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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Abstract

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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Author and article information

Contributors

Ik-Hyun Cho

Journal

Journal ID (nlm-ta): J Ginseng Res

Journal ID (iso-abbrev): J Ginseng Res

Title: Journal of Ginseng Research

Publisher: Elsevier

ISSN (Print): 1226-8453

ISSN (Electronic): 2093-4947

Publication date PMC-release: 11 September 2020

Publication date (Print): May 2021

Publication date (Electronic): 11 September 2020

Volume: 45

Issue: 3

Pages: 433-441

Affiliations

[1 ]Department of Convergence Medical Science, College of Korean Medicine, Kyung Hee University, Seoul, Republic of Korea

[2 ]Department of Science in Korean Medicine and Brain Korea 21 Plus Program, Graduate School, Kyung Hee University, Seoul, Republic of Korea

[3 ]Laboratory of Analysis R&D Headquarters, Korea Ginseng Corporation, Daejeon, Republic of Korea

[4 ]Department of Anatomy, College of Veterinary Medicine, Konkuk University, Seoul, Republic of Korea

[5 ]Ginsentology Research Laboratory and Department of Physiology, College of Veterinary Medicine and Bio/Molecular Informatics Center, Konkuk University, Seoul, Republic of Korea

[6 ]Institute of Korean Medicine, College of Korean Medicine, Kyung Hee University, Seoul, Republic of Korea

Author notes

[∗ ]Corresponding author. Department of Convergence Medical Science, Brain Korea 21 Plus Program, and Institute of Korean Medicine, College of Korean Medicine, Kyung Hee University, 26 Kyungheedae-ro, Dongdaemun-gu, Seoul, 02447, Republic of Korea. ihcho@ 123456khu.ac.kr

[☆]

These authors contributed equally to this work.

Article

Publisher Item ID: S1226-8453(20)30136-6

DOI: 10.1016/j.jgr.2020.09.001

PMC ID: 8134843

PubMed ID: 34025136

SO-VID: bad03201-1ad2-4754-b756-86c5410c4c6d

License:

This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

History

Date received : 9 July 2019

Date revision received : 29 August 2020

Date accepted : 8 September 2020

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