RESUMO
Multiple sclerosis (MS) is an inflammatory demyelinating disease of CNS. Astragalus polysaccharides (APS), the main active extract from astragalus membranaceus which is a kind of traditional Chinese medicinal herb, is associated with a variety of immunomodulatory activities. We have evaluated the therapeutic effects of APS in the animal model of MS, experimental autoimmune encephalomyelitis (EAE). It was found that APS could effectively alleviate EAE through inhibiting MOG35-55-specific T cell proliferation and reducing the expression of proinflammatory cytokines, which is mediated by up-regulating the expression of PD-1/PD-Ls signaling pathway. Our results demonstrated that EAE could be suppressed significantly by APS administration. It indicated that APS might be a potential of developing innovative drug for the therapy of MS.
Assuntos
Anti-Inflamatórios/uso terapêutico , Astragalus propinquus/química , Antígeno B7-H1/biossíntese , Encefalomielite Autoimune Experimental/tratamento farmacológico , Fitoterapia , Gomas Vegetais/uso terapêutico , Proteína 2 Ligante de Morte Celular Programada 1/biossíntese , Receptor de Morte Celular Programada 1/biossíntese , Transdução de Sinais/efeitos dos fármacos , Animais , Anti-Inflamatórios/farmacologia , Antígeno B7-H1/genética , Antígeno B7-H1/fisiologia , Citocinas/biossíntese , Citocinas/genética , Encefalomielite Autoimune Experimental/induzido quimicamente , Feminino , Inflamação , Camundongos , Camundongos Endogâmicos C57BL , Glicoproteína Mielina-Oligodendrócito/toxicidade , Fragmentos de Peptídeos/toxicidade , Gomas Vegetais/farmacologia , Proteína 2 Ligante de Morte Celular Programada 1/genética , Proteína 2 Ligante de Morte Celular Programada 1/fisiologia , Receptor de Morte Celular Programada 1/genética , Receptor de Morte Celular Programada 1/fisiologia , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , Medula Espinal/efeitos dos fármacos , Medula Espinal/imunologia , Medula Espinal/patologia , Subpopulações de Linfócitos T/efeitos dos fármacos , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/patologia , Regulação para Cima/efeitos dos fármacosRESUMO
Influenza viruses can bring about acute respiratory diseases and are a potential hazard to human health. Antiviral drugs are the main ways to control the influenza virus infection except the vaccine. In this study, the immune regulation activity of pterodontic acid isolated from Laggera pterodonta induced by influenza A virus in vitro was evaluated. In studies on anti-influenza activity, our results showed that it maybe target the influenza protein of polymerase basic 1 (PB1), polymerase basic 2 (PB2), polymerase acid (PA), nuclear protein (NP), non-structural protein (NS), and matrix protein (M) but not hemagglutinin (HA) and neuraminidase (NA). In studies on immune regulation, our results demonstrated that pterodontic acid can inhibit the Retinoic acid inducible gene-I (RIG-I) expression in mRNA and protein level at 100 µg/ml, then further to clarify its action on the signalling pathway, The results indicated that pterodontic acid can inhibit the Tumor Necrosis Factor-related Apoptosis-inducing Ligand/Fas Ligand (TRAIL/Fasl) expression in mRNA level at 100 µg/ml; the cleaved caspase 3/7, p-NF-KB, and p-ERK were all suppressed in protein level by pterodontic acid at 100 µg/ml. This confirmed its mechanism that restrained the nuclear export of viral RNPs. The interferon system was also affected, the STAT1, IFN-α, IFN-ß expression were also inhibited by pterodontic acid at 25-100 µg/ml and also, the important programmed death-ligand of PD-L1 and PD-L2 was inhibited at 50-100 µg/ml. The mechanisms of pterodontic acid against influenza virus infection may be a cascade inhibition and it has the anti-inflammatory activity, which has no side effect, and can be as a supplement drug in clinical influenza virus infection.