PMID- 25170865 OWN - NLM STAT- MEDLINE DCOM- 20150406 LR - 20171116 IS - 1423-0313 (Electronic) IS - 0031-7012 (Linking) VI - 93 IP - 5-6 DP - 2014 TI - Paeonol attenuates advanced oxidation protein product-induced oxidative stress injury in THP-1 macrophages. PG - 286-95 LID - 10.1159/000363577 [doi] AB - 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. AIMS: 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. MATERIALS AND 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-kappaB pyrrolidine dithiocarbamate (PDTC) prior to incubation with AOPP, and the levels of intracellular reactive oxygen species (ROS) production and tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1beta, 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-alpha, IL-1beta, 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. CI - (c) 2014 S. Karger AG, Basel. FAU - Ping, Mao AU - Ping M AD - Department of Pharmacy, Nanfang Hospital, Southern Medical University, Guangzhou, PR China. FAU - Xiao, Wei AU - Xiao W FAU - Mo, Liqian AU - Mo L FAU - Xiao, Xiaoyan AU - Xiao X FAU - Song, Shaolian AU - Song S FAU - Tang, Waijiao AU - Tang W FAU - Yang, Xixiao AU - Yang X LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20140821 PL - Switzerland TA - Pharmacology JT - Pharmacology JID - 0152016 RN - 0 (Acetophenones) RN - 0 (Advanced Oxidation Protein Products) RN - 0 (Anti-Inflammatory Agents) RN - 0 (Antioxidants) RN - 0 (CD36 Antigens) RN - 0 (Cytokines) RN - 0 (RNA, Messenger) RN - 0 (Reactive Oxygen Species) RN - 0 (Receptor for Advanced Glycation End Products) RN - 0 (Receptors, Immunologic) RN - 0 (SCARB1 protein, human) RN - 0 (Scavenger Receptors, Class A) RN - 0 (Scavenger Receptors, Class B) RN - 31C4KY9ESH (Nitric Oxide) RN - 3R834EPI82 (paeonol) RN - EC 1.14.13.39 (NOS2 protein, human) RN - EC 1.14.13.39 (Nitric Oxide Synthase Type II) SB - IM MH - Acetophenones/*pharmacology MH - Advanced Oxidation Protein Products MH - Anti-Inflammatory Agents/*pharmacology MH - Antioxidants/*pharmacology MH - CD36 Antigens/genetics MH - Cell Line MH - Cell Survival/drug effects MH - Cytokines/genetics MH - Humans MH - Macrophages/*drug effects/metabolism MH - Nitric Oxide/metabolism MH - Nitric Oxide Synthase Type II/genetics MH - Oxidative Stress/drug effects MH - RNA, Messenger/metabolism MH - Reactive Oxygen Species/metabolism MH - Receptor for Advanced Glycation End Products MH - Receptors, Immunologic/genetics MH - Scavenger Receptors, Class A/genetics MH - Scavenger Receptors, Class B/genetics EDAT- 2014/08/30 06:00 MHDA- 2015/04/07 06:00 CRDT- 2014/08/30 06:00 PHST- 2013/12/06 00:00 [received] PHST- 2014/05/13 00:00 [accepted] PHST- 2014/08/30 06:00 [entrez] PHST- 2014/08/30 06:00 [pubmed] PHST- 2015/04/07 06:00 [medline] AID - 000363577 [pii] AID - 10.1159/000363577 [doi] PST - ppublish SO - Pharmacology. 2014;93(5-6):286-95. doi: 10.1159/000363577. Epub 2014 Aug 21.