6-Shogaol protects against ischemic acute kidney injury by modulating NFκB and heme oxygenase-1 pathways.
Am J Physiol Renal Physiol. 2019 Jul 17. Epub 2019 Jul 17. PMID: 31313953
Sang Jun Han
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 activationand. Consistent with these findings, pretreatment with a HO-1 inhibitor Zinc Protoporphyrin IX completely prevented 6-Shogaol-mediated protection against ischemic AKI in mice. Taken together, our studies show that 6-Shogaol protects against ischemic AKI by attenuating NFκB activation and inducing HO-1 expression. 6-Shogaol may provide a potential therapy for ischemic AKI during the perioperative period.