RESUMEN
BACKGROUND: Cyclophosphamide is an alkylating antineoplastic agent and its major limitation is injury to normal tissue, leading to multiple organ toxicity, including kidney, heart, liver and reproductive toxicity. Croton macrostachyus (Euphorbiaceae) has been used in Ethiopian traditional medicine to manage renal diseases. OBJECTIVE: The present study aims to assess the protective effect of the stem bark extract and solvent fractions of Croton macrostachyus on cyclophosphamide-induced nephrotoxicity in rats. METHODS: Nephrotoxicity was induced using cyclophosphamide 200 mg/kg i.p injection on the first day of the experiment. The negative control groups were administered with cyclophosphamide alone (200 mg/kg, i.p.). The crude extracts were administered at three dose levels (100, 200, and 400 mg/kg), while aqueous and ethyl acetate fractions were given at two dose levels (100 and 200 mg/kg). Excepting the normal control, all groups were subjected to cyclophosphamide toxicity on the first day. RESULTS: Treatment with crude extract 100 mg/kg and ethyl acetate fraction significantly decreased kidney-to-body weight ratio (P < 0.001). In addition, treatment with Croton macrostachyus crude extract and solvent fractions significantly decreased serum blood urea nitrogen (BUN) level (P < 0.001). Treatment with 100 and 200 mg/kg of ethyl acetate fraction significantly decreased serum creatinine level. Histopathological results confirmed the protective effect of the crude extract and solvent fractions of Croton macrostachyus. CONCLUSION: Croton macrostachyus possesses nephroprotective activities and it could be a possible source of treatment for cyclophosphamide-induced nephrotoxicity.
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ABSTRACT Indigofera linnaei Ali. (Tamil Name: Cheppu Nerinjil) belongs to the family Fabaceae, used for the treatment of various ailments in the traditional system of medicine. In the present study, the beneficial effects of methanol extract of whole plant of I. linnaei (MEIL) were evaluated on inflammation and nociception responses in rodent models. In vitro nitric oxide (NO), lipoxygenase (LOX) and cyclooxygense (COX) inhibitory activities were also performed to understand the mode of action. MEIL at the dose of 200 & 400 mg/kg, p.o. significantly inhibited carrageenan induced rat paw volume and reduced the weight of granuloma in cotton pellet granuloma model. The results obtained were comparable with the standard drug aceclofenac. The anti-nociceptive effect of MEIL in mice was evaluated in hot plate and acetic acid induced writhing model. The plant extract significantly reduced the number of writhes and the analgesic effect was higher than that of the standard drug aspirin. However, the extract fails to increase the latency period in hot plate method suggesting that the extract produce nociception by peripheral activity. The extract produced inhibitory effect on NO, LOX and COX in concentration dependent manner. The extract exhibited pronounced and selective COX-2 inhibition. Altogether, these results suggested that the methanol extract of Indigofera linnaei could be considered as a potential anti-inflammatory and analgesic agent.
RESUMO Indigofera linnaei Ali pertence à família Leguminosae e é utilizada para o tratamento de várias doenças na medicina tradicional. No presente estudo, os efeitos benéficos do extrato metanólico da planta inteira de I. linnaei (MEIL) foram avaliados em respostas inflamatórias e nocicepção em modelos de roedores. Testes in vitro de atividade inibitória do óxido nítrico (NO), lipoxigenase (LOX) e ciclooxigenase (COX) também foram realizados para compreender o modo de ação. MEIL nas doses de 200 e 400 mg/kg, p.o. inibiu significativamente o volume da pata de rato induzido por carragenana e reduziu o peso do granuloma no modelo de pélete de algodão. Os resultados obtidos foram comparáveis ao do fármaco padrão, aceclofenaco. O efeito anti-nociceptivo de MEIL foi avaliado em camundongos no modelo de placa quente e de contorção induzida por ácido acético. O extrato da planta reduziu significativamente o número de contorções e o efeito analgésico foi maior do que o do fármaco padrão, ácido acetilsalicílico. Porém, o extrato não conseguiu aumentar o período de latência no método da placa quente, sugerindo que este produz nocicepção por atividade periférica. O extrato produziu efeito inibitório sobre o NO, LOX e COX dependente da concentração. O extrato exibiu inibição acentuada e seletiva da COX-2. No seu conjunto, estes resultados sugerem que o extrato metanólico de Indigofera linnaei poderia ser considerado como agente anti-inflamatório e analgésico potencial.
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Ratas , Roedores , Indigofera/clasificación , Indigofera/efectos de los fármacos , Plantas Medicinales/clasificación , Lipooxigenasa/análisis , Analgésicos/análisis , Antiinflamatorios/clasificación , Óxido Nítrico/clasificaciónRESUMEN
OBJECTIVE: To evaluate the antitumor, cytotoxic and antioxidant activities of methanolic leaf extract of Indigofera cassioides (MEIC) against transplantable tumors and human cancer cell lines. METHODS: MEIC was investigated for its short term cytotoxicity on EAC and DLA cells by trypan blue dye exclusion method and in vitro cytotoxicity on HeLa, HEp-2, HEpG-2, MCF-7, HT-29, Vero and NIH 3T3 cells by MTT assay. In vivo antitumor activity was studied on EAC and DLA tumor bearing mice. Activity was assessed by monitoring the mean survival time, effect on hematological parameters, antioxidant enzyme levels and solid tumor volume. RESULTS: MEIC exhibit potent in vitro cytotoxicity against all the tested cancer cell lines, but it was found to be safe on normal cells. The extract significantly (P < 0.001) increase the mean survival time and also have a protective effect on the hemopoietic system at the tested dose levels (200 and 400 mg/kg). The extract prevented lipid peroxidation and restored the antioxidant enzymes catalase, superoxide dismutase, glutathione peroxidase and glutathione-s-transferase in the liver of tumor control animals. It also significantly (P < 0.01) reduce the solid tumor volume. CONCLUSIONS: The results strongly support that MEIC shows potent antitumor and cytotoxic effects against EAC, DLA and human cancer cell lines. The extract prevents lipid peroxidation and promotes the enzymatic antioxidant defense system in tumor bearing animals which might be due to activities like scavenging of free radicals by the phytochemicals in MEIC.
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Antineoplásicos Fitogénicos/farmacología , Indigofera , Neoplasias Experimentales/tratamiento farmacológico , Extractos Vegetales/farmacología , Animales , Antineoplásicos Fitogénicos/uso terapéutico , Antioxidantes/farmacología , Línea Celular Tumoral , Chlorocebus aethiops , Humanos , Peroxidación de Lípido/efectos de los fármacos , Masculino , Ratones , Células VeroRESUMEN
Methanol extract of Indigofera linnaei (MEIL) was investigated for antitumor, cytotoxic and antioxidant activities against transplantable tumors and human cancer cell lines. In vitro cytotoxicity was evaluated in HeLa, Hep-2, HepG-2, MCF-7, HT-29, Vero and NIH 3T3 cells by MTT assay and in vivo antitumor activity with Ehrlich ascites carcinoma (EAC) and Dalton's ascites lymphoma (DLA) tumor-bearing mice. Activity was measured by monitoring the mean survival time, effect on hematological parameters, antioxidant enzyme levels and solid tumor volume. The extract exhibited strong in vitro cytotoxicity against all the tested cancer cell lines, but it was found to be safe with normal cells. MEIL at the dose of 200 and 400 mg/kg, significantly increase the mean survival time (P<0.001), exerted a protective effect on the hemopoietic system, demonstrated in vivo antioxidant activity and significantly reduce solid tumor volume (P<0.01). These results show a significant antitumor and cytotoxic effect of MEIL against EAC, DLA and human cancer cell lines and support the ethnomedical use of Indigofera linnaei.
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Antineoplásicos Fitogénicos/uso terapéutico , Apoptosis/efectos de los fármacos , Carcinoma de Ehrlich/tratamiento farmacológico , Indigofera/química , Linfoma/tratamiento farmacológico , Fitoterapia , Extractos Vegetales/uso terapéutico , Animales , Carcinoma de Ehrlich/patología , Células Cultivadas , Chlorocebus aethiops , Humanos , Masculino , Metanol/química , Ratones , Células 3T3 NIH , Neoplasias/tratamiento farmacológico , Neoplasias/patología , Tasa de Supervivencia , Carga Tumoral , Células VeroRESUMEN
Consumption of fruits and vegetables has been associated with a low incidence of cardiovascular and other chronic diseases. The present study was aimed at evaluating the protective effects of fresh apple extract (AE) on human umbilical vein endothelial cells (HUVEC) exposed to cytotoxic glycated protein (GFBS)/iron (FeCl(3)) chelate. The experimental design comprised 10 groups with 5 flasks in each group. Group I was treated with 15% foetal bovine serum (FBS). Groups II, III and IV were treated with GFBS (70 microM), FBS + FeCl(3) (20 microM), and GFBS + FeCl(3), respectively. The other six groups were as follows: Group V, GFBS + AE (100 microg); Group VI, FBS + FeCl(3) + AE (100 microg); Group VII, GFBS + FeCl(3) + AE (100 microg); Group VIII, GFBS + AE (250 microg); Group IX, FBS + FeCl(3) + AE (250 microg); and Group X, GFBS + FeCl(3) + AE (250 microg). After 24 h incubation, cells were collected from all the experimental groups and assessed for lipid peroxidation (LPO) and activities of the antioxidant enzymes cytochrome c reductase and glutathione S-transferase (GST). HUVEC incubated with glycated protein (GFBS) either alone or combined with iron chelate showed a significant (p < 0.001) elevation of LPO accompanied by depletion of superoxide dismutase, catalase, glutathione peroxidase (GPx) and glutathione reductase (GR), in addition to increased microsomal cytochrome c reductase and decreased GST activities. Treatment of GFBS- or GFBS + FeCl(3)-exposed HUVEC with AE at 100 or 250 microg significantly decreased the level of LPO and returned the levels of antioxidants cytochrome c reductase and GST to near normal in a dose-dependent manner. The extracts recovered viability of HUVEC damaged by GFBS-iron treatment in a concentration-dependent manner. These findings suggest a protective effect of AE on HUVEC against glycated protein/iron chelate-induced toxicity, which suggests that AE could exert a beneficial effect by preventing diabetic angiopathies.
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Células Endoteliales/efectos de los fármacos , Glicoproteínas/toxicidad , Malus/química , Extractos Vegetales/farmacología , Venas Umbilicales/citología , Línea Celular , Productos Finales de Glicación Avanzada/toxicidad , Humanos , Peróxidos Lipídicos/metabolismo , Extractos Vegetales/químicaRESUMEN
A flavanone has been isolated first time from the stem of Bauhinia variegata, and its structure was identified by colour reactions and spectral analysis. In a search for novel anticancer compounds from medicinal plants, the isolated flavanone was tested for cytotoxic activity against 57 human tumour lines, representing leukaemia, non-small cell lung, colon, central nervous system, melanoma, ovarian, renal, prostate and breast cancers. The results showed that the flavanone has cytotoxic activity against human tumour cell lines.
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Bauhinia/química , Proliferación Celular/efectos de los fármacos , Flavanonas/química , Flavanonas/farmacología , Tallos de la Planta/química , Línea Celular Tumoral , Flavanonas/aislamiento & purificación , Humanos , Estructura MolecularRESUMEN
The protective effect of methanol extracts of Cassia fistula (flowers, leaves and bark) was examined in vitro in human umbilical vein endothelial cells (HUVEC) against toxicity induced by glycated protein (GFBS) in vitro. The experiments consisted of eight groups of HUVEC with five flasks in each group. Group I was treated with 15% FBS, group II with GFBS (70 microM) alone, and the other six groups were treated with GFBS plus 25 and 50 microg of each of the three types of C. fistula extracts. After 72 h of incubation, cells were collected and tested for lipid peroxidation, antioxidant enzyme activities and glutathione S-transferase (GST). The protective effect of C. fistula extracts against GFBS-induced cytotoxicity was examined in HUVEC by using trypan blue exclusion and MTT assays. Results showed that HUVEC incubated with GFBS alone showed a significant (P < 0.001) elevation of lipid peroxidation accompanied by depletion of superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx) and glutathione reductase (GR), in addition to decreased cytosolic GST. Treatment of HUVEC with C. fistula extracts at a concentration of 25 and 50 microg significantly decreased lipid peroxidation and normalized the activities of the antioxidant enzymes and GST levels in a concentration-dependent manner. Morphological changes of HUVEC were compared with respective controls; in addition, the C. fistula extracts increased the viability of HUVEC damaged by GFBS. A protective effect of C. fistula extracts on HUVEC against GFBS-induced toxicity suggested a potential beneficial effect of the extract in preventing diabetic angiopathies.
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Proteínas Sanguíneas/metabolismo , Cassia , Células Endoteliales/efectos de los fármacos , Glicoproteínas/metabolismo , Sustancias Protectoras/farmacología , Animales , Antioxidantes/metabolismo , Proteínas Sanguíneas/toxicidad , Bovinos , Células Cultivadas , Relación Dosis-Respuesta a Droga , Células Endoteliales/citología , Células Endoteliales/enzimología , Endotelio Vascular/citología , Flores , Glutatión Transferasa/metabolismo , Productos Finales de Glicación Avanzada/metabolismo , Glicoproteínas/toxicidad , Glicosilación , Humanos , Peroxidación de Lípido/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Corteza de la Planta , Extractos Vegetales/farmacología , Hojas de la Planta , Suero , Venas Umbilicales/citologíaRESUMEN
To evaluate the antitumor and cytotoxic activity of methanol extract of Phyllanthus polyphyllus (MPP) in mice and human cancer cell lines, the antitumor activity of MPP was evaluated against an Ehrlich ascites carcinoma (EAC) tumor model. The activity was assessed using survival time, hematological studies, lipid peroxidation (LPO), antioxidant enzymes such as superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx), glutathione S-transferase (GST), solid tumor mass, and short-term in vitro cytotoxicity. The cytotoxic activity of MPP was evaluated using human breast cancer (MCF7), colon cancer (HT29), and liver cancer (HepG2) cell lines Oral administration of MPP (200 and 300 mg/kg) increased the survival time and significantly reduced the solid tumor volume in a dose-dependent manner. Hematological parameters, protein, and packed cellular volume (PCV), which were altered by tumor inoculation, were restored. MPP significantly decreased the levels of LPO, GPx, GST, and significantly increased the levels of SOD and CAT. In a cytotoxicity study against human cancer cell lines, MPP was found to have IC50 values of 27, 42 and 38 microg/ml on MCF-7, HT-29, and HepG2 cells respectively. MPP possessed significant antitumor and cytotoxic activity on EAC and human cancer cell lines.
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Carcinoma de Ehrlich/tratamiento farmacológico , Carcinoma de Ehrlich/patología , Phyllanthus/química , Fitoterapia , Extractos Vegetales/farmacología , Animales , Antioxidantes/metabolismo , Carcinoma de Ehrlich/metabolismo , Línea Celular Tumoral , Humanos , Peroxidación de Lípido/efectos de los fármacos , Masculino , Ratones , Extractos Vegetales/química , Extractos Vegetales/uso terapéutico , Extractos Vegetales/toxicidad , Tasa de Supervivencia , Factores de Tiempo , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
The present study was performed to investigate the efficacy of an ethanol extract of the roots of Tragia cannabina for antihyperglycemic and antioxidant effects in streptozotocin (STZ)-induced diabetic rats. Male Wistar rats were administered T. cannabina (250 mg/kg) orally for 21 days, and blood glucose level was measured weekly. At the end of 21 days, concentrations of serum lipids such as total cholesterol, triglycerides, and high-density lipoprotein (HDL) and protein markers such as total protein, albumin, globulin, and albumin:globulin ratio (A:G) were estimated. Also, levels of enzymes such as serum glutamate oxaloacetate transaminase (SGOT), serum glutamate pyruvate transaminase (SGPT), and alkaline phosphatase (ALP) were determined. Antioxidant activity of the extract was evaluated by estimating lipid peroxides (LPO), superoxide dismutase (SOD), and catalase in liver of normal control and STZ- and extract-treated rats. Histopathological changes of liver and kidney were also studied in STZ-induced diabetic animals and normal controls. All these effects produced by the extract were compared with glibenclamide, a standard antidiabetic drug. Oral administration of T. cannabina for 21 days resulted in a significant reduction in blood glucose level, lipid concentration, and SGOT, SGPT, ALP, and LPO levels accompanied by an increase in the levels of SOD and catalase in liver tissues of STZ-induced diabetic rats. Altered levels of protein markers also reverted back to normal. Histopathological changes of liver and kidney were returned to normal. The effects produced by the extract were comparable to that of glibenclamide. In conclusion, the T. cannabina showed significant antihyperglycemic and antioxidant effects in STZ-induced diabetic rats.
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Diabetes Mellitus Experimental/tratamiento farmacológico , Euphorbiaceae/química , Hipoglucemiantes/uso terapéutico , Fitoterapia , Extractos Vegetales/uso terapéutico , Alanina Transaminasa/sangre , Fosfatasa Alcalina/sangre , Animales , Antioxidantes/análisis , Aspartato Aminotransferasas/sangre , Glucemia/análisis , Diabetes Mellitus Experimental/sangre , Diabetes Mellitus Experimental/patología , Riñón/patología , Peróxidos Lipídicos/sangre , Lípidos/sangre , Hígado/patología , Masculino , Extractos Vegetales/química , Raíces de Plantas/química , Ratas , Ratas WistarRESUMEN
The chemopreventive effect of ethanol extract of Indigofera aspalathoides (EIA) on N-nitrosodiethylamine (DEN, 200 mg/kg)-induced experimental liver tumor was investigated in male Wistar rats. Oral administration of ethanol extract of Indigofera aspalathoides (250 mg/kg) effectively suppressed liver tumor induced with DEN as revealed by decrease in the levels of extend of serum glutamate pyruvate transaminase (SGPT), serum glutamate oxaloacetate transaminase (SGOT), alkaline phosphatase (ALP), total bilirubin, gamma glutamate transpeptidase (GGTP), lipid peroxidase (LPO), glutathione peroxidase (Gpx) and glutathione S-transferase (GST) with a concomitant increase in enzymatic antioxidant (superoxide dismutase and catalase) levels when compared to those in liver tumor bearing rats. The histopathological changes of liver sample were compared with respective control. Our results show a significant chemopreventive effect of EIA against DEN induced liver tumor.
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Dietilnitrosamina/toxicidad , Indigofera , Neoplasias Hepáticas Experimentales/prevención & control , Fenobarbital/toxicidad , Animales , Quimioprevención , Sinergismo Farmacológico , Neoplasias Hepáticas Experimentales/inducido químicamente , Masculino , Extractos Vegetales/aislamiento & purificación , Extractos Vegetales/uso terapéutico , Tallos de la Planta , Ratas , Ratas WistarRESUMEN
Ethanol extract of Solanum nigrum LINN was investigated for its hepatoprotective activity against CCl4-induced hepatic damage in rats. The ethanol extract showed remarkable hepatoprotective activity. The activity was evaluated using biochemical parameters such as serum aspartate amino transferase (AST), alanine amino transferase (ALT), alkaline phosphatase (ALP) and total bilirubin. The histopathological changes of liver sample in treated animals were compared with respect to control.
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Intoxicación por Tetracloruro de Carbono/prevención & control , Frutas , Hepatopatías/prevención & control , Solanum nigrum , Animales , Intoxicación por Tetracloruro de Carbono/metabolismo , Enfermedad Hepática Inducida por Sustancias y Drogas , Hepatopatías/metabolismo , Masculino , Ratones , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , RatasRESUMEN
Ethanol and aqueous extracts of Carica papaya has been evaluated for its anti hepatotoxic activity. The ethanol and aqueous extracts of Carica papaya showed remarkable hepatoprotective activity against CCl(4) induced hepatotoxicity. The activity was evaluated by using biochemical parameters such as serum aspartate amino transferase (AST), alanine amino transferase (ALT), alkaline phosphatase, total bilirubin and gamma glutamate transpeptidase (GGTP). The histopathological changes of liver sample was compared with respect to control.