Sirtuin 3 ameliorates inflammatory bowel disease via inhibiting intestinal inflammation and oxidative stress.

Sirtuin 3 involved in development of various diseases, but its role in inflammatory bowel disease is still unknown. We used inflammatory bowel disease biopsies, colitis animal model, and vitro cells RAW264.7 to study the role of Sirtuin 3 in the pathophysiology of inflammatory bowel disease. Sirtuin 3 negatively correlated with intestinal TNF-α. Sirt3 was less pronounced in pediatric and adult inflammatory bowel disease patients compared with corresponding control group. Sirtuin 3 activator Honokiol suppressed dextran sulfate sodium induced colonic manifestations, while Sirt3 inhibitor caused opposite results. Honokiol inhibited colonic oxidative stress by and reduced intestinal permeability. Honokiol repressed inflammatory response by reducing macrophage infiltration, pro-inflammatory cytokines TNF-α, IL-1ß, and IL-6 levels, and inhibiting activation of NF-κB p65 in the colitis mice. However, Sirt3 inhibitor amplified colonic oxidative stress and inflammatory response. In vitro study, Sirt3 inhibitor or siRNA Sirtuin 3 activated NF-κB p65 and enhanced TNF-α, IL-1ß, and IL-6 secretion from LPS stimulated RAW264.7, while Honokiol remarkably attenuated these pro-inflammatory cytokines secretion. Finally, knockdown of Sirt3 in Caco-2 cells enhanced TNF-α induced intestinal barrier integrity injury. Sirtuin 3 negatively regulates inflammatory bowel disease progression via reducing colonic inflammation and oxidative stress. Sirtuin 3 is a promising therapeutic target in clinical application for inflammatory bowel disease therapy.

Isobavachalcone ameliorates diabetic nephropathy in rats by inhibiting the NF-κB pathway.

Isobavachalcone (ISO) exhibits good anti-inflammatory activity. We evaluated the renoprotective effects of ISO against diabetic nephropathy (DN). Diabetic rats established by the single injection of streptozotocin (STZ) were orally treated with ISO. The levels of serum creatinine (Scr), blood urea nitrogen (BUN), and 24 hr urinary protein were measured. In this study, ISO effectively ameliorated renal damage by reducing BUN, Scr, and 24 hr urinary protein and also improved kidney pathological appearances. ISO prevented STZ-caused apoptosis in the glomerular tissue in vivo and blocked the high glucose (HG)-induced growth inhibitory effect in human renal glomerular endothelial cells in vitro. Moreover, ISO reduced pro-inflammatory mediator production and blocked the NF-κB pathway in the damaged renal tissues and HG-treated HRGEC cells. Taken together, the results of this study indicate that ISO consumption might have significant beneficial effects on the DN and this action might be correlated with the modulation of the NF-κB pathway. PRACTICAL APPLICATIONS: ISO is an active compound from the dried ripe fruit of Psoralea corylifolia L. seed, which is traditionally served as a food ingredient in Asia. In this investigation, we observed the beneficial effects of ISO on a murine model with DN. Further research revealed that the protective action of ISO might be connected with its weak hypoglycaemic and notable anti-inflammatory effects. Our research data suggest that ISO-enriched food might be a good choice for people suffering from DN.