Filicene obtained from Adiantum cuneatum interacts with the cholinergic, dopaminergic, glutamatergic, GABAergic, and tachykinergic systems to exert antinociceptive effect in mice.

In the present study, we describe the antinociceptive effect of filicene, a triterpene isolated from Adiantum cuneatum (Adiantaceae) leaves, in several models of pain in mice. When evaluated against acetic acid-induced abdominal constrictions, filicene (10, 30 and 60 mg/kg, i.p.) produced dose-related inhibition of the number of constrictions, being several times more potent [ID(50)=9.17 (6.27-13.18) mg/kg] than acetaminophen [ID(50)=18.8 (15.7-22.6) mg/kg], diclofenac [ID(50)=12.1(9.40-15.6) mg/kg] and acetylsalicylic acid [ID(50)=24.0(13.1-43.8) mg/kg] in the same doses as those used for the standard drugs. Filicene also produced dose-related inhibition of the pain caused by capsaicin and glutamate, with mean ID(50) values of 11.7 (8.51-16.0) mg/kg and <10 mg/kg, respectively. Its antinociceptive action was significantly reversed by atropine, haloperidol, GABA(A) and GABA(B) antagonists (bicuculline and phaclofen, respectively), but was not affected by L-arginine-nitric oxide, serotonin, adrenergic and the opioid systems. Together, these results indicate that the mechanisms involved in its action are not completely understood, but seem to involve interaction with the cholinergic, dopaminergic, glutamatergic, GABAergic and tachykinergic systems.

Relation between lipophilicity of alkyl gallates and antifungal activity against yeasts and filamentous fungi.

The antifungal activity of a complete series of 15 n-alkyl gallates and six analogues acting against a representative panel of opportunistic pathogenic fungi was studied in order to analyze their role in: the importance of the fungi tested, the importance of the hydroxyls, the influence of the chain length and the hydrophobicity of the compounds. It was demonstrated that dermatophytes were the most susceptible species and that hydroxyls appear to be necessary but not sufficient for the activity. When the logP of each gallate was calculated and related to the different values of MIC against Microsporum gypseum it was observed that hexyl, heptyl, octyl and nonyl gallates exhibit a significant positive deviation from the curve corresponding to a polynomial equation obtained for the other gallates. This suggests that these compounds have a further mode of action besides their hydrophobicity, possibly the inhibition of some enzyme involved in ergosterol biosynthesis.

Two new 11alpha,12alpha-epoxy-ursan-28,13beta-olides and other triterpenes from Cecropia catharinensis.

Three new triterpenes, 2alpha-acetoxy-3beta,19alpha-dihydroxy-11alpha,12alpha-epoxy-ursan-28,13beta-olide, 3beta-acetoxy-2alpha,19alpha-dihydroxy-11alpha,12alpha-epoxy-ursan-28,13beta-olide and 2-O-acetyl-euscaphic acid together eight known triterpenes were isolated from the roots and stems of Cecropia catharinensis. Their structures were determined by detailed analysis of NMR spectra and the relative configurations established by difference nOe experiments. In addition, four flavonoid glucosides (vitexin, isovitexin, orientin and isoorientin) were found in the leaves.

Analgesic potential of marrubiin derivatives, a bioactive diterpene present in Marrubium vulgare (Lamiaceae).

Marrubiin, a furane labdane diterpene, is the main analgesic compound present in Marrubium vulgare, a medicinal plant used in Brazil and other countries to treat several ailments. Considering its important pharmacological action, as well as its high yield, some structural modifications were performed in order to obtain more active compounds. Success was obtained in reducing the lactonic function, in the formation of marrubiinic acid and two esterified derivatives, which exhibited significant analgesic effect against the writhing test in mice. Marrubiinic acid showed better activity and excellent yield, and its analgesic effect was confirmed in other experimental models of pain in mice, suggesting its possible use as a model to obtain new and potent analgesic agents.

Pharmacological and phytochemical investigations of different parts of Calophyllum brasiliense (Clusiaceae).

Continuing our search for antinociceptive agents from natural sources, this study analyzed the antinociceptive effects of some fractions obtained from different parts (roots, flowers and fruits) of Calophyllum brasiliense, a Brazilian medicinal plant used to treat several diseases, including inflammation and pain. For this purpose, the writhing and formalin induced-pain models in mice were used. We also analyzed the chemical composition of these different parts and tested two pure compounds isolated from chloroform fraction (roots) identified as friedelin (1) and 1,5-dihydroxyxanthone (3), by direct comparison with authentic samples. The results showed that some fractions and both compounds exhibited considerable antinociception properties, particularly against the writhing test, and that these are more potent than acetyl salicylic acid and acetaminophen, two reference drugs used here for comparison.

Antifungal activity of fractions and two pure compounds of flowers from Wedelia paludosa (Acmela brasiliensis) (Asteraceae).

Wedelia paludosa (Acmela brasiliensis) (Asteraceae), a traditionally used native Brazilian medicinal plant, showed antifungal activity against dermatophytes in dilution tests. The hexane, dichloromethane and butanol fractions displayed activity against Epidermophyton floccosum, Trichophyton rubrum and Trichophyton mentagrophytes, with minimal inhibitory concentrations between 250 and 1000 microg/mL. Two pure compounds, identified as kaurenoic acid (1) and luteolin (2), also showed activity against these dermatophytes.

Antifungal activity of sterols and triterpenes isolated from Ganoderma annulare.

Three sterols, 5alpha-ergost-7-en-3beta-ol, 5alpha-ergosta-7,22-dien-3beta-ol and 5,8-epidioxy-5alpha,8alpha-ergosta-6,22-dien-3beta-ol and five triterpenes, applanoxidic acids A, C, F, G and H, have been isolated from Ganoderma annulare. The applanoxidic acids A, C and F were found to inhibit the growth of the fungi Microsporum cannis and Trichophyton mentagrophytes at concentrations of 500 to 1000 microg/ml.

Antinociceptive action of extracts and fractions from Rubus imperialis (Rosaceae).

Rubus imperialis is a Brasilian medicinal plant which previously exhibited therapeutical perspectives. This work describes the antinociceptive action of methanolic extracts obtained from different parts of the plant (roots and branches) as well as hexane, chloroform and ethyl acetate fractions obtained from branches. Such extracts or fractions caused significative inhibition in the writhing test in mice at 10 mg/kg, given intraperitoneally. They were more active than two reference drugs, aspirin and paracetamol. The fractions also exhibited antinociceptive activity in the writhing test when administered orally at 200 mg/kg. When analyzed in the formalin test, the chloroform fraction was the most active, causing considerable inhibition against both neurogenic and inflammatory phases of pain.

Hypolipidaemic activity of methanol extract of Aleurites moluccana.

The lipid-lowering action of the leaves of the Aleurites moluccana methanol extract was studied in Triton W-1339 and high-fat-diet fed rats. The serum lipids (total cholesterol, LDL- and HDL-cholesterol and triglycerides) and body weight were found to be lowered by A. moluccana (300 mg/kg, b.w.) in rats with Triton-induced hypercholesterolaemia and on a hyperlipaemic diet. The results suggest that the lipid lowering action of this natural product is mediated through inhibition of hepatic cholesterol biosynthesis and reduction of lipid absorption in the intestine.

Phytochemical analysis and analgesic properties of Curcuma zedoaria grown in Brazil.

The present study describes the phytochemical analysis and analgesic activity of Curcuma zedoaria rhizomes grown in Brazil. The results showed that the hydroalcoholic extract, fractions, specially dichloromethane, and a pure compound, denoted as curcumenol (1), exhibited potent and dose-related analgesic activity when evaluated in several models of pain in mice, including writhing, formalin and capsaicin. Compound (1), which seems to be the main active principle from this plant, presented promising analgesic effects, being several times more potent than different reference drugs evaluated in the same experimental models. The calculated ID50 values (micromol/kg, i.p) were 22 and 12 when evaluated in writhing and capsaicin tests, respectively, and 29 micromol/kg in relation to the second phase of the formalin model. The lack of effect in the hot plate test suggests that (1) act by a mechanism which do not involves the participation of the opioid system. The phytochemical analysis indicated that the chemical composition of the plant grown in Brazil is similar to that grown in other countries. The results confirm and justify the popular use of this plant for the treatment of dolorous processes.

Phytochemical and pharmacological investigations of Virola oleifera leaves.

A methanolic extract and two fractions (n-hexane and ethyl acetate) from Virola oleifera leaves and some compounds (one lignan and two flavonoids) were investigated to verify the analgesic activity by using the writhing test in mice. The crude methanolic extract showed a moderate analgesic effect (about 40% of inhibition in this test at 10 mg/kg), whereas n-hexane and ethyl acetate fractions caused inhibition of 51.3 +/- 5.9% and 50.5 +/- 6.3%, respectively. Oleiferin-C (1), a lignan isolated from the n-hexane fraction, showed an interesting analgesic potential in this model when compared to two standard drugs, paracetamol (4-acetamidophenol) and aspirin (acetylsalicylic acid). The ID50 calculated for this compound was 17.25 micromol/kg, with confidence interval between 13.7 and 21.3 micromol/kg, being about 8 times more potent than the standard drugs. The mixture of two glycoside-flavonoids, identified as astilbin (2) and quercitrin (3), also exhibited good analgesic activity, causing 63% of reduction of abdominal constriction in mice. These results suggest beneficial effect of this plant to treat dolorous processes.

Evaluation of the antinociceptive action caused by ether fraction and a triterpene isolated from resin of Protium kleinii.

This study investigates the antinociception caused by i.p. and p.o. administration of ether fraction and the triterpene identified as urs-12-ene-3beta-16beta-diol, known as Brein, isolated from Protium kleinii in several models of nociception in mice. The systemic administration of ether fraction (0.3 to 10 mg/kg, i.p. or 3 to 60 mg/kg, p.o.) caused a dose-related antinociception when assessed against acetic acid-induced writhing, with mean ID50 values of 1.2 and 16.4 mg/kg, respectively. The ether fraction (5 to 60 mg/kg, i.p. or 30 to 300 mg/kg, p.o.) also produced dose-related inhibition of both phases of formalin induced licking. The mean ID50s values for the early phase were > 60.0 and 62.1 mg/kg, while for the late phase they were 15.4 and 60.0 mg/kg, respectively, given by i.p. and p.o. routes. The ether fraction (3 to 30 mg/kg, i.p. or 10 to 100 mg/kg, p.o.) produced significant inhibition of the neurogenic nociception caused by topical injection of capsaicin, with mean ID50 values of 6.2 and 16.0 mg/kg, respectively. Given orally (1 to 30 mg/kg) the ether fraction produced graded and pronounced inhibition of glutamate-induced hyperalgesia in mice with a mean ID50 value of 15.2 mg/kg. In contrast, the ether fraction failed to produce antinociception when assessed in the thermal model of pain, the tail flick and hot plate tests. The antinociception caused by the ether fraction, in contrast to that of morphine, was not reversed by naloxone when assessed in the formalin-induced licking. The ether fraction did not affect motor coordination or the core body temperature in mices. The triterpene Brein isolated from P. kleinii, given by i.p. route (10 to 100 mg/kg) produced dose-related inhibition of both phases of formalin induced-licking, with mean ID50s values of 15.3 and 20.6 for the early and the late phases, respectively. These data show that the active principle(s) present in the ether fraction from the resin of P. kleinii elicited pronounced antinociception when assessed by i.p. or p.o routes, against both inflammatory and neurogenic nociception. Such effects seem, at least in part, to be related to the presence of the triterpene Brein in the extract. The mechanisms responsible for the antinociceptive action are at this moment not completely understood, but the involvement of the opioid pathway seems unlikely.

Chemical composition and analgesic activity of Calophyllum brasiliense leaves.

This paper describes a phytochemical and pharmacological study with Calophyllum brasiliense leaves, a medicinal plant employed in folk medicine for the treatment of several ailments. Based on spectroscopic evidence, five phenolic compounds were identified as hyperin (hyperoside), amentoflavone, quercetin, gallic acid, and protocatechuic acid. The fractions and some phenolic compounds exhibited significant analgesic activity against the writhing test and in relation to the second phase (inflammatory pain) of the formalin test in mice, suggesting that this plant can be useful for the treatment of dolorous processes.

Triterpenes from the resin of Protium heptaphyllum.

From the neutral fraction of the resin of Protium heptaphyllum, a mixture of alpha- and beta-amyrin, a mixture of maniladiol and brein have been isolated as main components, and the novel 3 beta,24-dihydroxy-urs-12-ene (1), 3-oxo-20S-hydroxytaraxastane (2) and 3 beta,20S-dihydroxytaraxastane (3) as minor components. NMR data of the last three compounds are provided.

A comparative chemical study of Maytenus ilicifolia mart. reiss and Maytenus robusta reiss (Celastraceae).

This work describes a comparative qualitative and quantitative chemical analysis of Maytenus ilicifolia and Maytenus robusta (Celastraceae), extracts by high-resolution gas chromatography (HRGC), using external standards as the method of determination and thin layer chromatographic (TLC). The results show that both plants have a similar chromatographic profile. However, M. robusta exhibited about three times higher concentration of triterpene friedelin than M. ilicifolia.

Additional evidence for the anti-inflammatory and anti-allergic properties of the sesquiterpene polygodial.

This study evaluates further the anti-inflammatory and anti-allergic properties of polygodial, a sesquiterpene extracted from the barks plant Drymis winteri (Winteraceae). Polygodial (12.8-128.1 micromol/kg, i.p.) 30 min prior, inhibited significantly the mouse paw oedema induced by prostaglandin E2, bradykinin (BK) substance P (SP), dextran, platelet activating factor (PAF) or carrageenan. Polygodial also inhibited arachidonic acid-, capsaicin- and croton oil-induced ear oedema in mice. Polygodial (42.7 micromol/kg, i.p.), significantly inhibited both exudation and cell influx when assessed in the pleurisy induced by SP and histamine, and to a less extent the inflammatory response caused by carrageenan, PAF, BK and des-Arg9-BK. Finally, polygodial (4.2-42.7 micromol/kg, i.p.) produced dose-related inhibition of paw oedema induced by ovalbumin, protecting in a time-dependent manner the anaphylactic shock induced by endovenous administration of ovalbumin in animals which had been actively sensitised by this antigen. These and our previous results indicate that the major component present in the bark of the plant D. winteri, the sesquiterpene polygodial exerts an interesting anti-inflammatory and anti-allergic properties when assessed in rats and mice.

Phytochemical and pharmacological analysis of Bauhinia microstachya (Raddi) Macbr. (Leguminosae).

This paper describes the isolation of four phytoconstituents from the leaves of Bauhinia microstachya, a Brazilian medicinal plant used in folk medicine for the treatment of several ailments. Based on spectroscopic evidence, these compounds were identified as methyl gallate (1), kaempferol 3-O-rhamnosyl (2), quercitrin (3) and myricitrin (4). The crude methanolic extract and two compounds (3 and 4) were tested as analgesic using the writhing test in mice. The extract and compound 3 caused potent and dose-related analgesic effects, confirming the popular use of this plant for the treatment dolorous processes.

I3-naringenin-II8--4'OMe-eriodictyol: a new potential analgesic agent isolated from Rheedia gardneriana leaves.

This paper describes the isolation, identification and analgesic activity of a new biflavonoid from Rheedia gardneriana leaves, which correspond to I3-naringenin-II8-4'-OMe-eriodictyol (GB-2a-II-4'-OMe) (1), with a methoxyl group in position 4 of ring-II. Its structure was determined by spectroscopic data and confirmed by an alkaline hydrolysis. Its analgesic effect was evaluated in a writhing test and a formalin test in mice. It was found that this compound exhibits potent and dose-related analgesic action in both experimental models, with ID50's values of 4.5 micromol/kg against the writhing test and 8.2 and 6.8 micromol/kg against the first and second phase of the formalin test, respectively. It was several times more potent than some well-known analgesic drugs used as reference.

Antinociceptive activity of a hydroalcoholic extract obtained from aerial parts of Sebastiania schottiana (Euphorbiaceae).

This study analyzed the antinociceptive effects of a hydroalcoholic extract obtained from the aerial parts of Sebastiania schottiana, a Brazilian medicinal plant used to treat various painful diseases. For this purpose, the writhing test, capsaicin and formalin induced-pain in mice were used. The results showed that the hydroalcoholic extract exhibited considerable antinociception in all the models studied, being more potent than aspirin.