Marcelia Garcez Dória de Melo

Redox properties and cytoprotective actions of atranorin, a lichen secondary metabolite.

Atranorin (ATR) is a lichenic secondary metabolite with potential uses in pharmacology. Antinociceptive and antiinflammatory actions have been reported, and the use of atranorin-enriched lichen extracts in folk medicine is widespread. Nonetheless, very few data on ATR biological actions are available. Here, we evaluated free radical scavenging activities and antioxidant potential of ATR using various in vitro assays for scavenging activity against hydroxyl radicals, hydrogen peroxide, superoxide radicals, and nitric oxide. The total reactive antioxidant potential (TRAP) and total antioxidant reactivity (TAR) indexes and in vitro lipoperoxidation were also evaluated. Besides, we determined the cytoprotective effect of ATR on H(2)O(2)-challenged SH-SY5Y cells by the MTT assay. ATR exerts differential effects towards reactive species production, enhancing hydrogen peroxide and nitric oxide production and acting as a superoxide scavenger; no activity toward hydroxyl radical production/scavenging was observed. Besides, TRAP/TAR analysis indicated that atranorin acts as a general antioxidant, although it demonstrated to enhance peroxyl radical-induced lipoperoxidation in vitro. ATR was not cytotoxic, and also protected SH-SY5Y cells against H(2)O(2)-induced cell viability impairment. Our results suggest that ATR has a relevant redox-active action, acting as a pro-oxidant or antioxidant agent depending on the radical. Also, it will exert cytoprotective effects on cells under oxidative stress induced by H(2)O(2).

Antinociceptive activity of atranorin in mice orofacial nociception tests.

Physicochemical characterization and antinociceptive and anti-inflammatory activities of atranorin (AT) extracted from Cladina kalbii Ahti in formalin- and capsaicin-induced orofacial pain and anti-inflammatory tests in rodents were studied. Physicochemical characterization showed that AT has the general formula C19H18O8. Male Swiss mice were pretreated with AT (100, 200, and 400 mg/kg, i.p.), morphine (3 mg/kg, i.p.), or vehicle (0.9% saline with two drops of 0.2% Tween 80) before formalin (20 μl, 2%) or capsaicin (20 μl, 2.5 μg) were injected into the right vibrissa. Our results showed that i.p. treatment with AT displayed marked inhibitory effects in different orofacial pain tests in mice. AT (400 mg/kg, i.p.) was effective in reducing the nociceptive face-rubbing behavioural response in both phases of the formalin test, which was also naloxone-sensitive. Additionally, AT produced a significant antinociceptive effect at all doses in the capsaicin test. Such results were unlikely to be provoked by motor abnormality, since AT-treated mice exhibited no performance alteration on the rota rod apparatus. AT exhibited significant anti-inflammatory activity in the acute model of inflammation (leukocyte migration to the peritoneal cavity), carrageenan- and arachidonic acid-induced hind paw edema in rats. Additionally, AT exhibited a dose-dependent antioxidant activity in vitro, as assessed by total radical-trapping antioxidant parameter and total antioxidant reactivity assays. All these findings suggest that AT might represent an important tool for the management of orofacial pain and/or inflammatory disorders

Evidence of the mechanism of action of Erythrina velutina Willd (Fabaceae) leaves aqueous extract

ETHNOPHARMACOLOGICAL RELEVANCE Erythrina velutina is traditionally used for sleepiness, convulsions and nervous system excitation in Brazil. Although central effects have been reported for Erythrina velutina, little is known about its mechanism of action. AIM OF THE STUDY To investigate the pharmacological evidences of mechanism of action of Erythrina velutina leaves aqueous extract (AE). MATERIALS AND METHODS Terminal segments of the guinea-pig ileum (n=5-8) were mounted in an organ bath and isotonic contractions were recorded. Phytochemical screening was carried out on AE. RESULTS AE (0.025-2.50 mg/ml) produced contractile response in the guinea-pig ileum, yielding typical concentration-response curves (EC50=0.63 mg/ml). Electrically evoked contractions were significantly increased in the presence of AE. AE-elicited contractions were significantly reduced by bicuculline, tetrodotoxin, atropine, verapamil or incubation in low calcium-high potassium solution. Atropine along with verapamil abolished AE contractile response. Alkaloids, catechins, steroids, flavonols, flavononols, flavonoids, phenols, saponins, tannins, triterpenoids, and xanthones were detected in AE. CONCLUSIONS AE contains important constituents for pharmacological activities. AE-induced contractions seem to involve GABAA receptor activation, acetylcholine release, muscarinic receptor activation, augmentation of Ca2+ entry through L-type calcium channels, and calcium release from the intracellular stores. These findings provide further support for Erythrina velutina traditional uses.

Anti-inflammatory and toxicity studies of atranorin extracted from Cladina kalbii Ahti in rodents

Atranorina (ATR) e o principal composto do liquen Cladina kalbii Ahti, que cresce em terras aridas do nordeste brasileiro. Este estudo foi realizado para avaliar as propriedades antiinflamatorias e toxicologicas da ATR. Para avaliar as propriedades antiinflamatorias, o edema de pata foi induzido, administrando-se 0,1 mL de carragenina na regiao subplantar da pata traseira direita e a migracao leucocitaria foi induzida pela injecao de 500 µL de carragenina no peritonio. Alem disso, determinou-se a citotoxicidade da ATR, utilizando-se a linhagem celular L929, atraves do teste de MTT e dos testes de toxicidade aguda (5 g/kg - dose unica) e subcronica (50 mg/kg-30 dias) em ratos Wistar. Os resultados mostraram que nas doses de (100 mg/kg e 200 mg/kg) a ATR exibiu atividade antiinflamatoria significativa nos ensaios de edema de pata e migracao leucocitaria. Nos testes de toxicidade aguda, os animais apresentaram hipoatividade e letargia no periodo inicial (primeiras 6 horas) e aumento das proteinas totais, bilirrubinas total e indireta e fosfatase alcalina depois de 14 dias nos machos tratados. Para o ensaio subcronico, houve aumento das proteinas totais, gama-glutamil-transferase, fosfatase alcalina e bilirrubina total e direta nas femeas tratadas com ATR. Nao foram encontradas alteracoes na arquitetura e morfologia das lâminas histologicas observadas. Esses resultados sugerem que a ATR apresenta atividade antiinflamatoria significativa, sem apresentar significativa toxicidade aguda, subcronica e citotoxicidade.