RT Journal Article
SR Electronic
T1 Flavonoid Baicalein Attenuates Activation-Induced Cell Death of Brain Microglia
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 638
OP 645
DO 10.1124/jpet.102.047373
VO 305
IS 2
A1 Kyoungho Suk
A1 Heasuk Lee
A1 Sang Soo Kang
A1 Gyeong Jae Cho
A1 Wan Sung Choi
YR 2003
UL http://jpet.aspetjournals.org/content/305/2/638.abstract
AB Baicalein (5,6,7-trihydroxyflavone), a flavonoid originated from the root of Chinese medicinal herb Scutellaria baicalensis, has been shown to exert anti-inflammatory and antioxidant effects, and it is a well known inhibitor of 12-lipoxygenase. We have previously reported that neuroglia undergo nitric oxide (NO)-dependent and NO-independent apoptosis upon inflammatory activation. In the current work, we asked how anti-inflammatory baicalein influences autoregulatory apoptosis of activated microglia and their NO production. Baicalein attenuated NO production and apoptosis of lipopolysaccharide (LPS)-activated, but not interferon-γ-activated, BV-2 mouse microglial cells as well as rat primary microglia cultures. The inhibition of NO production by baicalein was due to the suppression of inducible NO synthase induction. Moreover, baicalein inhibited LPS-induced nuclear factor-κB (NF-κB) activity in BV-2 cells without affecting caspase-11 activation, interferon regulatory factor-1 induction, or signal transducer and activator of transcription-1 phosphorylation. Transfection of BV-2 cells with a p65 subunit of NF-κB abolished the apoptosis-attenuating effects of baicalein, indicating that the inhibition of NF-κB is a major mechanism of action. Baicalein, however, did not significantly affect NO donor-mediated cytotoxicity, and the apoptosis-attenuating effects of baicalein were independent of 12-lipoxygenase inhibition. Based on our previous findings that activation-induced cell death (AICD) of microglia occurs through two separate pathways (NO-dependent pathway and caspase-11-dependent pathway), our current results suggest that baicalein selectively inhibits the NO-dependent apoptotic pathway of activated microglia by suppressing cytotoxic NO production. Also, the AICD-inhibiting effects of baicalein were specific for the inflammatory stimulus that activated microglia. The American Society for Pharmacology and Experimental Therapeutics