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

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-α (TNF-α)-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-α.