Thymoquinone, a bioactive component of Nigella sativa Linn seeds or traditional spice, attenuates acute hepatic failure and blocks apoptosis via the MAPK signaling pathway in mice

Abstract

Thymoquinone (TQ), a bioactive natural product obtained from the black cumin seeds of Nigella sativa Linn, is a widely used spice or herb. The present study investigated the hepatoprotective effect of TQ on acute hepatic failure induced by D-galactosamine (D-GalN) and lipopolysaccharide (LPS) in mice. The mice were intragastrically administrated TQ (5 or 20 mg kg⁻¹) for 12 h and 1 h prior to D-GalN (700 mg kg⁻¹)/LPS (10 μg kg⁻¹) injections and then sacrificed 8 h after treatment with D-GalN/LPS. TQ pretreatment reduced the mortality induced by D-GalN/LPS and reversed liver damage. TQ attenuated D-GalN/LPS-induced hepatocyte apoptosis, which was confirmed by suppressing caspase activation, PARP cleavage and the Bax/Bcl-2 ratio. Importantly, TQ attenuated the D-GalN/LPS-mediated phosphorylation of JNK, ERK and p38. Furthermore, TQ suppressed the production of proinflammatory cytokines. These findings suggested that TQ could modulate D-GalN/LPS-mediated acute hepatic failure by inhibiting caspase activation, consistent with the mitochondrial pathway of apoptosis and the MAPK signaling pathway.