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Puerarin suppresses AGEs-induced inflammation in mouse mesangial cells: a possible pathway through the induction of heme oxygenase-1 expression.

Abstract
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.
AuthorsKi Mo Kim, Dong Ho Jung, Dae Sik Jang, Young Sook Kim, Jong Min Kim, Ha-Na Kim, Young-Joon Surh, Jin Sook Kim
JournalToxicology and applied pharmacology (Toxicol Appl Pharmacol) Vol. 244 Issue 2 Pg. 106-13 (Apr 15 2010) ISSN: 1096-0333 [Electronic] United States
PMID20060010 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright 2009 Elsevier Inc. All rights reserved.
Chemical References
  • Anti-Inflammatory Agents, Non-Steroidal
  • Glycation End Products, Advanced
  • Isoflavones
  • Heme Oxygenase-1
  • puerarin
Topics
  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal (pharmacology)
  • Cell Line, Transformed
  • Cells, Cultured
  • Enzyme Induction (drug effects, genetics, physiology)
  • Gene Expression Regulation, Enzymologic (drug effects)
  • Gene Knockdown Techniques
  • Glycation End Products, Advanced (antagonists & inhibitors, physiology)
  • Heme Oxygenase-1 (biosynthesis, genetics)
  • Inflammation (enzymology, metabolism, pathology)
  • Isoflavones (pharmacology)
  • Mesangial Cells (drug effects, metabolism, pathology)
  • Mice
  • Signal Transduction (drug effects, genetics, physiology)

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