Avaliação da atividade antiinflamatória do coentro (Coriandrum sativum L. ) em roedores / Evaluation of the anti-inflammatory activity of coriander (Coriandrum sativum L. ) in rodents

Coriandrum sativum L. (Umbelliferae), conhecido popularmente por coentro, é uma planta doméstica cultivada nas diversas partes do mundo, inclusive no Brasil. As folhas e frutos do coentro são utilizados como condimento em culinária e na medicina popular como analgésica, antirreumática, carminativa e colagoga. O objetivo deste estudo foi avaliar o efeito do tratamento com o óleo essencial (OEC) e o extrato hidroalcóolico (EHC) do coentro em modelos experimentais de inflamação em roedores. A atividade antiinflamatória do coentro foi avaliada por meio dos testes de pleurisia em ratos e formação do edema de orelha em camundongos. A pleurisia foi induzida pela carragenina em animais tratados ou não com EHC. O edema de orelha induzido pela aplicação tópica de óleo de cróton e a atividade da mieloperoxidase foi avaliada em camundongos tratados ou não com OEC ou EHC. No teste da pleurisia o tratamento com EHC promoveu significativa diminuição no edema pleural, mas não sobre a migração leucocitária. Além disso, diferentemente ao observado com o tratamento com OEC, o uso tópico de EHC diminui significativamente o edema de orelha e a migração celular induzidos pela aplicação do óleo de cróton. Os dados indicam que EHC apresenta atividade antiinflamatória quando administrado pelas via oral e tópica, enquanto que OEC não apresenta atividade antiinflamatória tópica.

Commonly known as coriander, Coriandrum sativum L. (Umbelliferae) is a home plant grown in several parts of the world, including Brazil. Its leaves and fruits have been used as condiment in cooking and in folk medicine as analgesic, antirheumatic, carminative and cholagogue. The aim of this study was to evaluate the effect of essential oil (EO) and hydroalcoholic extract (HE) from coriander on experimental inflammation models in rodents. Coriander anti-inflammatory activity was evaluated by pleurisy tests in rats and ear edema formation in mice. Pleurisy was induced by carrageenan in HE-treated or non-treated animals. The ear edema was induced by topical application of croton oil and the myeloperoxidase activity was evaluated in EO-treated and HE-treated or non-treated mice. In the pleurisy test, HE treatment significantly decreased pleural edema but not the leukocyte migration. Furthermore, differently from EO, the topical use of HE significantly decreased ear edema and cell migration induced by croton oil application. The results indicate that HE had anti-inflammatory activity when orally and topically administered, whereas EO did not present topical anti-inflammatory activity.

The role of adrenal corticosteroids in the anti-inflammatory effect of the whole extract of Harpagophytum procumbens in rats.

This study was carried out to evaluate whether the anti-inflammatory response in rats to the whole extract of Harpagophytum procumbens is a consequence of adrenal corticosteroid release. Carrageenan-induced inflammatory responses in the hindpaws were evaluated in control, sham-operated and adrenalectomized rats. The extract was administered orally (by gavage) or intraperitoneally, 30min prior to injury stimulus. Blood samples were then collected, and the number of circulating leukocytes was estimated. Pretreatment with the whole extract of H. procumbens reduced the intensity of inflammatory response in normal, sham-operated and adrenalectomized animals. When administered orally, the extract was ineffective. The reduced number of circulating leukocytes observed following intraperitoneal injection of the extract characterized adrenal hyperactivity. The inhibitory effect of the whole extract of H. procumbens on acute inflammatory response in the rat, when administered intraperitoneally, does not depend on the release of adrenal corticosteroids.

Efficiency of combined methotrexate/chloroquine therapy in adjuvant-induced arthritis.

The present study evaluates the effects of methotrexate (MTX) and chloroquine (CQ), and of combined MTX + CQ treatment, on the inflammatory response and on plasma and liver phosphatase and transaminase activities, employing an adjuvant-induced arthritis model in rats. Arthritis was induced by the intradermal injection of a suspension of Mycobacterium tuberculosis in mineral oil into the plantar surface of the hind paws. Development of the inflammatory response was assessed over a 21-day period. Animal groups received either: (i) MTX, administered i.p., weekly, in 0.15, 1.5, 3, 6 or 12 mg/kg doses; (ii) CQ, given intragastrically, in daily 25 or 50 mg/kg doses; or (iii) MTX + CQ, administered in two combinations (MTX1.5 mg/kg + CQ50 mg/kg, or MTX6 mg/kg + CQ50 mg/kg). At the end of the experimental period, the animals were anesthetized and killed, blood and liver samples were collected and prepared for measurement of acid and alkaline phosphatase (AP, ALP), and aspartate (AST) and alanine aminotransferase (ALT) activities. MTX at 6 and 12 mg/kg reduced the inflammatory response while CQ had no effect. MTX6 mg/kg + CQ50 mg/kg reduced the inflammatory response similar to MTX12 mg/kg, without affecting the bone marrow. Plasma AP and liver ALP activities were very elevated in the arthritic rats. While MTX treatment partially reduced both plasma AP and liver ALP activities at all doses used in the arthritic rats, CQ treatment reduced plasma AP, but increased liver AP activity. MTX + CQ treatment decreased plasma AP and liver ALP activities in the arthritic rats to control values. Plasma and liver AST activities were unaltered in the arthritic rats, and were unaffected by treatment. However, plasma and liver ALT activities were significantly reduced in the arthritic rats. While MTX or CQ treatment did not alter plasma transaminase activity in the arthritic rats, after MTX + CQ treatment, plasma ALT activity returned to normal values. In conclusion, the present data suggest that MTX + CQ treatment provides more effective anti-inflammatory protection against adjuvant-induced arthritis than does MTX alone, reverting the alterations in enzyme activities induced by this inflammatory disease in rats.

Immunomodulatory effect of Canova medication on experimental Leishmania amazonensis infection.

This study investigates the action of Canova medication (CM) on experimental infection by Leishmania (Leishmania) amazonensis, utilizing in vitro and in vivo assays. For the in vitro tests, Balb/c mouse peritoneal macrophages (5x10(5) cells in 500 microl of culture medium, supplemented with 10% fetal calf serum, penicillin (100 U/ml) and streptomycin (0.1 mg/ml) (were distributed in 24-well plates and CM was added at concentrations of 20 or 40%. Twenty-four hours later, the macrophages were infected with Leishmania amastigotes in culture medium. The effect of CM on macrophages leishmanicidal activity in 24 and 48 h cultures was evaluated by determining infection index and measuring nitric oxide (NO) production. The in vivo tests were performed in mice infected with 10(7)L. (L.) amazonensis promastigotes injected in to the right hind footpad (25 microl in phosphate buffered saline). The progression of the lesions was examined over a 9-week period by measuring footpad swelling, and the parasite load in regional lymph nodes and spleen. The in vitro results showed that at 40% CM reduced the infection index, and induced NO production in the elicited macrophages, which suggests that the inhibitory effect on infection index may be mediated by NO. In the in vivo infection, when administered, orally or subcutaneously in mice, CM reduced infection by L. (L.) amazonensis in the paws, resulting in smaller lesions. CM treatment also decreased parasite load in the regional popliteal lymph nodes and in the spleen. These results suggest that CM modulates experimental infection by L. (L.) amazonensis, controlling infection progression and limiting dissemination.

Glycogen levels and glycogen catabolism in livers from arthritic rats.

Hepatic glycogen catabolism and glycogen levels in rats with chronic arthritis were investigated. At 9:00 a.m., the hepatic glycogen contents of ad libitum fed arthritic and normal rats were 225.5+/-17.7 and 332.1+/-28.6 micromol glucosyl units x (g liver)(-1), respectively. Food intake of arthritic and normal rats was equal to 100.1+/-6.7 and 105.0+/-3.1 mg x (g body w)(-1) x (per 24 h)(-1), respectively. In isolated perfused livers from normal and arthritic rats the rates of glucose, lactate and pyruvate release were the same when substrate- and hormone-free perfusion was performed. During an infusion period of 20 min glucagon caused an increment in glucose release of 35.3+/-4.7 micromol x (g liver)(-1) in livers from arthritic rats; in the normal condition the corresponding increment was 69.6+/-5.7 micromol x (g liver)(-1). Lactate and pyruvate productions (indicators of glycolysis) were diminished by glucagon in livers from normal rats; in the arthritic condition an initial stimulation was found, followed by a slow decay, which did not result in significant inhibition at the end of the glucagon infusion period (20 min). The actions of cAMP and dibutyryl-cAMP were similar to those of glucagon. It was concluded that livers from arthritic rats show an impaired capacity of releasing glucose under the stimulus of glucagon. This can be partly due to the lower glycogen levels and partly to a smaller capacity of inhibiting glycolysis. Reduction in glycogen levels was not associated with reduction in food intake or failure in the energetic state of the hepatic cells. These changes in glycogen metabolism may be related to reduced gluconeogenic capacity of the livers and/or to production of inflammatory mediators observed in the arthritis disease.

The uncoupling effect of the nonsteroidal anti-inflammatory drug nimesulide in liver mitochondria from adjuvant-induced arthritic rats.

The aim of the present study was to evaluate the changes caused by adjuvant-induced arthritis in liver mitochondria and to investigate the effects of the nonsteroidal anti-inflammatory drug nimesulide. The main alterations observed in liver mitochondria from arthritic rats were: higher rates of state IV and state III respiration with beta-hydroxybutyrate as substrate; reduced respiratory control ratio and impaired capacity for swelling dependent on beta-hydroxybutyrate oxidation. No alterations were found in the activities of NADH oxidase and ATPase. Nimesulide produced: (1) stimulation of state IV respiration; (2) decrease in the ADP/O ratio and in the respiratory control ratio; (3) stimulation of ATPase activity of intact mitochondria; (4) inhibition of swelling driven by the oxidation of beta-hydroxybutyrate; (5) induction of passive swelling due to NH(3)/NH(4)+ redistribution. The activity of NADH oxidase was insensitive to nimesulide. Mitochondria from arthritic rats showed higher sensitivity to nimesulide regarding respiratory activity. The results of this work allow us to conclude that adjuvant-induced arthritis leads to quantitative changes in some mitochondrial functions and in the sensitivity to nimesulide. Direct evidence that nimesulide acts as an uncoupler was also presented. Since nimesulide was active in liver mitochondria at therapeutic levels, the impairment of energy metabolism could lead to disturbances in the liver responses to inflammation, a fact that should be considered in therapeutic intervention.

Effect of Maytenus aquifolium extract on the pharmacokinetic and antiinflammatory effectiveness of piroxicam in rats.

This study explored the interference by Maytenus aquifolium leaves hydroalcoholic (MALHE) extract, administered orally, on the pharmacokinetic and antiinflammatory activity of piroxicam in rats. The results showed no significant difference in piroxicam bioavailability with simultaneous application of MALHE. MALHE also had no effect on the inhibitory effect of piroxicam on inflammatory processes induced by carrageenan and complete Freund adjuvant.

Effects of the nonsteroidal anti-inflammatory drug nimesulide on energy metabolism in livers from adjuvant-induced arthritic rats.

The effects of nimesulide on energy metabolism and the hepatic metabolic alterations produced by adjuvant-induced arthritis were investigated in the perfused rat liver an in isolated liver mitochondria. Nimesulide, at therapeutic levels (20-50 microM), produced: (1) stimulation of oxygen consumption in the perfused rat liver and in isolated mitochondria, (2) inhibition of gluconeogenesis; (3) reduction of ADP/O ratio and the respiratory control ratio and stimulation of glycogenolysis in the livers from healthy rats, but not in livers from arthritic rats. These results indicate that nimesulide acts as a mitochondrial uncoupler. The main alterations produced by adjuvant-induced arthritis were: higher rates of oxygen consumption in both perfused livers and isolated mitochondria, with no decrease in the efficiency of mitochondrial energy transduction; (2) decreased gluconeogenesis and lack of glycogenolytic response to uncouplers, but not to alpha 1-agonists. These data allow to conclude that nimesulide-induced impairment of energy metabolism should worsen the hepatic disturbances that are already associated with the adjuvant disease.