Regulatory Effect of Volatile Oil from Sishenwan on TLR/MyD88 Signaling Pathway in Mice with Chronic Ulcerative Colitis / 中国实验方剂学杂志

ABSTRACT

Objective:To explore the underlying mechanism of volatile oil from Sishenwan in treating chronic ulcerative colitis through the Toll-like receptor （TLR）/myeloid differentiation factor 88 （MyD88） signaling pathway. Method:The BALB/c mice were randomly divided into a normal group （normal）， a model group ［dextran sodium sulfate （DSS）］， a Sishenwan volatile oil group， an Ershen pill volatile oil group， a Wuweizi powder volatile oil group， and a mesalazine control group. The chronic ulcerative colitis model was induced by DSS in mice. Seven days after intragastric administration， the efficacy was evaluated based on the body weight， colon weight， colon weight index， colon length， and pathological damage score under colonoscopy. The levels of interleukin （IL）-4， IL-10， IL-17A， IL-21， and interferon-<italic>γ </italic>（IFN-<italic>γ</italic>） in the supernatant of colon tissues were detected by enzyme-linked immunosorbent assay （ELISA）. Western blot was used to detect the expression levels of proteins related to the TLR/MyD88 signaling pathway in the colon mucosa of mice， including TLR2， MyD88， Ras-related C3 botulinum toxin substrate 1 （Rac1）， IL-1 receptor-associated kinase 4 （IRAK4）， IRAK1， tumor necrosis factor receptor （TNFR）-associated factor 6 （TRAF6）， transforming growth factor-<italic>β</italic>-activated kinase 1 binding protein 1 （TAB1）， TAB2， mitogen-activated protein kinase kinase 6 （MKK6）， p38 mitogen-activated protein kinase （p38 MAPK）， and cyclic adenosine monophosphate response element-binding protein （CREB）. Result:Compared with the normal group， the model group showed decreased colon length， increased colon weight， colon weight index， and pathological damage score under colonoscopy， decreased IL-10 level in the colon tissues， increased IL-4， IL-17A， IL-21， and IFN-<italic>γ</italic> levels （<italic>P<</italic>0.05， <italic>P<</italic>0.01）， and up-regulated protein expression of TLR2， MyD88， Rac1， IRAK4， IRAK1， TRAF6， TAB1， TAB2， MKK6， p38MAPK， and CREB （<italic>P<</italic>0.01）. Compared with the model group， the Sishenwan volatile oil group showed increased colon length， reduced colon weight， colon weight index， and pathological damage score under colonoscopy， elevated IL-10 level in the colon tissues， decreased IL-4， IL-17A， IL-21， and IFN-<italic>γ</italic> levels （<italic>P<</italic>0.05， <italic>P<</italic>0.01），and down-regulated protein expression of TLR2， MyD88， Rac1， IRAK4， IRAK1， TRAF6， TAB1， TAB2， MKK6， p38MAPK， and CREB （<italic>P<</italic>0.05， <italic>P<</italic>0.01）. Conclusion:The volatile oil from Sishenwan can effectively improve the inflammatory response of chronic ulcerative colitis， which may be achieved by regulating the TLR/MyD88 signaling pathway.