Quercetin-Loaded Microcapsules Ameliorate Experimental Colitis in Mice by Anti-inflammatory and Antioxidant Mechanisms

Quercetin (<b>1</b>) is an anti-inflammatory and antioxidant flavonoid. However, the oral administration of <b>1</b> did not lead to beneficial effects in experimental animal colitis models, which involve cytokines and oxidative stress. A possible explanation is that the absorption profile of <b>1</b> prevents its activity. Therefore, it was reasoned that the controlled release of <b>1</b> would improve its therapeutic effect. Thus, the therapeutic effect and mechanisms of <b>1</b>-loaded microcapsules in acetic acid-induced colitis in mice were evaluated. Microcapsules were prepared using pectin/casein polymer and <b>1</b>. The oral administration of <b>1</b>-loaded microcapsules decreased neutrophil recruitment, attenuated histological alterations, and reduced macroscopical damage, edema, and IL-1β and IL-33 production in the colon samples. Microcapsules loaded with <b>1</b> also prevented the reduction of anti-inflammatory cytokine IL-10 and the antioxidant capacity of the colon. These preclinical data indicate that pectin/casein polymer microcapsules loaded with <b>1</b> improved the anti-inflammatory and antioxidant effects of <b>1</b> compared to the nonencapsulated drug. Therefore, quercetin seems to be a promising active molecule in inflammatory bowel disease if provided with adequate controlled release

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

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 (100 μg/10 μL). Orally given HMC (3–30 mg/kg, 100 μL) reduced in a dose-dependent manner the MSU-induced hyperalgesia (44%, <i>p</i> < 0.05), edema (54%, <i>p</i> < 0.05), and leukocyte infiltration (70%, <i>p</i> < 0.05). HMC (30 mg/kg) inhibited MSU-induced infiltration of LysM-eGFP⁺ cells (81%, <i>p</i> < 0.05), synovitis (76%, <i>p</i> < 0.05), and oxidative stress (increased GSH, FRAP, and ABTS by 62, 78, and 73%, respectively; reduced O₂^– and NO by 89 and 48%, <i>p</i> < 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%, <i>p</i> < 0.05). HMC also inhibited MSU-induced NF-κB activation (41%, <i>p</i> < 0.05), gp91^phox (66%, <i>p</i> < 0.05) and NLRP3 inflammasome components mRNA expression in vivo (72, 77, 71, and 73% for NLRP3, ASC, pro-caspase-1, and pro-IL-1 β, respectively, <i>p</i> < 0.05), and induced Nrf2/HO-1 mRNA expression (3.9- and 5.1-fold increase, respectively, <i>p</i> < 0.05). HMC (30, 100, and 300 μM) 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 its therapeutic potential for the treatment of gout