HEPATOPROTECTIVE EFFICACY OF METHANOLIC EXTRACT OF INDIGOFERA SUFFRUTICOSA (MILL) ON PARACETAMOL-INDUCED LIVER DAMAGE IN MICE.

BACKGROUND: Indigofera suffruticosa Mill (Fabaceae) is abundant in northeastern Brazil and popularly used in the treatment of infectious and inflammatory processes. Several biological properties, such as anti-inflammatory, anticancer, antitumor, hepatoprotective and low toxicity, are reported for this plant. OBJECTIVE: This study investigated hepatoprotective activity and the antioxidant effect of methanolic extract of I. suffruticosa leaves (MEIS) on Swiss albino mice submitted to experimental models of acetaminophen-induced liver injury. METHODS: MEIS (50 mg/kg; p.o.) was standardized according to the LD50 and its hepatoprotective property on Swiss albino mice evaluated during a 7-day period. On the eighth day, the acetaminophen-induced hepatic injury was performed. Histomorphometric analysis of liver tissue, antioxidant activity and serum levels of alanine aminotransferase (AST), aspartate aminotransferase (ALT) and bilirubin were measured. RESULTS: MEIS (50 mg/kg; p.o.) restored serum enzyme levels and results were close to those of positive control (silymarin) when compared to the negative control. Histopathological and histomorphometric analyzes confirmed MEIS hepatoprotective activity, showing reorganization of structural units of cells, nuclei and sinusoidal capillaries of hepatocytes, reducing the damage on liver tissue and increasing organ regeneration rate. MEIS showed high antioxidant potential at concentrations of 1000 and 500 µg/mL. CONCLUSION: This study suggests that MEIS has hepatoprotective activity and high antioxidant potential.

Eficácia hepatoprotetora do extrato metanólico de Indigofera suffruticosa (Mill) em lesão hepática induzido por paracetamol em camundongos / Hepatoprotective efficacy of methanolic extract of indigofera suffruticosa (mill) on paracetamol-induced liver damage in mice

ABSTRACT BACKGROUND: Indigofera suffruticosa Mill (Fabaceae) is abundant in northeastern Brazil and popularly used in the treatment of infectious and inflammatory processes. Several biological properties, such as anti-inflammatory, anticancer, antitumor, hepatoprotective and low toxicity, are reported for this plant. OBJECTIVE: This study investigated hepatoprotective activity and the antioxidant effect of methanolic extract of I. suffruticosa leaves (MEIS) on Swiss albino mice submitted to experimental models of acetaminophen-induced liver injury. METHODS: MEIS (50 mg/kg; p.o.) was standardized according to the LD50 and its hepatoprotective property on Swiss albino mice evaluated during a 7-day period. On the eighth day, the acetaminophen-induced hepatic injury was performed. Histomorphometric analysis of liver tissue, antioxidant activity and serum levels of alanine aminotransferase (AST), aspartate aminotransferase (ALT) and bilirubin were measured. RESULTS: MEIS (50 mg/kg; p.o.) restored serum enzyme levels and results were close to those of positive control (silymarin) when compared to the negative control. Histopathological and histomorphometric analyzes confirmed MEIS hepatoprotective activity, showing reorganization of structural units of cells, nuclei and sinusoidal capillaries of hepatocytes, reducing the damage on liver tissue and increasing organ regeneration rate. MEIS showed high antioxidant potential at concentrations of 1000 and 500 µg/mL. CONCLUSION: This study suggests that MEIS has hepatoprotective activity and high antioxidant potential.

RESUMO CONTEXTO: Indigofera suffruticosa Mill (Fabaceae) é abundante no nordeste do Brasil e popularmente utilizada no tratamento de processos infecciosos e inflamatórios. Várias propriedades biológicas, como anti-inflamatório, anticâncer, antitumoral, hepatoprotetor e baixa toxicidade, são relatadas para esta planta. OBJETIVO: Este estudo investigou a atividade hepatoprotetora e o efeito antioxidante do extrato metanólico de folhas de I. suffruticosa (MEIS) em camundongos albinos suíços submetidos a modelos experimentais de lesão hepática induzida por paracetamol. MÉTODOS: O MEIS na dose de 50 mg/kg (via oral) foi padronizado de acordo com a LD50 e sua propriedade hepatoprotetora em camundongos albinos Swiss avaliados durante um período de sete dias. No oitavo dia, a lesão hepática foi induzida por paracetamol em todos grupos pre-tratados. Foram medidos os níveis sericos enzimaticos, alanina aminotransferase, aspartato aminotransferase e bilirrubina, análise histomorfométrica do tecido hepático e atividade antioxidante. RESULTADOS: O MEIS restaurou os níveis séricos de enzimas e os resultados foram próximos aos do controle positivo (silimarina) quando comparados ao controle negativo. As análises histopatológicas e histomorfométricas confirmaram a atividade hepatoprotetora do MEIS, mostrando reorganização das unidades estruturais das células, núcleos e capilares sinusoidais dos hepatócitos, reduzindo os danos no tecido hepático e aumentando a taxa de regeneração de órgãos. O MEIS apresentou alto potencial antioxidante nas concentrações de 1000 e 500 µg/mL. CONCLUSÃO: Este estudo sugere que I. suffruticosa tem atividade hepatoprotetora e alto potencial antioxidante.

Indigofera suffruticosa Mill (Fabaceae): hepatic responses in mice bearing sarcoma 180 / Indigofera suffruticosa Mill (Fabaceae): respuestas hepáticas en ratones portadores de sarcoma 180

Indigofera suffruticosa is a plant generally used to treat infectious and inflammatory processes. This work aims to evaluate the histopathological changes in the liver tissue of mice with Sarcoma 180 after subchronic treatment with aqueous extract obtained by infusion and maceration of Indigofera suffruticosa leaves. Male mice were divided into four groups of six animals: G1, G2 and G3 patients with Sarcoma 180 and Sarcoma 180 G4 without sarcoma. G1 and G2 were treated with infusion mashing respectively (50 mg/kg ip); G3 and G4 controls received saline (15 ml/kg ip). The histopathological and morphometric analysis of liver tissue after subchronic treatment with aqueous extracts by infusion and maceration of the groups G1, G2 and G4 were similar and showed no degraded areas or leukocyte infiltration compared to G3, which shows a marked destruction of liver architecture. The results showed that after subchronic treatment with the aqueous extract of leaves Indigofera Suffruticosa obtained by infusion and maceration, the hepatic architecture was preserved, suggesting its use as an alternative hepatoprotective agent.

Indigofera suffruticosa es una planta utilizada para tratar procesos infecciosos e inflamatorios. Este trabajo tiene como objetivo evaluar los cambios histopatológicos en el tejido del hígado de ratones con sarcoma 180 después del tratamiento subcrónica con el extracto acuoso obtenido por infusión y maceración de las hojas de Indigofera suffruticosa. Los ratones machos fueron divididos en cuatro grupos de seis animales: pacientes G1 , G2 y G3 con Sarcoma 180 y G4 sin Sarcoma. G1 y G2 fueron tratados con infusión de maceración respectivamente (50mg/kg.ip); Controles G3 y G4 recibieron solución salina (15 ml/kg.ip). El análisis histopatológico y morfométrico de tejido hepático después de un tratamiento subcrónico con extractos acuosos por infusión y la maceración de los grupos G1, G2 y G4 fueron similares y no mostraron áreas degradadas o la infiltración de leucocitos en comparación a G3, que muestra una marcada destrucción de la arquitectura del hígado. Los resultados mostraron que después de un tratamiento subcrónico con el extracto acuoso de hojas de Indigofera suffruticosa obtenidos por infusión y la maceración, se conservó la arquitectura hepática, lo que sugiere su uso como una alternativa de agente hepatoprotector.

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.

Preliminary study of the molluscicidal and larvicidal properties of some essential oils and phytochemicals from medicinal plants / Estudo preliminar das propriedades moluscicidas e larvicidas de alguns óleos essenciais e fitoconstituintes de plantas medicinais

This study aimed to evaluate the molluscicidal and larvicidal activity of some essential oils and phytochemicals from medicinal plants. Molluscicide and larvicidal activity were determined by, respectively, the lethality bioassays using Artemia salina Leach. Artemiidae and Aedes aegypti L. Culicidae larvae. Essential oils from Eugenia uniflora L. Myrtaceae, Laurus nobilis L. Lauraceae, Origanum vulgare L. Lamiaceae and the phytochemicals α-pinene and eugenol presented citotoxicity toward Artemia salina with CL50 values between 9.59 and 253.43 μL/mL. Essential oils from E. uniflora, M. piperita, O. vulgare and R. officinalis showed embryotoxicity on Aedes aegypti larvae with a viability inhibition between 40 and 100 percent. These results show the bioactivity of the assayed essential oils and phytochemicals and, partially, justify their insertion in further evaluation in order to establish a safe exploitation of their biological potentiality.

Este estudo teve como objetivo avaliar a atividade moluscicida e larvicida de alguns óleos essenciais e fitoconstituintes de plantas medicinais. A atividade moluscicida e larvicida foi determinada empregando-se, respectivamente, o teste de letalidade contra náupilos de Artemia salina Leach. Artemiidae e contra larvas de Aedes aegypti L. Culicidae. Os óleos essenciais de Eugenia uniflora L. Myrtaceae, Laurus nobilis L. Lauraceae, Origanum vulgare L. Lamiaceae e os fitoconstituintes α-pineno e eugenol mostraram bioatividade citotóxica frente A. salina com valores de CL50 entre 9,59 e 253,43 μL/mL. Os óleos essenciais de E. uniflora, M. piperita, O. vulgare e R. officinalis apresentaram atividade de embriotoxicidade sobre as larvas de A. aegypti mostrando uma variação de inibição de viabilidade entre 40 e 100 por cento. Estes resultados demonstram o potencial de bioatividade desses óleos essenciais e fitoconstituintes e justificam, parcialmente, o desenvolvimento de estudos com esses produtos para uso popular.

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.

Embryotoxicity in vitro with extract of Indigofera suffruticosa leaves.

Aqueous extract of leaves of Indigofera suffruticosa (AELIs) were studied for adverse effects in preimplantation mouse embryos. Two-cell mouse embryos were cultured for 94 h in human tubal fluid medium (HTF), and AELIs at a concentration of 5 or 10 mg/ml. On Day 4 of culture, morulae and blastocysts were collected for morphological analysis of blastomeres. We found that embryos exposed to the higher concentration of AELIs (10 mg/ml) did not develop and all embryos persisted at the two-cell stage. Those embryos exposed to the lower concentration (5 mg/ml) showed development until morula, blastocyst and hatched blastocyst stages that were similar to the controls. These results suggest that use of AELIs may be hazardous to humans who make use of it in folk medicine.

Estudo Toxicológico do Extrato Aquoso de Dioclea grandiflora Mart. Ex. Benth / Toxicological Studies of the Aqueous Extract of Dioclea grandiflora Mart. Ex. Benth

Objetivo: Determinar a toxicidade aguda e a Dose Letal 50 do extrato aquoso do caule de Dioclea grandiflora Mart. Ex. Benth. em camundongos albinos suícos. Material e métodos: O extrato aquoso do caule foi obtido por maceração, através de agitacão mecânica, por 24 horas e, posteriormente, tiofilizado. Para os estudos toxicológicos, vinte e quatro camundongos Mus musculus foram selecionados em seis grupos. Os animais permaneceram em jejum por dezoito horas antes de serem submetidos ao experimento. A via de administraçao utilizada foi a intraperitonal. Resultados: Os resultados sugerem que a atividade tóxica do extrato aquoso da casca do caule de Dioclea grandiflora, com Dose Letal 50 de 615mg/kg, foi baixa quando comparada com a casca de sua raiz. Conclusão: Diante do observado, conclui-se que existe uma relativa margem de segurança para o uso do extrato aquoso da casca do caule de Dioclea grandiflora como agente terapêutico