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

Min Jung Lee; Jong Hee Choi; Jinhee Oh; Young Hyun Lee; Jun-Gyo In; Byung-Joon Chang; Seung-Yeol Nah; Ik-Hyun Cho

doi:10.1016/j.jgr.2020.09.001

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

J Ginseng Res. 2021 May;45(3):433-441. doi: 10.1016/j.jgr.2020.09.001. Epub 2020 Sep 11.

Authors

Min Jung Lee¹, Jong Hee Choi¹, Jinhee Oh^{1

2}, Young Hyun Lee^{1

2}, Jun-Gyo In³, Byung-Joon Chang⁴, Seung-Yeol Nah⁵, Ik-Hyun Cho^{1

2

6}

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.

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.

Keywords: Blood-brain barrier; Chronic experimental autoimmune encephalomyelitis; NADPH oxidase; Rg3-enriched Korean Red Ginseng extract.