AS-IV protects against kidney IRI through inhibition of NF-κB activity and PUMA upregulation

Objective: To determine and explore the effect of Astragalus saponin IV (AS-IV) on ischemia/reperfusion (IR)-induced renal injury and its mechanisms. Methods: Experimental model of renal I/R was induced in rats by bilateral renal artery clamp for 45 min followed by reperfusion of 6 h. Rats were divided into three groups: (1) sham (2) IRI (3) IRI/AS-IV. In IRI/AS-IV groups, AS-IV was orally administered once a day to rats at 2 mg . kg(-1) . d(-1) for 7 days prior to ischemia. At 6 h after reperfusion, the inflammatory cytokines and renal function was assessed and NF-kappa B activity and PUMA expression was detected. Apoptotic cells was detected by TUNEL assay. Results: AS-IV significantly decreased serum and tissue levels of IL-6 and TNF-alpha, and reduced apoptotic cell counts and histological damage. AS-IV down-regulated the phosphorylation of p65 subunit of NF-kappa B (NF-kappa B p65) and PUMA expression, and the NF-kappa B activity compared to the I/R groups. Conclusions: AS-IV provided protection against IRI-induced renal injury by reducing apoptosis and inflammation through inhibition of NF-kappa B activity and PUMA expression. AS-IV pre-treatment ameliorated tubular damage and suppressed the NF-kappa B p65 expression.