Cytotoxic screening of plants from the Brazilian Atlantic Forest has led to the identification of Casearia arborea and Sorocea hilarii as sources of antitumor compounds.

In the present study, we have evaluated the cytotoxic activity of 282 extracts from 72 native plant species of the Brazilian Atlantic Forest biome. As a result, Casearia arborea and Sorocea hilarii leaves extracts showed cytotoxic activity against three tumour cell lines tested (B16F10, SW480 and Jurkat). After bioassay-guided fractionation, the bioactive fractions were submitted to the dereplication study via High-performance Liquid Chromatography, connected to High-resolution Mass Spectrometry (HPLC-ESI-QTOF/MS) analysis, combined with a Global Natural Products Social Molecular Networking (GNPS) tool. A combination of bioactivity-guided and dereplication approaches resulted in the putative annotation of 27 clerodane diterpenes and 9 flavonoids as main compounds present in the cytotoxic fractions of C. arborea. Regarding the active fraction of S. hilarii, 10 megastigmans, 17 spirostane steroids derivatives and 2 lignans were putatively identified. In conclusion, Casearia arborea and Sorocea hilarii are potential sources of antitumor compounds.

Strychnos pseudoquina A. St. Hil.: a Brazilian medicinal plant with promising in vitro antiherpes activity.

AIMS: To investigate the anti-HSV and anti-inflammatory effects of a standardized ethyl acetate extract (SEAE) prepared with the stem bark of Strychnos pseudoquina, along with two isolated compounds: quercetin 3-O-methyl ether (3MQ) and strychnobiflavone (SBF). METHODS AND RESULTS: The mechanisms of action were evaluated by different methodological strategies. SEAE and SBF affected the early stages of viral infection and reduced HSV-1 protein expression. Both flavonoids elicited a concentration-dependent inhibition of monocyte chemoattractant protein-1 (MCP-1), whereas 3MQ reduced the chemokine release more significantly than SBF. Conversely, both compounds stimulated the production of the cytokines TNF-α and IL-1-ß in LPS-stimulated cells, especially at the intermediate and the highest tested concentrations. CONCLUSIONS: SEAE and SBF interfered with various steps of HSV replication cycle, mainly adsorption, postadsorption and penetration, as well as with ß and γ viral proteins expression; moreover, a direct inactivation of viral particles was observed. Besides, both flavonoids inhibited MCP-1 selectively, a feature that may be beneficial for the development of new anti-HSV agents. SIGNIFICANCE AND IMPACT OF THE STUDY: The results indicated that the samples present anti-HSV and anti-inflammatory activities, at different levels, which is an interesting feature since cold and genital sores are accompanied by an inflammation process.

Avaliação fitoquímica e atividade antioxidante, antimutagênica e toxicológica do extrato aquoso das folhas de Ocimum gratissimum L / Phytochemical Assessment And Antioxidant, Antimutagenic And Toxicological Activity Of Ocimum gratissimum L. Leaf aqueous extract

A espécie Ocimum gratissimum L., popularmente conhecida como alfavaca, é uma planta muito usada na medicina tradicional brasileira, à qual são atribuídas diversas atividades terapêuticas quando usada na forma de infuso de suas folhas. Neste estudo foi realizada a caracterização fitoquímica, a avaliação da ação antioxidante e a investigação dos efeitos antimutagênico e antigenotóxico, além do efeito mutagênico e genotóxico potencial do extrato aquoso liofilizado a parir das folhas de O. gratissimum (EAOG). O conteúdo de polifenóis totais no extrato foi determinado pelo método Folin-Ciocalteu, sendo encontrado 11,3 µg EAG/mg de EAOG. A atividade antioxidante foi avaliada pelo teste do 1,1-difenil-2-picril hidrazil (DPPH•), apresentando IC50 de 83,0 µg/mL. A antimutagenicidade e mutagenicidade foram avaliadas em cepas de Salmonella typhimurium (TA98 e TA100) utilizando o teste Salmonella/microssoma (Salmonella typhimurium/microssomas) em diferentes concentrações. EAOG induziu a atividade antimutagênica para a cepa TA98. A mutagenicidade não foi observada para o extrato em ambas as linhagens. Adicionalmente, a ação antigenotoxica avaliada pelo teste de clivagem do DNA-plasmidial também foi observada para EAOG. Os resultados também demonstraram que o extrato não foi capaz de induzir a genotoxicidade pelo teste empregado. Este estudo relata, pela primeira vez, as propriedades antimutagênica e antigenotóxica do extrato aquoso de O. gratissimum.

The species Ocimum gratissimum L., popularly known as Clove Basil, is a plant widely used in traditional Brazilian medicine, and several therapeutic activities are attributed to it when used as infusion of its leaves. In this study, we carried out a phytochemical characterization and the assessment evaluation and investigation of the antioxidant action of the antimutagenic and antigenotoxic effects and the potential mutagenic and genotoxic effects of the freeze-dried aqueous extract of the O. gratissimum (EAOG) leaves. The total polyphenol content in the extract was determined by the Folin-Ciocalteu method, and we found 11.3 µg EAG/mg of EAOG. The antioxidant activity was assessed by the 1,1-diphenyl-2-picryl hidrazil (DPPH·), with IC50 of 83.0 µg/mL. Antimutagenicity and mutagenicity were assessed in Salmonella typhimurium (TA98 and TA100) strains using the Salmonella/microsome (Salmonella typhimurium/microsome) test in different concentrations. EAOG induced antimutagenic activity for strain TA98. Mutagenicity was not observed for the extract in both strains. Additionally, antigenotoxic action, assessed by cleavage of the DNA-damage, was also observed for EAOG. The results also show that the extract was not able to induce genotoxicity by the test used. This study reports for the first time the antimutagenic and antigenotoxic properties of the O. gratissimum aqueous extract.

Fitodefensivos em plantas medicinais: macromoléculas hidrofílicas de folhas de mil folhas (Achillea millefolium L. ) inibem o crescimento in vitro de bactérias fitopatogênicas / Agrochemicals in medicinal plants: hydrophilic macromolecules from leaves of "mil folhas" (Achillea millefolium L. ) inhibit in vitro growth of phytopathogenic bacteria

Extratos aquosos da planta medicinal Achillea millefolium contêm macromoléculas de interesse para desenvolver fitodefensivos para a agricultura. Duas frações de mil folhas foram obtidas por ultrafiltração, E1 (contendo moléculas maiores que 30 kDa), e E3 (peptídeos entre 1 e 10 kDa) que inibiram o crescimento das bactérias fitopatogênicas Ralstonia solanacearum, gram-negativa, e Clavibacter michiganensis subsp. michiganensis, gram-positiva, com dependência de concentração. Os valores de concentração inibitória mínima (CIM) para ambos os extratos e bactérias foram baixos, entre 20 e 80µM. A CIM relativa à proteína total evidenciou a presença de macromoléculas muito ativas em E3, embora com baixa concentração proteica. E3 se aplica à prospecção de peptídeos antimicrobianos. Estimar a CIM relativa à quantidade de amostra vegetal valorizou o potencial antimicrobiano natural de E1, que contém alta concentração proteica. E1e E3 se aplicam ao desenvolvimento de fitodefensivos para uso biotecnológico. A ultrafiltração fracionou as amostras de forma nativa, rápida, e com baixo custo; além de dessalinizar, clarificar, purificar, e concentrar E1 e E3. Esse estudo inédito sobre a separômica e a ação antimicrobiana de extratos macromoleculares aquosos de mil folhas sugere que plantas cicatrizantes podem apresentar grande potencial para desenvolver fitodefensivos agrícolas naturais não danosos, à semelhança de medicamentos fitoterápicos.

Aqueous extracts from the medicinal plant Achillea millefolium contain macromolecules of interest to develop agrochemicals for agriculture. Two fractions of "mil folhas" were obtained by ultrafiltration, E1 (containing molecules larger than 30 kDa) and E3 (peptides between 1 and 10 kDa), which inhibited the growth of phytopathogenic bacteria Ralstonia solanacearum, gram-negative, and Clavibacter michiganensis subsp. michiganensis, gram-positive, concentration-dependent. The values of minimum inhibitory concentration (MIC) for both extracts and both bacteria were low, ranging from 20 to 80µM. The MIC relative to total protein evidenced the presence of very active macromolecules in E3, although showing low protein concentration. E3 applies to the prospection of antimicrobial peptides. The estimated MIC relative to the amount of plant sample valued the natural antimicrobial potential of E1, which contains high protein concentration. E1 and E3 can be used in the development of agrochemicals for biotechnological purposes. The ultrafiltration procedure fractionated the samples in a rapid and native way and at a low cost; it also desalted, clarified, concentrated and purified both E1 and E3. This pioneering study on the separomics and on the antimicrobial activity of macromolecular aqueous extracts from "mil folhas" suggests that healing plants have great potential to develop non-harmful agricultural natural agrochemicals, similarly to the available phytotherapic drugs.

Produtos naturais ativadores de PPAR e marcadores associados ao processo inflamatório na Síndrome Metabólica / The inflammatory process in the metabolic syndrome: PPAR activators of natural products and markers associated with metabolic disorders

O processo inflamatório é o elo entre a síndrome metabólica e as doenças cardiovasculares. Para verificar a presença e o grau da inflamação, vários biomarcadores têm sido propostos e investigados. Este trabalho tem como objetivo revisar as recentes pesquisas que associam alguns marcadores expressos no tecido adiposo, enfatizando, dentre eles, a adiponectina, a resistina, a leptina e o transportador de glicose GLUT-4 na síndrome metabólica, a relação da inflamação decorrente desse conjunto de desordens metabólicas sob os receptores proliferadores peroxissomais (PPARs), bem como o efeito de diferentes extratos vegetais e produtos naturais bioativos na ativação desses receptores.

The inflammatory process is the link between metabolic syndrome and cardiovascular diseases. To verify the presence and degree of inflammation, several biomarkers have been proposed and different receptors have been investigated. This study aims to review recent researches involving some markers expressed in the adipose tissue, emphasizing, among them, adiponectin, resistin, leptin and glucose transporter GLUT-4 in the metabolic syndrome, the relationship of inflammation arising from this set of metabolic disorders on the peroxisome proliferator receptors (PPARs) and the effect of different bioactive compounds in the activation of these receptors.

Acute and chronic toxicological studies of Dimorphandra mollis in experimental animals.

Dimorphandra mollis Benth. (Caesalpiniaceae), known as "faveira" or "fava d'anta" is a common plant in central Brazilian cerrado that is used mainly as a vasoprotector. Its main marker is rutin. The present study aimed to evaluate the security of Dimorphandra mollis dry extract in rodents. The extract presented a rutin content of 76+/-3%. Acute and chronic (180 days) toxicity was evaluated after per os administration. In acute toxicity, 3500 and 5000 mg/kg doses presented reversible effects. In chronic toxicity, 1000 and 2000 mg/kg doses did not provoke significant changes in body weight of the animals and in water and food consumption. Behavioral reversible changes and in blood count parameters (hemoglobin, hematocrit and red cells decrease and platelets increase in male in rats) were observed only in 2000 mg/kg dose. In biochemical evaluation, the results varied a lot considering doses and sex, without a linear profile. Some parameters showed a significant difference but without a clinical correlation. In histopathological examination, lung hemorrhage was observed in 2000 mg/kg dose. In conclusion, the study suggest that the extract is safe in a 1000 mg/kg dose, whereas for 2000 mg/kg dose further studies are needed. In long-term use, caution is required.

Perfil de utilização de fitoterápicos em farmácias comunitárias de Belo Horizonte sob a influência da legislação nacional / Profile of the utilization of phytotherapie medicines in communitary pharmacies of Belo Horizonte, under the influence of the national legislation

Um panorama do consumo de fitoterápicos em farmácias comunitárias de Belo Horizonte (MG) é utilizado neste artigo como instrumento para analisar a influência da legislação nacional sobre este mercado. Para tal, foram entrevistados indivíduos que adquiriram fitoterápicos nos estabelecimentos farmacêuticos visitados. Observa-se que, na mesma nação detentora da maior biodiversidade do planeta e privilegiada por uma cultura popular conhecedora das propriedades terapêuticas das plantas, existe uma tendência de mercado para a utilização de plantas exóticas, oriundas de países desenvolvidos. A influência da legislação brasileira de fitoterápicos, que prima pela qualidade, eficácia e segurança desses medicamentos, mas que, ao mesmo tempo, tende a proscrever as drogas nativas que fazem parte da medicina popular brasileira, é discutida nesse trabalho. Verifica-se, assim, a pertinência de se discutir o perfil de usuário de fitoterápicos à luz das normas de registro desses fármacos no país no campo da saúde pública, tendo em vista que essa legislação repercute nas estratégias e/ou empecilhos para aumentar o acesso a medicamentos pela população.

An overview of the herbal drugs consumption in communitarian pharmacies in Belo Horizonte (MG), Brazil is used in this article as a tool to analyze the influence of the national law over this market. In order to reach this goal, individuals that had bought herbal drugs were interviewed at the pharmacies. It was observed that, in the same nation that has the highest biodiversity in the planet and is privileged by a popular culture knowledgeable in the therapeutic properties of the plants, there is a tendency in the market for the use of exotic plants, coming from developed countries. The influence of the Brazilian law about the herbal drugs, which constantly worries about the quality, efficiency and safety of these medicines, but at the same time, tends to proscribe the native drugs that are part of the popular medicine, is discussed in this assignment. It is concluded that it is pertinent to discuss the profile of the herbal drugs users in the spot of the laws of the country related to these drugs, in the field of the public health, since this legislation is reflected in the strategies and/or barriers to increase the access to the drugs by the population.

Evaluation of antinociceptive, anti-inflammatory and antiulcerogenic activities of Maytenus ilicifolia.

Maytenus ilicifolia (Celastraceae) is a native plant from Tropical Atlantic Forest (Mata Atlântica, Brazil) called 'espinheira-santa'. This plant is traditionally used as anti-inflammatory, analgesic and antiulcerogenic. Many studies focusing pharmacological and toxicological aspects of the plant have been performed. The aim of this study is to evaluate the efficacy (anti-inflammatory and antinociceptive activities and protection against gastric lesions, including cytoprotection and healing) and phytochemical profile of hexane and ethylacetate extracts of Maytenus ilicifolia. Per os administration of these extracts inhibited nociception and formaldehyde-induced paw oedema in mice and carrageenin-induced paw oedema in rats. Severity of gastric lesions induced by cold-restraint stress (-18 degrees C for 45 min) method was also clearly reduced in rats considering both cytoprotection and healing aspects. Administration of the extracts led to volume gastric and pH increase. These results suggest that hexane and ethylacetate extracts of Maytenus ilicifolia may represent an important clinical alternative in anti-inflammatory and antiulcerogenic therapeutics, though, further experiments should be performed to confirm this assertion.

Isolamento biomonitorado de uma substância tripanossomicida de Arrabidaea triplinervia (Bignoniaceae), o ácicIo ursólico

Como estratégia para a busca de novos agentes tripanossomicidas, de potencial utilização no controle da transmissão transfusional da doença de Chagas, realizou‑se uma triagem dos extratos etanólicos provenientes de espécies vegetais da família Bignoniaceae. Foram avaliadas diferentes metodologias de fracionamento dos extratos etanólicos, tais como, partição entre solventes imisciveis, cromatografias em coluna de poliamida e de gel de sílica, com monitoramento por testes in vitro contra formas tripomastigotas do Trypanosoma cruzi. Os fracionamentos em coluna de gel de sílica do extrato etanólico das folhas de Arrabidaea triplinervia e, posteriormente, da fração eluída desta coluna com diclorometano‑acetato de etila (1:1) resultaram no isolamento de uma substância tripanossomicida, o ácido ursólico (0,76 por cento).