Flavonoid wogonin from medicinal herb is neuroprotective by inhibiting inflammatory activation of microglia.
Wogonin (5,7-dihydroxy-8-methoxyflavone), a flavonoid originated from the root of a medicinal herb Scutellaria baicalensis Georgi, has been previously shown to have anti-inflammatory activities in various cell types including macrophages. In this work, we have found that wogonin is a potent neuroprotector from natural source. Wogonin inhibited inflammatory activation of cultured brain microglia by diminishing lipopolysaccharide-induced tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta, and nitric oxide (NO) production. Wogonin inhibited NO production by suppressing inducible NO synthase (iNOS) induction and NF-kappaB activation in microglia. Inhibition of inflammatory activation of microglia by wogonin led to the reduction in microglial cytotoxicity toward cocultured PC12 cells, supporting a neuroprotective role for wogonin in vitro. The neuroprotective effect of wogonin was further demonstrated in vivo using two experimental brain injury models; transient global ischemia by four-vessel occlusion and excitotoxic injury by systemic kainate injection. In both animal models, wogonin conferred neuroprotection by attenuating the death of hippocampal neurons, and the neuroprotective effect was associated with inhibition of the inflammatory activation of microglia. Hippocampal induction of inflammatory mediators such as iNOS and TNF-alpha was reduced by wogonin in the global ischemia model, and microglial activation was markedly down-regulated by wogonin in the kainate injection model as judged by microglia-specific isolectin B4 staining. Taken together, our results indicate that wogonin exerts its neuroprotective effect by inhibiting microglial activation, which is a critical component of pathogenic inflammatory responses in neurodegenerative diseases. The current study emphasizes the importance of medicinal herbs and their constituents as an invaluable source for the development of novel neuroprotective drugs.
Lee
Heasuk
H
Department of Anatomy and Neurobiology, Research Institute of Natural Science, Gyeongsang National University College of Medicine, 92 Chilam-dong, Jinju, Kyungnam 660-751, Korea.
Kim
Young Ok
YO
Kim
Hocheol
H
Kim
Sun Yeou
SY
Noh
Hae Sook
HS
Kang
Sang Soo
SS
Cho
Gyeong Jae
GJ
Choi
Wan Sung
WS
Suk
Kyoungho
K
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001921:Brain / Q000166:cytology / Q000473:pathology; D001927:Brain Diseases / Q000473:pathology / Q000517:prevention & control; D002478:Cells, Cultured; D004365:Drugs, Chinese Herbal / Q000494:pharmacology; D044950:Flavanones; D005419:Flavonoids / Q000494:pharmacology*; D017628:Microglia / Q000187:drug effects* / Q000276:immunology; D008954:Models, Biological; D018696:Neuroprotective Agents / Q000494:pharmacology*; D016716:PC12 Cells; D051381:Rats
D000893:Anti-Inflammatory Agents; D004365:Drugs, Chinese Herbal; D044950:Flavanones; D005419:Flavonoids; D018696:Neuroprotective Agents; C085514:wogonin