RESUMEN
BACKGROUND: Silymarin, a hepatoprotective agent, has poor oral bioavailability. However, the current dosage form of the drug does not target the liver and inflammatory cells selectively. The aim of the present study was to develop lecithin-based carrier system of silymarin by incorporating phytosomal-liposomal approach to increase its oral bioavailability and to make it target-specific to the liver for enhanced hepatoprotection. METHODS: The formulation was prepared by film hydration method. Release of drug was assessed at pH 1.2 and 7.4. Formulation was assessed for in vitro hepatoprotection on Chang liver cells, lipopolysaccharide-induced reactive oxygen species (ROS) production by RAW 267.4 (murine macrophages), in vivo efficacy against paracetamol-induced hepatotoxicity and pharmacokinetic study by oral route in Wistar rat. RESULTS: The formulation showed maximum entrapment (55%) for a lecithin-cholesterol ratio of 6:1. Comparative release profile of formulation was better than silymarin at pH 1.2 and pH 7.4. In vitro studies showed a better hepatoprotection efficacy for formulation (one and half times) and better prevention of ROS production (ten times) compared to silymarin. In in vivo model, paracetamol showed significant hepatotoxicity in Wistar rats assessed through LFT, antioxidant markers and inflammatory markers. The formulation was found more efficacious than silymarin suspension in protecting the liver against paracetamol toxicity and the associated inflammatory conditions. The liposomal formulation yielded a three and half fold higher bioavailability of silymarin as compared with silymarin suspension. CONCLUSIONS: Incorporating the phytosomal form of silymarin in liposomal carrier system increased the oral bioavailability and showed better hepatoprotection and better anti-inflammatory effects compared with silymarin suspension.
Asunto(s)
Hepatocitos/efectos de los fármacos , Macrófagos/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , Silimarina/administración & dosificación , Acetaminofén/toxicidad , Administración Oral , Animales , Disponibilidad Biológica , Línea Celular , Enfermedad Hepática Inducida por Sustancias y Drogas/etiología , Enfermedad Hepática Inducida por Sustancias y Drogas/prevención & control , Liberación de Fármacos , Hepatocitos/metabolismo , Humanos , Concentración de Iones de Hidrógeno , Lipopolisacáridos/farmacología , Liposomas , Hígado/citología , Hígado/efectos de los fármacos , Hígado/metabolismo , Macrófagos/metabolismo , Masculino , Ratones , Sustancias Protectoras/administración & dosificación , Sustancias Protectoras/farmacocinética , Ratas , Ratas Wistar , Silibina , Silimarina/farmacocinéticaRESUMEN
The active constituents of Sesamum indicum, sesamin and sesamolin, have already been explored for hypolipidemic action. In this study we have explored the anti-dyslipidemic activity of another active component and metabolite of sesamolin (sesamol), by using acute models of hyperlipidemia viz., a fat tolerance test, a tyloxapol-induced hyperlipidemia model and a chronic model of hyperlipidemia viz., a high-fat diet-induced hyperlipidemia model in Swiss albino mice. Sesamol (100 and 200 mg/kg) significantly (P < 0.05) decreased triacylglycerol absorption in the fat tolerance test by showing a dose-dependent decrease in triacylglycerol levels. The hypolipidemic effect of sesamol at 200 mg/kg was equivalent to 10 mg/kg of orlistat. In the tyloxapol-induced hyperlipidemia model, Sesamol at 200 mg/kg reversed the elevated levels of cholesterol and triacylglycerol compared with the tyloxapol group at 12 and 24 h, which indicates its probable effect on cholesterol synthesis. Chronic hyperlipidemia in mice was produced by feeding a high-diet, a mixture of cholesterol (2 % w/w), cholic acid (1 % w/w) and coconut oil 30 % (v/w) with standard powdered standard animal chow (up to 100 g). Niacin (100 mg/kg) and sesamol (100 mg/kg) significantly (P < 0.05) reduced the elevated body weight compared with the high fat diet control group. Elevated levels of cholesterol and triacylglycerol were significantly (P < 0.05) reversed by the sesamol (50 and 100 mg/kg), implying that it might reduce the absorption and increase the excretion of cholesterol as well.
Asunto(s)
Benzodioxoles/uso terapéutico , Colesterol/sangre , Hiperlipidemias/sangre , Hiperlipidemias/tratamiento farmacológico , Hipolipemiantes/uso terapéutico , Fenoles/uso terapéutico , Triglicéridos/sangre , Enfermedad Aguda , Animales , Antioxidantes/uso terapéutico , Peso Corporal/efectos de los fármacos , Enfermedad Crónica , Hiperlipidemias/patología , Masculino , Ratones , Sesamum/químicaRESUMEN
UNLABELLED: ETHNO-PHARMACOLOGICAL RELEVANCE: The seeds of Sesamum indicum Linn. (Pedaliaceae) has been used traditionally for the treatment of wounds in Buldhana district of Maharashtra state. Sesamol is the main anti-oxidative constituent contained mainly in the processed sesame seed oil which has not been explored scientifically for its wound healing activity. AIM OF THE STUDY: To investigate the influence of sesamol (SM) on wound repair, both in normal and dexamethasone (DM) delayed healing processes in albino rats. MATERIALS AND METHODS: Incision, excision and dead space wounds were inflicted on albino rats (180-220 g) of either sex, under ketamine anaesthesia. Group I served as control, group II received SM 50 mg/kg i.p., group III was treated with dexamethasone (DM) i.m. (0.17 mg/kg) and SM+DM was given to group IV. The tensile strength, wound contraction, hydroxyproline, lysyl oxidase and total RNA and DNA levels (in granulation tissue) were measured. RESULTS: The tensile strength significantly (p<0.05) increased with SM at 471.40±14.66 g when compared to control at 300.60±9.16 g in normal and DM suppressed healing. No significant change was observed in duration of wound contraction and lysyl oxidase when compared to control at 2.98±0.10 mg. SM treated rats showed a significant (p<0.05) rise in hydroxyproline levels at 6.45±0.45 mg when compared to control at 1.75±0.20 mg. CONCLUSION: These results indicate that sesamol could be a promising drug in normal as well as delayed wound healing processes.
Asunto(s)
Benzodioxoles/farmacología , Fenoles/farmacología , Sesamum , Cicatrización de Heridas/efectos de los fármacos , Animales , Antioxidantes/aislamiento & purificación , Antioxidantes/farmacología , Benzodioxoles/aislamiento & purificación , Dexametasona/toxicidad , Etnofarmacología , Femenino , Hidroxiprolina/metabolismo , India , Masculino , Medicina Tradicional , Fenoles/aislamiento & purificación , Fitoterapia , Proteína-Lisina 6-Oxidasa/metabolismo , Ratas , Ratas Wistar , Semillas/química , Sesamum/química , Resistencia a la Tracción/efectos de los fármacos , Cicatrización de Heridas/fisiologíaRESUMEN
OBJECTIVE: The aim of the present study was to analyze the effect Cissus quadrangularis plant petroleum ether extract on the development of long bones during the intra-uterine developmental stage in rats. METHODS: Pregnant rats (n=12) were randomly assigned into either a control group (n=6) or a Cissus quadrangularis treatment (n=6) group. Pregnant rats in the Cissus quadrangularis group were treated with Cissus quadrangularis petroleum ether extract at a dose of 500 mg/kg body weight from gestation day 9 until delivery. The animals in the control group received an equal volume of saline. Newborn pups were collected from both groups for alizarin red S - alcian blue staining to differentiate ossified and unossified cartilage. The ossified cartilage (bone) was morphometrically analyzed using Scion image software. RESULTS: Morphometric analysis revealed that the percentage of the total length of ossified cartilage (bone) in pups born to treated dams was significantly higher (P<0.001- -0.0001) than that of the control group. CONCLUSION: The results of the present study suggest that maternal administration of Cissus quadrangularis petroleum ether extract during pregnancy can stimulate the development of fetal bone growth during the intra-uterine developmental period.
Asunto(s)
Alcanos , Desarrollo Óseo/efectos de los fármacos , Cissus/química , Desarrollo Fetal/efectos de los fármacos , Extractos Vegetales/farmacología , Animales , Femenino , Embarazo , Distribución Aleatoria , Ratas , Ratas Wistar , Pruebas de Toxicidad AgudaRESUMEN
OBJECTIVE: The aim of the present study was to analyze the effect Cissus quadrangularis plant petroleum ether extract on the development of long bones during the intra-uterine developmental stage in rats. METHODS: Pregnant rats (n=12) were randomly assigned into either a control group (n=6) or a Cissus quadrangularis treatment (n=6) group. Pregnant rats in the Cissus quadrangularis group were treated with Cissus quadrangularis petroleum ether extract at a dose of 500 mg/kg body weight from gestation day 9 until delivery. The animals in the control group received an equal volume of saline. Newborn pups were collected from both groups for alizarin red S - alcian blue staining to differentiate ossified and unossified cartilage. The ossified cartilage (bone) was morphometrically analyzed using Scion image software. RESULTS: Morphometric analysis revealed that the percentage of the total length of ossified cartilage (bone) in pups born to treated dams was significantly higher (P<0.001- -0.0001) than that of the control group. CONCLUSION: The results of the present study suggest that maternal administration of Cissus quadrangularis petroleum ether extract during pregnancy can stimulate the development of fetal bone growth during the intra-uterine developmental period.
Asunto(s)
Animales , Femenino , Embarazo , Ratas , Alcanos , Desarrollo Óseo/efectos de los fármacos , Cissus/química , Desarrollo Fetal/efectos de los fármacos , Extractos Vegetales/farmacología , Distribución Aleatoria , Ratas Wistar , Pruebas de Toxicidad AgudaRESUMEN
Nonsteroidal antiinflammatory drugs like ibuprofen impede tissue repair by virtue of retarding inflammation. The present study was undertaken to explore if linking of nitrooxyethyl ester to ibuprofen reverses its healing-depressant propensity. Nitrooxyethyl ester of ibuprofen (NOE-Ibu) was synthesized in our laboratory through a well-established synthetic pathway. NOE-Ibu was screened for its influence on collagenation, wound contraction and epithelialization phases of healing, and scar size of healed wound in three wound models, namely, incision, dead space, and excision wounds. Besides, its influence on the oxidative stress (levels of GSH and TBARS) was also determined in 10-day-old granulation tissue. NOE-Ibu was further screened for its antiinflammatory activity in rat paw edema model. NOE-Ibu promoted collagenation (increase in breaking strength, granulation weight, and collagen content), wound contraction and epithelialization phases of healing. NOE-Ibu also showed a significant antioxidant effect in 10-day-old granulation tissue as compared to ibuprofen. Results vindicate that the esterification of ibuprofen with nitrooxyethyl group reverses the healing-suppressant effect of ibuprofen. The compound also showed equipotent antiinflammatory activity as ibuprofen.