RESUMO
Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system, in which the release of reactive oxygen species by infiltrating immune cells contributes to demyelination. American ginseng ( Panax quinquefolius ) is a natural health product with numerous beneficial properties, including anti-inflammatory and anti-oxidant effects. The purpose of this study was to determine whether ginseng could influence the course of the disease experimental autoimmune encephalomyelitis (EAE), an animal model of MS. C57BL/6J mice were immunized with MOG((35-55)) peptide to induce EAE. After clinical disease appeared, mice received either oral doses of an aqueous extract of ginseng (150 mg/kg body mass), or the vehicle. Clinical symptoms were recorded, and spinal cord tissue samples were analyzed for pathological signs of disease. The aqueous extract of ginseng significantly decreased (i) clinical signs of EAE, (ii) levels of circulating TNF-α, and (iii) central nervous system immunoreactive iNOS and demyelination scores, without a change in other neuropathological measures. This study shows that an aqueous extract of ginseng may be able to attenuate certain signs of EAE, suggesting that it may be a useful adjuvant therapy for MS.
Assuntos
Encefalomielite Autoimune Experimental/tratamento farmacológico , Panax/química , Extratos Vegetais/farmacologia , Animais , Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Modelos Animais de Doenças , Encefalomielite Autoimune Experimental/imunologia , Encefalomielite Autoimune Experimental/patologia , Feminino , Camundongos , Camundongos Endogâmicos C57BL , Esclerose Múltipla/tratamento farmacológico , Esclerose Múltipla/imunologia , Esclerose Múltipla/patologia , Glicoproteína Mielina-Oligodendrócito , Óxido Nítrico Sintase Tipo II/imunologia , Óxido Nítrico Sintase Tipo II/metabolismo , Medula Espinal/efeitos dos fármacos , Medula Espinal/imunologia , Medula Espinal/metabolismo , Medula Espinal/patologia , Fator de Necrose Tumoral alfa/imunologia , Fator de Necrose Tumoral alfa/metabolismoRESUMO
What is the origin of the complex vascular changes that exist in the CNS lesions of Multiple Sclerosis (MS)? From the beginning of the study of the pathological changes in MS in the 19th century, lesions were seen to be associated with veins. On a microscopic level, there have been numerous pathological changes to these vessels including altered structure and permeability, fibrinolysis, iron-related alterations and collagen deposition. Vascular changes in inflammatory conditions outside the CNS are well documented and we hypothesize that angiogenesis (the generation of new blood vessels from existing) is an integral process of lesion development and spread in MS. We demonstrated similar vascular abnormalities in MS and in the animal model, EAE. We measured the increase in angiogenesis-related genes in EAE and review herein the effectiveness of chemical inhibitors of angiogenesis (SU5416, thalidomide and several derivatives). We postulate that interference with angiogenesis provides a suitable non-immunological target for investigation in MS.
Assuntos
Inibidores da Angiogênese/administração & dosagem , Sistemas de Liberação de Medicamentos/métodos , Encefalomielite Autoimune Experimental/tratamento farmacológico , Esclerose Múltipla/tratamento farmacológico , Inibidores da Angiogênese/química , Animais , Sistemas de Liberação de Medicamentos/tendências , Encefalomielite Autoimune Experimental/fisiopatologia , Humanos , Indóis/administração & dosagem , Indóis/química , Esclerose Múltipla/fisiopatologia , Pirróis/administração & dosagem , Pirróis/química , Talidomida/administração & dosagem , Talidomida/químicaRESUMO
The precise mechanism-of-action of thalidomide remains uncertain and might differ between diseases and under different clinical condition. With implications in the treatment of a variety of inflammatory and autoimmune diseases, as well as for use as an anticancer agent, alone or in combination with established therapeutics, it is clear that thalidomide and its derivatives deserve further scrutiny. In particular, thalidomide was shown to be effective in a mouse model of multiple sclerosis (MS), an autoimmune inflammatory disorder, called experimental autoimmune encephalomyelitis (EAE). Herein, we describe the synthesis and preliminary biological evaluation of new macromolecular prodrugs of thalidomide bearing an aminoalkyl group on the phthalimide ring. The effectiveness of these compounds to limit EAE was investigated, and it was shown that, at 100â mg kg⻹ thalidomide-equivalent dose, they abrogated the clinical and pathological features of EAE.