Multiple sclerosis (MS) is presented as the most common autoimmune and demyelinating neurological disorder with incapacitating complications and with no definite therapy. Most treatments for MS mainly focus on attenuation of its severity and recurrence. To model MS reliably to study pathogenesis and efficacy of possible chemicals, experimental autoimmune encephalomyelitis (EAE) condition is induced in rodents. Ellagic acid is a neuroprotective polyphenol that can protect against demyelination. This study was planned and conducted to assess its possible beneficial effect in MOG-induced EAE model of MS with emphasis on uncovering its modes of action. Ellagic acid was given p.o. (at doses of 10 or 50 mg/kg/day) after development of clinical signs of MS to C57BL/6 mice immunized with MOG35-55. Results showed that ellagic acid can ameliorate severity of the disease and partially restore tissue level of TNFα, IL-6, IL-17A and IL-10. Besides, ellagic acid lowered tissue levels of NLRP3 and caspase 1 in addition to its mitigation of neuroinflammation, demyelination and axonal damage in spinal cord specimens of EAE group. As well, ellagic acid treatment prevented reduction of MBP and decreased GFAP and Iba1 immunoreactivity. Taken together, ellagic acid can decrease severity of EAE via amelioration of astrogliosis, astrocyte activation, demyelination, neuroinflammation and axonal damage that is partly related to its effects on NLRP3 inflammasome and pyroptotic pathway.

中文翻译：

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鞣花酸改善实验性自身免疫性脑脊髓炎的神经炎症和脱髓鞘：NLRP3 和细胞焦亡的参与

多发性硬化症 (MS) 是最常见的自身免疫性和脱髓鞘性神经系统疾病，具有致残并发症且没有明确的治疗方法。MS 的大多数治疗主要集中在减轻其严重程度和复发。为了可靠地模拟 MS 以研究可能化学物质的发病机制和功效，在啮齿动物中诱导了实验性自身免疫性脑脊髓炎 (EAE) 病症。鞣花酸是一种神经保护多酚，可以防止脱髓鞘。本研究旨在评估其在 MOG 诱导的 MS EAE 模型中可能的有益作用，重点是揭示其作用模式。在对用 MOG35-55 免疫的 C57BL/6 小鼠出现 MS 的临床症状后，口服鞣花酸（剂量为 10 或 50 mg/kg/天）。结果表明，鞣花酸可以减轻疾病的严重程度，部分恢复组织中TNFα、IL-6、IL-17A和IL-10的水平。此外，鞣花酸还降低了 NLRP3 和 caspase 1 的组织水平，此外还可以减轻 EAE 组脊髓标本的神经炎症、脱髓鞘和轴突损伤。同样，鞣花酸处理可防止 MBP 降低并降低 GFAP 和 Iba1 免疫反应性。总之，鞣花酸可以通过改善星形胶质细胞增生、星形胶质细胞活化、脱髓鞘、神经炎症和轴突损伤来降低 EAE 的严重程度，这部分与其对 NLRP3 炎症小体和细胞焦亡通路的影响有关。除了减轻 EAE 组脊髓标本的神经炎症、脱髓鞘和轴突损伤外，鞣花酸还降低了 NLRP3 和半胱天冬酶 1 的组织水平。同样，鞣花酸处理可防止 MBP 降低并降低 GFAP 和 Iba1 免疫反应性。总之，鞣花酸可以通过改善星形胶质细胞增生、星形胶质细胞活化、脱髓鞘、神经炎症和轴突损伤来降低 EAE 的严重程度，这部分与其对 NLRP3 炎症小体和细胞焦亡通路的影响有关。除了减轻 EAE 组脊髓标本的神经炎症、脱髓鞘和轴突损伤外，鞣花酸还降低了 NLRP3 和半胱天冬酶 1 的组织水平。同样，鞣花酸处理阻止了 MBP 的降低并降低了 GFAP 和 Iba1 的免疫反应性。总之，鞣花酸可以通过改善星形胶质细胞增生、星形胶质细胞活化、脱髓鞘、神经炎症和轴突损伤来降低 EAE 的严重程度，这部分与其对 NLRP3 炎症小体和细胞焦亡通路的影响有关。