Lee Min Jung, Choi Jong Hee, Oh Jinhee, Lee Young Hyun, In Jun-Gyo, Chang Byung-Joon, Nah Seung-Yeol, Cho Ik-Hyun
Department of Convergence Medical Science, College of Korean Medicine, Kyung Hee University, Seoul, Republic of Korea.
Department of Science in Korean Medicine and Brain Korea 21 Plus Program, Graduate School, Kyung Hee University, Seoul, Republic of Korea.
J Ginseng Res. 2021 May;45(3):433-441. doi: 10.1016/j.jgr.2020.09.001. Epub 2020 Sep 11.
Multiple sclerosis (MS) and its animal model, the experimental autoimmune encephalomyelitis (EAE), are primarily characterized as dysfunction of the blood-brain barrier (BBB). Ginsenoside-Rg3-enriched Korean Red Ginseng extract (Rg3-KRGE) is known to exert neuroprotective, anti-inflammatory, and anti-oxidative effects on neurological disorders. However, effects of Rg3-KRGE in EAE remain unclear.
Here, we investigated whether Rg3-KRGE may improve the symptoms and pathological features of myelin oligodendroglial glycoprotein (MOG) peptide - induced chronic EAE mice through improving the integrity of the BBB.
Rg3-KRGE decreased EAE score and spinal demyelination. Rg3-KRGE inhibited Evan's blue dye leakage in spinal cord, suppressed increases of adhesion molecule platelet endothelial cell adhesion molecule-1, extracellular matrix proteins fibronection, and matrix metallopeptidase-9, and prevented decreases of tight junction proteins zonula occludens-1, claudin-3, and claudin-5 in spinal cord following EAE induction. Rg3-KRGE repressed increases of proinflammatory transcripts cyclooxygenase-2, inducible nitric oxide synthase, interleukin (IL)-1 beta, IL-6, and tumor necrosis factor-alpha, but enhanced expression levels of anti-inflammatory transcripts arginase-1 and IL-10 in the spinal cord following EAE induction. Rg3-KRGE inhibited the expression of oxidative stress markers (MitoSOX and 4-hydroxynonenal), the enhancement of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 2 (NOX2) and NOX4, and NADPH activity in the spinal cord of chronic EAE mice. Furthermore, apocynin, a NOX inhibitor, mimicked beneficial effects of Rg3-KRGE in chronic EAE mice.
Our findings suggest that Rg3-KRGE might alleviate behavioral symptoms and pathological features of MS by improving BBB integrity through modulation of NOX2/4 expression.
多发性硬化症（MS）及其动物模型实验性自身免疫性脑脊髓炎（EAE）的主要特征是血脑屏障（BBB）功能障碍。富含人参皂苷Rg3的高丽红参提取物（Rg3-KRGE）已知对神经疾病具有神经保护、抗炎和抗氧化作用。然而，Rg3-KRGE在EAE中的作用仍不清楚。
在此，我们研究了Rg3-KRGE是否可通过改善BBB的完整性来改善髓鞘少突胶质细胞糖蛋白（MOG）肽诱导的慢性EAE小鼠的症状和病理特征。
Rg3-KRGE降低了EAE评分和脊髓脱髓鞘。Rg3-KRGE抑制了伊文思蓝染料在脊髓中的渗漏，抑制了黏附分子血小板内皮细胞黏附分子-1、细胞外基质蛋白纤连蛋白和基质金属肽酶-9的增加，并防止了EAE诱导后脊髓中紧密连接蛋白闭合蛋白-1、闭合蛋白-3和闭合蛋白-5的减少。Rg3-KRGE抑制了促炎转录本环氧合酶-2、诱导型一氧化氮合酶、白细胞介素（IL）-1β、IL-6和肿瘤坏死因子-α的增加，但增强了EAE诱导后脊髓中抗炎转录本精氨酸酶-1和IL-10的表达水平。Rg3-KRGE抑制了慢性EAE小鼠脊髓中氧化应激标志物（MitoSOX和4-羟基壬烯醛）的表达、烟酰胺腺嘌呤二核苷酸磷酸（NADPH）氧化酶2（NOX2）和NOX4的增强以及NADPH活性。此外，NOX抑制剂阿朴吗啡模拟了Rg3-KRGE对慢性EAE小鼠的有益作用。
我们的研究结果表明，Rg3-KRGE可能通过调节NOX2/4表达改善BBB完整性，从而减轻MS的行为症状和病理特征。
