RESUMEN
Multiple sclerosis (MS) is a common disabling autoimmune disease without an effective treatment in young adults. Ginsenoside Rd, extracted from Panax notoginseng, has multiple pharmacological effects and potential therapeutic applications in diseases of the central nervous system. In this study, we explore the efficacy of ginsenoside Rd in experimental autoimmune encephalomyelitis (EAE), an established model of MS. EAE was induced by myelin oligodendrocyte glycoprotein 35-55-amino-acid peptide. Ginsenoside Rd (10-80 mg/kg/day) or vehicle was intraperitoneally administered on the disease onset day, and the therapy persisted throughout the experiments. The dose of 40 mg/kg/day of ginsenoside Rd was selected as optimal. Ginsenoside Rd effectively ameliorated the clinical severity in EAE mice, reduced the permeability of the blood-brain barrier, regulated the secretion of interferon-gamma and interleukin-4, promoted the Th2 shift in vivo (cerebral cortex) and in vitro (splenocytes culture supernatants), and prevented the reduction in expression of brain-derived neurotrophic factor and nerve growth factor in both cerebral cortex and lumbar spinal cord of EAE mice. This study establishes the potency of ginsenoside Rd in inhibiting the clinical course of EAE. These findings suggest that ginsenoside Rd could be a promising agent for amelioration of neuroimmune dysfunction diseases such as MS.
Asunto(s)
Encefalomielitis Autoinmune Experimental/tratamiento farmacológico , Ginsenósidos/uso terapéutico , Análisis de Varianza , Animales , Barrera Hematoencefálica/efectos de los fármacos , Barrera Hematoencefálica/fisiopatología , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Permeabilidad Capilar/efectos de los fármacos , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Encefalomielitis Autoinmune Experimental/inducido químicamente , Encefalomielitis Autoinmune Experimental/patología , Ensayo de Inmunoadsorción Enzimática , Femenino , Ginsenósidos/química , Interferón gamma/metabolismo , Interleucina-4/metabolismo , Linfocitos/efectos de los fármacos , Linfocitos/metabolismo , Ratones , Ratones Endogámicos C57BL , Glicoproteína Mielina-Oligodendrócito/toxicidad , Fragmentos de Péptidos/toxicidad , Médula Espinal/efectos de los fármacos , Médula Espinal/metabolismo , Médula Espinal/patologíaRESUMEN
In the work presented here, a novel approach to comprehensive two-dimensional liquid chromatography is evaluated. Reversed-phase liquid chromatography was employed for the first-dimension separation and polyamine chromatography was chosen for the second-dimension separation mode. The two dimensions are highly orthogonal and the separation efficacy of the developed octadecylsilica × polyamine was tested by separating an extract from Anemarrhena asphodeloides. The steroid glycosides identified by comprehensive two-dimensional liquid chromatography in this experiment were compared to those obtained for monodimensional liquid chromatography. The comprehensive two-dimensional liquid chromatography system, thanks to the complementary separation selectivity and enhanced peak capacity provided by the two columns, allowed to distribute five compounds of low amounts otherwise unachievable by monodimensional liquid chromatography. In addition, four steroid isomers with similar fragmentation characteristics in MS/MS spectra, were newly separated based on their different chemical structures.
Asunto(s)
Anemarrhena/química , Cromatografía Líquida de Alta Presión/métodos , Glicósidos/química , Espectrometría de Masas/métodos , Fitosteroles/química , Extractos Vegetales/química , Cromatografía de Fase Inversa/métodos , IsomerismoRESUMEN
Shuang-Dan (SD) is a traditional Chinese prescription containing Cortex Moutan and Radix Salviae miltiorrhizae and commonly used for treating cardiovascular disease. Paeoniflorin is a main effective ingredient of Cortex Moutan and the pharmacokinetic differences of paeoniflorin following oral administration of pure paeoniflorin, Cortex Moutan extract and SD decoction to rats were studied with approximately the same dose of 30mg/kg paeoniflorin. At different time points (5, 10, 15, 30, 45, 60, 90, 120, 150, 210, 270, 360, 450min), plasma concentration of paeoniflorin was determined using a simple and rapid HPLC-MS method. Unpaired student's t-test was used for the statistical comparison. A bimodal phenomenon was observed in the plasma profile after oral administration of Cortex Moutan extract. Statistically significant increase (P<0.05) in pharmacokinetic parameters of paeoniflorin including AUC(0-t), AUC(0-infinity) and MRT were obtained after oral administration of Cortex Moutan or SD decoction comparing with pure paeoniflorin. The investigation showed that among all calculated parameters, AUC(0-t), AUC(0-infinity), MRT, k(e) and T(1/2), there were no significant differences between the two decoctions. The results indicated that the reason which delay the elimination of paeoniflorin and enhance its bioavailability might be some ingredients in Cortex Moutan extract.