RESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Albizia procera L. (Leguminosae) commonly known as Konda vagai in Tamil, is used for the treatment of stomach and intestinal disorders. A decoction of the bark is prescribed for rheumatism and haemorrhage. Traditionally, literature claims Albizia procera as a drug to have antirheumatic properties and hence used by Tribal for the management of chronic rheumatism. Consequently, the present study has been undertaken to illustrate the beneficial outcome of Albizia procera in adjuvant induced arthritic rat model with respect to its antioxidant and anti-inflammatory activities. AIM OF THE STUDY: The present study is aimed to investigate the oxidative stress and the expression of inflammatory markers in arthritic rats treated with ethanolic bark extract of Albizia procera. MATERIALS AND METHODS: Ethanolic bark extract was characterized by HPTLC analysis. Acute oral toxicity study was performed according to the OECD test guideline 423 - Acute toxic class method. The anti-inflammatory effect of ETBE (100, 200 mg/kg/day/p.o.) was evaluated in complete Freund's adjuvant induced arthritic rats using diclofenac as positive control (0.3 mg/kg/day/p. o.). Plasma levels of interleukins TNF- α, IFN-α, IL-2, IL-6, myeloperoxidase and Cathepsin D levels were measured to assess the inflammatory effect of ETBE extract of Albizia procera. Further, the effect of ETBE on superoxide dismutase (SOD), glutathione peroxidase (GPX), reduced glutathione (GSH) and lipid peroxidation (LPO) were assessed in plasma. RESULTS: HPTLC analysis showed the presence of 0.57% w/w of biochanin-A in ETBE. ETBE did not show any toxic signs up to 2000 mg/kg body weight. It exhibited the significant anti-inflammatory and antioxidant potential and did not show mortality up to 2000 mg/kg body weight. ETBE treatment significantly reduced the levels of TNF- α, IFN-α, IL-2, IL-6 and myeloperoxidase, and increased cathepsin D levels compared to vehicle treated animals. SOD, GSH and GPX levels were significantly restored to normal levels while LPO was significantly reduced at 200 mg/kg b. wt. Treated animals. Histopathological studies showed complete cartilage regeneration and near normal joint in ETBE treated arthritic rats. CONCLUSION: ETBE demonstrated potent anti-inflammatory activity by modulating the expression of inflammatory cytokines and restoring the antioxidant enzyme levels.
Asunto(s)
Albizzia , Antiinflamatorios/uso terapéutico , Antioxidantes/uso terapéutico , Artritis Experimental/tratamiento farmacológico , Extractos Vegetales/uso terapéutico , Animales , Antiinflamatorios/farmacología , Antiinflamatorios/toxicidad , Antioxidantes/farmacología , Antioxidantes/toxicidad , Artritis Experimental/sangre , Artritis Experimental/genética , Artritis Experimental/patología , Compuestos de Bifenilo/química , Citocinas/sangre , Citocinas/genética , Etanol/química , Femenino , Glutatión/sangre , Glutatión Peroxidasa/sangre , Articulaciones/efectos de los fármacos , Articulaciones/patología , Peroxidación de Lípido/efectos de los fármacos , Óxido Nítrico/química , Estrés Oxidativo/efectos de los fármacos , Picratos/química , Corteza de la Planta/química , Extractos Vegetales/química , Extractos Vegetales/farmacología , Extractos Vegetales/toxicidad , Ratas Sprague-Dawley , Solventes/química , Superóxido Dismutasa/sangreRESUMEN
PURPOSE OF RESEARCH: Since, transient focal cerebral ischaemia exhibits detrimental effect not only during the course of ischaemia but also after the onset of reperfusion, the current study is focussed on identifying the appropriate therapeutic time point at which NG-nitro-l-arginine methyl ester (l-NAME) exerts better neuroprotection. PRINCIPAL RESULTS: Pre-ischaemic administration of l-NAME ameliorated neurological deficits much better than the during ischaemic and post-ischaemic groups. Pre-ischaemic l-NAME has also mitigated glutamate excitotoxicity, increased glutamine synthetase activity, ATP and NAD levels, decreased nitrate/nitrite content, down regulated TNF-α and upregulated IL-10 expressions and reduced the cerebral infarction significantly than the during ischaemic and post-ischaemic groups. MAJOR CONCLUSION: Current study revealed that l-NAME improved neurological deficit at the pre-ischaemic state in transient focal cerebral ischaemia and has also significantly ameliorated glutamate excitotoxicity. Though l-NAME showed neuroprotective effects when administered at during and post-ischaemia (during reperfusion), it exerts considerable neuroprotection when administered pre-ischaemically.
Asunto(s)
Inhibidores Enzimáticos/uso terapéutico , Infarto de la Arteria Cerebral Media/tratamiento farmacológico , Infarto de la Arteria Cerebral Media/psicología , NG-Nitroarginina Metil Éster/uso terapéutico , Enfermedades del Sistema Nervioso/tratamiento farmacológico , Adenosina Trifosfato/metabolismo , Animales , Infarto Cerebral/tratamiento farmacológico , Infarto Cerebral/psicología , Antagonistas de Aminoácidos Excitadores/farmacología , Glutamato-Amoníaco Ligasa/antagonistas & inhibidores , Ácido Glutámico/toxicidad , Infarto de la Arteria Cerebral Media/complicaciones , Interleucina-10/metabolismo , Masculino , NAD/metabolismo , Enfermedades del Sistema Nervioso/etiología , Enfermedades del Sistema Nervioso/psicología , Ratas , Ratas Sprague-Dawley , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
BACKGROUND: The dried bulbs of Allium sativum (Garlic) and leaves of Lagerstroemia speciosa (Banaba) are used as medicinal food for the treatment of diabetes and other ailments. AIM: The present study was undertaken to ascertain whether the combination of both garlic and banaba extract produces synergistic therapeutic effect in diabetic state. METHODS: In the in vitro studies, the effect of standardized aqueous extract of Allium sativum (ASE), methanolic extract of Lagerstroemia speciosa (LSE) and their mixture (1:1 ratio), DIA-2 on insulin stimulated glucose uptake in 3T3-L1 cells, erythrocyte sorbitol accumulation and protein glycation were evaluated. Impetus from the in vitro findings triggered to screen the anti-diabetic potential of DIA-2 in rat model of type II diabetes and associated oxidative stress. In the in vivo studies, acute oral toxicity of DIA-2 was determined following OECD-423 guidelines in female rats. Anti-diabetic activity of DIA-2 was investigated in high fat diet/low dose streptozotocin induced type II diabetes at four dose levels (62.5, 125, 250 and 500 mg/kg b.w) in rats. RESULTS: Combination of ASE and LSE produced synergistic and a dose dependent increase in glucose uptake in 3T3 adipocyte cell lines when compared to the individual extracts. A similar effect was observed in the inhibition of sorbitol accumulation and protein glycation tests. DIA-2 restored the glucose and lipid level near to normal level without gain in body weight which is the most commonly encountered side effect with the use of conventional antidiabetic agents, particularly insulin, insulin secretagogues, sulfonylureas and thiazolidinediones. DIA-2 also decreased hepatic protein carbonyl content levels significantly in the diabetic rats. CONCLUSIONS: The study concluded that DIA-2 posses potent anti-diabetic activity and anti-oxidant effects.
Asunto(s)
Diabetes Mellitus Experimental/tratamiento farmacológico , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Hipoglucemiantes/farmacología , Extractos Vegetales/farmacología , Células 3T3-L1 , Animales , Antioxidantes/administración & dosificación , Antioxidantes/aislamiento & purificación , Antioxidantes/farmacología , Peso Corporal/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Sinergismo Farmacológico , Femenino , Ajo/química , Glucosa/metabolismo , Hiperglucemia/tratamiento farmacológico , Hipoglucemiantes/administración & dosificación , Hipoglucemiantes/aislamiento & purificación , Lagerstroemia/química , Ratones , Estrés Oxidativo/efectos de los fármacos , Extractos Vegetales/administración & dosificación , Ratas , Ratas Sprague-Dawley , Pruebas de Toxicidad AgudaRESUMEN
BACKGROUND: Hyperglycemia induced over production of free radicals in the mitochondrial electron transport chain is now considered as one of the central mechanisms in the pathogenesis of diabetic complications. Allium sativum and Lagerstroemia speciosa contains active principles possessing anti-diabetic and antioxidant properties. This study is aimed at evaluating the evidence that supports this traditional claim and investigates the possible synergistic effect on these herbs when given as a herbal mixture in vitro. AIM: The present study investigates the cytotoxic, antioxidant and a-glucosidase inhibitory potential of Allium sativum (ASE), Lagerstroemia speciosa (LSE) and their combinations using in vitro methods. MATERIALS AND METHODS: The total phenol, total flavonoid and total tannin content were determined in ASE and LSE. The cytotoxic effects of ASE, LSE and their combination in the ratio of 1:2, 1:1 w/w were evaluated using 3T3 L1 preadipocyte cells. Effect of ASE, LSE and its mixture on intracellular reactive oxygen species (ROS) production were determined by 2', 7'dichlorfluorescein diacetate (DCF DA) staining technique in 3T3-L1 adipocytes. The ability of the herbal extracts and their combination to scavenge super oxide radicals and to inhibit alpha-glucosidase enzyme (a carbohydrate metabolising enzyme) were measured using in vitro methods. RESULTS: The total phenols and tannins were expressed as microgram (microg) of gallic acid equivalents/mg of extract (GAE/mg), flavonoids as microg of quercetin equivalents/mg of extract (QE/mg). LSE had significant higher total phenol (300.11 +/- 1.99), flavonoid (53.12 +/- 0.48) and tannin content (118.90 +/- 0.15) compared to ASE which possessed total phenol (159.93 +/- 0.87); flavonoid (9.37 +/- 0.73) and tannin content (80.5 +/- 0.19). The IC50 value, the concentration of the extracts that cause 50% inhibition or cell death was measured as an index of cytotoxicity. The IC50 value was found to be in the following decreasing order: 1:2 mixture (98 microg/ml) > ASE (323.6 microg/ml) > 1:1 mixture (428.1 microg/ml) > LSE (2154 microg/ml). The 1:1 mixture was comparatively less cytotoxic under the tested concentration range (1 x 10(0) pg - 1 x 10(8) pg) than 1:2 combinations. The results observed with lactate dehydrogenase (LDH) release were similar to that of cell viability assay. The 1:1 mixture (DIA-2 hereafter) was considered for further investigations. DIA-2 inhibited the ROS levels, which is evidenced by the decreased DCF fluorescence. DIA-2 could also efficiently scavenge the super oxide radical generated from PMS/NADH-NBT system showing an IC50 value 69.99 microg/ml, the IC50 value of ASE (157.7 microg/ml), LSE (20.43 microg/ml), and ascorbic acid (49.64 microg/ml) used as positive control. The results of in vitro a-glucosidase inhibitory assay showed highest IC50 value with LSE (0.3 microg/ml) and DIA-2 (0.7 microg/ml) than ASE (136.3 microg/ml) and positive control miglitol (651.8 microg/ml). CONCLUSIONS: DIA-2 exerts synergistic effect in scavenging the ROS and inhibiting the enzyme alpha-glucosidase in vitro compared to its individual extracts. The possible synergistic therapeutic effects may be due the presence of the antioxidant rich flavonoids, phenols and tannins present in LSE and ASE.