Rehmannioside A Attenuates Inflammation via Inactivation of the p-p65 NF-?B and p-p38 MAPK Signaling in Abdominal...

Septic acute kidney injury (AKI) is the most common type of acute kidney failure observed in hospitalized patients, with inflammation playing a central role in its pathogenesis. The study aimed to investigate the influence of Rehmannioside A (Re A), a natural ingredient from the traditional Chinese herb Rehmanniae radix, on renal dysfunction and inflammation in septic AKI. Peripheral venous blood specimens were obtained from septic patients with and without AKI for comparing their clinical profiles. A rat model of sepsis was established through cecal ligation and puncture (CLP) surgery, followed by intraperitoneal injections of Re A. Biochemical analysis was performed to measure concentrations of kidney function indicators including blood urea nitrogen (BUN) and serum creatinine (Scr). Structural changes in kidney samples were evaluated by hematoxylin-eosin staining. Colony forming units of bacteria were counted in blood and renal samples of rats. Enzyme-linked immunosorbent assay was performed to measure serum and renal levels of proinflammatory cytokines (TNF? and IL-1?). Protein levels of factors related to MAPK and NF-?B pathways were quantified by western blotting. AKI patients showed increases in sepsis-related organ failure assessment (SOFA) score, BUN, Scr, TNF? and IL-1? levels compared to non-AKI patients. Re A improved the survival rate of CLP model rats and reversed CLP-induced increase in BUN and Scr levels. Pathological changes including renal tubular swelling and luminal narrowing induced by CLP were effectively ameliorated by Re A. In addition, Re A reduced bacterial load and proinflammatory cytokine levels in both blood and renal samples. As to the mechanism, Re A inactivated the phosphorylated levels of p38 MAPK and p65 NF-?B rat kidney samples. Re A plays renal-protective and anti-inflammatory properties in the rat model of septic AKI by inhibiting the activation of p38 MAPK and p65 NF-?B signaling. Keywords Acute kidney injury " Inflammation " Rehmannioside A " Renal dysfunction " Sepsis.