title: 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.
authors.affiliation: Diabetic Complications Research Center, Division of Traditional Korean Medicine (TKM) Integrated Research, Korea Institute of Oriental Medicine (KIOM), 483 Exporo, Yuseong-gu, Daejeon 305-811, South Korea.
authors.forename: Ki Mo
authors.initials: KM
authors.lastname: Kim
authors.forename: Dong Ho
authors.initials: DH
authors.lastname: Jung
authors.forename: Dae Sik
authors.initials: DS
authors.lastname: Jang
authors.forename: Young Sook
authors.initials: YS
authors.lastname: Kim
authors.forename: Jong Min
authors.initials: JM
authors.lastname: Kim
authors.forename: Ha-Na
authors.initials: HN
authors.lastname: Kim
authors.forename: Young-Joon
authors.initials: YJ
authors.lastname: Surh
authors.forename: Jin Sook
authors.initials: JS
authors.lastname: Kim
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D002461:Cell Line, Transformed; D002478:Cells, Cultured; D004790:Enzyme Induction / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D055785:Gene Knockdown Techniques; D017127:Glycation End Products, Advanced / Q000037:antagonists & inhibitors* / Q000502:physiology; D051547:Heme Oxygenase-1 / Q000096:biosynthesis* / Q000235:genetics; D007249:Inflammation / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D007529:Isoflavones / Q000494:pharmacology*; D050527:Mesangial Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics / Q000502:physiology*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D017127:Glycation End Products, Advanced; D007529:Isoflavones; D051547:Heme Oxygenase-1; C033607:puerarin