Sophoridine inhibits NF-kappaB signaling pathway activation in kidney tissue of endotoxemia mice.
- Author:
Ling HUANG
1
;
Jian-ning XIE
;
Jin-ping LIANG
;
Yun-hong LI
;
Ya ZHOU
Author Information
1. Department of Pathogenic Biology and Immunology, School of Basic Medical Sciences, Ningxia Medical University, Yinchuan 750004, China.
- Publication Type:Journal Article
- MeSH:
Alkaloids;
pharmacology;
Animals;
Antitoxins;
pharmacology;
Endotoxemia;
blood;
chemically induced;
genetics;
metabolism;
Female;
I-kappa B Kinase;
genetics;
metabolism;
Kidney;
metabolism;
Lipopolysaccharides;
Male;
Mice;
Mice, Inbred BALB C;
Phosphorylation;
Quinolizines;
pharmacology;
RNA, Messenger;
metabolism;
Random Allocation;
Signal Transduction;
drug effects;
Transcription Factor RelA;
metabolism;
Tumor Necrosis Factor-alpha;
blood;
genetics;
metabolism
- From:
Acta Pharmaceutica Sinica
2011;46(9):1072-1077
- CountryChina
- Language:Chinese
-
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.