[Search for TNF-alpha sensitivity degradation principles from medicinal foods-hepatoprotective amide constituents from Thai natural medicine Piper chaba].
Eighty percent (80%) aqueous acetone extract from fruit of Piper chaba (Piperaceae) was found to have a hepatoprotective effect on D-galactosamine (D-GalN)/lipopolysaccharide (LPS)-induced liver injury in mice. Among the isolates, several amide constituents inhibited D-GalN/tumor necrosis factor-alpha (TNF-alpha)-induced death of hepatocytes, and the following structural requirements were suggested: i) the amide moiety was essential for strong activity; ii) the 1,9-decadiene structure between the benzene ring and the amide moiety tended to enhance the activity. Moreover, a principal constituent, piperine, exhibited strong in vivo hepatoprotective effect at a dose of 5 mg/kg, p.o. and its mode of action was suggested to depend on the reduced sensitivity of hepatocytes to TNF-alpha.
Morikawa
Toshio
T
Pharmaceutical Research and Technology Institute Kinki University. morikawa@kindai.ac.jp
D000470:Alkaloids / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use; D000577:Amides / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D052117:Benzodioxoles / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use; D002478:Cells, Cultured; D056486:Chemical and Drug Induced Liver Injury / Q000188:drug therapy*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005688:Galactosamine; D022781:Hepatocytes / Q000378:metabolism*; D008070:Lipopolysaccharides; D051379:Mice; D031701:Piper / Q000737:chemistry*; D010880:Piperidines / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use; D053284:Polyunsaturated Alkamides / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use; D013329:Structure-Activity Relationship; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D000470:Alkaloids; D000577:Amides; D052117:Benzodioxoles; D008070:Lipopolysaccharides; D010880:Piperidines; D053284:Polyunsaturated Alkamides; D014409:Tumor Necrosis Factor-alpha; D005688:Galactosamine; C008922:piperine