Warifteine, an alkaloid of Cissampelos sympodialis, modulates allergic profile in a chronic allergic rhinitis model

ABSTRACT Cissampelos sympodialis Eichler, Menispermaceae, a Brazilian medicinal plant and its alkaloid warifteine present immunomodulatory activity on asthma experimental model by reducing antigen-specific IgE levels, eosinophil infiltration and lung hyperactivity. Allergic rhinitis is a chronic inflammatory disorder of the nasal tissue that affect the quality of life and it is a risk factor for asthma exacerbation. This study evaluated the effect of inhaled warifteine in an allergic ovalbumin rhinitis model. Inhaled warifteine (2 mg/ml) treatment of ovalbumin-sensitized BALB/c mice significant decreased total and differential number of cells on the nasal cavity and decreased ovalbumin-specific IgE serum levels. Hematoxylin & eosin staining of histological preparations of ovalbumin nasal tissues showed changes such as congestion and a massive cell infiltration in the perivascular and subepithelial regions characterizing the nasal inflammatory process. However, inhaled warifteine or dexamethasone treatment decreased cell infiltration into the perivascular regions and it was observed an intact nasal tissue. Periodic acidic staining of nasal epithelium of ovalbumin animals demonstrated high amount of mucus production by goblet cells and inhaled warifteine or dexamethasone treatment modulated the mucus production. In addition, toluidine blue staining of the nasal epithelium of ovalbumin animals demonstrated an increase of mast cells on the tissue and inhaled warifteine or dexamethasone treatment decreased in average of 1.4 times the number of these cells on the nasal epithelium. Taken these data together we postulate that warifteine, an immunomodulatory alkaloid, can be a medicinal molecule prototype to ameliorate the allergic rhinitis conditions.

Evaluation of Antifungal Activity and Mode of Action of New Coumarin Derivative, 7-Hydroxy-6-nitro-2H-1-benzopyran-2-one, against Aspergillus spp.

Aspergillus spp. produce a wide variety of diseases. For the treatment of such infections, the azoles and Amphotericin B are used in various formulations. The treatment of fungal diseases is often ineffective, because of increases in azole resistance and their several associated adverse effects. To overcome these problems, natural products and their derivatives are interesting alternatives. The aim of this study was to examine the effects of coumarin derivative, 7-hydroxy-6-nitro-2H-1-benzopyran-2-one (Cou-NO2), both alone and with antifungal drugs. Its mode of action against Aspergillus spp. Cou-NO2 was tested to evaluate its effects on mycelia growth and germination of fungal conidia of Aspergillus spp. We also investigated possible Cou-NO2 action on cell walls (0.8 M sorbitol) and on Cou-NO2 to ergosterol binding in the cell membrane. The study shows that Cou-NO2 is capable of inhibiting both the mycelia growth and germination of conidia for the species tested, and that its action affects the structure of the fungal cell wall. At subinhibitory concentration, Cou-NO2 enhanced the in vitro effects of azoles. Moreover, in combination with azoles (voriconazole and itraconazole) Cou-NO2 displays an additive effect. Thus, our study supports the use of coumarin derivative 7-hydroxy-6-nitro-2H-1-benzopyran-2-one as an antifungal agent against Aspergillus species.

3,6-Dimethoxy-6″,6″-Dimethyl-(7,8,2″,3″)-Chromeneflavone, a Flavonoid Isolated from Lonchocarpus Araripensis Benth. (Fabaceae), Reduces Nociceptive Behaviour in Mice.

Lonchocarpus araripensis Benth. is largely distributed in the northeast region of Brazil. It is popularly known as 'sucupira'. Recent studies have shown that some species of Lonchocarpus have interesting pharmacological activities. In this study, we evaluated the antinociceptive effect of a flavone isolated from L. araripensis. The chemical examination resulted in the isolation of 3,6-dimethoxy-6″,6″-dimethyl-(7,8,2″,3″)-chromeneflavone (DDF). The structure of the compound was established by spectral analysis. Antinociceptive activity of DDF was evaluated by measuring nociception by acetic acid, formalin and hot plate tests. The rota rod test was used to evaluate motor coordination. The results demonstrated that DDF was able to prevent acetic-acid-writhing-induced nociception (p < 0.001) in mice. Furthermore, DDF produced a significant reduction of the nociceptive behaviour at the early and late phases of paw licking in the formalin test. Also, DDF produced an inhibition of the nociceptive behaviour during a hot-plate test. No alteration in motor coordination was observed. These results confirm the hypothesis that DDF reduces the nociceptive behaviour in mice, probably through central mechanisms, but without compromising the motor coordination of animals.

Warifteine, an alkaloid purified from Cissampelos sympodialis, inhibits neutrophil migration in vitro and in vivo.

Cissampelos sympodialis Eichl is a plant from the Northeast and Southeast of Brazil. Its root infusion is popularly used for treatment of inflammatory and allergic diseases. We investigated whether warifteine, its main alkaloid, would have anti-inflammatory effect due to a blockage of neutrophil function. In vivo warifteine treatment inhibited casein-induced neutrophil migration to the peritoneal cavity but did not inhibit neutrophil mobilization from the bone marrow. Analysis of the direct effect of warifteine upon neutrophil adherence and migration in vitro demonstrated that the alkaloid decreased cell adhesion to P and E-selectin-transfected cells. In addition, fLMP-induced neutrophil migration in a transwell system was blocked by warifteine; this effect was mimicked by cAMP mimetic/inducing substances, and warifteine increased intracellular cAMP levels in neutrophils. The production of DNA extracellular traps (NETs) was also blocked by warifteine but there was no alteration on PMA-induced oxidative burst or LPS-stimulated TNF α secretion. Taken together, our data indicate that the alkaloid warifteine is a potent anti-inflammatory substance and that it has an effect on neutrophil migration through a decrease in both cell adhesion and migration.

Antibacterial activity of flavonoid 5.7.4’-trimethoxyflavone isolated from Praxelis clematides R.M. King & Robinson / Actividad antibacterial del flavonoide 5.7.4’-trimetoxiflavona aislada dePrexelis clematides R.M. King & Robinson

The flavonoids are a large class of polyphenolic compounds found in plants that are known to exhibit biological effects. In the study, the flavonoid 5.7.4’-trimethoxyflavone (TMF) extracted from Praxelis clematidea was evaluated for its antibacterial activity. Microdilution method was used for antibacterial assay of the flavonoid and eleven bacteria strains were used in the study for activities. The results were also compared with the standard drug, Chloramphenicol (100 ug/mL). The results obtained showed activity of the flavonoid against Gram positive and Gram negative bacteria.

Los flavonoides son una clase importante de compuestos polifenólicos encontrados en las plantas que se sabe que presentan efectos biológicos. En el estudio, el flavonoide 5.7.4 '-trimethoxyflavone (TMF) extraído de Praxelis clematidea fue evaluado por su actividad antibacteriana. Se utilizó el método de microdilución para el ensayo antibacteriano del flavonoide y once cepas de bacterias se usaron en el estudio de las actividades. Los resultados se compararon también con el fármaco estándar, Cloranfenicol (100 ug/mL). Los resultados obtenidos mostraron actividad del flavonoide contra bacterias Gram positivas y Gram negativas.

Bioactivities from marine algae of the genus Gracilaria.

Seaweeds are an important source of bioactive metabolites for the pharmaceutical industry in drug development. Many of these compounds are used to treat diseases like cancer, acquired immune-deficiency syndrome (AIDS), inflammation, pain, arthritis, as well as viral, bacterial, and fungal infections. This paper offers a survey of the literature for Gracilaria algae extracts with biological activity, and identifies avenues for future research. Nineteen species of this genus that were tested for antibacterial, antiviral, antifungal, antihypertensive, cytotoxic, spermicidal, embriotoxic, and anti-inflammatory activities are cited from the 121 references consulted.

Curine, a bisbenzylisoquinoline alkaloid, blocks L-type Ca²âº channels and decreases intracellular Ca²âº transients in A7r5 cells.

Curine is a novel bisbenzylisoquinoline alkaloid that has previously been reported as a vasodilator. The underlying mechanism(s) of the vasodilator effect of curine remains to be characterized. In this study, we investigated the cellular mechanism that is responsible for the vasodilator effect of curine in the rat aorta. The vasorelaxant activity of curine was recorded using a myograph. Ca(2+) currents in A7r5 cells were measured using the whole-cell patch-clamp technique. Intracellular Ca(2+) transients were determined using confocal microscopy. In a concentration-dependent manner, curine inhibited contractions elicited by high extracellular K(+) and Bay K8644 in the rat aorta and reduced the rise in the intracellular Ca(2+) concentration induced by membrane depolarization in response to an increase in extracellular K(+) concentration in vascular smooth muscle cells. Moreover, curine decreased the peak amplitude of L-type Ca(2+) currents (I(Ca,L)) in a concentration-dependent manner without changing the characteristics of the current density vs. voltage relationship and the steady-state activation of I(Ca,L). Furthermore, curine shifted the steady-state inactivation curve of I(Ca,L) toward more hyperpolarized membrane potentials. None of the following modified the effect of curine on I(Ca,L) amplitude: 3-isobutyl-1-methylxanthine, an inhibitor of phosphodiesterases; dibutyryl cyclic AMP, an activator of protein kinase A (PKA); or 8-Br-cyclic GMP, an activator of protein kinase G (PKG). Our results showed that curine inhibited the L-type voltage-dependent Ca(2+) current in rat aorta smooth muscle cells, which caused a decrease in intracellular global Ca(2+) transients that led to vasorelaxation.

Rotundifolone-induced relaxation is mediated by BK(Ca) channel activation and Ca(v) channel inactivation.

Rotundifolone is the major constituent of the essential oil of Mentha x villosa Hudson. In preliminary studies, rotundifolone induced significant hypotensive, bradycardic and vasorelaxant effects in rats. Thus, to gain more insight into the pharmacology of rotundifolone, the aim of this study was to characterize the molecular mechanism of action involved in relaxation produced by rotundifolone. The relaxant effect was investigated in rat superior mesenteric arteries by using isometric tension measurements and whole-cell patch-clamp techniques. Rotundifolone relaxed phenylephrine-induced contractions in a concentration-dependent manner. Pre-treatment with KCl (20 mM), charybdotoxin (10(-7) M) or tetraethylammonium (TEA 10(-3) or 3 × 10(-3) M) significantly attenuated the relaxation effect induced by rotundifolone. Additionally, whole-cell patch-clamp recordings were made in mesenteric smooth muscle cells and showed that rotundifolone significantly increased K(+) currents, and this effect was abolished by TEA (10(-3) M), suggesting the participation of BK(Ca) channels. Furthermore, rotundifolone inhibited the vasoconstriction induced by CaCl(2) in depolarizing nominally Ca(2+) -free medium and antagonized the contractions elicited by an L-type Ca(2+) channel agonist, S(-)-Bay K 8644 (2 × 10(-7) M), indicating that the vasodilatation involved inhibition of Ca(2+) influx through L-type voltage-dependent calcium channels (Ca(v) type-L). Additionally, rotundifolone inhibited L-type Ca(2+) currents (I(Ca) L), affecting the voltage-dependent activation of I(Ca) L and steady-state inactivation. Our findings suggest that rotundifolone induces vasodilatation through two distinct but complementary mechanisms that clearly depend on the concentration range used. Rotundifolone elicits an increase in the current density of BK(Ca) channels and causes a shift in the steady-state inactivation relationship for Ca(v) type-L towards more hyperpolarized membrane potentials.

Morphological and physiological changes in Leishmania promastigotes induced by yangambin, a lignan obtained from Ocotea duckei.

We have previously demonstrated that yangambin, a lignan obtained from Ocotea duckei Vattimo (Lauraceae), shows antileishmanial activity against promastigote forms of Leishmania chagasi and Leishmania amazonensis. The aim of this study was to determine the in vitro effects of yangambin against these parasites using electron and confocal microscopy. L. chagasi and L. amazonensis promastigotes were incubated respectively with 50 µg/mL and 65 µg/mL of pure yangambin and stained with acridine orange. Treated-parasites showed significant alterations in fluorescence emission pattern and cell morphology when compared with control cells, including the appearance of abnormal round-shaped cells, loss of cell motility, nuclear pyknosis, cytoplasm acidification and increased number of acidic vesicular organelles (AVOs), suggesting important physiological changes. Ultrastructural analysis of treated-promatigotes showed characteristics of cell death by apoptosis as well as by autophagy. The presence of parasites exhibiting multiples nuclei suggests that yangambin may also affect the microtubule dynamic in both Leishmania species. Taken together our results show that yangambin is a promising agent against Leishmania.

Atividade farmacológica da monocrotalina isolada de plantas do gênero Crotalaria / Pharmacological activity of monocrotalina isolated from plants of the genus Crotalaria

Crotalaria retusa é uma planta encontrada no Nordeste brasileiro, pertence ao gênero Crotalaria e à família Leguminosae, e possuem mais de seissentas espécies no mundo e mais de quarenta no Brasil. As variedades tóxicas mais conhecidas são C. spectabilis, C. crispata, C. retusa, C. dura e C. globifera. Plantas do gênero Crotalaria são de interesse porque são usadas na medicina popular. Esses gêneros são ricos em alcaloides pirrolizidínicos (AP), que são as principais toxinas e apresentam efeitos pneumotóxicos, nefrotóxicos, cardiotóxicos, fetotóxicos, carcinogênicos, inflamação, hemorragia e fibrose. A monocrotalina é o principal alcaloide pirrolizidínico encontrado nessas plantas e é ativamente oxidada in vivo pelo citocromo P450 no fígado, formando intermediários altamente reativos tipo pirrólicos que são responsáveis pela ligação cruzada do DNA-DNA e DNA-proteína. O presente trabalho teve como objetivo fazer um levantamento bibliográfico via internet, utilizando bancos de dados, programas de pesquisa científica e pesquisa em livros relacionados, acerca da atividade farmacológica e do mecanismo de ação da monocrotalina extraída de plantas do gênero Crotalaria, ressaltando desde os aspectos botânicos da planta, estrutura química dos alcaloides pirrolizidínicos, exemplos experimentais de toxicidade e provável mecanismo de ação.

Crotalia retusa is a plant found in Brazilian Northeast and belongs to the genus Crotalaria and the family Leguminosae, which comprises more than 600 species throughout the world and more than forty in Brazil. The most known toxic species are C. spectabilis, C. crispata, C. retusa, C. dura and C. globifera. Plants of the Crotalaria genus are of great interest because they are used by humans for folk medicine. These plants are rich in pyrrolizidine alkaloids (PA), which are the main toxins that cause effects such as pneumotoxic, nefrotoxic, cardiotoxic, fetotoxic, carcinogenic, inflammation, hemorrhage and fibrosis. Monocrotaline is the main pirrolizidinic alkaloid found in plants and is actively oxidated in vivo by the cytochrome P450 in the liver, yielding highly reactive pyrrolic type intermediates, which are responsible for DNA-DNA and DNA-protein cross-links reaction. The aim of this work is to make a bibliographic survey via internet, using databases, scientific research programs and related books, about pharmacological activity and mechanism of action of monocrotaline extracted from plants of Crotalaria genus, emphasizing plant botanical aspects, chemical structure of pirrolizidinic alkaloid, experimental examples of toxicity and probable action mechanism.

A chemical marker proposal for the Lantana genus: composition of the essential oils from the leaves of Lantana radula and L. canescens.

Essential oil extracts from the leaves of two Lantana species (L. radula Sw. and L. canescens Kunth), for which no prior analysis has been reported, were analyzed by GC-MS. This information was utilized to propose chemical markers for Lantana species so that identification between physically similar plant species can be achieved through chemical analysis. Results showed 33 constituents for L. canescens, among which beta-caryophyllene (43.9%), beta-cubebene (10.1%), elixene (8.6%), beta-phellandrene (6.1%), alpha-caryophyllene (2.6%) and dehydro-aromadendrene (2.6%) were the principle components. L. radula revealed the presence of 21 compounds, the most abundant of which were beta-cubebene (31.0%), beta-caryophyllene (20.8%), elixene (10.0%), alpha-salinene (6.4%), beta-phellandrene (6.1%), copaene (4.9%) cadinene (1.4%) and psi-limonene (1.4%). The high concentration of beta-caryophyllene in the samples tested here and those in the literature make it a good candidate for a chemical marker for Lantana species, with beta-cubebene, elixene and beta-phellandrene following as minor compounds identified more sporadically in this genus. On the other hand, Lippia species, which are morphologically similar to those from the Lantana genus, would contain limonene, citral, carvacrol, beta-myrcene, camphor and thymol as the main chemical markers. These chemical markers would be a powerful tool for maintaining quality control in the extraction of essential oils for use in medicinal applications, as well as in identification of plant specimens to a taxonomist.

Inhibitory effect of the alkaloid warifteine purified from Cissampelos sympodialis on B lymphocyte function in vitro and in vivo.

The aqueous fraction of the ethanolic extract of the plant CISSAMPELOS SYMPODIALIS (Menispermaceae) was previously described to inhibit B cell function. The alkaloid warifteine is the major component of this extract. In the present study we investigated the effect of warifteine on B lymphocyte function and characterized its mechanism of action. Purified splenic murine B lymphocytes were stimulated with either Toll-like receptor (TLR) ligands (LPS, Pam (3)Cys and CpG oligodeoxynucleotides) or anti-IgM antibody and the effect of warifteine on B cell response was investigated. Warifteine inhibited both the proliferative response and immunoglobulin (Ig) secretion induced by these stimuli. Kinetics studies demonstrated that warifteine blocked B cell function even when added after 24 h of a 72 h culture. The inhibitory effect of warifteine was also detected in cultures activated by phorbol myristate acetate and calcium ionophore. We investigated the signal transduction pathways blocked by warifteine. It did not modify the total protein phosphorylation pattern in LPS and anti-IgM-stimulated B cell cultures. It did, however, decrease the rise in intracellular calcium levels, the phosphorylation of the mitogen activated protein kinase (MAPK) ERK and the intranuclear levels of the transcription factor NFkappaB. Warifteine also induced an increase in cAMP and its effect on LPS-induced proliferation was mimicked by the control adenyl cyclase activator forskolin. IN VIVO Ig production induced by the TI-2 antigen TNP-ficoll was also inhibited by warifteine. Taking together, our data suggest that warifteine is a potent inhibitor of B cell response both IN VITRO and IN VIVO and that this effect may be due to the induction of increased intracellular cAMP levels, suggesting that this substance may be useful as a modulator of B cell function.

Phenylethanoid and lignan glycosides from polar extracts of Lantana, a genus of verbenaceous plants widely used in traditional herbal therapies.

Many references to the use of Lantana spp. can be found in the ethnopharmacological literature from locations around the globe. This study was focused on examining constituents from the polar extracts of Lantana radula Sw. and Lantana canescens Kunth, for which no prior chemical investigations had been reported. A new phenylethanoid glycoside, raduloside, and lignan glycoside, radulignan, were identified along with the known compounds alyssonoside, arenarioside, calceolarioside E, isonuomioside, samioside, and verbascoside.

Plants of the American continent with antimalarial activity: [review] / Plantas do continente Americano com atividade antimalárica: [revisão]

Malaria is a human parasitic disease caused by protozoa species of the Plasmodium genus. This disease has affected populations of the tropical and subtropical regions. About 500 million new cases occur annually on the world and therefore it is considered an emerging disease of important public health problem. In this context, the natural products as vegetables species have their bioactive molecules as targets for pharmacological, toxicological and phytochemical studies towards the development of more effective medicines for the treatment of many diseases. So this work intends to aid the researchers in the study of natural products to the treatment of malaria. In this review, 476 plants of the American continent were related for the antimalarial activity and of these vegetables species 198 were active and 278 inactive for some type of Plasmodium when they were evaluated through of in vitro or in vivo bioassays models.

Malária é uma doença parasitária humana causada por protozoários do gênero Plasmodium. Esta doença tem acometido populações que habitam regiões tropicais e subtropicais. Anualmente, cerca de 500 milhões de casos ocorrem no mundo, o que permite ser considerada uma doença emergente de importância para a saúde pública. Neste contexto, os produtos naturais, a exemplo das espécies vegetais, têm suas moléculas bioativas como alvo para estudos farmacológicos, toxicológicos e fitoquímicos destinados à síntese de medicamentos mais eficazes para o tratamento de inúmeras doenças. Portanto, este trabalho fornece subsídio às pesquisas com produtos naturais para o tratamento da malária. Nesta revisão, 476 espécies de plantas do continente Americano foram relatadas para a atividade antimalárica, sendo destas 198 ativas e 278 inativas para algum tipo de Plasmodium, quando avaliados através de modelos in vitro e in vivo.

(S)-reticuline induces vasorelaxation through the blockade of L-type Ca(2+) channels.

In Brazil, various species of the genus Ocotea are used in folk medicine for treating several diseases. The chemical characterization of this plant showed the presence of alkaloids belonging to the benzyltetrahydroisoquinoline family, the major component of which is (S)-reticuline. The present study investigated whether (S)-reticuline exerts an inhibitory effect on smooth muscle L-type Ca(2+) channels. Tension measurements and patch clamp techniques were utilized to study the effects of (S)-reticuline. Whole-cell Ca(2+) currents were measured using the A7r5 smooth muscle cell line. (S)-reticuline antagonized CaCl(2)- and KCl-induced contractions and elicited vasorelaxation. It also reduced the voltage-activated peak amplitude of I (Ca,L) in a concentration-dependent manner. (S)-reticuline did not change the characteristics of current density vs. voltage relationship. (S)-reticuline shifted leftwards the steady-state inactivation curve of I (Ca,L). The application of dibutyryl cyclic adenosine monophosphate to the cell decreased the amplitude of Ca(2+) currents. In cells pretreated with forskolin, an adenylate cyclase activator, the addition of (S)-reticuline caused further inhibition of the Ca(2+) currents suggesting an additive effect. The results obtained show that (S)-reticuline elicits vasorelaxation probably due to the blockade of the L-type voltage-dependent Ca(2+) current in rat aorta. The reported effect may contribute to the potential cardioprotective efficacy of (S)-reticuline.

Plants with anticonvulsant properties: a review: [revision] / Uma revisão de plantas com propriedades anticonvulsivantes: [revisão]

Seizures are resistant to treatment with currently available anticonvulsant drugs in about 1 out of 3 patients with epilepsy. Thus, there is a need for new, more effective anticonvulsant drugs for intractable epilepsy. However, nature is a rich source of biological and chemical diversity and a number of plants in the world have been used in traditional medicine remedies, i.e., anticonvulsant, anxiolytic, analgesic, antidepressant. This work constitutes a literature review on medicinal plants showing anticonvulsant properties. The review refers to 16 Brazilian plants and a total 355 species, their families, geographical distribution, the utilized parts, method and references. Some aspects of research on medicinal plants and a brief review of the most common animal models to discover antiepileptic drugs are discussed. For this purpose over 170 references were consulted.

Cerca de um terço dos pacientes epilépticos não conseguem ter um tratamento adequado com as drogas anticonvulsivantes atuais. Nesse sentido, as plantas medicinais surgem como uma fonte promissora de novas moléculas químicas com propriedades biológicas apreciáveis. Muitas plantas ou produtos de origem naturais têm sido propostos para o tratamento de várias patologias, tais como: epilepsia, diabetes, ansiedade, depressão, dentre outras. O presente trabalho realizou um extenso levantamento na literatura especializada de plantas medicinais com propriedades anticonvulsivantes. Um total de 355 espécies vegetais foi identificado, sendo 16 plantas encontradas na flora brasileira, com indicação para o tratamento de quadros convulsivos. Características como nome da espécie, família, partes utilizadas, país do estudo e /ou publicação, métodos e referências foram sumarizados. Além disso, os principais apectos dos modelos animais mais utilizados no estudo de plantas/substâncias com propriedades anticonvulsivantes foram revisados. Mais de 170 referências foram consultadas.

Antinociceptive activity of structural analogues of rotundifolone: structure-activity relationship.

Rotundifolone, a monoterpene isolated from the essential oil of the leaves of Mentha x villosa, is a constituent of several essential oils and known to have antinociceptive activity. Our recent study demonstrated that the analogues of rotundifolone showed also a significant antinociceptive effect. In the present report, to investigate the correlation between the structure and antinociceptive activity, rotundifolone and its analogues were evaluated in the acetic acid-induced writhing test in mice. All compounds showed to be more antinociceptive than rotundifolone against the pain response induced by acetic acid. Comparing the antinociceptive effect of rotundifolone with limonene oxide and (+)-pulegone, the results demonstrated that the epoxide group contributes as much as the ketone group to the antinociceptive activity of rotundifolone. Similarly, pulegone oxide and carvone epoxide were more antinociceptive than rotundifolone, thereby suggesting that the position of the functional group on the ring also influences the antinociceptive activity. (-)-Carvone produced maximal inhibition of the writhing response and was slightly more active than (+)-carvone. The study showed that by appropriate structural modification it may be possible to develop novel antinociceptive agents.

Natural products with antileprotic activity

Leprosy is a chronic infectious disease caused by Mycobacterium leprae bacillus. It was considered to be an incurable disease for ages. Nowadays leprosy is a vanishing disease although we can meet it principally in the tropical zone countries. Brazil has the second greatest number of leprosy cases around the world with almost 30,000 new cases diagnosed in 2005. The present work constitutes a literature review on plant extracts and chemically defined molecules of natural origin showing antileprotic activity. The review refers to 11 plants, their families, and geographical distribution, the utilized parts, the type of extract and the tested organism. It also includes 17 compounds isolated from higher plants and microorganisms, classified into appropriate chemical groups. Some aspects of recent antileprotic-activity-directed research on natural products are discussed. For this purpose 63 references were consulted.

A hanseníase é uma doença crônica infecciosa ocasionada pelo Mycobacterium leprae. Foi considerada incurável por muitos anos. Atualmente a lepra é uma doença em desaparecimento, apesar de podermos encontrá-la principalmente nos países da zona tropical. O Brasil é o país que tem o segundo maior número de casos de lepra ao redor do mundo com quase 30.000 novos casos diagnosticados em 2005. Este trabalho teve como objetivo revisar a literatura dos vegetais e substâncias de origem natural com atividade antileprótica. Foram encontradas 11 plantas e 17 substâncias isoladas de plantas e microrganismos que foram classificados em grupos químicos adequados. Alguns aspectos de pesquisa recente com produtos naturais direcionados à produção de drogas contra a lepra também são discutidos. Foram consultadas 63 referências.

Plants and chemical constituents with giardicidal activity / Plantas e constituintes químicos com atividade giardicida

Intestinal infection caused by Giardia lamblia represents a serious public health problem, with increased rates of prevalence in numerous countries. Increased resistance of the parasite and the side-effects of the reference drugs employed in the treatment of giardiasis make necessary to seek new therapeutic agents. Natural products, especially of plant origin, represent excellent starting point for research. The objective of this study is to review the literature on plant extracts, fractions and chemical constituents whose giardicidal activity has been investigated in vitro. The review describes 153 (one hundred and fifty-three) plant species from 69 (sixty-nine) families that were evaluated for their giardicidal activity. The geographical distribution of the plant species, the part used, preparation, strain of Giardia lamblia tested and the results obtained by the authors are also given. One hundred and one compounds isolated from plant species, classified by chemical class, are presented. Recent aspects of research on natural products of plant origin employed in the treatment of giardiasis are also discussed.

Infecção intestinal causada por Giardia lamblia representa grave problema de saúde pública, com elevadas taxas de prevalência em diversos países. O aumento de resistência do parasita e os efeitos colaterais dos fármacos de referência empregados no tratamento da giardíase, tornam necessário a busca de novos agentes terapêuticos. Produtos naturais, especialmente de origem vegetal, representam excelentes fontes de pesquisas. Este trabalho tem como objetivo revisar a literatura de extratos de plantas, frações e compostos químicos com estudos in vitro de avaliação da atividade giardicida. A revisão refere 153 (cento e cinqüenta e três) espécies vegetais de 69 (sessenta e nove) famílias que foram submetidas à avaliação da atividade giardicida. Descreve a distribuição geográfica das espécies vegetais, parte usada, preparação, cepa de Giardia lamblia testada e resultados por autores. Apresenta 101 (cento e um) compostos isolados de espécies vegetais classificados por classes químicas. Discute aspectos recentes da pesquisa de produtos naturais de origem vegetal empregados no tratamento da giardíase.

Natural products inhibitors of the enzyme acetylcholinesterase / Produtos naturais inibidores da enzima acetilcolinesterase

Alzheimer's disease (AD) is a progressive, neurodegenerative pathology that primarily affects the elderly population, and is estimated to account for 50-60 percent of dementia cases in persons over 65 years of age. The main symptoms associated with AD involve cognitive dysfunction, primarily memory loss. Other features associated with the later stages of AD include language deficits, depression, behavioural problems including agitation, mood disturbances and psychosis. One of the most promising approaches for treating this disease is to enhance the acetylcholine level in the brain using acetylcholinesterase (AChE) inhibitors. The present work reviews the literature on plants and plant-derived compounds inhibitors of enzyme acetylcholinesterase. The review refers to 309 plant extracts and 260 compounds isolated from plants, which are classified in appropriate chemical groups and model tested, and cites their activity. For this purpose 175 references were consulted.

A Doença de Alzheimer (DA) é uma patologia neurodegenerativa, progressiva, que afeta principalmente a população idosa, responsável por 50-60 por cento dos casos de demência em pessoas com mais de 65 anos de idade. Os principais sintomas associado a DA envolve deficiência orgânica cognitiva, principalmente perda de memória. Outras características associadas com os estágios avançados de DA inclui déficit na linguagem, depressão, problemas de comportamento, inclusive agitação, alterações de humor e psicose.Um dos mais promissores caminhos para tratar esta doença é aumentar o nível de acetilcolina no cérebro usando inibidores da acetilcolinesterase (AChE). Este trabalho teve como objetivo revisar a literatura das plantas e substâncias encontradas nas plantas, inibidores da enzima acetilcolinesterase. Foram levantadas 309 plantas e 260 substâncias isoladas de plantas que foram classificados em grupos químicos adequados, os modelo testados, e suas atividades. Foram consultados 175 referências.