Université Clermont Auvergne, INSERM 1107, Neuro-Dol, Clermont-Ferrand, France.
Université Clermont Auvergne, Faculté de Pharmacie, Clermont-Ferrand, France.
Front Immunol. 2022 Aug 17;13:960355. doi: 10.3389/fimmu.2022.960355. eCollection 2022.
Multiple sclerosis (MS), a multifactorial autoimmune disease of the central nervous system (CNS), is characterized by demyelination and chronic inflammation, as well as axonal and neuronal loss. There is no cure for MS, and despite a significant improvement in the therapeutic management of patients during the last 20 years, some symptoms are still resistant to treatment, and the evolution of the disease to progressive form seems still ineluctable. The etiology of MS is complex and still not fully understood. However, inflammation is a major driver of physiopathology and oxidative stress contributes to CNS lesions and promotes existing inflammatory response. Plant polyphenols are endowed with many therapeutic benefits through alleviating oxidative stress and inflammation, thus providing neuroprotection in MS. We presently evaluated the curative effect of grape seed extract (GSE) in an experimental autoimmune encephalomyelitis (EAE) mouse model of MS.
Six-week-old C57Bl/6J females were subjected to the EAE paradigm (using myelin oligodendrocyte glycoprotein peptide fragment (35-55), complete Freund's adjuvant, and pertussis toxin) and then chronically treated with GSE from day 10 to day 30 post-induction. Clinical score and body weight were monitored daily, while evaluation of sensitive, motor, cognitive, and anxiety-related behaviors was performed weekly. Then, the GSE effect was evaluated on whole brain and spinal cord samples through the evaluation of oxidative stress damage, antioxidant capacities, myelin alteration, astroglial and microglial proliferation, and sirtuin expression.
Grape seed extract curative chronic treatment corrected the clinical course of EAE, as well as the mechanical hypersensitivity, and avoided the development of EAE mouse thermal cold allodynia. The neuropathological evaluation showed that GSE reduced oxidative stress in the brain and spinal cord by decreasing the lipid and protein oxidation through correction of the three main antioxidant enzyme activities, namely, superoxide dismutase, catalase, and glutathione peroxidase, as well as restoring normal myelin protein expression and correcting microglial and astroglial protein overexpression and sirtuin downregulation.
These data strongly support GSE as an effective therapeutic approach in MS treatment.
多发性硬化症（MS）是一种中枢神经系统（CNS）的多因素自身免疫性疾病，其特征为脱髓鞘和慢性炎症以及轴突和神经元丢失。目前尚无治愈 MS 的方法，尽管在过去 20 年中患者的治疗管理取得了重大进展，但某些症状仍难以治疗，疾病向进行性形式的发展似乎仍然不可避免。MS 的病因复杂，尚未完全阐明。然而，炎症是病理生理学的主要驱动因素，氧化应激会导致 CNS 损伤并促进现有炎症反应。植物多酚通过缓解氧化应激和炎症提供 MS 的神经保护作用，从而具有许多治疗益处。我们目前评估了葡萄籽提取物（GSE）在 MS 的实验性自身免疫性脑脊髓炎（EAE）小鼠模型中的疗效。
将 6 周龄的 C57Bl/6J 雌性小鼠进行 EAE 模型（使用髓鞘少突胶质细胞糖蛋白肽片段（35-55）、完全弗氏佐剂和百日咳毒素），然后从诱导后第 10 天至第 30 天慢性给予 GSE。每天监测临床评分和体重，每周评估敏感、运动、认知和焦虑相关行为。然后，通过评估氧化应激损伤、抗氧化能力、髓鞘改变、星形胶质细胞和小胶质细胞增殖以及沉默调节蛋白表达，评估 GSE 对全脑和脊髓样本的影响。
葡萄籽提取物的慢性治疗纠正了 EAE 的临床过程，以及机械性超敏反应，并避免了 EAE 小鼠热冷感觉异常的发展。神经病理学评估显示，GSE 通过纠正三种主要抗氧化酶活性（超氧化物歧化酶、过氧化氢酶和谷胱甘肽过氧化物酶）来降低脑和脊髓中的氧化应激，减少脂质和蛋白质氧化，同时恢复正常的髓鞘蛋白表达，并纠正小胶质细胞和星形胶质细胞蛋白过度表达和沉默调节蛋白下调。
这些数据强烈支持 GSE 作为 MS 治疗的有效治疗方法。
