Nickel (Ni), one of hazardous environmental chemicals, is known to cause liver injury. Accumulating evidence showed that
puerarin (PU) possessed comprehensive
biological effects. The purpose of the current study was to test the hypothesis that the
puerarin protects against enhanced liver injury caused by Ni in mice. ICR mice received intraperitoneally
nickel sulfate (20 mg/kg/
body weight, daily) for 20 days, and
puerarin (200 and 400 mg/kg/
body weight) was applied before Ni exposure. The results indicated that
puerarin markedly inhibited Ni-induced liver injury, which was characterized by decreased
aminotransferase activities and
inflammation.
Puerarin also inhibited the oxidative stress and decreased the
metallothionein (MT) levels.
Puerarin decreased the level of pro-inflammatory
cytokines TNF-α and
IL-6 in livers.
Puerarin significantly inhibited the TLR4 activation and
p38 MAPK phosphorylation, which in turn inhibited NF-κB activity. Likewise, Ni-induced inflammatory responses were diminished by
puerarin as observed by a remarkable reduction in the levels of phosphorylated CREB. Furthermore,
puerarin also reduced inflammatory mediators such as
cyclooxygenase-2 (COX-2) and
prostaglandin E2 (
PGE2) levels in livers. Data from this study suggested that the inhibition of Ni-induced oxidative stress and inflammatory responses by
puerarin is due to its ability to modulate the TLR4/p38/CREB signaling pathway.