ABSTRACT
Bioassay-guided fractionation of the root extract of Asarum sieboldii led to the isolation of the four active compounds (-)-sesamin (1), (2E,4E,8Z,10E)-N-(2-methylpropyl)dodeca-2,4,8,10-tetraenamide (2), kakuol (3), and '3,4,5-trimethoxytoluene' (=1,2,3-trimethoxy-5-methylbenzene; 4), in terms of inhibition of lipopolysaccharide (LPS)-induced nitric oxide (NO) production. Compounds 1-4 showed potent inhibition of NO production, with IC(50) values in the low nanomolar-to-micromolar range. Also isolated were the known compounds methylkakuol (5), '3,5-dimethoxytoluene', safrole, asaricin, methyleugenol, and (-)-asarinin, which were found to be inactive in the above assay. Among the ten known isolates, compounds 1, 2, and 5 were found for the first time in this plant.
Subject(s)
Dioxoles/pharmacology , Lignans/pharmacology , Lipopolysaccharides/antagonists & inhibitors , Microglia/drug effects , Nitric Oxide/antagonists & inhibitors , Polyunsaturated Alkamides/pharmacology , Propiophenones/pharmacology , Toluene/analogs & derivatives , Animals , Aristolochiaceae/chemistry , Cell Line , Dioxoles/chemistry , Dioxoles/isolation & purification , Dose-Response Relationship, Drug , Lignans/chemistry , Lignans/isolation & purification , Lipopolysaccharides/pharmacology , Mice , Microglia/cytology , Microglia/metabolism , Molecular Structure , Nitric Oxide/biosynthesis , Plant Roots/chemistry , Polyunsaturated Alkamides/chemistry , Polyunsaturated Alkamides/isolation & purification , Propiophenones/chemistry , Propiophenones/isolation & purification , Stereoisomerism , Structure-Activity Relationship , Toluene/chemistry , Toluene/isolation & purification , Toluene/pharmacologyABSTRACT
OBJECTIVES: Agrimoniae Herba has been used as an anti-inflammatory agent in traditional medicine. Nitric oxide and proinflammatory cytokines produced by activated microglia may be a possible etiological factor of neurodegenerative disorders. We evaluated whether Agrimoniae Herba could have an anti-inflammatory effect on lipopolysaccharide-induced BV2 microglial cells. METHODS: The effects of Agrimoniae Herba on lipopolysaccharide-induced nitric oxide and proinflammatory cytokine production in BV2 microglial cells were evaluated by nitric oxide assay, enzyme-linked immunosorbent assay and western blotting. RESULTS: Agrimoniae Herba had no cytotoxicity and suppressed lipopolysaccharide-induced nitric oxide production in BV2 microglial cells. Agrimoniae Herba also suppressed lipopolysaccharide-induced production of proinflammatory cytokines such as tumor necrosis factor, interleukin 1 beta and interleukin 6 in a dose-dependent manner. Agrimoniae Herba inhibited the expression of inducible nitric oxide synthase. DISCUSSION: Taken together, these findings indicate that Agrimoniae Herba may be used as a form of pharmaceutical acupuncture therapy in the treatment of brain inflammation.