title: Prevention of inflammation-mediated neurotoxicity by butylidenephthalide and its role in microglial activation.
abstract: Microglial cells are the prime effectors in immune and inflammatory responses of the central nervous system (CNS). During pathological conditions, the activation of these cells helps restore CNS homeostasis. However, chronic microglial activation endangers neuronal survival through the release of various proinflammatory molecules and neurotoxins. Thus, negative regulators of microglial activation have been considered as potential therapeutic candidates to target neurodegeneration, such as that in Alzheimer's and Parkinson's diseases. The rhizome of Ligusticum chuanxiong Hort. (Ligusticum wallichii Franch) has been widely used for the treatment of vascular diseases in traditional oriental medicine. Butylidenephthalide (BP), a major bioactive component from L. chuanxiong, has been reported to have a variety of pharmacological activities, including vasorelaxant, anti-anginal, anti-platelet and anti-cancer effects. The aim of this study was to examine whether BP represses microglial activation. In rat brain microglia, BP significantly inhibited the lipopolysaccharide (LPS)-induced production of nitric oxide (NO), tumour necrosis factor-α and interleukin-1β. In organotypic hippocampal slice cultures, BP clearly blocked the effect of LPS on hippocampal cell death and inhibited LPS-induced NO production in culture medium. These results newly suggest that BP provide neuroprotection by reducing the release of various proinflammatory molecules from activated microglia.
authors: Graduate School of East-West Medical Science, Kyung Hee University, Yongin-si, 446-701, Korea.
authors: Kyong Nyon
authors: KN
authors: Nam
authors: Kyoo-Pil
authors: KP
authors: Kim
authors: Ki-Ho
authors: KH
authors: Cho
authors: Woo-Sang
authors: WS
authors: Jung
authors: Jung-Mi
authors: JM
authors: Park
authors: Seung-Yeon
authors: SY
authors: Cho
authors: Su-Kyung
authors: SK
authors: Park
authors: Tae-Hoon
authors: TH
authors: Park
authors: Young-Suk
authors: YS
authors: Kim
authors: Eunjoo H
authors: EH
authors: Lee
mesh_terms: D000818:Animals; D001921:Brain / Q000166:cytology / Q000187:drug effects* / Q000473:pathology; D016923:Cell Death / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D006624:Hippocampus / Q000187:drug effects / Q000473:pathology; D007249:Inflammation / Q000473:pathology / Q000517:prevention & control*; D053583:Interleukin-1beta / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors / Q000494:pharmacology; D017628:Microglia / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D010796:Phthalic Anhydrides / Q000494:pharmacology*; D051381:Rats; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000096:biosynthesis
chemical_list: D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D018696:Neuroprotective Agents; D010796:Phthalic Anhydrides; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; C026105:butylidenephthalide
keywords: IL-1β; TNF-α; brain inflammation; butylidenephthalide; microglia; neurotoxicity; nitric oxide; organotypic hippocampal slice culture