Antinociceptive Effects of Aza-Bicyclic Isoxazoline-Acylhydrazone Derivatives in Different Models of Nociception in Mice.

BACKGROUND: In a study recently published by our research group, the isoxazoline-acylhydrazone derivatives R-99 and R-123 presented promising antinociceptive activity. However, the mechanism of action of this compound is still unknown. OBJECTIVE: This study aimed to assess the mechanisms involved in the antinociceptive activity of these compounds in chemical models of pain. METHODS: Animals were orally pretreated and evaluated in the acetic acid-, formalin-, capsaicin-, carrageenan- and Complete Freund's Adjuvant (CFA)-induced pain models in mice. The effects of the compounds after pretreatment with naloxone, prazosin, yohimbine, atropine, L-arginine, or glibenclamide were studied, using the acetic acid-induced writhing test to verify the possible involvement of opioid, α1-adrenergic, α2-adrenergic or cholinergic receptors, and nitric oxide or potassium channels pathways, respectively. RESULTS: R-99 and R-123 compounds showed significant antinociceptive activity on pain models induced by acetic acid, formalin, and capsaicin. Both compounds decreased the mechanical hyperalgesia induced by carrageenan or CFA in mice. The antinociceptive effects of R-99 and R-123 on the acetic acid-induced writhing test were significantly attenuated by pretreatment with naloxone, yohimbine or atropine. R-99 also showed an attenuated response after pretreatment with atropine and glibenclamide. However, on the pretreatment with prazosin, there was no change in the animals' response to both compounds. CONCLUSION: R-99 and R-123 showed antinociceptive effects related to mechanisms that involve, at least in part, interaction with the opioid and adrenergic systems and TRPV1 pathways. The compound R-99 also interacts with the cholinergic pathways and potassium channels.

The Fatty Acid Composition of Vegetable Oils and Their Potential Use in Wound Care.

OBJECTIVE: To evaluate the similarities among fatty acid compositions of vegetable oils sold in the Brazilian market and those present in a reference health product used to treat wounds. METHODS: The relative amounts of fatty acids in 21 types of vegetable oils, purchased in the Brazilian market, were assessed using gas chromatography-mass spectrometry and flame ionization detection. MAIN RESULTS: The studied oils had similar fatty acid compositions to the reference product (caprylic acid, 18.8%; capric acid, 17.4%; oleic acid, 27.5%; and linoleic acid, 28.1%). The presence of caprylic acid (10.45% ± 0.07%), capric acid (5.8% ± 0.75%), lauric acid (45.63% ± 0.93%), and myristic acid (16.33% ± 2.23%) were detected in all the vegetable oils tested. Oleic acid (52.94% ± 12.54%) was present in andiroba, avocado, canola, copaiba, olive, palm, pequi, and pracaxi oils and featured prominently in olive oil (75.8%). Linoleic acid (57.09% ± 8.47%) was present in corn, cottonseed, grapeseed, passion fruit, and sunflower oils and in mixed oils (olive with soybean and sunflower with corn and canola). CONCLUSIONS: Most of the vegetable oils tested are products of plants from tropical climates, where they are abundant and easy to cultivate. It is possible that a balanced composition of fatty acids obtained from natural sources could be an effective alternative treatment for wounds.

Evaluation of anti-inflammatory activity and molecular docking study of new aza-bicyclic isoxazoline acylhydrazone derivatives.

The aim of this study was to investigate the anti-inflammatory effects of two new isoxazoline-acylhydrazone derivatives: N'-(4-methoxybenzylidene)-6-(4-nitro-benzoyl)-3a,5,6,6a-tetrahydro-4H-pyrrolo[3,2-d]isoxazole-3-carbohydrazide (R-123) and N'-(4-chlorobenzylidene)-6-(4-chlorobenzoyl)-3a,5,6,6a-tetrahydro-4H-pyrrolo[3,2-d]isoxazole-3-carbohydrazide (R-99). An air pouch induced by carrageenan was used for screening the best dose of R-99 and R-123. Using this mouse model, leukocyte migration and cytokine levels (TNF-α and IL-1ß) were determined. Paw edema induced by several phlogistic agents and vascular permeability induced by acetic acid were employed to investigate the mechanism of action of the isoxazoline-acylhydrazone derivatives. A docking study was performed with the human histamine H1 receptor to investigate potential antihistaminic activity. Treatment with the compounds reduced leukocyte migration in the air pouch at all doses tested. TNF-α and IL-1ß levels were similarly reduced by the two compounds. Vasoactive amines were inhibited in models of paw edema induced by several agents and vascular permeability induced by acetic acid. The docking study suggests that R-99 and R-123 may be inhibitors of the histamine H1 receptor. In conclusion, the results indicate that R-99 and R-123 exhibit promising anti-inflammatory activity related to their ability to inhibit TNF-α, IL-1ß, and vasoactive amine production, as well as reduce leukocyte migration and inhibit mast cell degranulation.

Antitumor activity of leaves of himatanthus drasticus (mart. ) plumel-apocynaceae (janaguba) in the treatment of Sarcoma 180 tumor

Himatanthus drasticus, also known as janaguba, is used popularly in Brazil's Northeastern region in the treatment of cancer. However, no scientific reports are available. The present study is the first investigation on the antitumor activity of crude methanolic extract from Himatanthus drasticus leaves against Sarcoma 180 tumor and on its side effects including acute oral toxicity. The OECD 423 methodology was used to study acute oral toxicity, and the STOCK methodology to assess antitumor activity. The crude extract showed low toxicity at the tested doses (50, 300 and 2000 mg/kg) administered orally. The histopathological analyses demonstrated alterations in liver lung, spleen and kidney. It also showed activity against Sarcoma 180 tumor in male Swiss albino mice, evidencing tumor growth inhibition of 67.7 percent and 68 percent at 300 mg/kg and 400 mg/kg doses, respectively.

Himatanthus drasticus, conhecida popularmente como janaguba, tem uma longa história de emprego na cura do câncer no nordeste brasileiro, porém quase sem registro na literatura. O objetivo desse trabalho foi investigar a atividade antitumoral do extrato bruto metanólico das folhas de Himatanthus drasticus frente ao modelo experimental Sarcoma 180 e avaliar sua toxicidade aguda. A determinação da toxicidade aguda foi realizada segundo a metodologia da OECD 423 e o transplante do tumor sólido de sarcoma 180 foi realizado seguindo a metodologia de Stock. O extrato apresentou baixa toxicidade nas doses testadas (50, 300 e 2000 mg/kg) por via oral. A análise histopatológica apresentou alterações em nível hepático, pulmonar, baço e renal. A atividade antineoplásica apresentou inibição tumoral significativa em relação ao grupo controle nas doses de 300 mg/kg e 400 mg/kg de peso do animal com um percentual de inibição de 67.7 por cento e 68 por cento respectivamente. Na menor dose analisada, 200 mg/kg, o percentual de inibição tumoral foi apenas de 32.8 por cento.