Binyamin Orli, Larush Liraz, Frid Kati, Keller Guy, Friedman-Levi Yael, Ovadia Haim, Abramsky Oded, Magdassi Shlomo, Gabizon Ruth
Department of Neurology, The Agnes Ginges Center of Human Neurogenetics, Hadassah University Hospital, Jerusalem, Israel.
Casali Institute of Chemistry, The Hebrew University of Jerusalem, Jerusalem, Israel.
Int J Nanomedicine. 2015 Nov 20;10:7165-74. doi: 10.2147/IJN.S92704. eCollection 2015.
Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system and is associated with demyelination, neurodegeneration, and sensitivity to oxidative stress. In this work, we administered a nanodroplet formulation of pomegranate seed oil (PSO), denominated Nano-PSO, to mice induced for experimental autoimmune encephalomyelitis (EAE), an established model of MS. PSO comprises high levels of punicic acid, a unique polyunsaturated fatty acid considered as one of the strongest natural antioxidants. We show here that while EAE-induced mice treated with natural PSO presented some reduction in disease burden, this beneficial effect increased significantly when EAE mice were treated with Nano-PSO of specific size nanodroplets at much lower concentrations of the oil. Pathological examinations revealed that Nano-PSO administration dramatically reduced demyelination and oxidation of lipids in the brains of the affected animals, which are hallmarks of this severe neurological disease. We propose that novel formulations of natural antioxidants such as Nano-PSO may be considered for the treatment of patients suffering from demyelinating diseases. On the mechanistic side, our results demonstrate that lipid oxidation may be a seminal feature in both demyelination and neurodegeneration.
多发性硬化症(MS)是一种中枢神经系统的慢性炎症性疾病,与脱髓鞘、神经退行性变以及对氧化应激的敏感性相关。在本研究中,我们将一种命名为纳米石榴籽油(Nano-PSO)的石榴籽油纳米液体制剂给予诱导实验性自身免疫性脑脊髓炎(EAE)的小鼠,EAE是一种公认的MS模型。石榴籽油含有高水平的石榴酸,这是一种独特的多不饱和脂肪酸,被认为是最强的天然抗氧化剂之一。我们在此表明,虽然用天然石榴籽油治疗的EAE诱导小鼠的疾病负担有所减轻,但当用特定尺寸纳米液滴的纳米石榴籽油以低得多的油浓度治疗EAE小鼠时,这种有益效果显著增强。病理检查显示,给予纳米石榴籽油可显著减少患病动物大脑中的脱髓鞘和脂质氧化,而这是这种严重神经疾病的特征。我们建议,像纳米石榴籽油这样的天然抗氧化剂新制剂可考虑用于治疗患有脱髓鞘疾病的患者。在机制方面,我们的结果表明脂质氧化可能是脱髓鞘和神经退行性变的一个关键特征。