Biomol Ther  
Neuroprotective Effects of 6-Shogaol and Its Metabolite, 6-Paradol, in a Mouse Model of Multiple Sclerosis
Arjun Sapkota1, Se Jin Park2,* and Ji Woong Choi1,*
1College of Pharmacy and Gachon Institute of Pharmaceutical Sciences, Gachon University, Incheon 21936,
2School of Natural Resources and Environmental Sciences, Kangwon National University, Chuncheon 24341, Republic of Korea
E-mail: pharmchoi@gachon.ac.kr (Choi JW), sejinpark@kangwon.ac.kr (Park SJ)
Tel: +82-32-820-4955 (Choi JW), +82-33-250-6441 (Park SJ)
Fax: +82-32-820-4829 (Choi JW), +82-33-259-5563 (Park SJ)
Received: May 17, 2018; Revised: May 23, 2018; Accepted: May 29, 2018; Published online: July 13, 2018.
© The Korean Society of Applied Pharmacology. All rights reserved.

Abstract
Multiple sclerosis (MS) is an autoimmune disease characterized by progressive neuronal loss, neuroinflammation, axonal degeneration, and demyelination. Previous studies have reported that 6-shogaol, a major constituent of ginger (Zingiber officinale rhizome), and its biological metabolite, 6-paradol, have anti-inflammatory and anti-oxidative properties in the central nervous system (CNS). In the present study, we investigated whether 6-shogaol and 6-paradol could ameliorate against experimental autoimmune encephalomyelitis (EAE), a mouse model of MS elicited by myelin oligodendrocyte glycoprotein (MOG35-55) peptide immunization with injection of pertussis toxin. Once-daily administration of 6-shogaol and 6-paradol (5 mg/kg/day, p.o.) to symptomatic EAE mice significantly alleviated clinical signs of the disease along with remyelination and reduced cell accumulation in the white matter of spinal cord. Administration of 6-shogaol and 6-paradol into EAE mice markedly reduced astrogliosis and microglial activation as key features of immune responses inside the CNS. Furthermore, administration of these two molecules significantly suppressed expression level of tumor necrosis factor-α, a major proinflammatory cytokine, in EAE spinal cord. Collectively, these results demonstrate therapeutic efficacy of 6-shogaol or 6-paradol for EAE by reducing neuroinflammatory responses, further indicating the therapeutic potential of these two active ingredients of ginger for MS.
Keywords: Multiple sclerosis, Experimental autoimmune encephalomyelitis, 6-Shogaol, 6-Paradol, Astrogliosis, Microglia


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