Regulatory Effect of Xiangshenwan on TLR/NF-κB Signal in Colonic Mucosa of Mice with Colitis / 中国实验方剂学杂志

ABSTRACT

Objective:To explore the effect and mechanism of Xiangshenwan on ulcerative colitis （UC） induced by dextran sulfate sodium （DSS） in mice based on the classic Toll-like receptor （TLR）/nuclear factor kappa B （NF-<italic>κ</italic>B） signaling pathway. Method:The experimental mice were divided into a normal group， a model group， a Xiangshenwan group， and a mesalazine group. The mice， except for those in the normal group， received 3% DSS solution for 7 days to establish the acute UC model and were treated with Xiangshenwan （5 g·kg^-1） and mesalazine （300 mg·kg^-1） continuously from the 1st day to the 10th day of modeling. The body weight， disease activity index （DAI）， colon weight， intestinal weight index， colon length， colon weight per unit length， and pathological changes of mice were evaluated respectively. The protein expression of TLR5， myeloid differentiation factor 88 （MyD88）， interleukin-1 receptor-associated kinase 4 （IRAK4）， tumor necrosis factor receptor-associated factor 6 （TRAF6）， transforming growth factor <italic>β</italic>-activated kinase 1 （TAK1）， p38 mitogen-activated protein kinase （MAPK）， NF-<italic>κ</italic>B， IRAK1， TAK1-binding protein 1 （TAB1）， TAB2， mitogen-activated protein kinase kinase 3 （MKK3）， MKK6 and cyclic adenosine monophosphate response element-binding protein （CREB） in colon tissues of mice was detected by Western blot. Result:Compared with the normal group， the model group showed decreased body weight of mice， increased DAI scores， elevated colon weight， intestinal weight index， and colon weight per unit length， shortened colon length， severe colonic mucosal injury， and up-regulated protein expression of TLR5， MyD88， IRAK4， TRAF6， TAK1， p38 MAPK， NF-<italic>κ</italic>B， IRAK1， TAB1， TAB2， MKK3， MKK6， and CREB in colon tissues （<italic>P</italic><0.05，<italic> P</italic><0.01<bold>）.</bold> Compared with the model group， the Xiangshenwan group and the mesalazine group displayed increased body weight of mice， decreased DAI scores， declining colon weight， intestinal weight index， and colon weight per unit length， increased colon length， improved colonic mucosal injury， and down-regulated protein expression of TLR5， MyD88， IRAK4， TRAF6， TAK1， p38 MAPK， NF-<italic>κ</italic>B， IRAK1， TAB1， TAB2， MKK3， MKK6， and CREB in colon tissues （<italic>P</italic><0.05，<italic> P</italic><0.01）. Conclusion:Xiangshenwan can effectively treat DSS-induced UC presumedly by the inhibition of TLR/NF-<italic>κ</italic>B signaling pathway.