Puerarin is a
natural product isolated from
Puerarin lobata and has various pharmacological effects, including anti-hyperglycemic and
anti-allergic properties. In the present study, we investigated the effect of
puerarin against
advanced glycation end products (AGEs)-induced
inflammation in mouse mesangial cells.
Puerarin acts by inducing the expression of
heme oxygenase-1 (HO-1) in a dose- and time-dependent manner.
Puerarin was able to enhance phosphorylation of
protein kinase C (PKC) delta, but not PKC alpha/beta II, in a time-dependent manner. Induction of HO-1 expression by
puerarin was suppressed by
GF109203X, a general inhibitor of PKC, and by
rottlerin, a specific inhibitor of PKC delta. However, induction was not suppressed by Gö6976, a selective inhibitor for PKC alpha/beta II. Additionally, the knockdown of endogenous PKC delta by
small interfering RNA (
siRNA) resulted in the inhibition of HO-1 expression and Akt phosphorylation.
Puerarin increased antioxidant response element (ARE)-
Luciferase activity in a dose- and time-dependent manner in transfected mouse mesangial cells. Mutation of the ARE sequence abolished
puerarin-induced HO-1 expression. Furthermore,
puerarin treatments resulted in a marked increase in NF-E2 related factor-2 (Nrf-2) translocation, leading to up-regulation of HO-1 expression. However, transfection of Nrf-2 specific
siRNA abolished HO-1 expression. Pretreatment with
puerarin inhibited the expressions of COX-2, MMP-2 and MMP-9. But, these effects were reversed by ZnPP, an inhibitor of HO-1. Taken together, our results demonstrate that
puerarin-induced expression of HO-1 is mediated by the PKC delta-Nrf-2-HO-1 pathway and inhibits N-
carboxymethyllysine (CML)-induced
inflammation in mouse mesangial cells.