title: Effect of Asiasarum Root Extract and Its Constituents on Interleukin-1β-Stimulated Matrix Metalloproteinase-1 Secretion from Human Gingival Fibroblasts.
abstract: Asiasarum root (roots and rhizome of Asiasarum sieboldii or A. heterotropoides var. mandshuricum) has been frequently used in traditional Chinese medicinal formulas for the management of oral malodor syndrome caused by periodontal disease. However, there are no scientific reports concerning these effects and the mechanism of action. The objective of this study was to examine the inhibitory effects of Asiasarum root and its constituents on oral malodor syndrome and periodontal disease. A 50% ethanolic extract of Asiasarum root (AR-ext) showed L-methionine γ-lyase (METase) inhibitory activity at a concentration of 200 µg/mL, and inhibited interleukin (IL)-1β-stimulated matrix metalloproteinase (MMP)-1 secretion from human gingival fibroblasts (HGFs) at a concentration of 10 and 50 µg/mL without cytotoxic effects. Activity-guided fractionation of the AR-ext suggested that METase inhibitory activity was attributable to a mixture of linoleic and oleic acid, because these unsaturated fatty acids showed weak METase inhibitory activities. Similar fractionation using MMP-1 secretion inhibitory activity led to the isolation of two unsaturated fatty acid amides, (2E,4E,8Z,10E)-N-(2-methylpropyl)dodeca-2,4,8,10-tetraenamide (1) and (2E,4E,8Z,10Z)-N-(2-methylpropyl)dodeca-2,4,8,10-tetraenamide (2), as active constituents with inhibitory activity on MMP-1 secretion from HGFs. To elucidate the inhibition mechanism on MMP-1 secretion, the effect of 2 on mitogen-activated protein kinase (MAPK) phosphorylation was examined. Western blotting analysis revealed that 2 (10 µM) reduced the phosphorylation of p38 and c-Jun-N-terminal kinase. These results suggested that 2 suppresses intracellular MMP-1 expression and MMP-1 secretion from IL-1β-stimulated HGFs by down-regulation of MAPK phosphorylation.
authors.affiliation: Faculty of Pharmacy, Kindai University.
authors.forename: Megumi
authors.initials: M
authors.lastname: Futamura-Masuda
authors.forename: Mami
authors.initials: M
authors.lastname: Yokota-Honda
authors.forename: Takuya
authors.initials: T
authors.lastname: Anraku
authors.forename: Kanae
authors.initials: K
authors.lastname: Nakanishi
authors.forename: Kazuya
authors.initials: K
authors.lastname: Murata
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Shinada
authors.forename: Hideaki
authors.initials: H
authors.lastname: Matsuda
mesh_terms: D029065:Aristolochiaceae; D013437:Carbon-Sulfur Lyases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism; D005881:Gingiva / Q000166:cytology*; D006209:Halitosis; D006801:Humans; D053583:Interleukin-1beta / Q000494:pharmacology; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D010936:Plant Extracts / Q000494:pharmacology*; D018517:Plant Roots; D016966:Porphyromonas gingivalis / Q000187:drug effects
chemical_list: D053583:Interleukin-1beta; D010936:Plant Extracts; D020928:Mitogen-Activated Protein Kinases; C522360:MMP1 protein, human; D020781:Matrix Metalloproteinase 1; D013437:Carbon-Sulfur Lyases; C021558:L-methionine gamma-lyase