Protective effects of amide constituents from the fruit of Piper chaba on D-galactosamine/TNF-alpha-induced cell death in mouse hepatocytes.

Hisashi Matsuda, Kiyofumi Ninomiya, Toshio Morikawa, Daisuke Yasuda, Itadaki Yamaguchi, Masayuki Yoshikawa

Index: Bioorg. Med. Chem. Lett. 18 , 2038-42, (2008)

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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.