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Sophocarpine attenuates toll‐like receptor 4 in steatotic hepatocytes to suppress pro‐inflammatory cytokines synthesis
Author(s) -
Song ChunYan,
Zeng Xin,
Wang Yang,
Shi Jian,
Qian Hui,
Zhang Yi,
Fang JiaQing,
Sheng Xia,
Zheng JianMing,
Chen YueXiang
Publication year - 2015
Publication title -
journal of gastroenterology and hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.214
H-Index - 130
eISSN - 1440-1746
pISSN - 0815-9319
DOI - 10.1111/jgh.12691
Subject(s) - proinflammatory cytokine , medicine , mapk/erk pathway , inflammation , nonalcoholic fatty liver disease , kinase , pharmacology , immunology , biochemistry , biology , fatty liver , disease
Background and Aim Sophocarpine, a tetracyclic quinolizidine alkaloid derived from Sophora alopecuroides L., has been documented that it can suppress pro‐inflammatory cytokines synthesis in alleviating nonalcoholic steatohepatitis ( NASH ) in vivo . Toll‐like receptor 4 ( TLR 4) is a pattern recognition receptor whose activation results in the production of several pro‐inflammatory cytokines. It has been reported that TLR 4 is upregulated in nonalcoholic fatty liver disease and plays an important role in the pathogenesis of NASH . This study aimed to examine the changes of TLR 4 and its signaling pathways in sophocarpine's anti‐inflammatory process on experimental NASH in vitro . Methods Primary hepatocytes were isolated, and oleic acid‐induced steatosis model was established. Cell Counting Kit‐8 assay was used to detect the number of metabolically active mitochondria and viable cells. Immunocytochemistry analysis was applied to evaluating pro‐inflammatory cytokines synthesis. Total RNA and protein were extracted for real‐time polymerase chain reaction and W estern blot detection. Results Enhanced expression of TLR 4 was observed in oleic acid‐induced steatotic hepatocytes. Sophocarpine suppressed pro‐inflammatory cytokines synthesis and reduced the expression of TLR 4 in steatotic hepatocytes. Expression of TLR 4 and pro‐inflammatory cytokines recovered after sophocarpine was removed. Moreover, sophocarpine restrained the activation of nuclear factor‐kappaB ( NF ‐κ B) , c‐Jun‐N‐terminal kinase ( JNK ), and Extracellular regulated protein kinases ( ERK ) signaling pathways in the anti‐inflammatory process. Conclusion Sophocarpine could decrease the expression of TLR 4 in steatotic hepatocytes and suppress pro‐inflammatory cytokines synthesis. NF ‐κ B , JNK, and ERK signaling pathways were important workable downstream pathways.