Acute and sub-acute toxicity study of ethanol extract from Nectandra leucantha Nees & Mart. (Lauraceae) barks.

Nectandra leucantha has been used in traditional medicine. Several metabolites isolated from N. leucantha extracts displayed immunomodulatory, antileishmanial properties, but the determination of the toxicological profile in mammals has not previously been performed. In this study, the ethanol extract from N. leucantha barks (EENl) was characterized by HPLC/HRESIMS. To study acute toxicity, female mice received EENl in a single dose of 100, 300, 1000, or 2000 mg/kg bw. Later, sub-acute toxicity was introduced in female and male mice by oral gavage at 100, 500 or 1000 mg/kg bw for 28 consecutive days. Hematological and biochemical profiles from the blood as well as histological analysis from the liver and kidney were performed. The HPLC/HRESIMS analysis of the EENl revealed the presence of six neolignans chemically related to dehydrodieugenol B. In the oral acute and sub-chronic studies, EENl did not produce in all doses evaluated any alteration in behavior, biochemical, hematological, body weight gain and food intake or sudden death in Swiss mice. In addition, histopathological data did not reveal any disturbance in liver and kidney morphology after 28 days of EENl treatment. Our results indicate that EENl at dosage levels up to 2000 mg/kg bw is non-toxic and can be considered safe for mammals.

Prevention of necrosis in ischemic skin flaps using hydrogel of Rhizophora mangle.

INTRODUCTION: Necrosis in ischemic cutaneous flaps (ISF) is a type of surgical failure more feared among surgical complications. Currently, synthetic drugs are applied during the treatment of necrosis in ISF and although several substances show improvement in viability, some require application at high systemic doses, which can produce important side effects. Therefore, the search for natural substances with fewer side effects is constant. The use of medicinal plants that stimulate angiogenesis is commonly mentioned in previous studies and in this case Rhizophora mangle L. (R. mangle) highlights that among its main compounds have tannins and flavonoids that are very chemically reactive in various biological activities. This study aimed to associate a natural hydrogel to the 5% extract of R. mangle and to evaluate its potential in the prevention of tissue necrosis in distal portions of ISF in rats, using the model proposed by Macfarlane, et al. (1965). METHODS: Ischemic skin flaps were made in the thin dorsal skin area of 28 Wistar rats and divided into 4 groups, group A: received only saline, group B where the aqueous extract of R. mangle was applied, group C received the 1.5% hydrogel of xanthan gum (XG) + placebo and group D was applied the hydrogel associated with 5% R. mangle extract. Morphometric analyses of the areas of tissue necrosis were performed from photographic records using the software Photoshop® and ImageJ®. In addition, 5 photomicrographs were taken from each histological sample of each animal for histomorphometric analysis that obtained the count of fibroblasts and blood vessels. RESULTS: The mean percentage of necrotic areas was: group (A) - 50,66%, group (B) - 40,49%, group (C) - 37,44% and group (D) - 34,25%. The statistical analysis, using the Kruskal-Wallis test, showed a significant difference (p < 0.001).

Evaluation of cytotoxic, immunomodulatory and antibacterial activities of aqueous extract from leaves of Conocarpus erectus Linnaeus (Combretaceae).

OBJECTIVES: This work evaluated the antibacterial activity, cytotoxicity and immunomodulatory effect on human peripheral blood mononuclear cells (PBMCs) promoted by aqueous extract from Conocarpus erectus leaves (AELCe). METHODS: The extract was characterized by thin layer chromatography and ultraperformance liquid chromatography coupled to mass spectrometry (UPLC-MS). Cytotoxicity of AELCe (6.25-50 µg/ml) was investigated using annexin V and propidium iodide. Cytokine and nitric oxide levels in PBMCs culture supernatants exposed or not to AELCe (12.5 µg/ml) were determined, and antibacterial activity was evaluated by disc diffusion and broth microdilution methods. KEY FINDINGS: AELCe contained 3',4'-OH flavonoids, phenylpropanoglycosides, saponins, polymeric proanthocyanidins and hydrolysable tannins. Moreover, 10 other compounds were identified through UPLC-MS technique. AELCe did not affect lymphocyte viability at 6.25 and 12.5 µg/ml. IL-2, IL-10, TNF-α, IFN-γ and nitric oxide was produced in higher levels by cells treated with AELCe. Proliferation and activation of CD8+ T lymphocytes were also stimulated. AELCe showed bacteriostatic activity against clinical and antibiotic-resistant strains of Staphylococcus aureus (MIC between 250 and 1000 µg/ml). CONCLUSIONS: AELCe showed a moderate bacteriostatic activity and promoted an immunomodulatory status through higher production of Th1 cytokines, nitric oxide release and T CD8+ lymphocytes stimulation.

Oviposition and Embryotoxicity of Indigofera suffruticosa on Early Development of Aedes aegypti (Diptera: Culicidae).

Aqueous extract of Indigofera suffruticosa leaves obtained by infusion was used to evaluate the oviposition, its effect on development of eggs and larvae, and morphological changes in larvae of Aedes aegypti. The bioassays were carried out with aqueous extract in different concentrations on eggs, larvae, and female mosquitoes, and the morphological changes were observed in midgut of larvae. The extract showed repellent activity on A. aegypti mosquitoes, reducing significantly the egg laying by females with control substrate (343 (185-406)) compared with the treated substrate (88 (13-210)). No eclosion of A. aegypti eggs at different concentrations studied was observed. The controleclodedin 35%. At concentration of 250 µg/mL, 93.3% of larvae remained in the second instar of development and at concentrations of 500, 750, and 1000 µg/mL the inhibitory effect was lower with percentages of 20%, 53.3%, and 46.6%, respectively. Morphological changes like disruption on the peritrophic envelope (PE), discontinued underlying epithelium, increased gut lumen, and segments with hypertrophic aspects were observed in anterior region of medium midgut of larvae of A. aegypti. The results showed repellent activity, specific embryotoxicity, and general growth retardation in A. aegypti by medium containing aqueous extract of I. suffruticosa leaves.

Indigofera suffruticosa: an alternative anticancer therapy.

Indigofera suffruticosa Mill (Fabeceae) occurs in the Northeast countryside and has intensive popular use in the treatment of infectious, inflammatory and other processes. The main aim of the present work was to investigate the cytotoxic and antitumor effects of aqueous extracts of leaves of I. suffruticosa obtained by infusion and maceration as well as to evaluate the toxicological properties. Aqueous extracts did not exhibit cytotoxicity against HEp-2 (human epidermoid cancer cell) cell lines by MTT method. From the aqueous extract by infusion, the toxicological assay showed low order of toxicity. The antitumor effect of aqueous extracts by infusion (64.53%) and maceration (62.62%) against sarcoma 180 in mice at a dose of 50 mg kg(-1) (intraperitoneally), based on low order of toxicity was comparable to the control group, which showed 100% development. Considering the low order of toxicity and that it is highly effective in inhibiting growth of solid tumors, the aqueous extracts of leaves of I. suffruticosa may be used as an alternative anticancer agent.

Atividade antitumoral de indigofera suffruticosa / Antitumoractivity of indigofera suffruticosa

Objetivo: Avaliar a atividade antitumoral de extratos aquosos por infusão e maceração de folhas de Indigofera suffruticosa (Fabaceae) em camundongos albinos suíços. Materiais e Métodos: Em trinta camundongos albinos suíços foram injetados via i.p. 0,3 ml de células do Sarcoma 180 (aproximadamente 3x106 células). Após 48 horas do implante, a quimioterapia foi iniciada com o uso do extrato aquoso de folhas de I. suffruticosa por infusão e maceração em concentrações diárias de 50mg/kg i.p. por 7 dias consecutivos. Para o grupo controle, 0,2 ml/Kg i.p. de solução salina foi administrada. No oitavo dia, os camundongos foram sacrificados para estudos tumorais. Os dados foram analisados utilizando-se Análise de Variância (ANOVA) ou o teste de Kruskal-Wallis. P<0,001 foi usado para rejeição da hipótese de nulidade. Resultados: A atividade antitumoral dos extratos aquosos por infusão (64,5%) e maceração (62,6%) sob Sarcoma 180 em camundongos na dose de 50 mg/kg i.p., baseada na baixa ordem de toxicidade, foi comparada com o grupo controle que mostrou desenvolvimento tumoral de 100% Conclusão: O extrato aquoso de folhas de I. suffruticosa apresenta propriedade antitumoral.

Antimicrobial Activity of Indigofera suffruticosa.

Various organic and aqueous extracts of leaves of Indigofera suffruticosa Mill (Fabaceae) obtained by infusion and maceration were screened for their antibacterial and antifungal activities. The extracts were tested against 5 different species of human pathogenic bacteria and 17 fungal strains by the agar-solid diffusion method. Most of the extracts were devoid of antifungal and antibacterial activities, except the aqueous extract of leaves of I. suffruticosa obtained by infusion, which showed strong inhibitory activity against the Gram-positive bacteria Staphylococcus aureus with a minimal inhibitory concentration (MIC) of 5000 microg ml(-1). The MIC values to dermatophyte strains were 2500 microg ml(-1) against Trichophyton rubrum (LM-09, LM-13) and Microsporum canis. This study suggests that aqueous extracts of leaves of I. suffruticosa obtained by infusion can be used in the treatment of skin diseases caused by dermatophytes.