Multiple-modulation effects of Oridonin on the production of proinflammatory cytokines and neurotrophic factors in LPS-activated microglia.
Microglial activation has been implicated in many neurological disorders for its inflammatory and/or neurotrophic effects. In this study, we investigated the effects upon activated microglia of Oridonin (Ori), an effective component isolated from Rabdosia rubescens. We pretreated rat primary microglia with or without Ori, then stimulated with lipopolysaccharide (LPS). We found that Ori pretreatment inhibited the release of proinflammatory mediators including nitric oxide (NO), tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1beta) and interleukin-6 (IL-6). Such suppressive effects were accompanied by inhibition of DNA binding activity of the critical transcription factor nuclear factor-kappa B (NF-kappaB). In addition, Ori upregulated the production of the neurotrophic factor, nerve growth factor (NGF). Our findings suggest that Ori may have anti-inflammatory and neuroregulatory effects through modulation of multiple functions of microglia.
Xu
Yan
Y
Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200025, PR China.
Xue
Yang
Y
Wang
Ying
Y
Feng
Dechun
D
Lin
Shuting
S
Xu
Lingyun
L
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000737:chemistry / Q000494:pharmacology*; D002478:Cells, Cultured; D016207:Cytokines / Q000037:antagonists & inhibitors* / Q000378:metabolism; D045786:Diterpenes, Kaurane / Q000737:chemistry / Q000494:pharmacology*; D053583:Interleukin-1beta / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000276:immunology; D017628:Microglia / Q000187:drug effects* / Q000276:immunology; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism; D009414:Nerve Growth Factors / Q000096:biosynthesis*; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000378:metabolism; D000093242:Interleukin-6 Inhibitors
D000893:Anti-Inflammatory Agents; D016207:Cytokines; D045786:Diterpenes, Kaurane; D053583:Interleukin-1beta; D015850:Interleukin-6; D008070:Lipopolysaccharides; D016328:NF-kappa B; D009414:Nerve Growth Factors; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; D014409:Tumor Necrosis Factor-alpha; D000093242:Interleukin-6 Inhibitors; C011959:oridonin; C496318:Nos2 protein, rat