title: 6-Shogaol, a ginger product, modulates neuroinflammation: a new approach to neuroprotection.
abstract: Inflammatory processes in the central nervous system play an important role in a number of neurodegenerative diseases mediated by microglial activation, which results in neuronal cell death. Microglia act in immune surveillance and host defense while resting. When activated, they can be deleterious to neurons, even resulting in neurodegeneration. Therefore, the inhibition of microglial activation is considered a useful strategy in searching for neuroprotective agents. In this study, we investigated the effects of 6-shogaol, a pungent agent from Zingiber officinale Roscoe, on microglia activation in BV-2 and primary microglial cell cultures. 6-Shogaol significantly inhibited the release of nitric oxide (NO) and the expression of inducible nitric oxide synthase (iNOS) induced by lipopolysaccharide (LPS). The effect was better than that of 6-gingerol, wogonin, or N-monomethyl-l-arginine, agents previously reported to inhibit nitric oxide. 6-Shogaol exerted its anti-inflammatory effects by inhibiting the production of prostaglandin E(2) (PGE(2)) and proinflammatory cytokines, such as interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α), and by downregulating cyclooxygenase-2 (COX-2), p38 mitogen-activated protein kinase (MAPK), and nuclear factor kappa B (NF-κB) expression. In addition, 6-shogaol suppressed the microglial activation induced by LPS both in primary cortical neuron-glia culture and in an in vivo neuroinflammatory model. Moreover, 6-shogaol showed significant neuroprotective effects in vivo in transient global ischemia via the inhibition of microglia. These results suggest that 6-shogaol is an effective therapeutic agent for treating neurodegenerative diseases.
authors.affiliation: Graduate School of East-West Medical Science, Kyung Hee University Global Campus, #1732 Deogyeong-daero, Giheung-gu, Yongin, Gyeonggi-do 446-701, Republic of Korea.
authors.forename: Sang Keun
authors.initials: SK
authors.lastname: Ha
authors.forename: Eunjung
authors.initials: E
authors.lastname: Moon
authors.forename: Mi Sun
authors.initials: MS
authors.lastname: Ju
authors.forename: Dong Hyun
authors.initials: DH
authors.lastname: Kim
authors.forename: Jong Hoon
authors.initials: JH
authors.lastname: Ryu
authors.forename: Myung Sook
authors.initials: MS
authors.lastname: Oh
authors.forename: Sun Yeou
authors.initials: SY
authors.lastname: Kim
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000188:drug therapy / Q000378:metabolism; D002396:Catechols / Q000494:pharmacology* / Q000627:therapeutic use; D002478:Cells, Cultured; D018920:Coculture Techniques; D016207:Cytokines / Q000096:biosynthesis; D015232:Dinoprostone / Q000096:biosynthesis; D015536:Down-Regulation / Q000187:drug effects; D004660:Encephalitis / Q000188:drug therapy* / Q000378:metabolism; D018836:Inflammation Mediators / Q000494:pharmacology*; D008297:Male; D051379:Mice; D017628:Microglia / Q000187:drug effects* / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D009569:Nitric Oxide / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D010936:Plant Extracts / Q000494:pharmacology* / Q000627:therapeutic use; D017207:Rats, Sprague-Dawley
chemical_list: D002396:Catechols; D016207:Cytokines; D018836:Inflammation Mediators; D018696:Neuroprotective Agents; D010936:Plant Extracts; D009569:Nitric Oxide; C040115:shogaol; D052247:Nitric Oxide Synthase Type II; D015232:Dinoprostone