Pharmacological appraisal of phytochemicals and their mechanism of protection against inflammatory and fibrotic renal diseases

Abstract

quotFibrosis in kidneys is constantly associated with glomerulosclerosis and newlinetubulointerstitial fibrosis. Irrespective of the initial trigger of renal injury, progressive newlinerenal interstitial fibrosis is an important manifestation of chronic kidney disease (CKD). newlineThe CKD with the hallmark of tubulointerstitial fibrosis subsequently results in tissue newlinescarring, renal damage, and end-stage renal disease (ESRD). CKD affects roughly 10% newlineof the population across the globe. Renal fibrosis remains one of the challenging clinical newlinemanifestations of diabetic nephropathy (DN). DN or diabetic kidney disease represents newlinea serious microvascular complication of diabetes. It is recognized as the prominent cause newlineof glomerular dysfunction, hyperfiltration, and albuminuria that eventually culminates newlineinto ESRD. Despite extensive research, DN remains the leading cause of morbidity and newlinemortality among the global diabetic population posing an enormous public health newlineburden. Moreover, effective therapies inhibiting the clinical manifestations of DN newlineremain elusive. Naturally derived phytoestrogens, including flavonoids and newlineisoflavonoids, are extensively investigated for their broad biological activities. newlineBiochanin A (BCA) (5,7-dihydroxy-4 -methoxy-isoflavone) is one of the most widely newlineexplored dietary estrogens with pronounced pharmacological benefits. It shows a high newlineabundance of plant species like red clover, cabbage, soybean, chickpea, and alfalfa newlinesprouts. Moreover, it exhibits promising neuroprotective, cardioprotective, antidiabetic, newlineanti-inflammatory, and hepatoprotective activity. However, its effect on renal newlinetubulointerstitial fibrosis, diabetic nephropathy, and underlying molecular mechanism newlinehas not yet been clarified. The present study aimed to assess the pharmacological effect newlineof BCA on renal tubulointerstitial fibrosis, and diabetic nephropathy and to explore the newlineunderlying mechanism. The mouse model of unilateral ureteral obstruction (UUO) in newlinevivo and transforming growth factor (TGF)-and#946;1 activated renal fibrobl