최종희 (경희대학교)

한빛사논문

조회413

최종희Jong Hee Choi

경희대학교

Phytomedicine, 17 October 2023, 122 S0944-7113(23)00425-7 | https://doi.org/10.1016/j.phymed.2023.155065 Ginsenoside-Re inhibits experimental autoimmune encephalomyelitis as a mouse model of multiple sclerosis by downregulating TLR4/MyD88/NF-κB signaling pathways

Jinhee Oh^a,b,†, Tae Woo Kwon ^a,b,†, Jong Hee Choi^a,†, Yunna Kim^c, Sang-Kwan Moon ^d, Seung-Yeol Nah ^e, Ik-Hyun Cho ^a,b,f

^aDepartment of Convergence Medical Science, College of Korean Medicine, Kyung Hee University, Seoul 02447, Republic of Korea

^bDepartment of Science in Korean Medicine, Graduate School, Kyung Hee University, Seoul 02447, Republic of Korea

^cDepartment of Neuropsychiatry in Korean Medicine, Kyung Hee University Medical Center, Kyung Hee University, Seoul 02447, Republic of Korea

^dDepartment of Cardiology and Neurology, College of Korean Medicine, Kyung Hee University, Seoul 02447, Republic of Korea

^eGinsentology Research Laboratory and Department of Physiology, College of Veterinary Medicine and Bio/Molecular Informatics Center, Konkuk University, Seoul 05029, Republic of Korea

^fInstitute of Convergence Korean Medicine, College of Korean Medicine, Kyung Hee University, Seoul 02447, Republic of Korea

†These authors contributed equally to this work.

Correspondence to: Ik-Hyun Cho, D.V.M. & Ph.D

Abstract

Background: Ginsenosides are main active compounds of Panax ginseng with pharmacological effects on immunological/neurological diseases. Recently, ginsenoside-Re (G-Re) has been shown to exert neuroprotective effects on neurodegenerative diseases such as Alzheimer's disease. However, whether G-Re has an effect on multiple sclerosis (MS), a representative autoimmune disease of the central nervous system (CNS), has not been revealed yet.

Purpose and methods: The purpose of this study was to investigate pharmacological effects of G-Re and related molecular mechanisms using a myelin oligodendrocyte glycoprotein peptide-immunized experimental autoimmune encephalomyelitis (EAE) animal model of MS and lipopolysaccharide (LPS)-stimulated bEND.3 cells as an in vitro model of the blood-brain barrier (BBB).

Results: G-Re attenuated motor impairment of EAE, demyelination, and inflammation in spinal cords of EAE mice. G-Re reduced infiltration/activation of microglia/macrophages and decreased mRNA expression levels of pro-inflammatory cytokines (IL-1β and IL-6), chemokines (MIP-1α, MCP-1, and RANTES), and enzymes (iNOS) in spinal cords of EAE mice. G-Re inhibited alterations of BBB constituents (such as astrocytes, cell adhesion molecule (platelet endothelial cell adhesion molecule-1), and tight junctional molecules (occludin and zonula occludens-1)) and toll like receptor 4 (TLR4)/MyD88/nuclear factor kappa-B (NF-κB) signaling pathways in spinal cords of EAE mice and LPS-stimulated bEND.3 cells. Interestingly, combination treatment with G-Re and TLR4 inhibitor (TAK242) significantly inhibited the upregulation of TLR4/MyD88/NF-κB pathway in LPS-stimulated bEND.3 cells. TLR4 inhibitor- and activator-treated EAE mice showed conflicting behavior patterns.

Conclusion: G-Re might alleviate motor impairment of EAE and its pathological/inflammatory events in the spinal cord by preventing BBB disruption via downregulation of TLR4/MyD88/NF-κB signaling pathways. These findings for the first time suggest that G-Re might be a potential therapeutic for MS through maintenance of BBB integrity.

논문정보

형식Research article
게재일2023년 10월 (BRIC 등록일 2023-10-23)
연구진국내 연구진
분야 의약학 > 신경의학

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