Antiproliferative potential of solidagenone isolated of Solidago chilensis

ABSTRACT Plants are considered among the main sources of biologically active chemicals. The species Solidago chilensis Meyen, Asteraceae, is native to the southern parts of South America, where the aerial parts of the plant are commonly used for the treatment of inflammatory conditions. However, the effects of S. chilensis on human cancer cells remain to be elucidated. In this study, we evaluated the antiproliferative effects of the hydroalcoholic and dichloromethane extracts of S. chilensis, as well as their chemical constituents quercitrin and solidagenone against the five human tumor cell lines in vitro. The dichloromethane extract showed a promisor antiproliferative effects in vitro, especially against glioma cell line. Besides, the hydroalcoholic extract and quercitrin were inactive. The diterpene solidagenone showed highly potent antiproliferative effects against breast (MCF-7), kidney (786-0), and prostate cancer (PC-3) cells (total growth inhibition: TGI < 6.25 µg/ml). Solidagenone meets the theoretical physico-chemical criteria for bioavailability of drugs, according to the "Rule of Five" and, by theorical studies, the observed biological effects were probably related to the interaction of the molecule with nuclear receptors and as an enzymatic inhibitor. This study contributes to chemical study and to the identification of antiproliferative molecules in S. chilensis.

Antiproliferative effects of pinostrobin and 5,6-dehydrokavain isolated from leaves of Alpinia zerumbet

Abstract Natural products are a major source of drugs for the treatment of cancer. The species Alpinia zerumbet (Pers.) B.L. Burtt & R.M. Sm, Zingiberaceae, is widely distributed in Brazil where it is known as "colônia". The leaves are commonly used in the treatment of hypertension and dyspepsia, however, the effects of A. zerumbet extracts and isolated substances on human cancer cells remain to be elucidated. This study was designed to identify the chemical constituents of hydroalcoholic and dichloromethane extracts from A. zerumbet leaves and to investigate their in vitro antiproliferative activity. The isolated phytochemicals included kaempferol, dihydro-5,6-dehydrokavain, 5,6-dehydrokavain, and pinostrobin. The hydroalcoholic extract inhibited cellular proliferation only at high concentrations, while the dichloromethane extract showed a moderate antiproliferative effect against leukemia and lung tumor cell lines. 5,6-Dehydrokavain showed potent cytostatic activity against glioblastoma cells and a moderate effect on all other tumor cell lines. Pinostrobin showed potent activity against leukemia and breast tumor cell lines and moderate cytostatic effect against ovarian cell. Furthermore, this is the first report on the isolation of kaempferol and pinostrobin from A. zerumbet leaves. Moreover, the purification process described in this study was effective. These results suggest that A. zerumbet leaves are a promising source of anticancer compounds.

Antiproliferative activity of methanol extracts of four species of Croton on different human cell lines

Several species of Croton have been described with biological activities, mainly due to diterpenes, alkaloids and/or other secondary metabolites. These activities account for the traditional use of Croton species to treat certain diseases in South America, Asia and Western Africa. The crude methanol extracts obtained from leaves and steam bark of Croton dichrous Müll. Arg., C. erythroxyloides Baill., C. myrianthus Müll. Arg. and C. splendidus Mart. ex Colla were tested for antiproliferative activity against ten human cancer cell lines. Chemical analyses of all extracts were carried out by GC/MS and HPLC/MS/MS. The leaf extract obtained from C. erythroxyloides showed potent activity against PC-3 (prostate) and OVCAR-3 (ovary) cell lines. Lupeol is suggested to be involved in such activity. Tiliroside, an acyl-glycosilated flavonoid ubiquitous in all tested extracts, seems to play an important role in the observed moderate activity of most extracts against the leukemia K562 cell lineage.

Isolation, structural identification and cytotoxic activity of hexanic extract, cyperenoic acid, and jatrophone terpenes from Jatropha ribifolia roots

The cytotoxicity of a hexanic fraction produced from the ethanolic crude extract, obtained from Jatropha ribifolia (Pohl) Baill, Euphorbiaceae, roots was evaluated against ten human cancer cell lines (MCF-7, NCI-ADR/RES, OVCAR-3, PC-3, HT-29, NCI-H460,786-O, UACC-62, K-562, U251) compared with doxorrubicine as positive control. Compounds jatrophone and cyperenoic acid were isolated from the hexanic extract and characterized by spectroscopic techniques (NMR of ¹H, 13C and IR). The in vitro antiproliferative activity of jatrophone showed selectivity in a concentration dependent way with Total Inhibition growth of: glioma 0.57 µg mL-1 (U251), breast cancer 9.2 µg mL-1 (MCF-7), adriamycin-resistant ovarian cancer 0.96 µg mL-1 (NCI-ADR/RES), kidney 4.2 µg mL-1 (786-0), prostate cancer 8.4 µg mL-1 (PC-3), colon cancer 16.1 µg mL-1 (HT29) and leukemia 0.21 µg mL-1 (K-562).

Capacidade antioxidante e triagem farmacológica de extratos brutos de folhas de Byrsonima crassifolia e de Inga edulis / Antioxidant capacity and pharmacologic screening of crude extracts of Byrsonima crassifolia and Inga edulis leaves

Com o objetivo de avaliar o efeito de duas espécies amazônicas em doenças relacionadas aos processos de oxidação, determinou-se a capacidade antioxidante (método Oxygen Radical Absorbance Capacity), o teor de polifenóis totais (método Folin-Ciocalteu - PT), bem como os efeitos farmacológicos in vitro (efeito antiproliferativo) e in vivo (antinociceptivo, antiinflamatório, antiulcerogênico) dos extratos hidroalcoólicos (65:35; v/v; etanol:água) das folhas de Byrsonima crassifolia (BC) e Inga edulis (IE). Os extratos de BC e IE apresentaram elevada capacidade antioxidante (1.422 e 694 µmol de Trolox Equivalente g-1 de folha seca - FS, respectivamente) e um valor relativamente alto de PT (35,93 e 24,50 mg Equivalente ácido gálico g-1 FS, respectivamente). Essa atividade antioxidante não teve relação direta com o teor de compostos fenólicos dos extratos, sugerindo a contribuição de outros grupos químicos nessa atividade. Em cultura de células tumorais humanas (nove linhagens), os extratos não apresentaram atividade antiproliferativa significante, com efeito citotóxico somente na concentração mais elevada. Em modelo de nocicepção induzida pelo calor (placa quente), o extrato de IE apresentou efeito antinociceptivo (P < 0,05) após 30 (250 e 500 mg kg-1) e 60 min (125 e 500 mg kg-1) de sua administração oral. Nos modelos de inflamação houve somente redução do edema para IE na concentração de 500 mg kg-1. Os extratos das duas espécies reduziram as lesões ulcerativas produzidas por etanol em até 84% (P < 0,05), sugerindo uma possível ligação com a atividade antioxidante observada e indicando a necessidade de estudos para a elucidação do mecanismo de ação envolvido.

In order to evaluate the effect of two Amazonian species on chronic diseases linked with the oxidative processes, we performed antioxidant capacity analyses (Oxygen Radical Absorbance Capacity - ORAC and Folin-Ciocalteu - PT assays) and pharmacological effects in vitro (antiproliferative effect) and in vivo (antinociceptive, antiinflammatory, antiulcerogenic effects) for ethanolic extracts (65:35; v/v; ethanol:water) from Byrsonima crassifolia (BC) and Inga edulis (IE) leaves. Both BC and IE extracts showed high ORAC values (1,422 and 694 mmol of Trolox equivalent/g of dry leaf, respectively) and high PT contents (35.93 and 24.50 mg gallic acid equivalent g-1 dry leaf, respectively). The ORAC values had no correlation with PT, suggesting the presence of other chemical groups in the antioxidant activity value. The two extracts did not present significant antiproliferative activity on nine lines of human tumor cells, and cytotoxic effect was detected only at the highest concentration. The antinociceptive effect was investigated using the hot plate test, and IE extract presented a longer latency (P < 0.05) 30 and 60 min after oral administration. The antiinflammatory activity was only observed at the highest concentration, suggesting that the antinociceptive effect observed was not due to the antiinflammatory effect. The extracts of both species reduced the ulcerative lesions produced by ethanol up to 84% (P < 0.05), suggesting a relation with the antioxidant capacity. More studies are necessary to elucidate the mechanisms of action involved on antiulcerative effects.

Constituents and antiproliferative activity of extracts from leaves of Croton macrobothrys

Croton macrobothrys Baill, Euphorbiaceae, is a tree from the Atlantic Forest in Southern Brazil, used in traditional medicine and popularly known as "dragon's blood" and "pau-sangue". Leaf n-hexane, dichloromethane and methanol extracts were analyzed by GC/MS and evaluated for their in vitro antiproliferative activity on cell lines 786-0 (kidney), HT-29 (colon), K562 (leukemia), NCI-ADR/RES (drug resistant ovary), NCI-H460 (lung), MCF-7 (mammary), PC-3 (prostate), OVCAR-3 (ovary), U251 (glioma) and UACC-62 (melanoma). The dicloromethane extract exhibited activity against all cell lines at the concentration 25 µg/mL, in particular on cell lines NCI-H460 (GI50 0.33 μg/mL) and K5662 (GI50 0.91 μg/mL). Relevant constituents in dichloromethane extract are the alkaloids corydine and salutaridine, as well as the diterpenes geranylgeraniol and crotonin-derived clerodanes.

Effect of Artemisia annua L. leaves essential oil and ethanol extract on behavioral assays / Efeito do extrato etanólico bruto e óleo essencial das folhas de Artemisia annua em modelos comportamentais

Artemisia annua has been used as a traditional plant for the treatment of malaria and fever in China because of the presence of its active compound, artemisinin. The present study evaluated the central activity of the essential oil and the crude ethanol extract of A. annua L. in animals as a part of a psychopharmacological screening of this plant. The extract was prepared in ethanol (AEE) and the essential oil (AEO) obtained by hydrodistillation, both with fresh leaves. Induced immobility, the forced swimming test (FST) and the open-field test (OFT) are well-known animal models to study drug-induced depression. The administration of A. annua essential oil or crude ethanol extract increased the immobility time in the FST and decreased other activities (ambulation, exploration, rearing and grooming) in the OFT in animals. Both AEO and AEE prolonged pentobarbital-induced sleep as well, but the essential oil had a marked effect. Observing these results, it is possible to suggest that A. annua crude ethanol extract and essential oil could act as depressors on the Central Nervous System (CNS).

Artemisia annua tem sido utilizada tradicionalmente para o tratamento de malária e febre na China devido à presença do princípio ativo, artemisinina. O presente trabalho avaliou a atividade central de do óleo essencial obtido por hidrodestilação e do extrato etanólico bruto de folhas frescas de A. annua em modelo in vivo como parte de um screening farmacológico dessa espécie. Sono induzido por pentobarbital, nado forçado e o ensaio de campo aberto são modelos de estudo conhecidos para o estudo de fármacos sobre depressão induzida. A administração do óleo essencial ou extrato bruto etanólico de A. annua aumentaram o tempo de imobilidade no teste do nado forçado. Por outro lado, diminuíram outros parâmetros no campo aberto, como ambulação, exploração, o ato de lamber as patas ou se lamber. Ambos produtos aumentaram o tempo de sono induzido por pentobarbital, com o óleo essencial apresentando um efeito superior ao do extrato. Pela análise dos resultados, é possível sugerir que tanto o extrato bem como o óleo essencial podem atuar como depressores do Sistema Nervoso Central (SNC).

Farmacologia e Toxicologia de Peumus boldus e Baccharis genistelloides / Pharmacology and toxicology of Peumus boldus and Baccharis genistelloides

Um grande número de espécies com uso medicinal tradicional ainda continua sem comprovação da eficácia e da segurança de seu uso. Este artigo apresenta uma pequena revisão sobre os trabalhos publicados com boldo (Peumus boldus) e carqueja (Baccharis genistelloides). Os estudos farmacológicos realizados com P. boldus e B. genistelloides comprovam várias das atividades atribuídas popularmente a esses chás, além de correlacionarem esses efeitos a compostos puros, isolados a partir desses extratos. Já os estudos toxicológicos sugerem que o chá de boldo deve ser consumido com moderação e cuidado, principalmente no primeiro trimestre da gravidez (indícios de teratogenia) e no uso por tempo prolongado (indícios de hepatotoxicidade), enquanto o consumo do chá de carqueja deve ser proibido para gestantes (risco comprovado de aborto) e para pacientes que utilizam drogas para tratamento de problemas pressóricos (ação hipotensora). Estes relatos reforçam a necessidade de um maior conhecimento sobre as plantas medicinais utilizadas popularmente, não apenas para a confirmação das atividades descritas pelo uso tradicional, mas também para que o uso seguro seja estabelecido.

There are a great number of medicinal plants without any scientific confirmation about their efficacy and safety. This paper is a short review about two medicinal plants, "boldo do chile" (Peumus boldus) and "carqueja" (Baccharis genistelloides). Pharmacological studies have confirmed several popular indications for P. boldus and B. genistelloides, besides have established a relationship between isolated compounds from these extracts and the pharmacological effects observed. On the other hand, toxicological researches have pointed out that P. boldus tea should not be consumed during a long period (potential hepatotoxicity) and by pregnant, especially during the first three months. Moreover, B. genistelloides tea must be prohibited for pregnant because of confirmed abortive action, and for patients using medicines for blood pressure disorders. These studies point out the continuous necessity of more studies about medicinal plants; only with this knowledge it will be possible a safe and efficient use.

Sleep habits and starting time to school in Brazilian children

OBJETIVOS: Estudar os hábitos de sono nas crianças brasileiras de acordo com a idade, sexo e período escolar. MÉTODO: Estudamos 2.482 crianças em idade escolar de 7 a 10 anos. Comparamos hábitos de sono, sexo e período escolar (matutino e vespertino). RESULTADOS: 61% das crianças apresentaram rituais de sono antes de dormir. Beber leite antes de dormir foi mais freqüente entre as crianças de 7 anos de idade. Encontramos redução progressiva com a idade em se manter a luz acesa. Meninas possuíam mais objetos para dormir que os meninos. As crianças que estudavam no período matutino apresentaram redução do tempo total de sono, tinham sono mais cedo e os cochilos eram mais freqüentes do que as crianças que estudavam no período vespertino. CONCLUSÃO: O horário escolar tem muita influência nos hábitos de sono das crianças brasileiras da cidade de São Paulo, os rituais de sono sendo muito prevalentes.