Carnosic acid improves diabetic nephropathy by activating Nrf2/ARE and inhibition of NF-κB pathway

Background Diabetic nephropathy (DN), one of the most serious complications of diabetes , is the leading cause of morbidity and mortality of end-stage renal disease. Our previous research found that carnosic acid (CA) or rosemary extract can effectively improve glucose and lipid metabolism disorder by inhibiting SREBPs . Purpose In this study, we aimed to explore the therapeutic effects of CA on the DN. Methods The mice glomerular mesangial cells (mGMCs) were used to evaluate the anti-oxidative and anti-inflammation effects of CA under high glucose (HG) condition. Furthermore, db/db mice and streptozotocin (STZ)-induced diabetic mice were used to investigate the effects of CA against DN in vivo . Results The results showed that CA activated Nrf2, inhibited NF-κB pathway and regulated related downstream genes in mGMC under HG condition. A 14-week treatment of mice with CA reduced water uptake and urine volume, attenuated diabetes-induced albuminuria , increased urine creatinine , and subsequently improved the glomerular sclerosis and mesangial expansion in db/db mice. Similarly, a 20-week oral administration of CA improved kidney damage in STZ-induced diabetic mice. In addition, CA inhibited the expression of profibrotic factors, such as TGF-β1, fibronectin and E-cadherin. Compared to irbesartan , CA exerted better glucose lowering effect, and in kidney, CA was more potent to reduce fibronectin and E-cadherin expression. In all the animal experiment, CA did not lead to abnormal damages to other tissues. Conclusion These findings suggest that CA is a safe compound which exerts the protective effects on diabetes-induced kidney complications.