Y-40138, a multiple cytokine production modulator, protects against d-galactosamine and lipopolysaccharide-induced hepatitis

The inhibition of apoptosis by glycyrrhizin in hepatic injury induced by injection of lipopolysaccharide / D-galactosamine in mice

“…Thus, it appears that TNF-induced by LPS/D-GalN plays an important role in the pathogenesis of this model. A recent report showed that Y-40138, a synthetic compound, inhibits liver injury evoked by LPS/D-GalN through the suppression of TNF-and monocyte chemoattractant protein-1 and the augmentation of IL-10 (Fukuda et al, 2006). According to Okamoto (2000), GL prevents anti-Fas antibody-induced mouse liver injury but has no effect on the upregulation of TNF-mRNA expression in the liver.…”

“…Glycyrrhizin (GL), an aqueous extract of licorice root, has been used for the treatment of chronic hepatitis to reduce liver infl ammation (Takahara et al, 1994;Ito et al, 1997;Yoshikawa et al, 1997), but its effects on acute hepatic injury are unclear. A recent report showed that Y-40138, a synthetic compound, inhibits liver injury evoked by LPS/D-GalN through the suppression of TNF-and monocyte chemoattractant protein-1 and the augmentation of IL-10 (Fukuda et al, 2006). GL prevents anti-Fas antibody-induced mouse liver injury but has no effect on the upregulation of TNFmRNA expression in the liver (Okamoto, 2000).…”

“…GL had no effect on the production of TNF-, IL-6, IL-10, or IL-12, whereas it significantly inhibited the increase in ALT levels and IL-18 production. Our previous results indicate that the inhibitory effect of GL differs from that of inhibitors for TNF-production, such as Y-40138 (Fukuda et al, 2006) and bicyclol, a new synthetic antihepatitis drug (Wang et al, 2006). IL-18 was originally identifi ed as an interferon (IFN)--inducing factor (Okamura et al, 1995) and has been suggested to be a potent inflammatory cytokine that regulates autoimmune and inflammatory diseases (Nakanishi et al, 2001;Dinarello et al, 2003;Gracie et al, 2003).…”

Novel Mechanism Supporting Therapeutic Effects of Glycyrrhizin in Acute or Chronic Hepatitis

“…GL, an aqueous extract of licorice root, has been used for the treatment of chronic hepatitis to reduce the liver inlammation [15][16][17], but its efects on acute hepatic injury have been unclear. A recent report showed that Y-40138, a synthetic compound, inhibits liver injury evoked by LPS/GalN through the suppression of TNF-α and monocyte chemoatractant protein-1 and the augmentation of IL-10 [18]. GL prevents anti-Fas antibody-induced mouse liver injury but has no efect on the upregulation of TNF-α mRNA expression in the liver [6].…”

“…GL had no efect on the production of TNF-α, IL-6, IL-10, and IL-12, whereas it signiicantly inhibited the increase in ALT levels and IL-18 production. We have so far indicated that the inhibitory efect of GL is diferent from that of inhibitor for TNF-α production, such as Y-40138 [18] and bicyclol, a new synthetic anti-hepatitis drug [20].…”