide (2 mg/Kg, i.p.), a blocker of KATP-channels but not by Naloxone (1mg/Kg, s.c.), a mi-opioid receptor antagonist. In addition, EOCS (50, 100 and 200 mg/kg, p.o.) significantly suppressed the capsaicin- induced nociception, which was also significantly blocked by glibenclamide and not by naloxone. These results suggest the participation of the orphan receptors like 1 (ORL1) in the effect of EOCS. These receptors posses 60% of homology with opioid receptors, they are associated to channels of KATP and are sensitive to the glibenclamide but insensitive to the naloxone. Besides, EOCS seems to exercise only a peripheral and or spinal level of action since it failed to produced antinociceptive activity in hot-plate test that detects the supraspinal nociception. In the tests of locomotion (open-field) and sedation (pentobarbital-sleep time) EOCS did not show any significant influence indicating that the observed antinociception is unrelated to sedative or CNS depressant effects of EOCS. Against gastric lesions induced by ethanol, EOCS offered gastroprotection at oral doses of 50 and 200 mg/Kg in a manner similar to capsaicin (5 mg/Kg, p.o.), a compound that stimulates gastric mucus, and N-acetylcysteine, a cellular antioxidant. At 50 mg/Kg, EOCS suppressed the gastric lesions induced by indomethacin (20 mg/Kg, p.o.) in a way similar to cimetidine (100 mg/Kg, p.o.), an antagonist H2. EOCS failed to influence the gastrointestinal transit in a significant manner and is free from overt toxicity. Oral administration up to 3 g/Kg did not cause any behavioral alteration or mortality in mice in the model of acute toxicity. In conclusion, EOCS possesses anti-inflammatory, antinocieptive and gastroprotective properties; the data obtained on the present study, associated to the literature ones, have suggested that guaiazulene, beta-caryophyllene and 1,8-cineole can contribute to the Pharmacological effects observed for EOCS.