RESUMEN
Mikania scandens, a twining herb that grows as a weed in India and Bangladesh is used as vegetables and is a good source of vitamin A, C, B complex, mikanin, sesquiterpenes, betasitosterin, stigmasterol and friedelin. The present communication reports CNS depressant activities with special emphasis to brain biogenic amines in mice. Ethanol extract of leaves of M. scandens (EEMS) was prepared by Soxhalation and analyzed chemically. EEMS potentiated sleeping time induced by pentobarbitone, diazepam and meprobamate and showed significant reduction in the number of writhes and stretches. EEMS caused significant protection against pentylene tetrazole-induced convulsion and increased catecholamines and brain amino acids level significantly. Results showed that EEMS produced good CNS depressant effects in mice.
Asunto(s)
Aminas Biogénicas/metabolismo , Encéfalo/efectos de los fármacos , Depresores del Sistema Nervioso Central/farmacología , Mikania/química , Extractos Vegetales/farmacología , Analgésicos/aislamiento & purificación , Analgésicos/farmacología , Animales , Anticonvulsivantes/aislamiento & purificación , Anticonvulsivantes/farmacología , Encéfalo/metabolismo , Depresores del Sistema Nervioso Central/aislamiento & purificación , Relación Dosis-Respuesta a Droga , Etanol/química , Femenino , Masculino , Ratones , Actividad Motora/efectos de los fármacos , Fitoterapia , Extractos Vegetales/aislamiento & purificación , Hojas de la Planta/química , Reflejo/efectos de los fármacos , Convulsiones/inducido químicamente , Convulsiones/prevención & control , Tetrazoles , Pruebas de Toxicidad AgudaRESUMEN
CONTEXT: Mimusops elengi (M. elengi) Linn. (Sapotaceae) has been used as a folk medicine in wound healing, and the treatment of pain, and inflammation in many parts of India. OBJECTIVE: The purpose of this investigation was to explore the antitumor activity of methanol extract of M. elengi (MEME) in Swiss albino mice against Ehrlich ascites carcinoma (EAC) cell line. MATERIALS AND METHODS: Twenty-four hours after intraperitoneal (i.p.) inoculation of tumor (EAC) cells in mice (n = 12), MEME was administered at 200 and 300 mg/kg body weight daily for 9 consecutive days. On day 10, half of the mice were dissected and the rest were kept alive for assessment of increase in life span. The antitumor effect of MEME was assessed by evaluating tumor volume, viable and nonviable tumor cell count, tumor weight, hematological parameter, and biochemical estimations. In vivo antioxidant parameters were assayed by estimating liver tissue enzyme. In vitro cytotoxicity assay of MEME was measured by using trypan blue exclusion method. RESULTS AND DISCUSSION: MEME showed significant (p < .001) decrease in tumor volume, packed cell volume, and viable cell count, and increased the life span of EAC bearing mice. Hematological, biochemical profile, and in vivo antioxidant parameters were significantly restored toward normal levels in MEME-treated mice as compared to EAC control. MEME also showed direct cytotoxicity on EAC cell line in a dose-dependent manner. CONCLUSIONS: The present study demonstrates that M. elengi leaves exhibited antitumor activity in Swiss mice, which may be due to its cytotoxic effect and antioxidant properties.
Asunto(s)
Antineoplásicos Fitogénicos/uso terapéutico , Antioxidantes/uso terapéutico , Carcinoma de Ehrlich/tratamiento farmacológico , Mimusops , Fitoterapia , Extractos Vegetales/uso terapéutico , Animales , Antineoplásicos Fitogénicos/farmacología , Antioxidantes/farmacología , Ascitis , Masculino , Ratones , Ratones Endogámicos , Extractos Vegetales/farmacología , Hojas de la PlantaRESUMEN
Tephrosia purpurea (Fabaceae) is a well-known traditional plant with diuretic effect but no scientific work published till date to support the claimed ethnomedical use. Therefore, the present study appraised the diuretic potential of methanol extract of Tephrosia purpurea (METP) in male wistar rats. The powdered plant material was extracted with methanol by hot extraction. The animals were divided into five groups for diuretic activity. The first group served as saline control (0.9%% saline solution, 25 ml/kg, body weight (b.w)), the second group received osmotic diuretic, urea (1 g/kg b.w), the third group received high-ceiling diuretic, furosemide (5 mg/kg b.w), and the other two groups were administered various concentrations of METP (200 mg/kg and 400 mg/kg b.w) orally to hydrated rats and their urine volume was measured at 5th and 24th hr after drug administration, while animals were deprived of food and water. After collection of urine, the parameters such as urine output, diuretic activity, electrolyte excretion of Na(++), K(++), Ca(2++), and Cl(-), and pH were analyzed. METP at various dose levels exhibited significant diuretic activity as evidenced by increased urine volume, electrolyte concentration, and alkaline pH in comparison to control group of animals. The present study provides a quantitative basis for explaining the folkloric use of Tephrosia purpurea as a diuretic agent in Indian traditional system of medicine.
Asunto(s)
Diuresis/efectos de los fármacos , Diuréticos/farmacología , Electrólitos/orina , Preparaciones de Plantas/farmacología , Tephrosia , Micción/efectos de los fármacos , Animales , Furosemida/farmacología , Concentración de Iones de Hidrógeno , Masculino , Medicina Ayurvédica , Ratas , Ratas Wistar , Urea/farmacologíaRESUMEN
CONTEXT: Clerodendrum infortunatum Linn. is a widely used plant in the Indian indigenous system of medicine for the treatment of tumors. OBJECTIVE: The present study evaluated the anticancer activity of methanol extract of C. infortunatum (MECI) against Ehrlich's ascites carcinoma (EAC) bearing Swiss albino mice and isolation of bioactive terpenoids from it. METHODS: HPLC analysis of the methanol extract showed the presence of three major components. Out of those, two compounds were isolated and characterized as oleanolic acid and clerodinin A. The anticancer activity of MECI was assessed by measuring the tumor growth response, percentage increase of life span, study of hematological parameters, lipid peroxidation, antioxidant enzyme activity like glutathion and CAT. In vitro cytotoxicity assay was also performed using EAC cell lines. RESULT AND CONCLUSION: Treatment with MECI causes significant decrease in the tumor cell volume and increase in the life span. The median survival time (MST) of EAC control group was found as 19.42 ± 0.91 d, whereas the MST was increased to 23.44 ± 2.69 d and 27.57 ± 2.57 d for the groups treated with MECI at 100 and 200 mg/kg, respectively. All the hematological parameters, malonaldehyde content and antioxidant enzymes' activity were restored towards the normal level. IC(50) value of MECI was found as 498.33 µg/mL in cytotoxicity study. The experimental results suggested that MECI has significant anticancer activity, which can be attributed to the presence of oleanolic acid and clerodinin A.
Asunto(s)
Antineoplásicos Fitogénicos/farmacología , Carcinoma de Ehrlich/tratamiento farmacológico , Clerodendrum/química , Terpenos/farmacología , Animales , Antineoplásicos Fitogénicos/administración & dosificación , Antioxidantes/metabolismo , Carcinoma de Ehrlich/patología , Línea Celular Tumoral , Cromatografía Líquida de Alta Presión/métodos , Relación Dosis-Respuesta a Droga , India , Concentración 50 Inhibidora , Peroxidación de Lípido/efectos de los fármacos , Medicina Tradicional , Ratones , Extractos Vegetales/administración & dosificación , Extractos Vegetales/farmacología , Tasa de Supervivencia , Terpenos/administración & dosificación , Terpenos/aislamiento & purificaciónRESUMEN
CONTEXT: Carbon tetrachloride (CCl4) is frequently used as a chemical inducer of tissue damage. Their effects on mouse peritoneal macrophages and also in peripheral blood lymphocytes are still unknown. OBJECTIVE: Therefore we tried to focus on intracellular oxidative stress produced by CCl4 in mouse macrophage and lymphocyte cells. METHODS: Intraperitoneal administration of CCl4 induces intracellular superoxide anions production in mouse macrophages and peripheral blood lymphocytes and leads a subsequent lipid peroxidation and protein oxidation. N-acetyl cystein (NAC) and vitamin C were administered intraperitoneally at a dose of 150 mg/kg and their effect on demodulating the oxidative stress is also checked. RESULT AND DISCUSSION: Several in vitro approaches have already been established as a free radical scavenging models, but this free radical screening models is not always correlated with the in vivo screening models. NAC and vitamin C were administered intraperitoneally and significant reduction of the oxidative stress in term of scavenging of toxic superoxide anion observed in both the macrophages and lymphocytes. CONCLUSION: Therefore we are hopeful that our work will light a new insight into the screening of in vivo free radical scavenging model for evaluating anti-inflammatory compounds.
Asunto(s)
Intoxicación por Tetracloruro de Carbono/metabolismo , Tetracloruro de Carbono/toxicidad , Linfocitos/metabolismo , Macrófagos Peritoneales/metabolismo , Estrés Oxidativo/efectos de los fármacos , Acetilcisteína/farmacología , Animales , Ácido Ascórbico/farmacología , Intoxicación por Tetracloruro de Carbono/patología , Depuradores de Radicales Libres/farmacología , Peroxidación de Lípido/efectos de los fármacos , Linfocitos/patología , Macrófagos Peritoneales/patología , Ratones , Superóxidos/metabolismoRESUMEN
CONTEXT: Celsia coromandelina Vahl (Scrophulariaceae) is a shrub found throughout Bangladesh and India, and it is distributed widely in the plains of West Bengal. It is used by the tribal people to treat diarrhea, dysentery, insomnia, skin eruption, fever, syphilis, helminthes infection, and to control fertility. OBJECTIVE: The objective of this study was to fractionate stigmasterol derivative and to investigate the effects of petroleum ether extract of C. coromandelina (PECC) aerial parts on the onset of reproductive maturity and the ovarian steroidogenesis in immature female mice. MATERIALS AND METHODS: PECC was prepared by hot extraction process and one compound was isolated by preparative TLC from it. PECC was completely freed from solvent and administered in immature female mice intraperitoneally once on every alternate day for nine doses. The sexual maturity was observed by means of vaginal opening, first estrus (days), rate of body growth, changes in weight of ovary, uterus and pituitary. The content of ascorbic acid, cholesterol, Δ5-3ß-hydroxy steroid dehydrogenase (Δ5-3ß-HSD) and glucose 6-phosphate dehydrogenase (G 6-PDH) activities in ovaries and carbonic anhydrase activity in uterus were measured by means of biochemical technique in control and treated mice. The activity of PECC was compared with standard marker compound ethinyl estradiol. RESULTS: The isolated compound was characterized as stigmasterol derivative. PECC treatment caused a remarkable delay (30.27 and 18.56%, respectively, by low dose) in sexual maturity compared to vehicle control as evidenced by the age of vaginal opening and appearance of first estrus (cornified smear). PECC treatment also caused a significant fall (58.6 and 50.0%, respectively, by low dose) in Δ5-3ß-HSD and G 6-PDH activities involved in ovarian steroidogenesis compared to vehicle control. Total cholesterol and ascorbic acid content in ovaries and carbonic anhydrase activity in uterus were increased significantly (low dose by 49.3, 424.6 and 82.4%, respectively) along with a reduction in the weight of ovary, uterus and pituitary in comparison to that of control. DISCUSSION AND CONCLUSION: Overall, these results demonstrate that PECC has a good antifertility effect and is responsible for the delayed development of sexual maturity, suppression of ovarian steroidogenesis and elevation of carbonic anhydrase activity in uterus of immature mice. This supports the claim by tribal people as a potential remedy for birth control.
Asunto(s)
Anticonceptivos Femeninos/farmacología , Ovario/efectos de los fármacos , Componentes Aéreos de las Plantas/química , Extractos Vegetales/farmacología , Scrophulariaceae/química , Maduración Sexual/efectos de los fármacos , Estigmasterol/análogos & derivados , 3-Hidroxiesteroide Deshidrogenasas/metabolismo , Alcanos/química , Animales , Anhidrasas Carbónicas/metabolismo , Anticonceptivos Femeninos/administración & dosificación , Anticonceptivos Femeninos/química , Anticonceptivos Femeninos/aislamiento & purificación , Relación Dosis-Respuesta a Droga , Etnofarmacología , Femenino , Glucosafosfato Deshidrogenasa/metabolismo , India , Ratones , Tamaño de los Órganos/efectos de los fármacos , Ovario/crecimiento & desarrollo , Ovario/metabolismo , Hipófisis/efectos de los fármacos , Hipófisis/crecimiento & desarrollo , Extractos Vegetales/administración & dosificación , Extractos Vegetales/química , Extractos Vegetales/aislamiento & purificación , Solventes/química , Estigmasterol/aislamiento & purificación , Estigmasterol/farmacología , Útero/efectos de los fármacos , Útero/crecimiento & desarrollo , Útero/metabolismoRESUMEN
Present study reports the chemopreventive effect of methanol extract of Wedelia calendulaceae (MEWC) against 20-methylcholanthrene (20-MC) induced carcinogenesis in Swiss albino mice. MEWC was administered orally at 250 and 500 mg/kg body weight for 90 consecutive days after 24h of single subcutaneous administration of 20-MC (200 µg) in mice and observed for 15 weeks to record tumor incidence (fibrosarcoma) and survival. After 15 weeks the mice were sacrificed for the estimation of hematological profiles and liver biochemical parameters viz. lipid peroxidation, reduced glutathione (GSH), glutathione-S-transferase (GST), superoxide dismutase (SOD) and catalase (CAT). MEWC treatment markedly reduced tumor incidence and prolonged life span of sarcoma bearing mice as compared to 20-MC control. Hematological profiles were significantly (p<0.001) restored to normal levels in MEWC treated mice. MEWC treatment significantly (p<0.001) modulated the aforesaid liver biochemical parameters as compared to 20-MC control. Therefore, W. calendulaceae possess remarkable chemopreventive efficacy in Swiss mice.
Asunto(s)
Anticarcinógenos/farmacología , Carcinógenos/antagonistas & inhibidores , Carcinógenos/toxicidad , Metilcolantreno/toxicidad , Wedelia/química , Animales , Recuento de Células Sanguíneas , Análisis Químico de la Sangre , Catalasa/metabolismo , Glutatión/metabolismo , Glutatión Transferasa/metabolismo , Pruebas de Función Hepática , Masculino , Ratones , Neoplasias Experimentales/inducido químicamente , Neoplasias Experimentales/epidemiología , Neoplasias Experimentales/prevención & control , Extractos Vegetales/farmacología , Superóxido Dismutasa/metabolismo , Sobrevida , Sustancias Reactivas al Ácido Tiobarbitúrico/metabolismoRESUMEN
Enhydra fluctuans (Compositae), an edible semi aquatic herbaceous vegetable plant, widely used in traditional system of Indian medicine. Total flavonoids of E. fluctuans (TFEF) were screened for analgesic and anti-inflammatory activity. Analgesic activity was studied in acetic acid induced writhing response and by hot plate method in Swiss albino mice. Anti-inflammatory activity was estimated by carrageenan and histamine induced acute inflammation and Freund's complete adjuvant (FCA) induced chronic inflammation in rats. Two flavonoids, baicalein 7-O-glucoside and baicalein 7-O-diglucoside, were isolated from the ethyl acetate fraction. Oral administration of TFEF at the doses of 200 and 400 mg/kg provide 27.05 and 55.49% protection respectively in acetic acid induced writhing method. It also increased the pain threshold in mice evidenced by hot plate method. TFEF showed more potent anti-inflammatory activity. The results of this study may be attributed to high free radical scavenging and antioxidant potential of the flavonoids present in ethyl acetate fraction of Enhydra fluctuans.
Asunto(s)
Antiinflamatorios/uso terapéutico , Antioxidantes/uso terapéutico , Asteraceae/química , Inflamación/tratamiento farmacológico , Dimensión del Dolor/efectos de los fármacos , Fitoterapia/métodos , Acetatos/química , Animales , Antiinflamatorios/aislamiento & purificación , Antiinflamatorios/farmacología , Antioxidantes/aislamiento & purificación , Antioxidantes/farmacología , Disacáridos/química , Disacáridos/aislamiento & purificación , Modelos Animales de Enfermedad , Evaluación Preclínica de Medicamentos/métodos , Flavonas/química , Flavonas/aislamiento & purificación , Flavonoides/aislamiento & purificación , Flavonoides/farmacología , Flavonoides/uso terapéutico , Glucósidos/química , Glucósidos/aislamiento & purificación , Inflamación/inducido químicamente , Masculino , Ratones , Dimensión del Dolor/métodos , Umbral del Dolor/efectos de los fármacos , Componentes Aéreos de las Plantas/química , Extractos Vegetales/química , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Ratas , Ratas WistarRESUMEN
CONTEXT: Sansevieria roxburghiana Schult. & Schult. f. (Agavaceae) is a herbaceous perennial plant traditionally used for coughs, rheumatism; as an expectorant, febrifuge, purgative, and tonic. OBJECTIVE: To evaluate the hydroalcoholic extract of S. roxburghiana rhizome (HASR) for antitumor activity against Ehrlich ascites carcinoma (EAC) in Swiss albino mice. METHODS: Twenty-Four hours after intraperitoneal inoculation of tumor (EAC) cells in mice, HASR was administered at 50 and 100 mg/kg body weight for nine consecutive days. On day 10 half of the mice were sacrificed and rest were kept alive for assessment of increase in life-span. The antitumor effect of HASR was assessed by evaluating tumor volume, packed cell count, viable and non-viable tumor cell count, median survival time and increase in life-span of EAC bearing hosts. Hematological profiles and serum biochemical parameters were estimated. Further, antioxidant properties were assessed by estimating lipid peroxidation, reduced glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT). RESULTS AND DISCUSSION: HASR showed a significant (p < 0.001) decrease in tumor volume, packed cell volume and viable cell count and increased the life span of EAC bearing mice. Hematological and serum biochemical profiles were restored to normal levels in HASR treated mice as compared to EAC control. HASR treatment significantly (p <0.001) decreased lipid peroxidation and recovered GSH, SOD and CAT towards normal as compared to EAC control. CONCLUSION: The present study demonstrates that S. roxburghiana rhizome exhibited remarkable antitumor activity in Swiss mice that is plausibly attributable to its augmenting endogenous antioxidant mechanisms.
Asunto(s)
Antineoplásicos Fitogénicos/farmacología , Carcinoma de Ehrlich/tratamiento farmacológico , Extractos Vegetales/farmacología , Sansevieria/química , Animales , Antineoplásicos Fitogénicos/administración & dosificación , Antineoplásicos Fitogénicos/aislamiento & purificación , Antioxidantes/administración & dosificación , Antioxidantes/aislamiento & purificación , Antioxidantes/farmacología , Carcinoma de Ehrlich/patología , Catalasa/metabolismo , Relación Dosis-Respuesta a Droga , Glutatión/efectos de los fármacos , Glutatión/metabolismo , Peroxidación de Lípido/efectos de los fármacos , Masculino , Ratones , Extractos Vegetales/administración & dosificación , Rizoma , Superóxido Dismutasa/efectos de los fármacos , Superóxido Dismutasa/metabolismoRESUMEN
Flavonoids obtained from Enhydra fluctuans (FEF) were screened for anticancer activity against Ehrlich's ascites carcinoma (EAC) bearing Swiss albino mice. The anticancer activity was assessed by measuring the tumor growth response, percentage increase of life span, hematological parameters, lipid peroxidation, and antioxidant enzyme activity, like GSH and CAT. Two flavonoids, baicalein 7-O-glucoside and baicalein 7-O-diglucoside, were isolated from the ethyl acetate fraction. Treatment with FEF caused a significant decrease in the tumor cell volume and increase of life span. All the hematological parameters, malonaldehyde content and antioxidant enzyme activity were restored towards the normal level. FEF was found to be cytotoxic in the in-vitro model.
Asunto(s)
Antineoplásicos Fitogénicos/farmacología , Asteraceae/química , Carcinoma de Ehrlich/tratamiento farmacológico , Flavonoides/farmacología , Animales , Antioxidantes/metabolismo , Carcinoma de Ehrlich/patología , Línea Celular Tumoral , Peroxidación de Lípido/efectos de los fármacos , RatonesRESUMEN
Saponin (SN1) isolated from C. infortunatum leaves in doses of 30, 50, 75 and 100 mg/kg, ip provided 36.28, 60.47, 90.71, 100% protection respectively from writhing induced by 1.2% v/v acetic acid. In hot plate method, SN1 not only produced analgesia in mice but also potentiated the analgesic action of pentazocine and aspirin. The anticonvulsant activity was tested by leptazol-induced seizures. SN1 decreased the duration of seizures and gave protection in a dose dependent manner against leptazol-induced convulsions. The results suggest that saponin has significant analgesic and anticonvulsant effects.
Asunto(s)
Analgésicos/uso terapéutico , Anticonvulsivantes/uso terapéutico , Clerodendrum , Fitoterapia , Extractos Vegetales/uso terapéutico , Hojas de la Planta/química , Saponinas/uso terapéutico , Convulsiones/prevención & control , Animales , Ratones , Convulsiones/inducido químicamenteRESUMEN
UNLABELLED: In drug discovery research, the compounds should not only to be potent and selective but also must possess acceptable pharmacokinetic properties such as absorption, distribution, metabolism, and excretion (ADME) to increase success rate in clinical studies. OBJECTIVE: Exploration of drug-like properties of 2-(2-methylquinolin-4-ylamino)-N-phenyl acetamide, a potent antileishmanial compound by performing some in vitro ADME experiments along with validation of such studies. MATERIALS AND METHODS: Experimental protocols were established and validated for stability (in PBS pH7.4, simulated gastric and intestinal fluid), solubility, permeability, distribution coefficient (Log D), plasma protein binding and metabolism by rat liver microsomes by using spectrophotometer or HPLC. Methods were considered valid if the results of the standard compounds matched with reported results or within acceptable range or with proper ranking (high-medium-low). RESULTS: The compound was found to be stable (>95% remaining) in all stability studies and aqueous solubility was 299.7 +/- 6.42 muM. The parallel artificial membrane permeability assay (PAMPA) indicated its medium permeability (Log Pe = -5.53 +/- 0.01). The distribution coefficients (Log D) in octanol/PBS and cyclohexane/PBS systems were found to be 0.54 and -1.33, respectively. The plasma protein binding study by the equilibrium dialysis method was observed to be 78.82 +/- 0.13% while metabolism by Phase-I enzymes for 1 hour at 37 degrees C revealed that 36.07 +/- 4.15% of the compound remained after metabolism. CONCLUSION: The methods were found to be very useful for day-to-day ADME studies. All the studies with the antileishmanial compound ascertained that the compound bears optimum pharmacokinetic properties to be used orally as a potential drug for the treatment of leishmaniasis.
RESUMEN
Shilajit is a panacea in Ayurveda, the Indian traditional system of medicine. The major bioactives of shilajit have been identified as dibenzo-alpha-pyrones (DBPs), its oligomers and aminoacyl conjugated derivatives. These bioactive compounds play a crucial role in energy metabolism in all animal cells including those of man. 3-hydroxydibenzo-alpha-pyrone (3-OH-DBP), a key DBP component of shilajit is converted, among other products, to another active DBP derivative, viz. 3,8-hydroxydibenzo-alpha-pyrone, 3,8(OH)2-DBP, in vivo, when its precursor is ingested. 3,8(OH)2-DBP is then involved in energy synthesis in the mitochondria in the reduction and stabilization of coenzyme Q10 in the electron transport chain. As the chemical synthesis of 3,8(OH)2-DBP is a complex, multi-step process and economically not readily viable, we envisioned the development of a process using microorganisms for bioconversion of 3-OH-DBP to 3,8(OH)2-DBP. In this study, the biotransformation of 3-OH-DBP is achieved using Aspergillus niger, which was involved in the humification process on sedimentary rocks leading to shilajit formation. A 60 percent bioconversion of 3-OH-DBP to 3,8(OH)2-DBP and to its aminoacyl derivatives was achieved. The products were characterized and estimated by high performance liquid chromatography (HPLC), high performance flash chromatography (HPFC) and gas chromatography-mass spectrometry (GC-MS) analyses. Among the Aspergillus species isolated and identified from native shilajit, A. niger was found to be the most efficient for this bioconversion.
Asunto(s)
Aspergillus niger , Compuestos Orgánicos/metabolismo , Plantas Medicinales , Biotransformación , Cromatografía Líquida de Alta PresiónRESUMEN
Bis(1,10-phenanthroline/2,2'-bipyridine) ruthenium(II)complexes containing TCP, TTZ OPBI, and BTSC ligands (where, TCP = 1-thiocarbamoyl-3,5-diphenyl-2-pyrazoline, TTZ = 2-(3,5-diphenyl-4,5-dihydropyrazol-1-yl)-4-phenylthiazole, OPBI = 2-hydroxyphenyl benzimidazole and BTSC = benzoin thiosemicarbazone) have been prepared and characterized. The spectral data suggested that the ligands were coordinated with the metal through nitrogen, sulfur and oxygen atoms. The target complexes were tested in vivo for anticancer activity against transplantable murine tumor cell line, Ehrlich's Ascitic Carcinoma (EAC). All these complexes increased the life span of the EAC-bearing mice, decreased their tumor volume and viable ascitic cell count as well as improved Hb, RBC and WBC counts. These results suggest that the Ru(II) complexes exhibit significant antitumor activity in EAC-bearing mice. It was also observed that the ruthenium complexes protected red blood cells from 2,2'-azo-bis(2-methylpropionamidine) dihydrochloride (AAPH)- induced hemolysis. The inhibitory effect was dose-dependent at a concentration of 20-120 microg/ml.
Asunto(s)
Antineoplásicos/síntesis química , Antineoplásicos/uso terapéutico , Compuestos de Rutenio/síntesis química , Compuestos de Rutenio/uso terapéutico , Animales , Antineoplásicos/química , Carcinoma de Ehrlich/tratamiento farmacológico , Carcinoma de Ehrlich/patología , Línea Celular Tumoral , Masculino , Ratones , Estructura Molecular , Compuestos de Rutenio/química , Relación Estructura-ActividadRESUMEN
These ligands (L) show a bidentate behavior, forming octahedral ruthenium complexes. The title complexes were subjected to in-vivo anticancer activity tests against a transplantable murine tumor cell line, Ehrlich's Ascitic Carcinoma (EAC) and in-vitro antibacterial activity against several Gram positive and Gram negative bacterial strains. [Ru(bpy)2(ihqs)]Cl2 and [Ru(bpy)2 (hc)]Cl2 (where bpy = 2,2'-bipyridine, ihqs = 7-iodo-8hydroxy quinoline-5-sulphonic acid and hc = 3-hydroxy coumarin) showed promising antitumor activity. Treatment with these complexes prolonged the life span of EAC bearing mice as well as decreased their tumor volume and viable ascitic cell count. All the tested complexes exhibited mild to moderate antibacterial activity.
Asunto(s)
Antibacterianos/síntesis química , Antibacterianos/farmacología , Antineoplásicos/síntesis química , Antineoplásicos/farmacología , Compuestos de Rutenio/síntesis química , Compuestos de Rutenio/farmacología , Animales , Carcinoma de Ehrlich , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Bacterias Gramnegativas , Bacterias Grampositivas/efectos de los fármacos , RatonesRESUMEN
AIM: To study the antitumor effect and antioxidant role of Bauhinia racemosa. METHODS: Antitumor activity and antioxidant status of methanol extract (50, 100, and 200 mg/kg) of Bauhinia racemosa stem bark was evaluated against Ehrlich ascites carcinoma (EAC) tumor in mice. Acute and short-term toxicity studies were performed initially in order to ascertain the safety of methanol extract of Bauhinia racemosa (MEBR). After 24 h of tumor inoculation, the extract was administered daily for 14 d. After administration of the last dose followed by 18 h fasting, mice were then sacrificed for observation of antitumor activity. The effect of MEBR on the growth of transplantable murine tumor, life span of EAC bearing hosts and simultaneous alterations in the hematological profile and liver biochemical parameters (lipid peroxidation, antioxidant enzymes) were estimated. RESULTS: The MEBR showed decrease in tumor volume, packed cell volume and viable cell count, and increased the nonviable cell count and mean survival time thereby increasing life span of EAC tumor bearing mice. Hematological profile reverted to more or less normal levels in extract treated mice. Treatment with MEBR decreased the levels of lipid peroxidation and increased the levels of glutathione, superoxide dismutase and catalase. CONCLUSION: The methanol extract of Bauhinia racemosa stem bark exhibited antitumor effect by modulating lipid peroxidation and augmenting antioxidant defense system in EAC bearing mice.
Asunto(s)
Antineoplásicos Fitogénicos/uso terapéutico , Antioxidantes/uso terapéutico , Bauhinia/química , Carcinoma de Ehrlich/tratamiento farmacológico , Plantas Medicinales/química , Animales , Antineoplásicos Fitogénicos/farmacología , Antioxidantes/farmacología , Carcinoma de Ehrlich/patología , Peroxidación de Lípido/efectos de los fármacos , Masculino , Ratones , Trasplante de Neoplasias , Corteza de la Planta/química , Extractos Vegetales/aislamiento & purificación , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéuticoRESUMEN
In search of potential anticancer drug candidates in ruthenium complexes, a series of mononuclear ruthenium complexes of the type [Ru(phen)(2)(nmit)]Cl(2) (Ru1), [Ru(bpy)(2)(nmit)]Cl(2) (Ru2), [Ru(phen)(2)(icpl)]Cl(2) (Ru3), Ru(bpy)(2)(icpl)]Cl(2) (Ru4) (phen=1,10-phenanthroline; bpy=2,2'-bipyridine; nmit=N-methyl-isatin-3-thiosemicarbazone, icpl=isatin-3-(4-Cl-phenyl)thiosemicarbazone) and [Ru(phen)(2)(aze)]Cl(2) (Ru5), [Ru(bpy)(2)(aze)]Cl(2) (Ru6) (aze=acetazolamide) and [Ru(phen)(2)(R-tsc)](ClO(4))(2) (R=methyl (Ru7), ethyl (Ru8), cyclohexyl (Ru9), 4-Cl-phenyl (10), 4-Br-phenyl (Ru11), and 4-EtO-phenyl (Ru12), tsc=thiosemicarbazone) were prepared and characterized by elemental analysis, FTIR, (1)H-NMR and FAB-MS. Effect of these complexes on the growth of a transplantable murine tumor cell line (Ehrlich Ascites Carcinoma) and their antibacterial activity were studied. In cancer study the effect of hematological profile of the tumor hosts have also been studied. In the cancer study, the complexes Ru1-Ru4, Ru10 and Ru11 have remarkably decreased the tumor volume and viable ascitic cell count as indicated by trypan blue dye exclusion test (p<0.05). Treatment with the ruthenium complexes prolonged the lifespan of Ehrlich Ascites Carcinoma (EAC) bearing mice. Tumor inhibition by the ruthenium chelates was followed by improvements in hemoglobin, RBC and WBC values. All the complexes showed antibacterial activity, except Ru5 and Ru6. Thus, the results suggest that these ruthenium complexes have significant antitumor property and antibacterial activity. The results also reflect that the drug does not adversely affect the hematological profiles as compared to that of cisplatin on the host.
Asunto(s)
Antibacterianos , Antineoplásicos , Compuestos Organometálicos , Rutenio , Animales , Antibacterianos/síntesis química , Antibacterianos/química , Antibacterianos/farmacología , Antineoplásicos/síntesis química , Antineoplásicos/química , Antineoplásicos/uso terapéutico , Carcinoma de Ehrlich/tratamiento farmacológico , Supervivencia Celular/efectos de los fármacos , Ratones , Pruebas de Sensibilidad Microbiana , Estructura Molecular , Compuestos Organometálicos/síntesis química , Compuestos Organometálicos/química , Compuestos Organometálicos/uso terapéutico , Rutenio/química , Rutenio/farmacología , Rutenio/uso terapéutico , Relación Estructura-Actividad , Células Tumorales CultivadasRESUMEN
The methanol extract of Caesalpinia bonducella FLEMING (Caesalpiniaceae) leaves (MECB) were evaluated for antitumor activity against Ehrlich ascites carcinoma (EAC)-bearing Swiss albino mice. The extract was administered at the doses of 50, 100, and 200 mg/kg body weight per day for 14 days after 24 h of tumor inoculation. After the last dose and 18 h fasting, the mice were sacrificed. The present study deals with the effect of MECB on the growth of transplantable murine tumor, life span of EAC-bearing hosts, hematological profile, and biochemical parameters such as lipid peroxidation (LPO), glutathione content (GSH), superoxide dismutase (SOD), and catalase (CAT) activities. MECB caused significant (P<0.01) decrease in tumor volume, packed cell volume, and viable cell count; and it prolonged the life span of EAC-tumor bearing mice. Hematological profile converted to more or less normal levels in extract-treated mice. MECB significantly (P<0.05) decreased the levels of lipid peroxidation and significantly (P<0.05) increased the levels of GSH, SOD, and CAT. The MECB was found to be devoid of conspicuous short-term toxicity in the mice when administered daily (i.p.) for 14 days at the doses of 50, 100, 200, and 300 mg/kg. The treated mice showed conspicuous toxic symptoms only at 300 mg/kg. The results indicate that MECB exhibited significant antitumor and antioxidant activity in EAC-bearing mice.
Asunto(s)
Antineoplásicos Fitogénicos/uso terapéutico , Antioxidantes/uso terapéutico , Caesalpinia , Carcinoma de Ehrlich/tratamiento farmacológico , Animales , Antineoplásicos Fitogénicos/farmacología , Antioxidantes/farmacología , Carcinoma de Ehrlich/metabolismo , Peroxidación de Lípido/efectos de los fármacos , Peroxidación de Lípido/fisiología , Masculino , Ratones , Extractos Vegetales/uso terapéutico , Hojas de la PlantaRESUMEN
The methanolic extract of both Cuscuta reflexa stem and Corchorus olitorius seed showed marked protection against convulsion induced by chemoconvulsive agents in mice. The catecholamines contained were significantly increased in the processed extract treated mice. The amount of GABA, which is most likely to be involved in seizure activity, was increased significantly in mice brain after a six week treatment. Results of the present study revealed that both the processed extracts showed a significant anticonvulsive property by altering the level of catecholamines and brain amino acids in mice.
Asunto(s)
Aminas Biogénicas/metabolismo , Química Encefálica/efectos de los fármacos , Corchorus/química , Cuscuta/química , Animales , Anticonvulsivantes/farmacología , Catecolaminas/metabolismo , Convulsivantes , Masculino , Ratones , Neurotransmisores/metabolismo , Extractos Vegetales/farmacología , Semillas/química , Convulsiones/inducido químicamente , Convulsiones/prevención & control , Serotonina/metabolismo , EstricninaRESUMEN
Methanol extract of Cuscuta reflexa Roxb. stem (MECR) contain flavonoids (0.2%) and Corchorus olitorius Linn. seed (MECO) was found to contain steroids and cardenolide glycosides. Effects of multiple weekly dose of MECR (25, 50, 75 mg/kg, i.p.) and MECO (15, 20, 25 mg/kg, i.p.) on liver and kidney functions and hematological parameters in mice were studied. No significant alteration of RBC count and hemoglobin content was observed in all dose level of treatment in MECR and MECO treated mice whereas significant increase of clotting time was seen in moderate and high doses in both case. MECR and MECO both caused significant increase in WBC count only in high dose level of treatment. Both the extracts in medium and high dose level increased SGOT, SGPT, NPN and plasma cholesterol significantly. Serum alkaline phosphatase and total bilirubin were also increased by both moderate and high dose level of treatments in MECR and MECO treated mice respectively. Low dose of both the extract did not exhibit any significant change of creatinine and serum protein level. But high dose level of MECR and MECO significantly increased creatinine level. Increase in plasma cholesterol may be due to decrease in cholesterol catabolism owing to liver dysfunction of due to the intake of MECO itself as it was found to be steroid in nature. Elevated level of SGOT, SGPT and serum alkaline phosphatase activity in moderate and high dose level of weekly treated mice may be due to improper liver function following the treatment. Increased urea, non protein nitrogen and creatinine content in blood have been observed with impaired renal function. The slightly higher toxicity in case of MECO treated mice may be due to the presence of cardenolide glycosides in the ME of C. olitorius seed. However, low doses of MECR and MECO (25 and 15 mg/kg, i.p. respectively) did not exhibit any remarkable change on liver and kidney functions and hematological parameters.