Prevention of Inflammation-Mediated Neurotoxicity by Rg3 and Its Role in Microglial Activation(Pharmacology)

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概要

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• Considering the importance of inflammation and apoptosis in neurodegenerative conditions, the potential suppressive effects of the Rg3, a by-product obtained during the steaming of red ginseng, may indicate that Rg3 could provide a beneficial therapeutic approach to treating or preventing neurodegenerative disease. We investigated the effect of Rg3 on Aβ42-mediated microglial activation and inflammation-mediated neurotoxicity in murine BV-2 microglial and Neuro-2a neuroblastoma cells, respectively. Rg3 effectively reduced inflammatory cytokine expression in Aβ42-treated BV-2, and inhibited the binding of NF-kB p65 to its DNA consensus sequences, and significantly reduced the expression of TNF-α in activated microglia. Pretreatment with Rg3 increased the survival rate of Neuro-2a exposed to TNF-α. These observations suggest that Rg3 reduced neurotoxicity by inhibiting chronic inflammation through the suppression of activated microglia. In addition, the expression of pro-inflammatory cytokines in BV-2 stimulated by Aβ42 was decreased but not eliminated by Rg3 when binding to the macrophage scavenger receptor type A (MSRA) was blocked with fucoidan. This implies that the inflammatory response may not be exclusively triggered via MSRA. More interestingly, iNOS was almost completely inhibited in the presence of Rg3 when MSRA binding was blocked with fucoidan. Moreover, Rg3 increased the expression of MSRA in BV-2 transfected with siRNA targeting MSRA mRNA, and this increased MSRA expression may play a role in the phagocytosis of Aβ42 peptides. Our results indicate that inhibition of the inflammatory repertoire of microglia, neuroprotection, and increased MSRA expression induced by Rg3 may at least partly explain its therapeutic effects in chronic neurodegenerative diseases.

• 公益社団法人日本薬学会の論文
• 2008-07-01

著者

• Hwang Kwang

  Department Of Immunology College Of Pharmacy Chung-ang University

• Kim Yun-bae

  Research Institute Of Veterinary Medicine Chungbuk National University

• JOO Seong

  Research Institute of Veterinary Medicine, Chungbuk University

• LEE Do

  Department of Materials Engineering, SungKyunKwan University

• YOO Yeong

  Research Institute of Veterinary Medicine, Chungbuk National University

• Lee Do

  Dep. Of Immunology Coll. Of Pharmacy Chung-ang Univ.

• Nam Sang

  Research Institute Of Veterinary Medicine Chungbuk National University

• Ahn Byung

  Research Institute Of Veterinary Medicine Chungbuk National University

• Yoo Yeong

  Research Institute Of Veterinary Medicine Chungbuk National University

• Lee Do

  Department Of Civil Environmental And Railroad Engineering Paichai University

• Hwang Kwang

  Department Of Immunology College Of Pharmacy Research Institute For Translational System Biomics Chu

• Joo Seong

  Research Institute Of Veterinary Medicine Chungbuk University

• Kim Yun-Bae

  Research Institute of Oceanography/School of Earth and Environmental Sciences, Seoul National University

• Joo Seong

  Research Institute of Veterinary Medicine, Chungbuk National University

• Lee Do

  Department of Chemical Engineering, Inha University, 253 Yonghyun-dong, Nam-gu, Incheon 402-751, Republic of Korea

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