Antitumor activity and toxicity of volatile oil from the leaves of Annona leptopetala

Abstract Annona leptopetala (R.E.Fr.) H. Rainer, Annonaceae, is used in folk medicine like antitumor and anti-inflammatory. The aim of this study was to determine chemical composition, toxicity and antitumor activity of A. leptopetala leaves volatile oil. Fresh leaves were hydrodistilled and then the volatile oil chemical composition was assessed by gas chromatography and mass spectrometry. Toxicity was assessed using haemolysis, micronucleus and acute toxicity protocols. Antitumor effects were determined in vitro and in vivo, using sulforhodamine B assay and sarcoma 180 murine tumor model, respectively. Spathulenol was the major component identified (12.56%). The volatile oil showed in vitro antitumor activity mainly in leukemia cell line (K-562), with Total growth inhibit (TGI) (concentration producing TGI) of 0.64 µg/ml. In other hand, the volatile oil <250 µg/ml did not inhibit HaCat non-tumor cell line growth. The concentration that produced 50% haemolysis was 372.8 µg/ml. The 50% lethal dose in mice was approximately 447.2 mg/kg intraperitoneally. Sarcoma 180 tumor growth inhibition rates were 59.29% and 58.77% at 100 and 150 mg/kg intraperitoneally, respectively. The volatile oil presented moderate gastrointestinal toxicity and no genotoxicity was observed at 350 mg/kg. Thus, the volatile oil shows antitumor activity with moderate toxicity.

Histopathological and biochemical assessment of d-limonene-induced liver injury in rats.

The aim of the present work was to develop a biochemical, histologic and immunohistochemical study about the potential hepatotoxic effect of d-limonene - a component of volatile oils extracted from citrus plants. Blood alkaline phosphatase (ALP), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) from d-limonene-treated animals were determined and compared to morphologic hepatic lesions in order to investigate the possible physiopathologic mechanisms involved in the liver toxicity, in experimental animals treated with d-limonene. Wistar rats were randomly divided into seven groups: two control groups (untreated or receiving only vehicle, tween-80); one positive control (vehicle); two experimental groups treated with d-limonene at doses of 25 mg/kg/day and 75 mg/kg/day for 45 days, and two other groups treated with the same doses for 30 days and kept under observation during 30 more days. Biochemical data showed significant reduction in ALT levels in the animals treated with 75 mg/kg of d-limonene. Histological analysis revealed some hepatocyte morphological lesions, including hydropic degeneration, microvesicular steatosis and necrosis, Kupffer cell hyperplasia and incipient fibrosis. By immunohistochemistry, influx of T (CD3+) and cytotoxic (CD8+) lymphocytes was observed in the rats treated with d-limonene at both dose levels. In conclusion, it is possible that d-limonene has been directly responsible for hepatic parenchymal and matrix damage following subchronic treatment with d-limonene.

Effect of the yellow passion fruit peel flour (Passiflora edulis f. flavicarpa deg.) in insulin sensitivity in type 2 diabetes mellitus patients.

BACKGROUND: A study with the yellow passion fruit peel flour showed positive action in blood glucose control as therapies' adjuvant in patients with type 2 diabetes mellitus. Therefore, we evaluated its effect on insulin sensitivity since there is a quest for studies that focus at better understanding of insulin resistance aspects in diabetic patients. Furthermore its relationship with chronic complications can also give good prospects for alternative treatments. METHODS: A total of 43 type 2 diabetes volunteers (28 females and 15 males) ingested 30 g/day of the yellow passion fruit peel flour for two months. The levels of blood glucose and fasting insulin, HOMA index and glycated hemoglobin were measured for each patient before and after dietary supplementation. RESULTS: There was a significant difference in the fasting blood glucose values (P = 0.000) and glycated hemoglobin (P = 0.032) after supplementation. It was also seen a reduction in HOMA IR (P = 0.005) in the supplemented group, however it was not observed changes in insulin values for females. HOMA beta (P = 0.000) showed significant increase in its values for the studied group. CONCLUSIONS: The supplementation used decreased insulin resistance in type 2 diabetic patients, suggesting a positive action in blood glucose control as adjuvant therapy in conventional treatments.

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.

Avaliação experimental do 2-octil-cianoacrilato na cicatrização da dura-máter / Experimental evaluation of 2-octyl-cyanoacrylate on dura mater healing

Objetivo: O objetivo do presente estudo foi avaliar o efeito desta cola tecidual sintética na cicatrização do fechamento da dura mater em coelhos. O estudo foi realizado para investigaro comportamento histológico e toxicológico do reparo dural usando sutura simples e reforçada com adesivo tecidual. Método: Um total de 54 coelhos foi dividido em 9 grupos de 6 animais, subdivididos em 3 grupos (A, B e C), cada um contendo 3 subgrupos de 6 coelhos, sacrificados aos 7, 30 e 60 dias respectivamente. Após craniectomia parassagital de 1cm e durotomia de 0,5cm, três procedimentos diversos foram realizados: o grupo A recebeu 2-octil-cianoacrilato, no grupoB foi instilada cola de fibrina e no grupo C foi realizada sutura da abertura dural. A integridade das suturas, existênciade abscesso, infecção da ferida e formação de aderência foram documentadas. As cabeças foram enviadas para exame histopatológico. Resultados: A cola sintética não interferiu no metabolismo dos animais. Os pesos médios de cada grupoaumentaram. As temperaturas não foram estatisticamente diferentes (p=0.210). O processo de cicatrização da duramater, através da atividade fibroblástica e infiltração de células inflamatórias, não diferiram estatisticamente entre os três grupos (p>0.05). Apenas a neovascularização aumentou no grupo controle. Conclusão: As secções histológicas obtidas da duramater tratada com o polímero 2-octil-cianoacrilato demonstraram resposta inflamatória mínima, similar a aquelas tratadas com cola de fibrina. Os resultados indicam que esta nova substância parece ter aplicações como um meio auxiliar no fechamento efetivo da duramater.

Efeito da farinha da casca do maracujá-amarelo (Passiflora edulis f. flavicarpa Deg.) nos níveis glicêmicos e lipídicos de pacientes diabéticos tipo 2 / Effect of the flour of the yellow passion fruit peel (Passiflora edulis f. flavicarpa Deg.) in the glycemic and lipid levels of type 2 diabetes patients

A suplementação da dieta com fibras solúveis pode ser considerada uma importante medida terapêutica no tratamento de pacientes diabéticos e obesos. Para avaliar o efeito da farinha da casca de maracujá amarelo rica em pectina, foi realizado um ensaio clínico fase II com 43 pacientes portadores de Diabetes Mellitus tipo 2. Estes receberam diariamente 30 g do produto testado durante 60 dias. Observou-se diferença estatística significante na glicemia de jejum (p = 0,000) acompanhada pela redução nos valores médios da hemoglobina glicada (p = 0,032). Em relação ao perfil lipídico, não foi verificado redução dos níveis de colesterol total e colesterol LDL nos pacientes ao longo deste estudo; entretanto, houve redução nos níveis de Triglicerídeos e aumento do colesterol HDL nos mesmos. Os níveis glicêmicos apresentados pelos pacientes antes e após o uso da farinha da casca do maracujá são compatíveis com uma ação positiva no controle da glicemia como adjuvante das terapias convencionais.

The supplementation of diet with soluble dietary fiber can be considered an important therapy measure in the treatment of diabetic and obese patients. In order to evaluate the effect of the flour of the yellow passion fruit peel which is rich in pectin, a phase II clinical trial with 43 patients with type 2 Diabetes Mellitus was performed. They received daily 30 g of the tested product for 60 days. Statistically significant difference was observed in fasting plasma glucose (p = 0.000) accompanied by a reduction in the average values of glycated hemoglobin (p = 0.032). In relation to the lipid profile, there were no reduced levels of total cholesterol and LDL-cholesterol in patients during this study; however, there were reduction in the levels of Triglycerides and increase in HDL cholesterol in them. The glycemic levels presented by the patients before and after the use of the passion fruit peel flour are compatible to a positive action to control blood glucose as an adjunct of conventional therapies.

Evaluación de la histotoxicidad del 2-octyl-cyanoacrilato en el cerebro del conejo / Histotoxicity evaluation of 2-octyl-cyanoacrylate on the rabbit's brain

The aim of the present study was to evaluate the effect of the 2-octyl-cyanoacrylate, on a rabbit's brain. The study was undertaken to investigate the histological behavior of the brain with this synthetic tissue adhesive. We evaluated a total of 12 rabbits, wich were randomized into 2 groups of 6 rabbits each. Following fronto-temporo-parietal craniectomy, 1 cm of the cranium was removed and the dura mater was 0,5 cm sectioned. In the control group, dura mater was sutured with 6-0 polypropylene interrupted sutures. In the study group, the brains were covered by using 2-octyl-cyanoacrylate (high viscosity), before closurewith 6-0 polypropylene suture. Rabbits were sacrificed on day 7 following operation. Integrity of the sutures, existence of abscess, wound infection and adhesion formation were recorded. The heads were removed including the site of operation and then, the specimens were sent for histological examination. Mean weights of each study group increased. The body temperatures of the animals were normal in the two groups. The histopathological evaluation of the brains treated with the synthetic glue revealed 50 per cent of inflammatory response with focal necrosis in the cortex. Only one rabbit had a normal brain. Results under experimental conditions, indicate that this new substance, 2-octyl-cyanoacrylate, can not be considered as safe supportive material for intradural procedures directly involving the brain tissue.

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.