6-Shogaol protects against ischemic acute kidney injury by modulating NF κB and heme oxygenase-1 pathways.

6-Shogaol protects against ischemic acute kidney injury by modulating NFκB and heme oxygenase-1 pathways. Am J Physiol Renal Physiol. 2019 Jul 17;: Authors: Han SJ, Kim M, D'Agati VD, Lee HT Abstract Acute kidney injury (AKI) due to renal ischemia reperfusion (IR) is a major clinical problem without effective therapy. Ginger is one of the most widely consumed spices in the world and 6-Shogaol, a major Ginger metabolite, has anti-inflammatory effects in neuronal and epithelial cells. Here, we demonstrate that 6-Shogaol treatment protected against renal IR injury with decreased plasma creatinine, blood urea nitrogen and kidney NGAL mRNA synthesis compared to vehicle-treated mice subjected to renal IR. In addition, 6-Shogaol treatment reduced kidney inflammation (decreased pro-inflammatory cytokine and chemokine synthesis as well as neutrophil infiltration) and apoptosis (decreased TUNEL positive renal tubular cells) when compared to vehicle-treated mice subjected to renal IR. In cultured human and mouse kidney proximal tubule cells, 6-Shogaol significantly attenuated TNF-α induced inflammatory cytokine and chemokine mRNA synthesis. Mechanistically, 6-Shogaol significantly attenuated TNF-α induced NFκB activation in human renal proximal tubule cells by reducing IKKαβ/IκBα phosphorylation. Furthermore, 6-Shogaol induced a cytoprotective chaperone heme oxygenase-1 (HO-1) via p38 MAPK activation in vitro and in vivo. Consistent wit...
Source: American Journal of Physiology. Renal Physiology - Category: Physiology Authors: Tags: Am J Physiol Renal Physiol Source Type: research