RESUMEN
This study examined the hepatoprotective effect of the HV-P411 complex, an herbal extract mixture from the seeds of Vitis vinifera, Schisandra chinensis and Taraxacum officinale, against D-galactosamine (D-GalN)-induced hepatitis. Hepatotoxicity was induced by D-GalN (700 mg/kg, i.p.), and the HV-P411 complex was administered orally 48, 24, and 2 h before and 6 h after D-GalN injection. Increases in serum aminotransferase activity and lipid peroxidation and a decrease in hepatic glutathione content were attenuated by the HV-P411 complex 24 h after D-GalN treatment. The HV-P411 complex attenuated the increases in serum tumor necrosis factor-α, interleukin (IL)-6 level and cyclooxygenase-2 protein production and their mRNA expressions, while increases in serum IL-10 level and heme oxygenase-1 protein production and their mRNA expressions were augmented by the HV-P411 complex. The increased translocation of nuclear factor-κB and c-Jun phosphorylation were attenuated by treatment with the HV-P411 complex. Our results suggest that the HV-P411 complex prevents D-GalN-induced hepatotoxicity via antioxidative and anti-inflammatory activities.
Asunto(s)
Antiinflamatorios/uso terapéutico , Antioxidantes/uso terapéutico , Enfermedad Hepática Inducida por Sustancias y Drogas/tratamiento farmacológico , Medicamentos Herbarios Chinos/uso terapéutico , Hígado/efectos de los fármacos , Magnoliopsida , Fitoterapia , Animales , Antiinflamatorios/farmacología , Antioxidantes/metabolismo , Antioxidantes/farmacología , Enfermedad Hepática Inducida por Sustancias y Drogas/metabolismo , Ciclooxigenasa 2/genética , Ciclooxigenasa 2/metabolismo , Medicamentos Herbarios Chinos/farmacología , Galactosamina , Glutatión/metabolismo , Hemo-Oxigenasa 1/genética , Hemo-Oxigenasa 1/metabolismo , Interleucina-10/sangre , Interleucina-10/genética , Interleucina-6/sangre , Interleucina-6/genética , Interleucina-6/metabolismo , Peroxidación de Lípido/efectos de los fármacos , Hígado/metabolismo , Masculino , FN-kappa B/metabolismo , Fosforilación , Plantas Medicinales , Proteínas Proto-Oncogénicas c-jun/metabolismo , ARN Mensajero/metabolismo , Ratas , Ratas Sprague-Dawley , Schisandra , Semillas , Taraxacum , Factor de Necrosis Tumoral alfa/metabolismo , VitisRESUMEN
Ferulic acid (FA), a phenolic compound found in various medicinal plants, has hepatoprotective effects against oxidative stress and inflammation. Here, we investigated the protective effects and the specific mechanisms of FA against hepatocyte apoptosis caused by ischemia/reperfusion (I/R). Mice were treated intraperitoneally with vehicle or FA 30 min prior to 60 min of ischemia. After 5h of reperfusion, serum aminotransferase activities and hepatic lipid peroxidation were elevated and hepatic glutathione content was depleted. These alterations were attenuated by FA. I/R increased caspase-3 activity and release of cytochrome c, and these were suppressed by FA. FA also attenuated the increases in the serum tumor necrosis factor (TNF)-α levels and TNF receptor type 1-associated DEATH domain protein and TNF receptor-associated factor 2 protein expressions. The cytosolic levels of Bcl-2-associated X protein (Bax), truncated BH3 interacting domain death agonist (tBid), and Bcl-2-like protein 11 were upregulated after reperfusion. The increases in Bax and tBid protein expression were attenuated by FA. Moreover, I/R induced c-Jun N-terminal kinase 1 (JNK1) and JNK2 phosphorylation, and FA attenuated the JNK activation. FA protects against I/R-induced hepatocyte apoptosis by attenuating oxidative stress and JNK activation.
Asunto(s)
Apoptosis/efectos de los fármacos , Ácidos Cumáricos/farmacología , Hígado/irrigación sanguínea , Hígado/efectos de los fármacos , MAP Quinasa Quinasa 4/antagonistas & inhibidores , Daño por Reperfusión/tratamiento farmacológico , Animales , Apoptosis/genética , Proteínas Reguladoras de la Apoptosis/genética , Proteínas Reguladoras de la Apoptosis/metabolismo , Proteína Proapoptótica que Interacciona Mediante Dominios BH3/genética , Proteína Proapoptótica que Interacciona Mediante Dominios BH3/metabolismo , Proteína 11 Similar a Bcl2 , Caspasa 3/genética , Caspasa 3/metabolismo , Caspasa 8/genética , Caspasa 8/metabolismo , Citocromos c/genética , Citocromos c/metabolismo , Citosol/efectos de los fármacos , Citosol/metabolismo , Glutatión/genética , Glutatión/metabolismo , Hepatocitos/efectos de los fármacos , Hepatocitos/metabolismo , Peroxidación de Lípido/efectos de los fármacos , Hígado/metabolismo , MAP Quinasa Quinasa 4/genética , MAP Quinasa Quinasa 4/metabolismo , Masculino , Proteínas de la Membrana/genética , Proteínas de la Membrana/metabolismo , Ratones , Ratones Endogámicos ICR , Estrés Oxidativo/efectos de los fármacos , Proteínas Proto-Oncogénicas/genética , Proteínas Proto-Oncogénicas/metabolismo , Daño por Reperfusión/genética , Daño por Reperfusión/metabolismo , Daño por Reperfusión/patología , Transducción de Señal/efectos de los fármacos , Proteína de Dominio de Muerte Asociada a Receptor de TNF/genética , Proteína de Dominio de Muerte Asociada a Receptor de TNF/metabolismo , Factor 2 Asociado a Receptor de TNF/genética , Factor 2 Asociado a Receptor de TNF/metabolismo , Transaminasas/sangre , Factor de Necrosis Tumoral alfa/sangre , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/metabolismo , Regulación hacia Arriba/efectos de los fármacos , Regulación hacia Arriba/genética , Proteína X Asociada a bcl-2/genética , Proteína X Asociada a bcl-2/metabolismoRESUMEN
This study evaluated the potential beneficial effect of Moutan Cortex Radicis (MCR) in a murine model of carbon tetrachloride (CCl(4))-, D-galactosamine (GalN)- and α-naphthylisothiocyanate (ANIT)-induced liver injury. Acute hepatotoxicity was induced by intraperitoneal injection of CCl(4) (10 µL/kg), GalN (700 mg/kg), and ANIT (40 mg/kg). Animals received MCR (30, 100, and 300 mg/kg ) orally at 48, 24, and 2 h before and 6 h after administration of CCl(4), GalN, and ANIT. Serum activities of aminotransferase were significantly higher at 24 h after CCl(4) or GalN treatment. These changes were attenuated by MCR. Histopathological analysis revealed multiple and extensive areas of portal inflammation, hepatocellular necrosis, and an increase in inflammatory cell infiltration. These changes were inhibited by MCR. Serum total bilirubin concentration increased and bile flow decreased significantly 48 h after ANIT treatment, which was attenuated by MCR. Our results suggest that MCR has a protective effect on acute liver injury.
Asunto(s)
Enfermedad Hepática Inducida por Sustancias y Drogas/prevención & control , Medicamentos Herbarios Chinos/farmacología , Hígado/efectos de los fármacos , Sustancias Protectoras/farmacología , 1-Naftilisotiocianato/toxicidad , Administración Oral , Animales , Bilirrubina/sangre , Tetracloruro de Carbono/toxicidad , Enfermedad Hepática Inducida por Sustancias y Drogas/sangre , Enfermedad Hepática Inducida por Sustancias y Drogas/patología , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Medicamentos Herbarios Chinos/administración & dosificación , Inyecciones Intraperitoneales , Hígado/lesiones , Hígado/patología , Masculino , Ratones , Paeonia , Sustancias Protectoras/administración & dosificación , Ratas , Ratas Sprague-Dawley , Transaminasas/sangreRESUMEN
Forsythiae Fructus is known to have diuretic, anti-bacterial, and anti-inflammatory activities. This study examined the hepatoprotective effects of pinoresinol, a lignan isolated from Forsythiae Fructus, against carbon tetrachloride (CCl(4))-induced liver injury. Mice were treated intraperitoneally with vehicle or pinoresinol (25, 50, 100, and 200 mg/kg) 30 min before and 2 h after CCl4 (20 microl/kg) injection. In the vehicle-treated CCl(4 )group, serum aminotransferase activities were significantly increased 24 h after CCl4 injection, and these increases were attenuated by pinoresinol at all doses. Hepatic glutathione contents were significantly decreased and lipid peroxidation was increased after CCl4 treatment. These changes were attenuated by 50 and 100 mg/kg of pinoresinol. The levels of protein and mRNA expression of inflammatory mediators, including tumor necrosis factor-alpha, inducible nitric oxide synthase, and cyclooxygenase-2, were significantly increased after CCl4 injection; and these increases were attenuated by pinoresinol. Nuclear translocation of nuclear factor-kappaB (NF-kappaB) and phosphorylation of c-Jun, one of the components of activating protein 1 (AP-1), were inhibited by pinoresinol. Our results suggest that pinoresinol ameliorates CCl4)-induced acute liver injury, and this protection is likely due to anti-oxidative activity and down-regulation of inflammatory mediators through inhibition of NF-kappaB and AP-1.