Sophoridine inhibits NF-kappaB signaling pathway activation in kidney tissue of endotoxemia mice / 药学学报

ABSTRACT

This study is to investigate the effects of sophoridine on NF-kappaB signaling pathway in kidney tissue of endotoxemia mice and the mechanism involved. BALB/c mice were challenged with lipopolysaccharide (LPS) caudal vein injection, then sophoridine was administered by intraperitoneal injection. Totally 50 mice were divided into 5 groups control group, LPS model group, sophoridine treatment 12 mg x kg(-1) group, 6 mg x kg(-1) group and 3 mg x kg(-1) group. All animals were sacrificed at 6 hours after treatment. Kidney and blood samples were harvested. IKKbeta mRNA and TNF-alpha mRNA expression of renal tissue was measured by the reverse transcription polymerase chain reaction (RT-PCR), and phosphorylation IKKbeta protein (pIKKbeta) was detected by immunohistochemistry. NF-kappaB P65 protein expression and distribution of renal tissue were observed by Western blotting and immunofluorescence laser confocal microscopy. Serum TNF-alpha level was detected by radioimmunoassay. The results showed that the sophoridine significantly reduced the expression of IKKbeta mRNA and pIKKbeta protein, and inhibited the expression of NF-kappaB P65 protein and decreased the entry nuclear rate of NF-kappaB P65 in the renal tissue of endotoxemia mice. Thereby the renal TNF-alpha mRNA expression and serum TNF-alpha level were significantly reduced. These results suggest that sophoridine could inhibit inflammatory reaction induced by LPS through inhibiting activation of NF-kappaB signaling pathway.