Sophoridine inhibits NF-κB signaling pathway activation in kidney tissue of endotoxemia mice

This study is to investigate the effects of sophoridine on NF-κB 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·kg⁻¹group, 6 mg·kg⁻¹ group and 3 mg·kg⁻¹ group.  All animals were sacrificed at 6 hours after treatment. Kidney and blood samples were harvested.  IKKβ mRNA and TNF-α mRNA expression of renal tissue was measured by the reverse transcription polymerase chain reaction (RT-PCR), and phosphorylation IKKβ protein (pIKKβ) was detected by immunohistochemistry.  NF-κB P65 protein expression and distribution of renal tissue were observed by Western blotting and immunofluorescence laser confocal microscopy.  Serum TNF-α level was detected by radioimmunoassay.  The results showed that the sophoridine significantly reduced the expression of IKKβ mRNA and pIKKβ protein, and inhibited the expression of NF-κB P65 protein and decreased the entry nuclear rate of NF-κB P65 in the renal tissue of endotoxemia mice.  Thereby the renal TNF-α mRNA expression and serum TNF-α level were significantly reduced.  These results suggest that sophoridine could inhibit inflammatory reaction induced by LPS through inhibiting activation of NF-κB signaling pathway.