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KMID : 0352720210450030433
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Journal of Ginseng Research
2021 Volume.45 No. 3 p.433 ~ p.441
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Rg3-enriched Korean Red Ginseng extract inhibits blood-brain barrier disruption in an animal model of multiple sclerosis by modulating expression of NADPH oxidase 2 and 4
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Lee Min-Jung
Choi Jong-Hee
Oh Jin-Hee
Lee Young-Hyun
In Jun-Gyo
Chang Byung-joon
Nah Seung-Yeol
Cho Ik-Hyun
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Abstract
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Background: 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.
Methods: Here, we investigated whether Rg3-KRGE may improve the symptoms and pathological features of myelin oligodendroglial glycoprotein (MOG)35-55 peptide ? induced chronic EAE mice through improving the integrity of the BBB.
Results: 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.
Conclusion: 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.
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KEYWORD
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Rg3-enriched Korean Red Ginseng extract, Blood-brain barrier, Chronic experimental autoimmune encephalomyelitis, NADPH oxidase
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