RESUMO
CONTEXT: The tuber of Amorphophallus paeoniifolius (Dennst.) Nicolson (Araceae), commonly called Suran or Jimmikand, has high medicinal value and is used ethnomedicinally for the treatment of different gastrointestinal and inflammatory disorders. OBJECTIVE: The present study evaluated the effects of extracts of Amorphophallus paeoniifolius tubers on acetic acid-induced ulcerative colitis (UC) in rats. MATERIALS AND METHODS: Wistar rats were orally administered methanol extract (APME) or aqueous extract (APAE) (250 and 500 mg/kg) or standard drug, prednisolone (PRDS) (4 mg/kg) for 7 days. On 6th day of treatment, UC was induced by transrectal instillation of 4% acetic acid (AA) and after 48 h colitis was assessed by measuring colitis parameters, biochemical estimations and histology of colon. RESULTS: APME or APAE pretreatment significantly (p < .05-.001) prevented AA-induced reduction in body weight and increase in colitis parameters viz. stool consistency, colon weight/length ratio and ulcer score, area and index. Extracts treatment attenuated (p < .001) increase in alkaline phosphatase and lactate dehydrogenase in serum and myeloperoxidase activity and cytokines in colon tissue due to AA administration. Extracts treatment prevented AA-induced elevation in lipid peroxidation and decline in activities of superoxide dismutase and catalase and reduced-glutathione content (p < .05-.001) along with histopathological alterations. PRDS also showed similar ameliorative effect on colitis. DISCUSSION AND CONCLUSION: APME and APAE showed a preventive effect on UC, and ameliorated inflammation and oxidative damage in colon. The effects may be attributed to presence of phytochemicals, betulinic acid, ß-sitosterol, and glucomannan. In conclusion, the tuber of Amorphophallus paeoniifolius exhibited an anticolitic effect through anti-inflammatory and antioxidant action.
Assuntos
Amorphophallus/química , Anti-Inflamatórios/farmacologia , Colite Ulcerativa/prevenção & controle , Colo/efeitos dos fármacos , Fármacos Gastrointestinais/farmacologia , Extratos Vegetais/farmacologia , Ácido Acético , Fosfatase Alcalina/sangue , Animais , Anti-Inflamatórios/isolamento & purificação , Anti-Inflamatórios/toxicidade , Biomarcadores/sangue , Catalase/metabolismo , Colite Ulcerativa/sangue , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/patologia , Colo/metabolismo , Colo/patologia , Citocinas/metabolismo , Citoproteção , Modelos Animais de Doenças , Fármacos Gastrointestinais/isolamento & purificação , Fármacos Gastrointestinais/toxicidade , Glutationa/metabolismo , Mediadores da Inflamação/metabolismo , L-Lactato Desidrogenase/sangue , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Estresse Oxidativo/efeitos dos fármacos , Peroxidase/metabolismo , Fitoterapia , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/toxicidade , Tubérculos , Plantas Medicinais , Prednisolona/farmacologia , Ratos Wistar , Solventes/química , Superóxido Dismutase/metabolismoRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Amorphophallus paeoniifolius (Dennst.) Nicolson (Family- Araceae) is a crop of south East Asian origin. In India, its tuber is widely used in ethnomedicinal practices by different tribes for the treatment of piles (hemorrhoids). AIM: The present study evaluated the effect of methanolic and aqueous extract of Amorphophallus paeoniifolius tuber on croton oil induced hemorrhoids in rats. MATERIALS AND METHODS: The methanolic extract was standardized with the major phenolic compound, betulinic acid, by HPLC. The hemorrhoids were induced by applying 6% croton oil preparation in the ano-rectal region. Rats were orally administered methanolic and aqueous extract at doses of 250 and 500mg/kg, each for 7 days. Pilex (200mg/kg) was used as reference anti-hemorrhoidal drug. Hemorrhoids were assessed on eighth day by measuring hemorrhoidal and biochemical parameters along with histology of ano-rectal tissue. RESULTS: Croton oil application caused induction of hemorrhoids as indicated by significant (p<0.001) increase in plasma exudation of Evans blue in ano-rectal tissue, macroscopic severity score and ano-rectal coefficient as compared to normal rats. It significantly (p<0.001) elevated lactate dehydrogenase and cytokines (TNF-α and IL-6) levels in serum and increased myeloperoxidase activity and lipid peroxidation in ano-rectal tissue along with marked histological damage as compared to normal rats. Treatment with tuber extracts and pilex significantly (p<0.05-p<0.001) ameliorated Evans blue exudation, hemorrhoidal parameters and other biochemical parameters with attenuation of tissue damage compared to hemorrhoid control rats. The results indicate that tuber extracts exhibited curative action on hemorrhoids. The aqueous extract showed more pronounced effect than methanolic extract. The effects may be attributed to anti-inflammatory and antioxidant properties. CONCLUSION: Results indicate that tuber of Amorphophallus paeoniifolius exhibited curative action on hemorrhoids through anti-inflammatory and antioxidant properties. The study validates the ethnomedicinal use of tuber in hemorrhoids and implicates its therapeutic potential as an anti-hemorrhoidal agent.
Assuntos
Amorphophallus/química , Canal Anal/efeitos dos fármacos , Anti-Inflamatórios/farmacologia , Hemorroidas/tratamento farmacológico , Extratos Vegetais/farmacologia , Tubérculos/química , Reto/efeitos dos fármacos , Canal Anal/metabolismo , Canal Anal/patologia , Animais , Anti-Inflamatórios/isolamento & purificação , Antioxidantes/isolamento & purificação , Antioxidantes/farmacologia , Biomarcadores/sangue , Cromatografia Líquida de Alta Pressão , Óleo de Cróton , Modelos Animais de Doenças , Hemorroidas/sangue , Hemorroidas/induzido quimicamente , Hemorroidas/patologia , Mediadores da Inflamação/sangue , Interleucina-6/sangue , L-Lactato Desidrogenase/sangue , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Metanol/química , Triterpenos Pentacíclicos , Peroxidase/metabolismo , Extratos Vegetais/isolamento & purificação , Ratos Wistar , Reto/metabolismo , Reto/patologia , Indução de Remissão , Índice de Gravidade de Doença , Solventes/química , Triterpenos/isolamento & purificação , Triterpenos/farmacologia , Fator de Necrose Tumoral alfa/sangue , Água/química , Ácido BetulínicoRESUMO
AIMS: Exposure to toxic metals remains a widespread occupational and environmental problem in world. Chelation therapy is a mainstream treatment used to treat heavy metal poisoning. This paper describes the synthesis, characterization and therapeutic evaluation of monoisoamyl 2,3-dimercaptosuccinic acid (MiADMSA)-encapsulated polymeric nanoparticles as a detoxifying agent for arsenic poisoning. MATERIALS & METHODS: Polymeric nanoparticles entrapping the DMSA monoester, which can evade the reticulo-endothelial system and have a long circulation time in the blood, were prepared. Particle characterization was carried out by transmission electron microscopy and dynamic light scattering. An in vivo study was conducted to investigate the therapeutic efficacy of MiADMSA-encapsulated polymeric nanoparticles (nano- MiADMSA; 50 mg/kg orally for 5 days) and comparison drawn with bulk MiADMSA. Swiss albino mice exposed to sodium arsenite for 4 weeks were treated for 5 days to evaluate alterations in blood, brain, kidney and liver oxidative stress variables. The study also evaluated the histopathological changes in tissues and the chelating potential of the nanoformulation. RESULTS: Our results show that nano-MiADMSA have a narrow size distribution in the 50-nm range. We observed an enhanced chelating potential of nano-MiADMSA compared with bulk MiADMSA as evident in the reversal of biochemical changes indicative of oxidative stress and efficient removal of arsenic from the blood and tissues. Histopathological changes and urinary 8-OHdG levels also prove better therapeutic efficacy of the novel formulation for arsenic toxicity. CONCLUSION: The results from our study show better therapeutic efficacy of nano-MiADMSA in removing arsenic burden from the brain and liver.
Assuntos
Intoxicação por Arsênico/tratamento farmacológico , Quelantes/administração & dosagem , Portadores de Fármacos/química , Nanopartículas/química , Succímero/análogos & derivados , Animais , Arsênio/sangue , Arsênio/metabolismo , Intoxicação por Arsênico/sangue , Intoxicação por Arsênico/metabolismo , Intoxicação por Arsênico/patologia , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Encéfalo/patologia , Quelantes/uso terapêutico , Rim/efeitos dos fármacos , Rim/metabolismo , Rim/patologia , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Masculino , Camundongos , Nanopartículas/ultraestrutura , Coelhos , Ratos , Ratos Wistar , Succímero/administração & dosagem , Succímero/uso terapêuticoRESUMO
Sulfur mustard (SM)-induced dermatotoxicity can be prevented by an immediate use of decontamination agents. However, practically due to the time lapse between decontamination and exposure, there is always a possibility of wound formation. In view of this, a hydrophilic decontamination formulation of CC-2 (DRDE/WH-03) was fortified with Aloe vera gel and betaine (DRDE/WH-01) for improving its wound healing ability. Swiss albino mice were exposed to SM percutaneously (5 mg/kg) once, and after 24 hours, DRDE/WH-01, DRDE/WH-03, framycetin, and aloe gel were applied topically, daily for 7 days. Skin sections were subjected to histopathology, histomorphologic grading, tissue leukocytosis, and immunohistochemistry of inflammatory-reparative biomarkers on 3 and 7 days, respectively. DRDE/WH-01, framycetin, and aloe gel showed better reepithelialization, angiogenesis, and fibroplasia compared with DRDE/WH-03 and SM control. On the basis of histomorphologic scale, DRDE/WH-01, framycetin, and aloe gel were found to be equally efficacious. Up-regulation of interleukin-6 and infiltrating leukocytes, endothelial nitric oxide synthase and angiogenesis, fibroblast growth factor, and transforming growth factor-alpha with fibroplasia and reepithelialization were well correlated at various stages of the healing process. DRDE/WH-01 was equally effective as framycetin and has shown improved wound healing efficacy compared with DRDE/WH-03. Thus, DRDE/WH-01 can be recommended as a universal decontaminant and wound healant against vesicant-induced skin injury.
Assuntos
Aloe , Antibacterianos/farmacologia , Betaína/farmacologia , Queimaduras Químicas/tratamento farmacológico , Clorobenzenos/farmacologia , Fármacos Dermatológicos/farmacologia , Framicetina/farmacologia , Compostos de Fenilureia/farmacologia , Pele/patologia , Administração Cutânea , Animais , Queimaduras Químicas/patologia , Substâncias para a Guerra Química/toxicidade , Descontaminação/métodos , Fármacos Dermatológicos/administração & dosagem , Quimioterapia Combinada , Feminino , Géis , Camundongos , Gás de Mostarda/toxicidade , Fitoterapia , Preparações de Plantas/farmacologia , Pele/metabolismo , Cicatrização/efeitos dos fármacosRESUMO
Water-soluble nanoparticles of curcumin were synthesized, characterized and applied as a stable detoxifying agent for arsenic poisoning. Chitosan nanoparticles of less than 50 nm in diameter containing curcumin were prepared. The particles were characterized by TEM, DLS and FT-IR. The therapeutic efficacy of the encapsulated curcumin nanoparticles (ECNPs) against arsenic-induced toxicity in rats was investigated. Sodium arsenite (2mg/kg) and ECNPs (1.5 or 15 mg/kg) were orally administered to male Wistar rats for 4 weeks to evaluate the therapeutic potential of ECNPs in blood and soft tissues. Arsenic significantly decreased blood δ-aminolevulinic acid dehydratase (δ-ALAD) activity, reduced glutathione (GSH) and increased blood reactive oxygen species (ROS). These changes were accompanied by increases in hepatic total ROS, oxidized glutathione, and thiobarbituric acid-reactive substance levels. By contrast, hepatic GSH, superoxide dismutase and catalase activities significantly decreased on arsenic exposure, indicative of oxidative stress. Brain biogenic amines (dopamine, norepinephrine and 5-hydroxytryptamine) levels also showed significant changes on arsenic exposure. Co-administration of ECNPs provided pronounced beneficial effects on the adverse changes in oxidative stress parameters induced by arsenic. The results indicate that ECNPs have better antioxidant and chelating potential (even at the lower dose of 1.5 mg/kg) compared to free curcumin at 15 mg/kg. The significant neurochemical and immunohistochemical protection afforded by ECNPs indicates their neuroprotective efficacy. The formulation provides a novel therapeutic regime for preventing arsenic toxicity.
Assuntos
Intoxicação por Arsênico/tratamento farmacológico , Arsênio/toxicidade , Curcumina/administração & dosagem , Nanopartículas/administração & dosagem , Nanopartículas/química , Animais , Arsênio/farmacocinética , Intoxicação por Arsênico/sangue , Aminas Biogênicas/metabolismo , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Curcumina/farmacologia , Glutationa/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Wistar , Espécies Reativas de Oxigênio/metabolismo , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo , Distribuição TecidualRESUMO
OBJECTIVES: Persistent hyperglycaemia results in oxidative stress along with the generation of oxygen free radicals and appears to be an important factor in the production of secondary complications in diabetes. The aim of this work was to evaluate markers of oxidative stress in heart tissue along with the protective, antioxidant and antidiabetic activity of 30%Aloe vera gel in diabetic rats. METHODS: Streptozocin was given as a single intravenous injection and 30%Aloe vera gel was given in two doses for 20 days, orally. Blood glucose, glycosylated haemoglobin, blood reduced glutathione, serum lactate dehydrogenase and serum creatine kinase levels were measured on day 21 after drug treatment. Heart rate and mean blood pressure were recorded at the end of the study. Different biochemical variables were evaluated in the heart tissue, including thiobarbituric acid reactive substance (TBARS), reduced glutathione, superoxide dismutase and catalase in diabetic and in Aloe vera-treated diabetic rats. KEY FINDINGS: In streptozocin diabetic rats, the TBARS level was increased significantly, superoxide dismutase and reduced glutathione significantly decreased, and the catalase level was significantly increased. Aloe vera 30% gel (200 mg/kg) treatment in diabetic rats reduced the increased TBARS and maintained the superoxide dismutase and catalase activity up to the normal level. Aloe vera gel increased reduced glutathione by four times in diabetic rats. CONCLUSIONS: Aloe vera gel at 200 mg/kg had significant antidiabetic and cardioprotective activity.