Fonseca-Kelly Zoe, Nassrallah Mayssa, Uribe Jorge, Khan Reas S, Dine Kimberly, Dutt Mahasweta, Shindler Kenneth S
Department of Ophthalmology, F.M. Kirby Center for Molecular Ophthalmology, University of Pennsylvania Scheie Eye Institute Philadelphia, PA, USA.
Front Neurol. 2012 May 24;3:84. doi: 10.3389/fneur.2012.00084. eCollection 2012.
Resveratrol is a naturally occurring polyphenol that activates SIRT1, an NAD-dependent deacetylase. SRT501, a pharmaceutical formulation of resveratrol with enhanced systemic absorption, prevents neuronal loss without suppressing inflammation in mice with relapsing experimental autoimmune encephalomyelitis (EAE), a model of multiple sclerosis (MS). In contrast, resveratrol has been reported to suppress inflammation in chronic EAE, although neuroprotective effects were not evaluated. The current studies examine potential neuroprotective and immunomodulatory effects of resveratrol in chronic EAE induced by immunization with myelin oligodendroglial glycoprotein peptide in C57/Bl6 mice. Effects of two distinct formulations of resveratrol administered daily orally were compared. Resveratrol delayed the onset of EAE compared to vehicle-treated EAE mice, but did not prevent or alter the phenotype of inflammation in spinal cords or optic nerves. Significant neuroprotective effects were observed, with higher numbers of retinal ganglion cells found in eyes of resveratrol-treated EAE mice with optic nerve inflammation. Results demonstrate that resveratrol prevents neuronal loss in this chronic demyelinating disease model, similar to its effects in relapsing EAE. Differences in immunosuppression compared with prior studies suggest that immunomodulatory effects may be limited and may depend on specific immunization parameters or timing of treatment. Importantly, neuroprotective effects can occur without immunosuppression, suggesting a potential additive benefit of resveratrol in combination with anti-inflammatory therapies for MS.
白藜芦醇是一种天然存在的多酚，可激活SIRT1（一种NAD依赖性脱乙酰酶）。SRT501是一种具有增强全身吸收性的白藜芦醇药物制剂，在复发型实验性自身免疫性脑脊髓炎（EAE，一种多发性硬化症（MS）模型）小鼠中可预防神经元丢失而不抑制炎症。相比之下，据报道白藜芦醇可抑制慢性EAE中的炎症，尽管未评估其神经保护作用。当前研究检测了白藜芦醇在C57/Bl6小鼠中由髓鞘少突胶质细胞糖蛋白肽免疫诱导的慢性EAE中的潜在神经保护和免疫调节作用。比较了每日口服两种不同制剂白藜芦醇的效果。与载体处理的EAE小鼠相比，白藜芦醇延迟了EAE的发病，但未预防或改变脊髓或视神经中的炎症表型。观察到显著的神经保护作用，在患有视神经炎症的白藜芦醇处理的EAE小鼠的眼睛中发现了更多的视网膜神经节细胞。结果表明，白藜芦醇在这种慢性脱髓鞘疾病模型中可预防神经元丢失，类似于其在复发型EAE中的作用。与先前研究相比，免疫抑制方面的差异表明免疫调节作用可能有限，且可能取决于特定的免疫参数或治疗时机。重要的是，神经保护作用可在无免疫抑制的情况下发生，这表明白藜芦醇与MS抗炎疗法联合使用可能具有潜在的附加益处。
