title: Paeonol attenuates advanced oxidation protein product-induced oxidative stress injury in THP-1 macrophages.
abstract: BACKGROUND
  Paeonol (2'-hydroxy-4'-methoxyacetophenone) is thought to possess a broad range of clinically curative effects that are likely mediated by its anti-inflammatory and antioxidant activities.
  
  
  OBJECTIVE
  To elucidate the efficacy of paeonol's anti-inflammatory and antioxidant activities and the underlying mechanism of paeonol in advanced oxidation protein product (AOPP) stimulation of THP-1 macrophages.
  
  
  METHODS
  After incubating cells with AOPP plus paeonol, nitric oxide (NO) production and the levels of inducible NO synthase (iNOS), receptor for advanced glycation end products (RAGE), CD36, scavenger receptor (SR)-A, and SR-B1 were calculated. Moreover, THP-1 macrophages were preincubated with paeonol, the free radical scavenger N-acetylcysteine (NAC), NADPH oxidase inhibitors [apocynin, diphenylene iodonium (DPI)], and the specific inhibitor of nuclear factor-κB pyrrolidine dithiocarbamate (PDTC) prior to incubation with AOPP, and the levels of intracellular reactive oxygen species (ROS) production and tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6, and monocyte chemotactic protein 1 (MCP-1) were determined.
  
  
  RESULTS
  Paeonol increased NO production and the mRNA level of iNOS, whereas it decreased ROS production. ROS production was also effectively attenuated by apocynin, DPI, NAC, and PDTC. Furthermore, these inhibitors and paeonol could downregulate the mRNA and protein levels of proinflammatory cytokines (TNF-α, IL-1β, IL-6, and MCP-1). Paeonol significantly reduced the expression levels of RAGE and CD36 but increased the expression levels of SR-A and SR-B1.
  
  
  CONCLUSIONS
  These results indicate that paeonol can decrease proinflammatory cytokines in THP-1 macrophages, likely through RAGE-, CD36-, SR-A-, and SR-B1-mediated signals involving NADPH oxidase-dependent ROS generation. This suggests that paeonol can be used as a therapeutic agent for diseases contributing to oxidative stress injury.
authors.affiliation: Department of Pharmacy, Nanfang Hospital, Southern Medical University, Guangzhou, PR China.
authors.forename: Mao
authors.initials: M
authors.lastname: Ping
authors.forename: Wei
authors.initials: W
authors.lastname: Xiao
authors.forename: Liqian
authors.initials: L
authors.lastname: Mo
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Xiao
authors.forename: Shaolian
authors.initials: S
authors.lastname: Song
authors.forename: Waijiao
authors.initials: W
authors.lastname: Tang
authors.forename: Xixiao
authors.initials: X
authors.lastname: Yang
mesh_terms: D000098:Acetophenones / Q000494:pharmacology*; D062107:Advanced Oxidation Protein Products; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology*; D018955:CD36 Antigens / Q000235:genetics; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D016207:Cytokines / Q000235:genetics; D006801:Humans; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000235:genetics; D018384:Oxidative Stress / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000235:genetics; D051117:Scavenger Receptors, Class A / Q000235:genetics; D051122:Scavenger Receptors, Class B / Q000235:genetics
chemical_list: D000098:Acetophenones; D062107:Advanced Oxidation Protein Products; D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D018955:CD36 Antigens; D016207:Cytokines; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; C495124:SCARB1 protein, human; D051117:Scavenger Receptors, Class A; D051122:Scavenger Receptors, Class B; D009569:Nitric Oxide; C013638:paeonol; C496319:NOS2 protein, human; D052247:Nitric Oxide Synthase Type II