Ellagic acid, an NF-κB inhibitor, ameliorates renal function in experimental diabetic nephropathy

Diabetic nephropathy (DN) is a serious complication confronted by diabetic patients. Available data indicate that the development of DN is linked to inflammation. In this context, nuclear factor-kappa B (NF-κB) has received much attention. Ellagic acid (2,3,7,8-tetrahydroxy-chromeno[5,4,3-cde]chromene-5,10-dione), found abundantly in plant extracts and fruits, possesses numerous medicinal properties. We investigated the nephroprotective effects of oral treatment of ellagic acid in high fat diet/low dose streptozotocin (HFD/STZ)-induced type 2 diabetic Wistar albino rats. Ellagic acid treatment for 16weeks post induction of diabetes significantly attenuated renal dysfunction and oxidative stress. Ellagic acid significantly inhibited the renal NF-кB activation. Moreover, ellagic acid significantly lowered renal pathology and suppressed transforming growth factor-beta (TGF-β) and fibronectin expressions in renal tissues. Ellagic acid also significantly reduced the serum levels of pro-inflammatory cytokines, interleukin-1beta (IL-1β), IL-6 and tumor necrosis factor-alpha (TNF-α). In cultured rat NRK 52E proximal tubular epithelial cells, ellagic acid treatment inhibited high glucose-induced activation of NF-κB and pro-inflammatory cytokine synthesis. These results suggest that ellagic acid exhibited renal protective effect in diabetic rats partly through antihyperglycemia which was accompanied by attenuation of inflammatory processes via inhibition of NF-κB pathway.