Kaempferol attenuates diabetic nephropathy by inhibiting RhoA/Rho-kinase mediated inflammatory signalling

Abstract

RhoA/Rho-associated coiled-coil forming protein serine/threonine kinase (ROCK) has appeared as a potential therapeutic target in numerous diseases, because of its preventing action on various enzymes providing antioxidant and cytoprotective action. Progression and pathophysiology of diabetic nephropathy have also shown potential involvement of oxidative stress and inflammatory pathways. In the present study, we investigated the effect of kaempferol on hyperglycemia-induced activation of RhoA kinase and associated inflammatory signaling cascade. Currently there is only small literature available on the mechanism of anti-diabetic and nephroprotective action of this compound, which creates a void. Therefore, we focused here on the investigation of molecular mechanisms for kaempferol by means of in vitro testing, using rat (NRK-52E) and human renal tubular epithelial cells (RPTEC). Our findings suggest that kaempferol inhibits hyperglycemia-induced activation of RhoA and decreased oxidative stress, pro-inflammatory cytokines (TNF-α and IL-1β) and fibrosis (TGF-β1 expression, extracellular matrix protein expression) in NRK-52E and RPTEC cells. Therefore, kaempferol can be used as a potential therapeutic for the treatment of diabetic nephropathy.

Keywords: Anti-inflammatory; Anti-oxidant; Diabetic nephropathy; Hyperglycemia; NRK-52 cells; RPTEC; RhoA.