Hepatoprotective amide constituents from the fruit of Piper chaba: Structural requirements, mode of action, and new amides

• Published in: Bioorganic & medicinal chemistry 2009-10, Vol.17 (20), p.7313-7323
• Main Authors: Matsuda, Hisashi, Ninomiya, Kiyofumi, Morikawa, Toshio, Yasuda, Daisuke, Yamaguchi, Itadaki, Yoshikawa, Masayuki
• Format: Article
• Language: English
• Subjects: Amides - chemistry; Amides - pharmacology; Animals; Anti-TNF-α activity; Biological and medical sciences; Cells, Cultured; General pharmacology; Hepatoprotective activity; Lipopolysaccharides - toxicity; Liver - drug effects; Liver - injuries; Magnetic Resonance Spectroscopy; Male; Medical sciences; Mice; Models, Molecular; Molecular Structure; Pharmacognosy. Homeopathy. Health food; Pharmacology. Drug treatments; Piper; Piper - chemistry; Piper chaba; Piperaceae; Piperchabamide; Piperine
• ISSN: 0968-0896; 1464-3391
• DOI: 10.1016/j.bmc.2009.08.050

The 80% aqueous acetone extract from the fruit of Piper chaba (Piperaceae) was found to have hepatoprotective effects on d-galactosamine ( d-GalN)/lipopolysaccharide-induced liver injury in mice. From the ethyl acetate-soluble fraction, three new amides, piperchabamides E, G, and H, 33 amides, and four aromatic constituents were isolated. Among the isolates, several amide constituents inhibited d-GalN/tumor necrosis factor-α (TNF-α)-induced death of hepatocytes, and the following structural requirements were suggested: (i) the amide moiety is essential for potent activity; and (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 effects at doses of 5 and 10 mg/kg, po and its mode of action was suggested to depend on the reduced sensitivity of hepatocytes to TNF-α. The 80% aqueous acetone extract from the fruit of Piper chaba (Piperaceae) was found to have hepatoprotective effects on d-GalN/LPS-induced liver injury in mice. From the ethyl acetate-soluble fraction, three new amides, piperchabamides E, G, and H, 33 amides, and four aromatic constituents were isolated. Among the isolates, several amide constituents inhibited d-GalN/TNF-α-induced death of hepatocytes, and the following structural requirements were suggested: (i) the amide moiety is essential for strong activity; and (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 effects at doses of 5 and 10 mg/kg, po and its mode of action was suggested to depend on the reduced sensitivity of hepatocytes to TNF-α.