The inhibitory effects of Orengedokuto on inducible PGE2 production in BV-2 microglial cells

[Background and aim] Reactive microglia has been associated with neuroinflammation caused by the production of proinflammatory molecules such as cytokines, nitric oxide, and prostaglandins. The overexpression of these molecules may provoke neuronal damage that can cause neurodegenerative diseases. A traditional herbal medicine, Orengedokuto (OGT), has been widely used for treating inflammation-related diseases. However, how it influences neuroinflammation remains poorly understood. [Experimental procedure] This study investigated the effects of OGT on inflammatory molecule induction in BV-2 microglial cells using real-time RT-PCR and ELISA. An in vivo confirmation of these effects was then performed in mice. [Results and conclusion] OGT showed dose-dependent inhibition of prostaglandin E2 (PGE2) production in BV-2 cells stimulated with lipopolysaccharide (LPS). To elucidate the mechanism of PGE2 inhibition, we examined cyclooxygenases (COXs) and found that OGT did not suppress COX-1 expression or inhibit LPS-induced COX-2 upregulation at either the transcriptional or translational levels. In addition, OGT did not inhibit COX enzyme activities within the concentration that inhibited PGE2 production, suggesting that the effect of OGT is COX-independent. The inhibitory effects of OGT on PGE2 production in BV-2 cells were experimentally replicated in primary cultured astrocytes and mice brains. OGT can be useful in the treatment of neuroinflammatory diseases by modulating PGE2 expression

ラット ノ カイフク シゲキ ニ タイスル コウカン シンケイ ハンノウ ニ オケル CRF1 ジュヨウタイ ノ ヤクワリ

京都大学0048新制・課程博士博士(医学)甲第11825号医博第2901号新制||医||905(附属図書館)23585UT51-2005-K491京都大学大学院医学研究科外科系専攻(主査)教授 中尾 一和, 教授 北 徹, 教授 野間 昭典学位規則第4条第1項該当Doctor of Medical ScienceKyoto UniversityDA