Tumour growth inhibitory effect of Ibervillea sonorae phytopreparations in cervical cancer xenografts.

Cucurbitacin IIb, a triterpene obtained from the Ibervillea sonorae plant, reduces tumour development in a preclinical model of cervical cancer. Acetison and Etanison, phytopreparations made from I. sonorae, present biological activity analogous to CIIb in HeLa. This research evaluated the tumour growth inhibitory effect of these phytopreparations in a HeLa xenograft tumour model in BALB/c nude mice. Tumours in mice were treated every 3 days for 12 days with cisplatin (2 mg/kg), CIIb (5 mg/kg), Acetison (20 mg/kg), Etanison (30 mg/kg), and DMSO at 2%. For histological observations, tumours were stained with H&E. Fingerprinting of both phytopreparations was performed using HPLC-UV and UHPLC-APCI-IT-MS. Both phytopreparations and CIIb inhibit tumour development as well as Cisplatin (75.5%); Etanison (77.7%), Acetison (73.6%), and CIIb (73.0%). Furthermore, only tumours treated with cisplatin showed invasion of bone tissue. The results show the potential use of I. sonorae phytopreparations in the treatment of cervical cancer.

A Comprehensive Description of the Anatomy and Histochemistry of Psychotria capillacea (Müll. Arg.) Standl. and an Investigation into Its Anti-Inflammatory Effects in Mice and Role in Scopolamine-Induced Memory Impairment.

Species of the genus Psychotria are used in popular medicine for pain, inflammatory symptoms, and mental disorders. Psychotria capillacea (Müll. Arg.) Standl. (Rubiaceae) is commonly known as coffee and some scientific studies have demonstrated its therapeutic potential. The goal of this study was to investigate the anti-inflammatory and neuroprotective effects, and acetylcholinesterase (AChE) inhibitory activity of a methanolic extract obtained from leaves of P. capillacea (MEPC), as well as the micromorphology and histochemistry of the leaves and stems of this plant. In addition, the MEPC was analyzed by UHPLC-MS/MS and the alkaloidal fraction (AF) obtained from the MEPC was tested in a mouse model of inflammation. MEPC contained three indole alkaloids, one sesquiterpene (megastigmane-type) and two terpene lactones. MEPC (3, 30 and 100 mg/kg) and AF (3 and 30 mg/kg) were evaluated in inflammation models and significantly inhibited edema at 2 h and 4 h, mechanical hyperalgesia after 4 h and the response to cold 3 h and 4 h after carrageenan injection. Scopolamine significantly increased the escape latency, and reduced the swimming time and number of crossings in the target quadrant and distance, while MEPC (3, 30 and 100 mg/kg), due to its neuroprotective actions, reversed these effects. AChE activity was significantly decreased in the cerebral cortex (52 ± 3%) and hippocampus (60 ± 3%), after MEPC administration. Moreover, micromorphological and histochemical information was presented, to aid in species identification and quality control of P. capillacea. The results of this study demonstrated that P. capillacea is an anti-inflammatory and antihyperalgesic agent that can treat acute disease and enhance memory functions in mouse models.

A potential antiviral against COVID-19 obtained from Byrsonima coccolobifolia leaves extract.

In this study, we specifically focused on the crude methanolic leaf extract of Byrsonima coccolobifolia, investigating its antifungal potential against human pathogenic fungi and its antiviral activity against COVID-19. Through the use of high-performance liquid chromatography coupled with electrospray ionization ion trap tandem mass spectrometry, direct infusion electrospray ionization ion trap tandem mass spectrometry, and chromatographic dereplication procedures, we identified galloyl quinic acid derivatives, catechin derivatives, proanthocyanidins, and flavonoid glycosides. The broth dilution assay revealed that the methanolic leaf extract of B. coccolobifolia exhibits antifungal activity against Cryptococcus neoformans (IC50 = 4 µg/mL). Additionally, docking studies were conducted to elucidate the interactions between the identified compounds and the central residues at the binding site of biological targets associated with COVID-19. Furthermore, the extract demonstrated an in vitro half-maximum effective concentration (EC50 = 7 µg/mL) and exhibited significant selectivity (>90%) toward SARS-CoV-2.

Chemical profile and evaluation of the pharmacological activity of the dry extract and fraction of ethyl acetate obtained from the leaves of Mimosa caesalpiniifolia.

ETHNOPHARMACOLOGICAL RELEVANCE: Mimosa caesalpiniifolia (Sansão-do-Campo) is a native species of the caatinga in northeastern Brazil that has been studied for its potential anti-inflammatory and antidepressant activity. It is popularly consumed as a medicinal plant and its pharmacological benefits are evidenced in the literature. AIM OF THE STUDY: The present work was carried out to promote the chemical profile and evaluate the pharmacological activity of the dry extract and the ethyl acetate fraction obtained from the dry leaves of Mimosa caesalpiniifolia. MATERIALS AND METHODS: The leaves were collected in the municipality of Alfenas-MG and subjected to drying, followed by division in a knife mill. The preparation of the dry extract was carried out by the extraction method using simple percolation and the fraction was obtained by liquid-liquid partition. Part of the extractive solution was concentrated in a rotary evaporator followed by a drying process using the spray technique with the addition of colloidal silicon dioxide. The dry extract (33.33%) showed a higher yield in mass when compared to the yield of the ethyl acetate fraction (19.67%). The in vivo pharmacological evaluation was conducted with a total of 82 male Wistar rats that underwent cecal ligation and perforation surgery to induce the inflammatory process. One week after surgery, these animals were treated for 7 days with the dry extract and the ethyl acetate fraction and submitted to behavioral tests (open field and forced swimming). RESULTS: The chemical results were obtained through analysis by HPLC-PDA coupled to a mass spectrometer, enabling the verification of the presence of phenolic acids, flavonoids, aglycones, and glycosides, in addition to tannins. This corroborates with data present in the literature for the genus Mimosa sp. Some compounds had their structure determined, where they were identified as catechin (m/z 288.97), cassiaocidentalin A (m/z 560.75), and procyanidin B2 [(epi)catechin-(epi)catechin; m/z 576.83)]. It was found that the animals that were submitted to the treatment did not present statistically significant results, demonstrating that the pharmacological action evaluated in the test was not highlighted in this type of experiment. The groups that underwent treatment had an aggravated locomotor activity. CONCLUSIONS: The results found with the chemical study contributed to the knowledge of the plant species studied. On the other hand, further studies are needed to provide a better understanding of the pharmacological evaluation of Mimosa caesalpiniifolia.

New selective and sustainable ultrasound-assisted extraction procedure to recover carnosic and rosmarinic acids from Rosmarinus officinalis by sequential use of bio-based solvents.

Carnosic (CA) and rosmarinic (RA) acids are the primary phenolic acids in hydrophilic rosemary extracts. Their combination exhibits high antioxidant activity and can be explored in several applications. This study aimed to develop an extraction procedure using bio-based solvents to recover two rosemary extracts, one rich in CA and the other in RA. By using ultrasound-assisted extraction (UAE) and a pool of 34 solvents, we evaluated nominal power (W), extraction time (min), and solvent water percentage (% H2O) regarding yield and selectivity. The authors propose a sequential UAE procedure validated by applying ethanol 99.5 % (v/v), 240 W, and 5 min to recover a rich fraction of 24.0 mgCA.gbiomass-1; followed by a second step using AmAc:LA (1:2 M ratio), 20 % H2O (m/m), 320 W, and 5 min that resulted in 8.4 mgRA.gbiomass-1. Our results indicate that modulating the solvent composition and process temperature is critical to increasing extraction yields and selectivity.

Effects of Mimosa caesalpiniifolia pre-formulation on the intestinal barrier during sodium dextran sulfate-induced colitis in Wistar rats / Efectos de la preformulación de Mimosa caesalpiniifolia sobre la barrera intestinal durante la colitis inducida por sulfato de dextrano sódico en ratas Wistar

Introduction. Anti-inflammatories, immunosuppressants, and immunobiological are commonly used in the treatment of inflammatory bowel disease. However, some patients do not present an adequate response or lose effective response during the treatment. A recent study found a potential anti-inflammatory effect of the hydroalcoholic extract of Mimosa caesalpiniifolia on trinitrobenzene sulfonic acid-induced colitis in Wistar rats. Objective. To evaluate the effects of M. caesalpiniifolia pre-formulation on the intestinal barrier using dextran sulfate sodium-induced colitis model. Materials and methods. Leaf extracts were prepared in 70% ethanol and dried with a Buchi B19 Mini-spray dryer using 20% Aerosil® solution. Thirty-two male Wistar rats were randomized into four groups: basal control, untreated colitis, pre-formulation control (125 mg/kg/day), and colitis treated with pre-formulation (125 mg/kg/day). Clinical activity index was recorded daily and all rats were euthanized on the ninth day. Colon fragments were fixed and processed for histological and ultrastructural analyses. Stool samples were collected and processed for analysis of the short-chain fatty acid. Results. Treatment with the pre-formulation decreased the clinical activity (bloody diarrhea), inflammatory infiltrate, and the ulcers. Pre-formulation did not repair the epithelial barrier and there were no significant differences in the goblet cells index. There was a significant difference in butyrate levels in the rats treated with the pre-formulation. Conclusions. The pre-formulation minimized the clinical symptoms of colitis and intestinal inflammation, but did not minimize damage to the intestinal barrier.

Introducción. Los antiinflamatorios, inmunosupresores e inmunobiológicos se utilizan comúnmente para tratar la enfermedad intestinal inflamatoria. Sin embargo, algunos pacientes no presentan una respuesta adecuada o pierden respuesta efectiva durante el tratamiento. En un estudio reciente, se encontró un potencial efecto antiinflamatorio del extracto hidroalcohólico de Mimosa caesalpiniifolia en la colitis inducida por el ácido trinitrobenceno sulfónico utilizando ratas Wistar. Objetivo. Evaluar los efectos de la preformulación de M. caesalpiniifolia sobre la barrera intestinal durante la colitis inducida por sulfato de dextrano sódico. Materiales y métodos. Los extractos de hojas se prepararon con una solución que contenía 70 % de etanol y se secaron con un secador por aspersión Mini B19 de Buchi usando una solución con 20 % de Aerosil®. Treinta y dos ratas Wistar macho se aleatorizaron en cuatro grupos: control basal, colitis sin tratar, control con preformulación (125 mg/kg/ día) y colitis tratada con preformulación (125 mg/kg/día). El índice de actividad clínica se registró diariamente y todas las ratas se sacrificaron el noveno día. Los fragmentos de colon se fijaron y se procesaron para análisis histológicos y ultraestructurales. Se recolectaron muestras de heces y se procesaron para el análisis de ácidos grasos de cadena corta. Resultados. El tratamiento con la preformulación disminuyó la actividad clínica (diarrea sanguinolenta), el infiltrado inflamatorio y las úlceras. La preformulación no reparó la barrera epitelial y no hubo diferencias significativas en el índice de células caliciformes. Se obtuvo una diferencia significativa en los niveles de butirato en las ratas tratadas con la preformulación. Conclusiones: La preformulación minimizó los síntomas clínicos de colitis e inflamación intestinal pero no minimizó el daño a la barrera intestinal.

Effects of Mimosa caesalpiniifolia pre-formulation on the intestinal barrier during sodium dextran sulfate-induced colitis in Wistar rats / Efectos de la preformulación de Mimosa caesalpiniifolia sobre la barrera intestinal durante la colitis inducida por sulfato de dextrano sódico en ratas Wistar

Introduction. Anti-inflammatories, immunosuppressants, and immunobiological are commonly used in the treatment of inflammatory bowel disease. However, some patients do not present an adequate response or lose effective response during the treatment. A recent study found a potential anti-inflammatory effect of the hydroalcoholic extract of Mimosa caesalpiniifolia on trinitrobenzene sulfonic acid-induced colitis in Wistar rats.Objective. To evaluate the effects of M. caesalpiniifolia pre-formulation on the intestinal barrier using dextran sulfate sodium-induced colitis model.Materials and methods. Leaf extracts were prepared in 70% ethanol and dried with a Buchi B19 Mini-spray dryer using 20% Aerosil® solution. Thirty-two male Wistar rats were randomized into four groups: basal control, untreated colitis, pre-formulation control (125 mg/kg/day), and colitis treated with pre-formulation (125 mg/kg/day). Clinical activity index was recorded daily and all rats were euthanized on the ninth day. Colon fragments were fixed and processed for histological and ultrastructural analyses.Stool samples were collected and processed for analysis of the short-chain fatty acid.Results. Treatment with the pre-formulation decreased the clinical activity (bloody diarrhea), inflammatory infiltrate, and the ulcers. Pre-formulation did not repair the epithelial barrier and there were no significant differences in the goblet cells index. There was a significant difference in butyrate levels in the rats treated with the pre-formulation.Conclusions. The pre-formulation minimized the clinical symptoms of colitis and intestinal inflammation, but did not minimize damage to the intestinal barrier.

Bioprospecting as a strategy for conservation and sustainable use of the Brazilian Flora / Bioprospecção como estratégia para a conservação e uso sustentável da Flora Brasileira

Abstract In Brazil, research with natural products had a strong impulse when FAPESP supported the creation of the Laboratory of Chemistry of Natural Products of the Institute of Chemistry of USP (1966). In 1999, FAPESP launched the Research Program in the Characterization, Conservation, Restoration and Sustainable Use of Biodiversity (BIOTA-FAPESP), which intensified the sustainable exploitation of biodiversity, and which evolved to form the Biota Network for Bioprospection and Bioassays (BIOprospecTA), which integrates groups from all over the country, optimizing the use of the skills already installed for the bioprospecting of microorganisms, plants, invertebrates, vertebrates and marine organisms. Of the 104 projects related to plant sciences, 35 carried out bioprospection of Brazilian flora, belonging to the areas of Chemistry, Botany, Genetics, Plant Physiology, Plant Morphology, Plant (Chemo)taxonomy, Ecosystem Ecology, Plant Genetics. Physical Sciences, Forest Resources, Forestry Engineering, Agronomy, leading to thousands of publications, engagement of hundreds of students and a deeper understanding of natural products in different biological models through macromolecules analysis aided by computational and spectrometric strategies, in addition to pharmacological evaluations. The development of omics approaches led to a more comprehensive view of the chemical profile of an organism, and enabled integrated and concomitant studies of several samples, and faster annotation of known molecules, through the use of hyphenated and chemometric techniques, and molecular networking. This also helped to overcome the lack of information on the safety and efficacy of herbal preparations, in projects dealing with the standardization of herbal products, according to international standards. The BIOTA-FAPESP program has also focused on environmental aspects, in accordance with the principles of Green Chemistry and has had positive effects on international collaboration, on the number and impact of scientific publications and on partnership with companies, a crucial step to add value and expand the production chain of bioproducts. Also, the compilation, systematization and sharing of data were contemplated with the creation of the NUBBEDB database, of free access, and that integrates with international databases (ACD/labs, American Chemical Society - ACS), helping researchers and companies in the development from different areas of science, technology, strengthening the bioeconomy and subsidizing public policies.

Resumo No Brasil, as pesquisas com produtos naturais tiveram um forte impulso quando a FAPESP apoiou a criação do Laboratório de Química de Produtos Naturais do Instituto de Química da USP (1966). Em 1999, a FAPESP lançou o Programa de Pesquisa em Caracterização, Conservação, Restauração e Uso Sustentável da Biodiversidade (BIOTA-FAPESP), que intensificou a exploração sustentável da biodiversidade, e que evoluiu para formar a Rede Biota de Bioprospecção e Bioensaios (BIOprospecTA), que integra grupos de todo o país, otimizando o aproveitamento das competências já instaladas para a bioprospecção de microrganismos, plantas, invertebrados, vertebrados e organismos marinhos. Dos 104 projetos relacionados às ciências vegetais, 35 realizaram a bioprospecção da flora brasileira, em diversas áreas como Química, Botânica, Fisiologia e Morfologia Vegetal, (Quimio)taxonomia Vegetal, Ecologia de Ecossistemas, Genética Vegetal, Recursos Florestais, Engenharia Florestal, dentre outros, levando a milhares de publicações, ao engajamento de centenas de estudantes e ao entendimento mais profundo dos produtos naturais em diferentes modelos biológicos por meio da análise de micromoléculas auxiliada por estratégias computacionais e espectrométricas, além de avaliações farmacológicas. O desenvolvimento de abordagens ômicas ampliou a visão sobre perfil químico dos organismos, possibilitou o estudo integrado e concomitante de várias amostras, e a anotação mais rápida de moléculas conhecidas, por meio do uso de técnicas hifenadas, quimiométricas e redes moleculares. Isso também contribuiu para superar a falta de informação sobre a segurança e eficácia dos fitopreparados, em projetos que tratam da padronização de produtos fitoterápicos, de acordo com normas internacionais. O programa BIOTA-FAPESP também tem focado em aspectos ambientais, de acordo com os princípios da Química Verde e teve reflexos positivos na colaboração internacional, no número e no impacto das publicações científicas e na parceria com empresas, etapa crucial para agregar valor e expandir a cadeia produtiva de bioprodutos. Ainda, a compilação, sistematização e compartilhamento de dados foram contemplados com a criação da base de dados NUBBEDB, de livre acesso, e que se integra com bases internacionais (ACD/labs, American Chemical Society - ACS), auxiliando pesquisadores e empresas no desenvolvimento de diferentes áreas da ciência, tecnologia, fortalecendo a bioeconomia e subsidiando políticas públicas.

Antiproliferative Effect of Urera baccifera Leaves Against Ovarian Carcinoma Cell Line (OVCAR-3)

Abstract Natural products, especially phytochemicals, have been extensively studies and have exhibited important antiproliferative effects. The American native species Urera baccifera (L.) Gaudich. ex Wedd. (Urticaceae) is widely distributed in Brazil, where it is known as urtiga-vermelha or urtigão. The leaves are popularly used as anti-inflammatory, antirheumatic and in the treatment of gastric disorders. However, the antiproliferative potential of this plant against human tumor cells remain to be elucidated. In this study, we evaluated the antiproliferative effects of U. baccifera leaves extracts and fractions against a panel of human tumor cell lines in vitro besides a chemical evaluation of the most active sample by mass spectrometry (ESI-IT-MSn). The hydroalcoholic extract was inactive while dichloromethane extract showed moderate cytostatic activity against ovarian carcinoma cell line (OVCAR-3, GI50 = 1.5 μg/mL). More, the ethyl acetate and n-butanol fractions did not show important activity against tumour cell while the dichloromethane and hexane fractions showed moderate cytostatic activity against ovarian tumor cell line (OVCAR-3, GI50 = 12.7 and 9.4 μg/mL, respectively). Finally, the chemical profile evaluated by mass spectrometry (ESI-IT-MSn) allowed the detection of flavonoids in the HEU and hydroxylated fatty acid in DEU that can explain partially the biological effects observed. This is the first report of the antiproliferative effects of U. baccifera, and DEU has shown potential as a promising source of bioactive compounds.

Antioxidant and hepatoprotective effects of ethanolic and ethyl acetate stem bark extracts of Copaifera multijuga (Fabaceae) in mice / Efeitos antioxidante e hepatoprotetor dos extratos brutos etanólico e acetato de etila da casca do caule da Copaifera multijuga(Fabaceae) em camundongos

The properties of oil-resin of copaiba, Copaifera multijuga are commonly mentioned in the literature, but there are few studies on extracts from its stem bark. We evaluated the antioxidant effects of ethanolic (EE) and ethyl acetate (EA) crude stem bark extracts from copaiba and compared them to rutin in a paracetamol (PCM)-induced oxidative stress model in mice. All test comparisons differed significantly. Hepatic catalase (CAT) and glutathione-S-transferase (GST) activity decreased in the PCM group, and there was an increase of protein carbonyls in the liver, kidney and brain. However, the protein carbonyls decreased in the liver for the PCM + EE group, in the kidneys for the PCM + EA and PCM + Rutin groups, and in the brain for all treatments. Hepatic GSH decreased in the PCM group and increased in the PCM + EE group. The extracts showed a positive effect on ascorbic acid (ASA), since they were able to restore the levels of parameters that had been changed by PCM. There was an increase of ALT and AST activity in the plasma within the PCM group. Even though ALT decreased in the PCM + Rutin, PCM + EE and PCM + EA groups, EE and EA did not have an effect on AST. The strongest antioxidant effect was observed for EE, due to the presence of the phenolic compounds epicatechin and epiafzelechin, as well as the highest concentration of total phenols and an excellent antioxidant potential observed in the DPPH· test.

As propriedades do óleo-resina da copaíba, Copaifera multijuga são comumente citadas na literatura, mas há poucos estudos sobre extratos da casca do caule. Avaliamos os efeitos antioxidantes de extratos brutos etanólico (EE) e acetato de etila (EA) da casca do caule da copaíba e os comparamos à rutina no modelo de estresse oxidativo induzido por paracetamol (PCM) em camundongos. Todas as comparações de teste diferiram significativamente. A atividade da catalase hepática (CAT) e da glutationa-S-transferase (GST) diminuiu no grupo PCM, e houve um aumento de proteínas carboniladas no fígado, rim e cérebro. No entanto, as proteínas carboniladas diminuíram no fígado para o grupo PCM + EE, nos rins para os grupos PCM + EA e PCM + rutina, e no cérebro para todos os tratamentos. A GSH hepática diminuiu no grupo PCM e aumentou no grupo PCM + EE. Os extratos mostraram um efeito positivo sobre o ácido ascórbico (ASA), uma vez que foram capazes de restaurar os níveis dos parâmetros que foram alterados pelo PCM. Houve um aumento da atividade de ALT e AST no plasma dentro do grupo PCM. Embora a ALT tenha diminuído nos grupos PCM + rutina, PCM + EE e PCM + EA, EE e EA não afetaram a AST. O efeito antioxidante mais forte foi observado para o EE, provavelmente devido à presença dos compostos fenólicos epicatequina e epiafzelequina, assim como à maior concentração de fenóis totais e um excelente potencial antioxidante observado no teste DPPH·

Operculina macrocarpa: chemical and intestinal motility effect in mice

ABSTRACT Operculina macrocarpa (L.) Urb., Convolvulaceae, is used by the population as a laxative. In this work we described the isolation of the three phenolic acids present in the hydroethanolic extract of the O. macrocarpa roots. The quantification of the caffeic, chlorogenic acids and of the new caffeic dimer in the hydroethanolic and infusion extracts was performed by high-performance liquid chromatography coupled photodiode array detector. These analyses showed the higher content of the chlorogenic, caffeic and the new 3,4'-dehydrodicaffeic acid in hydroethanolic and hydroethanolic extracts without resin in which infusion. The acid found in greater quantity is caffeic acid followed by the 3,4'-dehydrodicaffeic acid. The laxative activity was evaluated by different experimental models of intestinal transit with the hydroethanolic and infusion extracts, and the resin fraction, caffeic, chlorogenic and ferulic acids. The results showed all extracts and compounds tested had significant activity in the experimental model tested. These results obtained are essential for the future development of a pharmaceutical product with safety and efficacy.

Oleanane-type triterpenoid: an anti-inflammatory compound of the roots Arrabidaea brachypoda

AbstractArrabidaea brachypoda Bureau, Bignoniaceae, known as "cipó-una", is widely used in traditional medicine in Southeastern and Northeastern Brazil for kidney stones and painful joints. This study was aimed at evaluating the anti-inflammatory proprieties of the oleanane-type triterpenoid 3β-estearioxy-olean-12-ene isolated from the roots of A. brachypoda. Carrageenan-induced paw oedema, formalin test and hot plate test were used to investigate the antiinflammatory activity of 3β-estearioxy-olean-12-ene in animals. We observed that 3β-estearioxy-olean-12-ene at doses of 5, 10 and 15 mg/kg p.o. demonstrated anti-inflammatory effects, by reduced (p < 0.05) paw oedema induced by carrageenan and by decreased (p < 0.05) licking time caused by a subplantar injection of formalin. In conclusion, 3β-estearioxy-olean-12-ene, a triterpene isolated from the roots of A. brachypoda, demonstrate anti-inflammatory effect in different tests. Thus, it may be useful in the treatment of inflammatory disorders, which supports previous claims of its traditional use.

Evaluation of mutagenicity and metabolism-mediated cytotoxicity of the naphthoquinone 5-methoxy-3,4-dehydroxanthomegnin from Paepalanthus latipes

A large number of quinones have been associated with antitumor, antibacterial, antimalarial, and antifungal activities. Results of previous studies of 5-methoxy-3,4-dehydroxanthomegnin, a naphthoquinone isolated from Paepalanthus latipes Silveira, Eriocaulaceae, revealed antitumor, antibacterial, immunomodulatory, and antioxidant activities. In this study, we assessed the mutagenicity and metabolism-mediated cytotoxicity of 5-methoxy-3,4-dehydroxanthomegnin by using the Ames test and a microculture neutral red assay incorporating an S9 fraction (hepatic microsomal fraction and cofactors), respectively. We also evaluated the mutagenic activity in Salmonella typhimurium strains TA100, TA98, TA102, and TA97a, as well as the cytotoxic effect on McCoy cells with and without metabolic activation in both tests. Results indicated that naphthoquinone does not cause mutations by substitution or by addition and deletion of bases in the deoxyribonucleic acid sequence with and without metabolic activation. As previously demonstrated, the in vitro cytotoxicity of 5-methoxy-3,4-dehydroxanthomegnin to McCoy cells showed a significant cytotoxic index (CI50) of 11.9 μg/ml. This index was not altered by addition of the S9 fraction, indicating that the S9 mixture failed to metabolically modify the compound. Our results, allied with more specific biological assays in the future, would contribute to the safe use of 5-methoxy-3,4-dehydroxanthomegnin, compound that has showed in previous studies beneficial properties as a potential anticancer drug.

Esteroide e Triterpenos de espécies de Qualea - Bioatividade sobre Mycobacterium tuberculosis / Sterol and Triterpenes from Qualea species: Bioactivity on Mycobacterium tuberculosis

O extrato clorofórmico das cascas de Qualea parviflora (Vochysiaceae) foi fracionado em cromatografia em coluna usando sílica gel para fornecer triterpenos (lupeol, lupenona, betulina, ácido epibetulínico, e friedelina) e um esteroide (β-sitosterol). Os compostos β- sitosterol, lupenona e lupeol foram identificados também em Q. grandiflora e Q. multiflora, enquanto friedelina foi detectada apenas em Q. multiflorautilizando a cromatografia gasosa acoplada à espectrometria de massas. A atividade anti Mycobacterium tuberculosis do extrato clorofórmico e dos compostos isolados foi determinada por MABA e o valor da CIM variou de 250,0 a 31,2 μg/mL. Esta investigação constitui o primeiro relato do estudo químico e antitubercular de compostos apolares das espécies de Qualea.

The chloroform extract of bark of the tropical tree Qualea parviflora (Vochysiaceae) was fractionated by column chromatography on silica gel, yielding triterpenes (lupeol, lupenone, betulin, epibetulinic acid and friedelin) and a steroid (β-sitosterol). β-sitosterol, lupenone and lupeol were also identified in Q. grandiflora and Q. multiflora, while friedelin was detected only in Q. Multiflora, by means of gas chromatography-mass spectrometry. The anti-Mycobacterium tuberculosis activity of the chloroform extract and isolated compounds was assayed by MABA and MIC values ranged from 250.0 to 31.2 μg/mL. This study is the first to investigate the chemistry and antitubercular activity of apolar compounds from Qualeaspecies.

Paepalanthus spp: antimycobacterial activity of extracts, methoxylated flavonoids and naphthopyranone fractions

Paepalanthus spp., Eriocaulaceae, are native plants from Brazil known as "sempre-vivas" (everlasting flowers). In this work, we evaluated the potential anti-mycobacterial activity of two methoxylated flavonoids (flavonoid 7-methylquercetagetin and 7-methylquercetagetin-4'-O-β-D-glucopyranoside) isolated and identified from P. latipes and the naphthopyranone fractions from P. bromeliodes ethanolic extracts. The MIC value of 500 µg/mL was verified for all compounds tested against M. tuberculosis H37Rv. For M. avium, the MIC value ranged from 1000-2000 µg/mL excepting to naphthopyranone fractions with MIC of 500 µg/mL. This is the first report of activity determination of Paepalanthus spp. flavonoids activity against Mycobacterium tuberculosis and M. avium.

Anti-Helicobacter pylori activity and oxidative burst inhibition by the naphthoquinone 5-methoxy-3,4-dehydroxanthomegnin from Paepalanthus latipes

Helicobacter pylori is a bacterium recognized as the major cause of chronic gastritis and peptic ulcers. Infection by H. pylori induces inflammatory responses and pathological changes in the gastric microenvironment. The host Keywords: immune cells (especially neutrophils) release inflammatory mediators and large 5-methoxy-3,4-dehydroxanthomegnin amounts of reactive oxygen species (ROS), which are associated with an increased Helicobacter pyloririsk of developing gastric cancer. In this study, we evaluated the anti-H. pylori and oxidative burst antioxidantactivitiesofa1,4-naphthoquinone-5-methoxy-3,4-dehydroxanthomegnin. Paepalanthus latipes The antimicrobial activity was assessed using a spectrophotometric microdilution technique, and antioxidant activity was assessed by noting the effect of 5-methoxy3,4-dehydroxanthomegnin on the neutrophil oxidative burst using luminol-and lucigenin-amplified chemiluminescence. The results showed that 5-methoxy-3,4dehydroxanthomegnin is a potent anti-H. pylori compound (MIC 64 µg/mL and MBC 128 µg/mL) and a strong antioxidant. 5-Methoxy-3,4-dehydroxanthomegnin decreased luminol- and lucigenin-amplified chemiluminescence, with ED50 values of 1.58±0.09 µg/mL and 5.4±0.15 µg/mL, respectively, reflecting an inhibitory effect on the oxidative burst. These results indicate that 5-methoxy-3,4-dehydroxanthomegnin is a promising compound for the prevention and treatment of diseases caused by H. pylori infection, such as gastritis, peptic ulceration, and gastric cancer, because reactive oxygen intermediates are involved in the pathogenesis of gastric mucosal injury induced by H. pylori infections.

Antitumor and immunomodulatory effects of the naphthoquinone 5-methoxy-3,4-dehydroxanthomegnin

Large number of quinones has been associated with antitumor, antibacterial, antimalarial and antifungal activities. In this work we describe the effect of the naphthoquinone, 5-methoxy-3,4-dehydroxanthomegnin, on murine tumor cells (LP07 and LM2) and its immunomodulatory effect on nitric oxide (NO) production on LPS-stimulated macrophages. The results have shown that 5-methoxy-3,4-dehydroxanthomegnin was a significant inhibitor of LPS-stimulated NO generation from macrophage (inhibition percentage ranged from 97.4 to 98.9 percent) and a strong cytotoxic agent against both tumor cells LP07 and LM2 (CI50 6.2±0.36 µM and 74.6±1.9 µM, respectively). These results indicate that the 5-methoxy-3,4-dehydroxanthomegnin may show promising activity in the treatment of murine breast and lung cancer by immunomodulatory and antiproliferative activities.

Antitumoral, mutagenic and (anti)estrogenic activities of tingenone and pristimerin

Cancer constitutes the second main mortality cause in the world, after cardiovascular diseases. In spite of the progresses in the chemotherapeutics treatments, many patients fail chemotherapy, mainly because of side effects or multi-drugs resistance, proving the need and importance of the research for new molecules with anticancer activity, more effective and with smaller adverse effects. Various compounds derived from plant secondary metabolites are commonly used in the chemotherapy against cancer and the natural products play an important role in the research for new molecules. Among several molecules of natural origin evaluated by MTT assay in murine tumor cell lines [breast (LM3) and lung (LP07)] the quinona-methide triterpenes tingenone and pristimerin showed marked cytotoxic activity presenting IC50 around 2 and 5 µM respectively. The structure-activity relationship suggests that rings A and B containing an α, ß-unsaturated carbonyl group are essential for the observed cytotoxic activity. The interaction between these positions and acetylcisteyne residues suggests a probable mechanism of action. The in vitro mutagenic activity was also evaluated by the Salmonella microsome assay (Ames test) for pristimerin and tingenone with and without metabolic activation (S9) in the strains TA98, TA97a, TA100 and TA102, none of which showed mutagenic potential in any strains. Estrogenic and anti-estrogenic activities were also studied by the e-screen assay in MCF-7 cells with negative results. The present data point to the importance of pristimerin and tingenone as representative of an emerging class of potential anticancer chemicals.

Assessment of estrogenic, mutagenic and antimutagenic activity of nemorosone

Currently, a wide range of research involving natural products is focused on the discovery of new drugs in many different therapeutic areas. A great number of the synthetic compounds on the market were derived from natural products, especially plants. Nemorosone is the major constituent of the floral resin of Clusia rosea Jacq., Clusiaceae, and in Cuban propolis. In vitro studies have shown cytotoxic activity in this substance against various tumor cell lines, including those resistant to various cytotoxic drugs, whereas it has low cytotoxicity to non-tumoral cells. Therefore, in order to characterize the biological activity of nemorosone, a substance with potential antitumor activity, and in view of preclinical testing of the toxicity of drug candidate compounds, the main aim of this study was to determine the mutagenic and antimutagenic activity of nemorosone by the Ames test, using the strains TA97a, TA98, TA100 and TA102 of Salmonella typhimurium. Secondly, to characterize the estrogenic activity in an experimental recombinant yeast model (Recombinant Yeast Assay) mutagenic activity was observed at in any of the concentrations in any of the test strains. To evaluate the antimutagenic potential, direct and indirect mutagenic agents were used: 4 nitro-o-phenylenediamine (NPD), mitomycin C (MMC) and aflatoxin B1 (AFL). Nemorosone showed moderate antimutagenic activity (inhibition level 31 percent), in strain TA100 in the presence of AFL, and strong antimutagenic activity in TA102 against MMC (inhibition level 53 percent). Estrogenic activity was observed, with an EEq of 0.41±0.16 nM at various tested concentrations.

Chronic administration of Abarema cochliacarpos attenuates colonic inflammation in rats

Inflammatory bowel diseases are characterized by a chronic clinical course of relapse and remission associated with self-destructive inflammation of the gastrointestinal tract. Active extracts from plants have emerged as natural potential candidates for its treatment. Abarema cochliacarpos (Gomes) Barneby & Grimes, Fabaceae (Barbatimão), is a native medicinal plant in to Brazil. Previously we have demonstrated in an acute colitis model a marked protective effect of a butanolic extract, so we decided to assess its anti-inflammatory effect in a chronic ulcerative colitis model induced by trinitrobenzensulfonic acid (TNBS). Abarema cochliacarpos (150 mg/day, v.o.) was administered for fourteen consecutive days. This treatment decreased significantly macroscopic damage as compared with TNBS. Histological analysis showed that the extract improved the microscopic structure. Myeloperoxidase activity (MPO) was significantly decreased. Study of cytokines showed that TNF-α was diminished and IL-10 level was increased after Abarema cochliacarpos treatment. In order to elucidate inflammatory mechanisms, expression of cyclooxygenase (COX)-2 and nitric oxide synthase (iNOS) were studied showing a significant downregulation. In addition, there was reduction in the JNK and p-38 activation. Finally, IκB degradation was blocked by Abarema cochliacarpos treatment being consistent with an up-regulation of the NF-kappaB-binding activity. These results reinforce the anti-inflammatory effects described previously suggesting that Abarema cochliacarpos could provide a source for the search for new anti-inflammatory compounds useful in ulcerative colitis treatment.