Anti-inflammatory evaluation of Coronopus didymus in the pleurisy and paw oedema models in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Mastrunço (Coronopus didymus--CD) is currently considered as a medicinal specie often used in Brazil, especially in southeast region, for the treatment of several diseases in which pain and inflammation are common. Treatment with the plant can be done by infusion, decoction, or through food. The aim of this study was: to investigate the anti-inflammatory effect of hydroalcoholic extract obtained from the leaves of CD following the traditional procedure. MATERIALS AND METHODS: The anti-inflammatory activity was determined using mouse of pleurisy and paw oedema models, both process being induced by different flogistic agents such as: carrageenan (Cg), bradykinin (BK), histamine (HIS), substance P (SP), dextran (DEX) or prostaglandin E(2) (PGE(2)). We evaluated the effect of CD (200-600 mg/kg) administered by oral route (p.o.) upon leukocytes migration, myeloperoxidase (MPO), and adenosine-deaminase (ADA) activities and nitric oxide (NO) levels. RESULTS: CD (200-600 mg/kg) inhibited the leukocytes by 60.0+/-1.42%, neutrophils by 82.75+/-1.29%, MPO by 42.30+/-4.23%, and ADA activities by 57.89+/-1.94%, as well as NO levels by 64.28+/-2.15% in Cg induced pleurisy. CD also inhibited total and differential leukocytes in the pleurisy induced by BK (1.30+/-0.11/0.29+/-0.02), HIS (1.20+/-0.09/0.42+/-0.05) and SP (0.74+/-0.06/0.14+/-0.01). In addition, CD was effective in reducing paw oedema induced by Cg by 72.79+/-1.13%, SP by 68.26.+/-0.78%, BK by 66.66.+/-0.77%, PGE(2) by 53.346.+/-1.18 and DEX by 65.14+/-2.35%. CONCLUSION: Several mechanisms, including the inhibition of enzymes (MPO and ADA) and mediators (BK, HIS, SP, NO and PGE(2)) release and/or action, appear to account for the anti-inflammatory effect of Coronopus didymus.

Evaluation of behavioral and pharmacological effects of Hedyosmum brasiliense and isolated sesquiterpene lactones in rodents.

ETHNOPHARMACOLOGICAL RELEVANCE: Hedyosmum brasiliense Miq. (Chloranthaceae) is an essential Brazilian species largely found in the Atlantic Forest. It is popularly known as "cidrão" and in folk medicine, this aromatic species is widely used as a calmative/tranquilizer and to treat sleep disorders. AIM OF THE STUDY: To examine the neurochemical properties of ethanol extract (EEHb), fractions and compounds of fresh leaves of Hedyosmum brasiliense and the antidepressant effect of the isolated sesquiterpene lactones podoandin and 13-hydroxy-8,9-dehydroshizukanolide. MATERIALS, METHODS AND RESULTS: The effects of EEHb were demonstrated by the open field, elevated-plus-maze, forced swimming, pentobarbital-induced sleeping time, PTZ-induced seizure, and inhibitory avoidance tests. EEHb did not show a protective effect against PTZ-induced convulsions. In the plus-maze test, EEHb (100mg/kg, i.p.) exhibited an anxiolytic effect through the effective enhancement of the frequency and time spent in the open arms of the maze. Conversely, the time spent and the number of entrances to the closed arms were decreased. All these effects were also completely reversed by pre-treatment with flumazenil (2.5mg/kg, i.p./a benzodiazepine receptor agonist), similar to the results observed with diazepam used as a positive standard. In this test, the anxiolytic effect of EEHb was also totally blocked by pre-treatment with reserpine (2.0mg/kg, i.p.), a drug known to induce depletion of biogenic amines. In the forced swimming test, the treatment of EEHb (100mg/kg, i.p. or 100mg/kg, p.o.) given in acute and chronic form (10, 50 and 100mg/kg), produced a decrease in immobility time, similar to that of imipramine (10mg/kg, i.p.), the positive control. The dichloromethane and hexane fractions (100mg/kg, p.o.) also produced a decrease in immobility time. In addition, the two isolated compounds tested in a single dose (10mg/kg, i.p.), the antidepressant effect was observed only with the compound podoandin, which also caused a decrease in immobility time. EEHb (10-100mg/kg) a dose-dependent manner also caused a decrease in barbiturate sleeping time in mice, and in high doses (100mg/kg), did not interfere in memory consolidation. CONCLUSIONS: The results suggest that EEHb presents psychopharmacological activities, including anxiolytic, antidepressant, and hypnotic effects.

Antinociceptive action of limonexic acid obtained from Raulinoa echinata.

The antinociceptive effect of the limonexic acid isolate of Raulinoa echinata Cowan in four models of pain in mice is described. When evaluated against acetic acid-induced abdominal constrictions, limonexic acid (10, 30 and 60 mg kg(-1), i.p.) produced dose-related inhibition of the number of constrictions, with a mean ID50 value of 43 (2.3-79) micromol kg(-1), and was more potent than some standard drugs. In the formalin test, limonexic acid inhibited both the first and second phases of formalin-induced pain. Furthermore, the effect was more pronounced in the second phase, with a mean ID50 value of 13.66 (9.35-19.61) micromol kg(-1), and had a pharmacological profile that was similar to standard drugs such as acetaminophen and acetyl salicylic acid. Limonexic acid also produced dose-related inhibition of glutamate- and capsaicin-induced pain, with mean ID50 values of 11.67 (8.51-16.0) micromol kg(-1) and 47.17 (36.51-60.93) micromol kg(-1), respectively. The mechanism of action is not completely understood, but seems to involve direct interaction with the GABAergic and nitroxidergic pathways.

Effects of NS1608, a BK(Ca) channel agonist, on the contractility of guinea-pig urinary bladder in vitro.

1. The functional effects of NS1608 ((N-(3-(trifluoromethyl)phenyl)-N'-(2-hydroxy-5-chlorophenyl)urea), an opener of the large conductance, Ca2+-activated K+ (BK(Ca)) channel, on the contractility of guinea-pig urinary bladder muscle are described. 2. NS1608 (0.3-30 microM) had no significant effect on the integrated myogenic activity (tension integral) or the electrically evoked twitches of detrusor muscle strips. Possible mechanisms for the discrepancy between the lack of functional effects of NS1608 per se on detrusor contractility and this drug's agonistic effect on BK(Ca) currents in isolated bladder myocytes are discussed. 3. 4-Aminopyridine (1 mM), a blocker of voltage-gated K+ (K(V)) channels, increased the tension integral 2.7-fold, on average. NS1608 (30 microM) counteracted this effect. 4. Apamin (100 nM), a selective blocker of the small conductance, Ca2+-activated K+ (SK(Ca)) channel, increased the tension integral 1.7-fold, on average. This effect was reversed by NS1608 (30 microM). 5. Ryanodine (10 microM), a modulator of the sarcoplasmic reticulum (SR) Ca2+-release channel, increased the tension integral 1.9-fold, on average. This effect was reversed by NS1608 (30 microM). 6. Iberiotoxin (IbTX, 50 nM), a selective blocker of the BK(Ca) channel, caused additional increases in the tension integral of detrusor strips pretreated with apamin or ryanodine and prevented the inhibitory effects of NS1608 (30 microM) in detrusor contractility. 7. The present study shows that blockade of repolarizing currents carried by, respectively apamin- and 4-aminopyridine-sensitive K+ channels unmasks an activation of BK(Ca) in guinea-pig urinary bladder smooth muscle strips.