Triptolide inhibits TNF-alpha, IL-1 beta and NO production in primary microglial cultures.
Microglia are believed to participate in the mediation of neurodegeneration through producing a variety of cytotoxic factors upon activation. Pharmacological intervention in microglial activation may therefore exert a neuroprotective effect. In exploring pharmacological agents that can affect microglial activation, we found in this study that triptolide possesses a powerful inhibitory influence over microglia. Pretreatment with triptolide was able to dose-dependently reduce the lipopolysaccharide (LPS)-induced nitrite accumulation and tumor necrosis factor-alpha and interleukin-1beta release from LPS-activated microglia as revealed by Griess reaction and ELISA, respectively. Triptolide reduced LPS-stimulated mRNA expression of all three inflammatory factors. The results obtained from this study demonstrate that triptolide can inhibit inflammatory responses of microglia to inflammatory stimulation via a mechanism involving the inhibition of the synthesis and release of inflammatory factors.
Zhou
Hui-Fang
HF
Neuroscience Research Institute, Peking University, Beijing, PR China.
Niu
Dong-Bin
DB
Xue
Bing
B
Li
Feng-Qiao
FQ
Liu
Xian-Yu
XY
He
Qi-Hua
QH
Wang
Xin-Hong
XH
Wang
Xiao-Min
XM
D000818:Animals; D002478:Cells, Cultured; D004224:Diterpenes / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004852:Epoxy Compounds; D007375:Interleukin-1 / Q000037:antagonists & inhibitors* / Q000096:biosynthesis*; D008297:Male; D017628:Microglia / Q000187:drug effects* / Q000378:metabolism; D009569:Nitric Oxide / Q000037:antagonists & inhibitors* / Q000096:biosynthesis*; D010616:Phenanthrenes; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000096:biosynthesis*
D004224:Diterpenes; D004852:Epoxy Compounds; D007375:Interleukin-1; D010616:Phenanthrenes; D014409:Tumor Necrosis Factor-alpha; C001899:triptolide; D009569:Nitric Oxide