title: Anti-inflammatory and antinociceptive effects in rodents of the essential oil of Croton cajucara Benth.
abstract: The plant Croton cajucara Benth. (Euphorbiaceae) is widely used in Amazonian folk medicine for the treatment of a wide range of illnesses. In this investigation the analgesic and anti-inflammatory properties of the essential oil from the bark of C. cajucara Benth., administered orally, were determined in several standard rodent models of pain and inflammation. We observed that pretreatment with essential oil significantly reduced the latency of sleeping time evoked by pentobarbital compared with the control group (P < 0.001). Doses of 100 or 1000 mg kg(-1) also increased the sleeping time induced by pentobarbital (30.9 +/- 3.91 and 52.1 +/- 15.6 min, respectively) compared with the negative control (12.4 +/- 4.27 min). We investigated the antinociceptive effect of the essential oil in chemical (acetic acid) and thermal (hot-plate) models of nociception in mice. Dipyrone (200 mg kg(-1)) and the highest doses of the essential oil (1000 mg kg(-1)) significantly inhibited acetic acid-induced abdominal constriction in mice (5.00 +/- 1.38 and 6.8 +/- 2.1 constrictions, respectively) compared with the negative control (33.1 +/- 2). The same dose of essential oil also raised the pain thresholds of mice in the hot-plate test and significantly (P < 0.05) increased the latency at all observation times. In acetic acid-induced abdominal constriction in mice pretreatment of the animals with naloxone (5 mg kg(-1)) significantly reversed the analgesic effect of morphine and of the essential oil at the highest dose (1000 mg kg(-1)). The essential oil of C. cajucara was also investigated for its anti-inflammatory properties. At the lowest dose (100 mg kg(-1)) the essential oil had anti-inflammatory effects in animal models of acute (carrageenin-induced paw oedema in mice) and chronic (cotton pellet granuloma) inflammation. The essential oil at doses of 50, 100 and 200 mg kg(-1) significantly and dose-dependently inhibited carrageenan-induced oedema (49 +/- 5; 37 +/- 5; 34 +/- 8 mg, respectively) compared with the negative control (74 +/- 8 mg). The essential oil (100 mg kg(-1)) also inhibited chronic inflammation by 38% whereas diclofenac inhibited it by 36%. However, the essential oil did not inhibit the migration of neutrophils into the peritoneal cavity. These data show that the essential oil from C. cajucara contains compounds that had a significant antinociceptive effect when the oil was administered at the highest dose. This effect seems to be related to interaction with the opioid system. The essential oil also had a significant anti-inflammatory effect in acute and chronic inflammation models when administered at lower doses. This effect seems to be related to cyclooxygenase inhibition.
authors.affiliation: Departimento de Farmacologia, Faculadade de Ciências Medicas, Kingston, Brazil.
authors.forename: E J
authors.initials: EJ
authors.lastname: Bighetti
authors.forename: C A
authors.initials: CA
authors.lastname: Hiruma-Lima
authors.forename: J S
authors.initials: JS
authors.lastname: Gracioso
authors.forename: A R
authors.initials: AR
authors.lastname: Brito
mesh_terms: D000701:Analgesics, Opioid / Q000302:isolation & purification / Q000494:pharmacology*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000302:isolation & purification / Q000494:pharmacology*; D001938:Brazil; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009822:Oils, Volatile / Q000302:isolation & purification / Q000494:pharmacology*; D010147:Pain Measurement; D010946:Plants, Medicinal / Q000737:chemistry*; D051381:Rats; D017208:Rats, Wistar; D019685:Rosales / Q000737:chemistry*
chemical_list: D000701:Analgesics, Opioid; D000893:Anti-Inflammatory Agents; D009822:Oils, Volatile