1 research outputs found
Protective Effects of Lupeol against d‑Galactosamine and Lipopolysaccharide-Induced Fulminant Hepatic Failure in Mice
This study examined the hepatoprotective
effects of lupeol (<b>1</b>, a major active triterpenoid isolated
from <i>Adenophora
triphylla</i> var. <i>japonica</i>) against d-galactosamine (GalN) and lipopolysaccharide (LPS)-induced fulminant
hepatic failure. Mice were orally administered <b>1</b> (25,
50, and 100 mg/kg; dissolved in olive oil) 1 h before GalN (800 mg/kg)/LPS
(40 μg/kg) treatment. Treatment with GalN/LPS resulted in increased
levels of serum alanine aminotransferase, tumor necrosis factor (TNF)-α,
and interleukin (IL)-6, as well as increased mortality, all of which
were attenuated by treatment with <b>1</b>. In addition, levels
of toll-like receptor (TLR)4, myeloid differentiation primary response
gene 88, TIR-domain-containing adapter-inducing interferon-β
(TRIF), IL-1 receptor-associated kinase (IRAK)-1, and TNF receptor
associated factor 6 protein expression were increased by GalN/LPS.
These increases, except TRIF, were attenuated by <b>1</b>. Interestingly, <b>1</b> augmented GalN/LPS-mediated increases in the protein expression
of IRAK-M, a negative regulator of TLR signaling. Following GalN/LPS
treatment, nuclear translocation of nuclear factor-κB and the
levels of <i>TNF-α</i> and <i>IL-6</i> mRNA
expression increased, which were attenuated by <b>1</b>. Together,
the present findings suggest that lupeol (<b>1</b>) ameliorates
GalN/LPS-induced liver injury, which may be due to inhibition of IRAK-mediated
TLR inflammatory signaling