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1.
J Ethnopharmacol ; 217: 36-48, 2018 May 10.
Artículo en Inglés | MEDLINE | ID: mdl-29428242

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: Bu Shen Yi Sui capsule (BSYSC), based on traditional Chinese formula Liu Wei Di Huang pill, is effective for the treatment of multiple sclerosis (MS) in clinical experience and trials. Our previous studies confirmed that BSYSC had the neuroprotective effect in MS and its animal model, experimental autoimmune encephalomyelitis (EAE); however, its mechanism of action was not clear. Thus, the effect of BSYSC on remyelination and the underlying mechanisms were investigated in the EAE mice. MATERIALS AND METHODS: The EAE model was established by injecting subcutaneously myelin oligodendrocyte protein (MOG) 35-55 in mice. Mice were treated with BSYSC (3.02 g/kg) or vehicle daily by oral gavage for 40 days. The body weight and clinical score of mice were evaluated. Brain was observed by magnetic resonance imaging. The inflammation infiltrate of brain and spinal cord was determined by hematoxylin-eosin staining, while the structure of myelin sheath was visualized by transmission electron microscopy on days 23 and 40 post immunization (dpi), respectively. The protein and mRNA levels of platelets-derived growth factor receptor (PDGFR) α and 2', 3'-cyclic nucleotide-3'-phosphodiesterase (CNPase) were measured by immunohistochemistry, western blot and quantitative real-time polymerase chain reaction. The protein expressions of semaphorins (Sema) 3A, Neuropilin (NRP) - 1, leukemia inhibitory factor (LIF), LIF receptor (LIFR) and Nkx6.2 were further investigated by western blot. RESULTS: BSYSC treatment improved the body weight and clinical score of EAE mice, alleviated inflammatory infiltration and nerve fiber injuries. It also protected the ultrastructural integrity of myelin sheath. BSYSC significantly increased expressions of PDGFRα and CNPase in mice with EAE on 40 dpi. Furthermore, BSYSC treatment increased the expressions of LIF, LIFR and Nkx6.2 and reduced Sema3A and NRP-1 in EAE mice on 40 dpi. CONCLUSIONS: The data demonstrated that BSYSC exhibited the neuroprotective effect against EAE by promoting oligodendrocyte progenitor cells (OPCs) proliferation and differentiation, thus facilitating remyelination. Sema3A/NRP-1, LIF/LIFR and Nkx6.2 are likely contributed to the effects of BSYSC on OPCs.


Asunto(s)
Encéfalo/efectos de los fármacos , Medicamentos Herbarios Chinos/farmacología , Encefalomielitis Autoinmune Experimental/tratamiento farmacológico , Proteínas de Homeodominio/metabolismo , Subunidad alfa del Receptor del Factor Inhibidor de Leucemia/metabolismo , Factor Inhibidor de Leucemia/metabolismo , Vaina de Mielina/efectos de los fármacos , Neuropilina-1/metabolismo , Fármacos Neuroprotectores/farmacología , Semaforina-3A/metabolismo , Médula Espinal/efectos de los fármacos , Factores de Transcripción/metabolismo , 2',3'-Nucleótido Cíclico Fosfodiesterasas/metabolismo , Administración Oral , Animales , Encéfalo/metabolismo , Encéfalo/ultraestructura , Cápsulas , Diferenciación Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Medicamentos Herbarios Chinos/administración & dosificación , Encefalomielitis Autoinmune Experimental/inducido químicamente , Encefalomielitis Autoinmune Experimental/metabolismo , Encefalomielitis Autoinmune Experimental/patología , Femenino , Ratones Endogámicos C57BL , Vaina de Mielina/metabolismo , Vaina de Mielina/ultraestructura , Glicoproteína Mielina-Oligodendrócito , Fármacos Neuroprotectores/administración & dosificación , Células Precursoras de Oligodendrocitos/efectos de los fármacos , Células Precursoras de Oligodendrocitos/metabolismo , Células Precursoras de Oligodendrocitos/patología , Fragmentos de Péptidos , Receptor alfa de Factor de Crecimiento Derivado de Plaquetas/metabolismo , Transducción de Señal/efectos de los fármacos , Médula Espinal/metabolismo , Médula Espinal/ultraestructura , Factores de Tiempo
2.
J Pharmacol Sci ; 131(4): 259-66, 2016 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-27562703

RESUMEN

The leaves and stems of Perilla frutescens var. acuta Kudo (PF) have been used to prevent threatened abortion in traditional medicine in the East Asian countries. Because reduced receptivity of endometrium is a cause of abortion, we analyzed the action of PF on the endometrial receptivity. PF increased the level of leukemia inhibitory factor (LIF), a major cytokine regulating endometrial receptivity, and LIF receptor in human endometrial Ishikawa cells. The PF-induced LIF expression was mediated by c-jun N-terminal kinase (JNK) and p38 pathways. Adhesion between Ishikawa cells and trophoblastic JAr cells stimulated by PF treatment was abolished by knock down of LIF expression or antagonism of LIFR. In addition, the expressions of integrin ß3 and ß5 were increased by PF treatment in Ishikawa cells. The PF-induced expression of integrin ß3 and ß5 was reduced with an LIFR antagonist. Neutralization of both integrins successfully blocked PF-stimulated adhesion of JAr cells and Ishikawa cells. These results suggest that PF enhanced the adhesion between Ishikawa cells and JAr cells by increasing the expression of integrin ß3 and ß5 via an LIF-dependent pathway. Given the importance of endometrial receptivity in successful pregnancy, PF can be a novel and effective candidate for improving pregnancy rate.


Asunto(s)
Endometrio/efectos de los fármacos , Cadenas beta de Integrinas/biosíntesis , Factor Inhibidor de Leucemia/metabolismo , Perilla frutescens/química , Extractos Vegetales/farmacología , Antracenos/farmacología , Butadienos/farmacología , Adhesión Celular/efectos de los fármacos , Células Cultivadas , Femenino , Humanos , Imidazoles/farmacología , Cadenas beta de Integrinas/metabolismo , Subunidad alfa del Receptor del Factor Inhibidor de Leucemia/antagonistas & inhibidores , Subunidad alfa del Receptor del Factor Inhibidor de Leucemia/metabolismo , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Nitrilos/farmacología , Hojas de la Planta/química , Raíces de Plantas/química , Piridinas/farmacología , ARN Interferente Pequeño/farmacología , Transducción de Señal/efectos de los fármacos
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