Carnosic acid, a pro-electrophilic compound, inhibits LPS-induced activation of microglia.
In the previous studies, we reported that carnosic acid (CA) protects cortical neurons by activating the Keap1/Nrf2 pathway, which activation is initiated by S-alkylation of the critical cysteine thiol of the Keap1 protein by the "electrophilic"quinone-type CA. Here, we found that the pro-electrophilic CA inhibited the in vitro lipopolysaccharide (LPS)-induced activation of cells of the mouse microglial cell line MG6. LPS induced the expression of IL-1β and IL-6, typical inflammatory cytokines released from microglial cells. CA inhibited the NO production associated with a decrease in the level of inducible NO synthase. Neither CA nor LPS affected cell survival at the concentrations used here. These actions of CA seemed to be mediated by induction of phase 2 genes (gclc, gclm, nqo1 and xct). We propose that an inducer of phase 2 genes may be a critical regulator of microglial activation. Thus, CA is a unique pro-electrophilic compound that provides both a protective effect on neurons and an anti-inflammatory one on microglia through induction of phase 2 genes.
Department of Welfare Engineering, Faculty of Engineering, Iwate University, Morioka, Iwate 020-8551, Japan.
Mika
M
Yanagitai
Sayaka
S
Itoh
Tomomi
T
Kitagawa
Takato
T
Takenouchi
Hiroshi
H
Kitani
Takumi
T
Satoh
D045784:Abietanes / Q000494:pharmacology*; D027182:Amino Acid Transport System y+ / Q000235:genetics; D000818:Animals; D002460:Cell Line; D016195:G2 Phase / Q000187:drug effects* / Q000235:genetics; D005721:Glutamate-Cysteine Ligase / Q000235:genetics; D053583:Interleukin-1beta / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis; D008070:Lipopolysaccharides / Q000276:immunology; D051379:Mice; D017628:Microglia / Q000187:drug effects* / Q000276:immunology*; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000235:genetics; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors; D010936:Plant Extracts / Q000494:pharmacology*; D000093242:Interleukin-6 Inhibitors
D045784:Abietanes; D027182:Amino Acid Transport System y+; D005721:Glutamate-Cysteine Ligase; D053583:Interleukin-1beta; D015850:Interleukin-6; D008070:Lipopolysaccharides; D016660:NAD(P)H Dehydrogenase (Quinone); D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; D010936:Plant Extracts; D000093242:Interleukin-6 Inhibitors; C492255:Slc7a11 protein, mouse; C496317:Nos2 protein, mouse; C491732:Nqo1 protein, mouse; C560749:GCLM protein, mouse; C018381:salvin