RESUMEN
OBJECTIVE: The present study was designed to explore the potential anti-inflammatory and anti-arthritic effects of ellagic acid (EA) in collagen-induced arthritis (CIA). METHODS: CIA rats were treated with MTX (0.25 mg/kg body wt.) and EA (50 mg/kg b.wt.) for a period of 20 days. The effects of treatment in the rats were assessed biochemically by analyzing inflammatory mediators (NF-kB, iNOS, TNF-α, IL-1ß, IL-6 and IL-10) and oxidative stress related parameters (MPO, NO, LPO, catalase, SOD, GSH). In addition, we also assessed the expression of some inflammatory mediators TNF-α, CD8 + though immunohistochemistry in the joint tissue. RESULTS: In the present study, we found expression and synthesis of transcription factor NF-kB was prominent in CIA rats. In addition, main pro-inflammatory cytokines such as TNF-α, IL-1ß, IL-6, and the anti-inflammatory IL-10, was also stand out. Further, reactive oxygen/nitrogen species was also elevated in CIA rats. Treatment with EA ameliorates all the above mentioned inflammatory and oxidative stress related parameters to near normal. Further, we also confirmed the expression of TNF-α, CD8+ T cells through immunohistochemistry was mitigates in joint tissue of EA treated rats. We find EA significantly inhibited the developmental phase of arthritis. CONCLUSION: These results suggest that EA act as potent anti-arthritic and anti-inflammatory agent that could be used as a tool for the development of new drug for the treatment of arthritis.
Asunto(s)
Artritis Experimental , Animales , Antiinflamatorios/uso terapéutico , Artritis Experimental/inducido químicamente , Artritis Experimental/tratamiento farmacológico , Artritis Experimental/metabolismo , Linfocitos T CD8-positivos/metabolismo , Catalasa/metabolismo , Citocinas/metabolismo , Ácido Elágico/efectos adversos , Mediadores de Inflamación/metabolismo , Interleucina-10/metabolismo , Interleucina-6/metabolismo , FN-kappa B/metabolismo , Nitrógeno/efectos adversos , Oxígeno/efectos adversos , Fosforilación , Ratas , Ratas Wistar , Superóxido Dismutasa/metabolismo , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
Benign prostate hyperplasia (BPH) is an age-related disease in men characterized by the growth of prostate cells and hyperproliferation of prostate tissue. This condition is closely related to chronic inflammation. In this study, we highlight the therapeutic efficacy of ellagic acid (EA) for BPH by focusing on the AR signaling axis and STAT3. To investigate the effect of EA on BPH, we used EA, a phytochemical abundant in fruits and vegetables, to treat testosterone propionate (TP)-induced BPH rats and RWPE-1 human prostate epithelial cells. The EA treatment reduced prostate weight, prostate epithelial thickness, and serum DHT levels in the TP-induced BPH rat model. In addition, EA improved testicular injury by increasing antioxidant enzymes in testis of the BPH rats. EA reduced the protein levels of AR, 5AR2, and PSA. It also induced apoptosis by regulating Bax, Bcl_xL, cytochrome c, caspase 9, and caspase 3 with increasing mitochondrial dynamics. Furthermore, EA reduced the expression of IL-6, TNF-α, and NF-κB, as well as phosphorylation of STAT3 and IκBα. These findings were also confirmed in TP-treated RWPE-1 cells. Overall, our data provide evidence of the role of EA in improving BPH through inhibition of AR and the STAT3 pathway.
Asunto(s)
Hiperplasia Prostática , Propionato de Testosterona , Andrógenos/farmacología , Animales , Ácido Elágico/efectos adversos , Humanos , Hiperplasia/patología , Masculino , Extractos Vegetales/farmacología , Próstata/metabolismo , Hiperplasia Prostática/inducido químicamente , Hiperplasia Prostática/tratamiento farmacológico , Hiperplasia Prostática/metabolismo , Ratas , Ratas Sprague-Dawley , Factor de Transcripción STAT3/metabolismo , Propionato de Testosterona/efectos adversosRESUMEN
Epilobium hirsutum (EH) is a medicinal plant for treating various diseases. Despite its wide usage, there is no available information about its potential influences on drug metabolism. The present study was undertaken to determine the in vivo effects of EH on hepatic CYP2B, CYP2C, CYP2D, and CYP3A enzymes that are primarily involved in drug metabolism. Male Wistar rats were injected intraperitoneally with EH water extract (EHWE) and ellagic acid (EA) at a daily dose of 37.5 and 20 mg/kg, respectively, for 9 days and hepatic drug-metabolizing enzymes were assessed at activity, protein and mRNA levels. Erythromycin N-demethylase activity was inhibited by 53 and 21 % in EHWE- and EA-treated rats, respectively. Benzphetamine N-demethylase and 7-benzyloxyresorufin-O-debenzylase activities were decreased by 53 and 43 %, and 57 and 57 % in EHWE-and EA-treated rats, respectively. Moreover, protein levels of CYP2B1, CYP2C6, CYP2D2, and CYP3A1 also decreased by 55, 15, 33, and 82 % as a result of EHWE treatment of rats, respectively. Similarly, CYP2B1, CYP2C6, CYP2D2, and CYP3A1 protein levels decreased by 62, 63, 49, and 37 % with EA treatment, respectively. qRT-PCR analyses also showed that mRNA levels of these enzymes were significantly inhibited with bothEHWE and EA treatments. In conclusion, inhibition of drug clearances leading to drug toxicity because of the lowered activity and expression of drug-metabolizing enzymes might be observed in the people who used EH as complementary herbal remedy that might be contributed by its EA content.
Asunto(s)
Sistema Enzimático del Citocromo P-450/metabolismo , Ácido Elágico/efectos adversos , Ácido Elágico/farmacología , Epilobium/efectos adversos , Inactivación Metabólica/efectos de los fármacos , Extractos Vegetales/efectos adversos , Extractos Vegetales/farmacología , Animales , Masculino , Tasa de Depuración Metabólica/efectos de los fármacos , Oxidorreductasas N-Desmetilantes/metabolismo , Plantas Medicinales/efectos adversos , Ratas , Ratas WistarRESUMEN
The purpose of this study was to investigate the effects of ellagic acid on platelet expression via the cyclooxygenase (COX) pathway by examining its effects on platelet activation and comparing them with known COX inhibitors in male Sprague-Dawley rats. Ellagic acid is a major compound found in certain fruits and nuts. It has been attributed as having anti-inflammatory, free radical scavenging, and coagulation properties as well as effects on tumor genesis in multiple forms of cancer. We assessed the similarities of ellagic acid to known COX-2 specific and nonspecific COX inhibitors by examining their effects on platelet activation via use of P-selectin flow cytometry. Compared with the vehicle group, both the ellagic acid (P = .035) and the ketorolac (P = .038) groups demonstrated a significant decrease in platelet activation (P = .026). Furthermore, compared with all other groups, ellagic acid plus ketorolac group showed a significant decrease in platelet activation (P = .01). Our findings suggest that ellagic acid is likely a nonspecific COX inhibitor. It also suggests that combining ellagic acid with a known nonspecific COX inhibitor such as ketorolac may cause a significant decrease in platelet activity and an increase in blood loss.
Asunto(s)
Ácido Elágico/farmacología , Citometría de Flujo , Selectina-P , Activación Plaquetaria/efectos de los fármacos , Anestesia , Animales , Ciclooxigenasa 2/efectos de los fármacos , Inhibidores de la Ciclooxigenasa/farmacología , Suplementos Dietéticos/efectos adversos , Suplementos Dietéticos/estadística & datos numéricos , Evaluación Preclínica de Medicamentos , Quimioterapia Combinada , Ácido Elágico/efectos adversos , Citometría de Flujo/métodos , Hemorragia/inducido químicamente , Interacciones de Hierba-Droga/fisiología , Ketorolaco/farmacología , Masculino , Meloxicam , Selectina-P/análisis , Selectina-P/efectos de los fármacos , Fitoterapia/efectos adversos , Fitoterapia/estadística & datos numéricos , Ratas , Ratas Sprague-Dawley , Tiazinas/farmacología , Tiazoles/farmacologíaRESUMEN
OBJECTIVE: To establish and evaluate a hypercoagulable animal model for the assessment of anticoagulants. METHODS: Forty mice, thirty-two rats, and twenty-four rabbits were randomly and equally divided into control group (saline) and three ellagic acid (EA)-treated groups (low, middle, and high doses). In the mice, bleeding time (BT) was estimated with tail transaction, and clotting time (CT) with template method. Prothrombin time (PT) and the activated partial thromboplastin time (APTT) in rats and rabbits were measured by means of Quick's one-stage assay and modified APTT assay respectively. In addition, thrombin activity was estimated in rats with PT assay using a hemagglutination analyzer. The circulating platelet aggregates were detected in rabbits through platelet counting and presented as the circulating platelet aggregate ratio (CPAR). RESULTS: EA shortened BT and CT in mice, PT and APTT in rats, and increased thrombin activity and CPAR, all in a dose-dependent manner. EA also brought reduction of PT and APTT in rabbits in dose- and time-dependent manners. CONCLUSION: EA could induce hypercoagulable state through activating coagulation system and platelets in mice, rats, and rabbits.
Asunto(s)
Anticoagulantes/uso terapéutico , Trastornos de la Coagulación Sanguínea/inducido químicamente , Trastornos de la Coagulación Sanguínea/tratamiento farmacológico , Ácido Elágico/efectos adversos , Modelos Animales , Animales , Evaluación Preclínica de Medicamentos , Femenino , Masculino , Ratones , Ratones Endogámicos ICR , Agregación Plaquetaria/efectos de los fármacos , Tiempo de Protrombina , Conejos , Ratas , Ratas Sprague-DawleyRESUMEN
Ellagic acid (EA) is a potent antioxidant marketed as a nutritional supplement. Its pharmacological activity has been reported in wide variety of disease models; however its use has been limited owing to its poor biopharmaceutical properties, thereby poor bioavailability. The objective of the current study was to develop chitosan-glycerol phosphate (C-GP) in situ gelling system for sustained delivery of ellagic acid (EA) via subcutaneous route. EA was incorporated in the system employing propylene glycol (PG) and triethanolamine (TEA) as co-solvents; on the other hand EA loaded PLGA nanoparticles (np) were dispersed in the gelling system using water. These in situ gelling systems were thoroughly characterized for mechanical, rheological and swelling properties. These systems are liquid at room temperature and gels at 37 degrees C. The EA C-GP system showed an initial burst release in vitro with about 85% drug released in 12 h followed by a steady release till 160 h, on the other hand EA nanoparticles entrapped in the C-GP system displayed sustained release till 360 h. The histopathological analysis indicates the absence of inflammation on administration, suggesting that these formulations are safe during the studied period. Furthermore, the antioxidant potential of EA C-GP and EA np C-GP gels has been evaluated against cyclosporine induced nephrotoxicity in rats. The data indicates that formulations were effective against cyclosporine induced nephrotoxicity, where the EA C-GP gels showed activity at 10 times lower dose and the EA np C-GP gels at 150 times lower dose when compared to orally given EA. Formulating nanoparticles of EA and incorporating them in C-GP system results in 15 times lowering of dose in comparison EA C-GP gels which is quite significant. Together, these results indicate that the bioavailability of ellagic acid can be improved by subcutaneous formulations administered as simple EA or EA nps.
Asunto(s)
Antioxidantes/farmacología , Ácido Elágico/farmacología , Riñón/efectos de los fármacos , Nanopartículas/química , Animales , Antioxidantes/efectos adversos , Disponibilidad Biológica , Quitosano/química , Ciclosporina/toxicidad , Relación Dosis-Respuesta a Droga , Evaluación Preclínica de Medicamentos , Ácido Elágico/efectos adversos , Etanolaminas/química , Geles , Glicerol/química , Inmunosupresores/toxicidad , Riñón/patología , Cinética , Ácido Láctico/química , Masculino , Ácido Poliglicólico/química , Copolímero de Ácido Poliláctico-Ácido Poliglicólico , Polímeros/química , Propilenglicol/química , Ratas , Ratas Sprague-Dawley , Solventes/química , Temperatura , Agua/químicaRESUMEN
A recent profusion of pomegranate nutraceutical products, "standardized to 40% ellagic acid," has appeared in the marketplace. This Perspective reviews the chemical and functional studies of pomegranate as well as the virtues and dangers of ellagic acid, and concludes that synergy among the various pomegranate fractions and phytochemicals is the most important factor for assessing strength of pomegranate nutraceutical preparations, and not simply the concentration of ellagic acid. Ellagic acid concentration in final products is likely to have an optimal therapeutic range, which very likely is less than 40%. The wisdom of designing and engineering pomegranate nutraceutical products to maximize therapeutic or chemopreventive synergy is suggested, as opposed to preparations that are designed and engineered simply to maximize the concentration of a single phytochemical. The implications of this strategy may be generalized for the optimization of nutraceutical preparations from other medicinal plants as well.
Asunto(s)
Ácido Elágico/análisis , Lythraceae/química , Anticarcinógenos , Antioxidantes , Relación Dosis-Respuesta a Droga , Sinergismo Farmacológico , Ácido Elágico/efectos adversos , Frutas/química , Promoción de la Salud , Fenómenos Fisiológicos de la NutriciónRESUMEN
Extracts of leaves of Alchornea cordifolia were studied for their antiplasmodial activities. Chloroformic and ether extracts were found to be inactive while the ethanolic extract exhibited mild in vitro activity against Plasmodium falciparum. Fractionation of this extract led us to isolate ellagic acid as the active constituent of the extract with IC(50) in the range of 0.2-0.5 microM. Cytotoxicity of ethanolic fraction and ellagic acid was also estimated on human fibroblasts cells (IC(50) on Hela cells = 7.3 microM at 24 h for ellagic acid).