PMID- 30333752 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20200929 IS - 1663-9812 (Print) IS - 1663-9812 (Electronic) IS - 1663-9812 (Linking) VI - 9 DP - 2018 TI - Trans-Chalcone Attenuates Pain and Inflammation in Experimental Acute Gout Arthritis in Mice. PG - 1123 LID - 10.3389/fphar.2018.01123 [doi] LID - 1123 AB - Gouty arthritis is characterized by an intense inflammatory response to monosodium urate crystals (MSU), which induces severe pain and reduction in the life quality of patients. Trans-Chalcone (1,3-diphenyl-2-propen-1-one) is a flavonoid precursor presenting biological activities such as anti-inflammatory and antioxidant proprieties. Thus, the aim of this work was to evaluate the protective effects of trans-Chalcone in experimental gout arthritis in mice. Mice were treated with trans-Chalcone (3, 10, or 30 mg/kg, per oral) or vehicle (Tween 80 20% plus saline) 30 min before intra-articular injection of MSU (100 mug/knee joint, intra-articular). We observed that trans-Chalcone inhibited MSU-induced mechanical hyperalgesia, edema, and leukocyte recruitment (total leukocytes, neutrophils, and mononuclear cells) in a dose-dependent manner. Trans-Chalcone also decreased inflammatory cell recruitment as observed in Hematoxylin and Eosin (HE) staining and the intensity of fluorescence of LysM-eGFP+ cells in the confocal microscopy. Trans-Chalcone reduced MSU-induced oxidative stress as observed by an increase in the antioxidant defense [Glutathione (GSH), Ferric Reducing (FRAP), and 2,2'-Azinobis-3-ethylbenzothiazoline 6-sulfonic acid (ABTS assays)] and reduction in reactive oxygen and nitrogen species production [superoxide anion (NBT assay) and nitrite (NO assay)]. Furthermore, it reduced in vivo MSU-induced interleukin-1beta (IL-1beta), Tumor necrosis factor-alpha (TNF-alpha), and IL-6 production, and increased Transforming growth factor-beta (TGF-beta) production. Importantly, trans-Chalcone reduced nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kappaB) activation and thereby the mRNA expression of the inflammasome components Nlrp3 (cryopyrin), Asc (apoptosis-associated speck-like protein containing a CARD), Pro-caspase-1 and Pro-IL-1beta. In vitro, trans-Chalcone reduced the MSU-induced release of IL-1beta in lipopolysaccharide (LPS)-primed macrophages. Therefore, the pharmacological effects of trans-Chalcone indicate its therapeutic potential as an analgesic and anti-inflammatory flavonoid for the treatment of gout. FAU - Staurengo-Ferrari, Larissa AU - Staurengo-Ferrari L AD - Departamento de Ciencias Patologicas, Universidade Estadual de Londrina, Londrina, Brazil. FAU - Ruiz-Miyazawa, Kenji W AU - Ruiz-Miyazawa KW AD - Departamento de Ciencias Patologicas, Universidade Estadual de Londrina, Londrina, Brazil. FAU - Pinho-Ribeiro, Felipe A AU - Pinho-Ribeiro FA AD - Departamento de Ciencias Patologicas, Universidade Estadual de Londrina, Londrina, Brazil. FAU - Fattori, Victor AU - Fattori V AD - Departamento de Ciencias Patologicas, Universidade Estadual de Londrina, Londrina, Brazil. FAU - Zaninelli, Tiago H AU - Zaninelli TH AD - Departamento de Ciencias Patologicas, Universidade Estadual de Londrina, Londrina, Brazil. FAU - Badaro-Garcia, Stephanie AU - Badaro-Garcia S AD - Departamento de Ciencias Patologicas, Universidade Estadual de Londrina, Londrina, Brazil. FAU - Borghi, Sergio M AU - Borghi SM AD - Departamento de Ciencias Patologicas, Universidade Estadual de Londrina, Londrina, Brazil. FAU - Carvalho, Thacyana T AU - Carvalho TT AD - Departamento de Ciencias Patologicas, Universidade Estadual de Londrina, Londrina, Brazil. FAU - Alves-Filho, Jose C AU - Alves-Filho JC AD - Department of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Brazil. FAU - Cunha, Thiago M AU - Cunha TM AD - Department of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Brazil. FAU - Cunha, Fernando Q AU - Cunha FQ AD - Department of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Brazil. FAU - Casagrande, Rubia AU - Casagrande R AD - Departamento de Ciencias Farmaceuticas, Universidade Estadual de Londrina, Londrina, Brazil. FAU - Verri, Waldiceu A Jr AU - Verri WA Jr AD - Departamento de Ciencias Patologicas, Universidade Estadual de Londrina, Londrina, Brazil. LA - eng PT - Journal Article DEP - 20181002 PL - Switzerland TA - Front Pharmacol JT - Frontiers in pharmacology JID - 101548923 PMC - PMC6176465 OTO - NOTNLM OT - flavonoids OT - gout flare OT - gouty arthritis OT - inflammation OT - joint pain OT - natural products OT - rheumatic disease OT - trans-Chalcone EDAT- 2018/10/20 06:00 MHDA- 2018/10/20 06:01 PMCR- 2018/10/02 CRDT- 2018/10/19 06:00 PHST- 2018/06/16 00:00 [received] PHST- 2018/09/13 00:00 [accepted] PHST- 2018/10/19 06:00 [entrez] PHST- 2018/10/20 06:00 [pubmed] PHST- 2018/10/20 06:01 [medline] PHST- 2018/10/02 00:00 [pmc-release] AID - 10.3389/fphar.2018.01123 [doi] PST - epublish SO - Front Pharmacol. 2018 Oct 2;9:1123. doi: 10.3389/fphar.2018.01123. eCollection 2018.