title: Flavonoid wogonin from medicinal herb is neuroprotective by inhibiting inflammatory activation of microglia.
abstract: 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.
authors.affiliation: Department of Anatomy and Neurobiology, Research Institute of Natural Science, Gyeongsang National University College of Medicine, 92 Chilam-dong, Jinju, Kyungnam 660-751, Korea.
authors.forename: Heasuk
authors.initials: H
authors.lastname: Lee
authors.forename: Young Ok
authors.initials: YO
authors.lastname: Kim
authors.forename: Hocheol
authors.initials: H
authors.lastname: Kim
authors.forename: Sun Yeou
authors.initials: SY
authors.lastname: Kim
authors.forename: Hae Sook
authors.initials: HS
authors.lastname: Noh
authors.forename: Sang Soo
authors.initials: SS
authors.lastname: Kang
authors.forename: Gyeong Jae
authors.initials: GJ
authors.lastname: Cho
authors.forename: Wan Sung
authors.initials: WS
authors.lastname: Choi
authors.forename: Kyoungho
authors.initials: K
authors.lastname: Suk
mesh_terms: 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
chemical_list: D000893:Anti-Inflammatory Agents; D004365:Drugs, Chinese Herbal; D044950:Flavanones; D005419:Flavonoids; D018696:Neuroprotective Agents; C085514:wogonin