Dipeptidyl-peptidase IV inhibitors (DPP-4) have gain popularity day by day as anti-diabetic agents and now are broadly used in the treatment of type 2 diabetes with chronic renal dysfunction.DPP-4 inhibitors have potential to reduce the glucose level independent of the renal function either reduce the level of glycated albumin without inducing the hypoglycaemic effects. Studies suggest that DPP-4 exert the renal protective effect via maintain the incidence of albuminuria. The current experimental study was make attempt to explore the renal protective effect of gallic acid- metformin (GA-Met) against the STZ induced diabetic rats via inhibition of DPP-4 and TGF-β.

GA-Met was scrutinizing against the DPP-4 inhibitor. GA-Met were also examined via Insilco study with the structure of DPP-4 to identify the critical interactions for its bioactivity. STZ was used for induction the type 2 diabetes and blood glucose level, biochemical, antioxidant, cytokines and inflammatory mediators were estimated.

: DPP-4 assay, GA-Met was found as potential drug with IC50 value = 4.34 µM. GA-Met Insilco interacted with various residue of DPP-4 inhibitor. GA-Met significantly reduced the blood glucose level (67%) and increased the plasma insulin level (45.5%). GA-Met improve the interstitial fibrosis, tubulointerstitial injury and inflammatory cell infiltration in animal tissue. GA-Met exhibited the significantly decrease the level of TNF-α (45%), Il-1β (54.3%). IL-6 (56.1%), caspase-1 (43%), caspase-3 (40.4%), COX-2 (65%). PGE2 (60.3%) and NF-kB (52.3%). Oxidative stress marker and the expression of transforminggrowth factor-β (TGF-β) in the renal tissue of diabetic rats were significantly (P<0.001) altered by GA-Met treated group rats.

The current investigation suggests that GA-Met Conjugates exert the renal protective effect against the STZ induced DN rats via inhibition of DPP4 and TGF-β.