title: Protective effects of amide constituents from the fruit of Piper chaba on D-galactosamine/TNF-alpha-induced cell death in mouse hepatocytes.
abstract: The methanolic extract from the fruit of Piper chaba (Piperaceae) was found to have a hepatoprotective effect on D-galactosamine (D-GalN)/lipopolysaccharide (LPS)-induced liver injury in mice. From the ethyl acetate-soluble fraction, a new amide constituent named piperchabamide E together with twenty known amide constituents (e.g., piperine, piperchabamides A-D, and piperanine) and two aromatic constituents were isolated as the hepatoprotective constituents. With regard to structure-activity relationships, the amide moiety and the 1,9-decadiene structure between the benzene ring and amide moiety were suggested to be important for strong inhibition of D-GalN/tumor necrosis factor-alpha (TNF-alpha)-induced death of hepatocytes. Furthermore, a principal amide constituent, piperine, dose-dependently inhibited increase in serum GPT and GOT levels at doses of 2.5-10 mg/kg (p.o.) in D-GalN/LPS-treated mice, and this inhibitory effect was suggested to depend on the reduced sensitivity of hepatocytes to TNF-alpha.
authors.affiliation: Kyoto Pharmaceutical University, Misasagi, Yamashina-ku, Kyoto 607-8412, Japan.
authors.forename: Hisashi
authors.initials: H
authors.lastname: Matsuda
authors.forename: Kiyofumi
authors.initials: K
authors.lastname: Ninomiya
authors.forename: Toshio
authors.initials: T
authors.lastname: Morikawa
authors.forename: Daisuke
authors.initials: D
authors.lastname: Yasuda
authors.forename: Itadaki
authors.initials: I
authors.lastname: Yamaguchi
authors.forename: Masayuki
authors.initials: M
authors.lastname: Yoshikawa
mesh_terms: D000410:Alanine Transaminase / Q000378:metabolism; D000470:Alkaloids / Q000494:pharmacology; D000577:Amides / Q000737:chemistry*; D000818:Animals; D001219:Aspartate Aminotransferases / Q000378:metabolism; D052117:Benzodioxoles / Q000494:pharmacology; D016923:Cell Death / Q000187:drug effects*; D002851:Chromatography, High Pressure Liquid; D005638:Fruit / Q000737:chemistry*; D005688:Galactosamine / Q000633:toxicity*; D022781:Hepatocytes / Q000187:drug effects*; D008070:Lipopolysaccharides / Q000633:toxicity; D008099:Liver / Q000187:drug effects / Q000293:injuries / Q000473:pathology; D008107:Liver Diseases / Q000188:drug therapy / Q000209:etiology / Q000517:prevention & control; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D015394:Molecular Structure; D026321:Piperaceae / Q000737:chemistry*; D010880:Piperidines / Q000494:pharmacology; D010936:Plant Extracts / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D053284:Polyunsaturated Alkamides / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
chemical_list: D000470:Alkaloids; D000577:Amides; D052117:Benzodioxoles; D008070:Lipopolysaccharides; D010880:Piperidines; D010936:Plant Extracts; D053284:Polyunsaturated Alkamides; D014409:Tumor Necrosis Factor-alpha; D005688:Galactosamine; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; C008922:piperine