Exploring Potential of Phytochemicals in Diabetic Nephropathy

Abstract

Diabetic nephropathy involves pathophysiological changes in renal morphology and newlinechanges in functional proficiency. These changes can be listed as but are not limited to newlineglomerular hyperfiltration, increased urinary albumin excretion, proliferative newlineexpansion of mesangial cells, accumulation of excessive ECM (extra cellular matrix), newlinethickening of basement membrane of the tubules and the glomerulus along with newlinetubulointerstitial fibrosis, glomerular and renal hypertrophy. These changes lead to end newlinestage renal disease (ESRD) and chronic kidney disease (CKD). newlineProgression of DN involves various molecular mechanisms. Three major mechanisms newlineare reported which are triggered by elevated blood glucose level. First mechanism is newlineactivation of polyol pathway (Nakamura et al., 2005), protein kinase C (PKC) pathway newline(Juan et al., 2012) and hexosamine pathway (Riedl et al., 2011) due to abnormality of newlineintracellular signalling and metabolism. Another mechanism is increased oxidative newlinestress (Zhou et al., 2012) and formation of advanced glycation end products (AGEs) newline(Ishibashi et al., 2013) due to generation of free radicals and non-enzymatic glycation, newlinerespectively. Glomerular hyperfiltration and related hypertension is the third pathway newlinewhich causes activation of the renin-angiotensin system. These mechanisms follow a newlinecommon pathway of microinflammation and extracellular matrix (ECM) expansion newlinewhich lead to diabetic nephropathy (Titan et al., 2012). newlineNow it is well studied and accepted that transforming growth factor beta (TGF-and#946;) plays newlinea central role in the progression of diabetic nephropathy via various molecular newlinemediators and intracellular signalling pathways (Garud and Kulkarni, 2014). newlineTranscription and translation of TGF-and#946; is up regulated by increased plasma glucose newlinelevel through various mechanisms. Abnormal intracellular signalling and metabolism, newlineincreased oxidative stress and non-enzymatic glycation, activation of renin angiotensin system are the key pathways by which TFG-and#946; is up regulated in diabetic condition. newline