Hepatoprotective effect of plant components: Inhibition of tumornecrosis factor-α-dependent inflammatory liver injury

There is evidence to suggest that the upregulation of serum tumor necrosis factor (TNF-α) and the emergence of hepatocyte apoptosis are involved in the pathogenesis of human alcoholic and viral hepatitis. In experimental liver injuries induced by d-Galactosamine (d-GalN)/lipopolysaccharide (LPS), d-GalN/TNF-α or Propionibacterium acnes/LPS, TNF-α induces hepatocyte apoptosis which triggers an inflammatory reaction and subsequent massive hepatocyte necrosis, playing a central role in the pathological process. These models provide a promising experimental basis not only for understanding the pathophysiological mechanisms of various hepatic disorders but also for evaluating the hepatoprotective efficacy of natural products. A diverse array of plant-derived compounds including saponins, polyphenols, iridoids and alkaloids have been reported to have a hepatoprotective effect in the TNF-α-dependent inflammatory liver injury models. Some of these compounds impede TNF-α-mediated hepatocyte apoptosis and consequently block the progression of liver injury, whereas others protect against hepatocyte necrosis occurring at the final stage. The protection against apoptosis by hepatoprotective compounds can be explained by the inhibition of TNF-α production from macrophages or by attenuation of the hepatotoxic function of TNF-α. This review discusses the recent progress in TNF-α-dependent liver injury models and the hepatoprotective action of plant constituents in such models.