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Depression: 21st Century Solutions + The Dark Side of Wheat

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Abstract Title:

Hesperidin Methylchalcone Suppresses Experimental Gout Arthritis in Mice by Inhibiting NF-κB Activation.

Abstract Source:

J Agric Food Chem. 2018 Jun 27 ;66(25):6269-6280. Epub 2018 Jun 13. PMID: 29852732

Abstract Author(s):

Kenji W Ruiz-Miyazawa, Felipe A Pinho-Ribeiro, Sergio M Borghi, Larissa Staurengo-Ferrari, Victor Fattori, Flavio A Amaral, Mauro M Teixeira, Jose C Alves-Filho, Thiago M Cunha, Fernando Q Cunha, Rubia Casagrande, Waldiceu A Verri

Article Affiliation:

Kenji W Ruiz-Miyazawa

Abstract:

Gout arthritis is a painful inflammatory disease induced by monosodium urate (MSU) crystals. We evaluate the therapeutic potential of the flavonoid hesperidin methylchalcone (HMC) in a mouse model of gout arthritis induced by intra-articular injection of MSU (100μg/10 μL). Orally given HMC (3-30 mg/kg, 100 μL) reduced in a dose-dependent manner the MSU-induced hyperalgesia (44%, p<0.05), edema (54%, p<0.05), and leukocyte infiltration (70%, p<0.05). HMC (30 mg/kg) inhibited MSU-induced infiltration of LysM-eGFPcells (81%, p<0.05), synovitis (76%, p<0.05), and oxidative stress (increased GSH, FRAP, and ABTS by 62, 78, and 73%, respectively; reduced Oand NO by 89 and 48%, p<0.05) and modulated cytokine production (reduced IL-1β, TNF-α, IL-6, and IL-10 by 35, 72, 37, and 46%, respectively, and increased TGF-β by 90%, p<0.05). HMC also inhibited MSU-induced NF-κB activation (41%, p<0.05), gp91(66%, p<0.05) and NLRP3 inflammasome components mRNA expression in vivo (72, 77, 71, and 73% for NLRP3, ASC, pro-caspase-1, and pro-IL-1β, respectively, p<0.05), and induced Nrf2/HO-1 mRNA expression (3.9- and 5.1-fold increase, respectively, p<0.05). HMC (30, 100, and 300μM) did not inhibit IL-1β secretion by macrophages primed by LPS and challenged with MSU (450 μg/mL), demonstrating that the anti-inflammatory effect of HMC in gout arthritis depends on inhibiting NF-κB but not on direct inhibition of inflammasome. The pharmacological effects of HMC indicate itstherapeutic potential for the treatment of gout.

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Sayer Ji
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Depression: 21st Century Solutions + The Dark Side of Wheat

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