Exploring Synergistic Mechanism of Vinegar-processed Olibanum in Treatment of Ulcerative Colitis Based on Bile Acid-regulated "Gut-liver" Crosstalk / 中国实验方剂学杂志

ABSTRACT

ObjectiveTo investigate the synergistic mechanism of vinegar-processed Olibanum on ulcerative colitis（UC） via the bile acids regulating "gut-liver" crosstalk. MethodRats were randomly divided into normal group， model group， Olibanum group and vinegar-processed Olibanum group. UC model of rats was induced by intracolonic instillation of 2，4，6-trinitrobenzenesulfonic acid（TNBS）. Ultra high performance liquid chromatography-triple quadrupole-mass spectrometry（UPLC-QQQ-MS） was used to perform the qualitative analysis of 30 bile acids in the colon of rats. Real-time fluorescence quantitative polymerase chain reaction（Real-time PCR） and Western blot were used to detect changes in the expression of farnesoid X receptor（FXR）， fibroblast growth factor 15（FGF15） and FGF receptor 4（FGFR4） in "gut-liver" crosstalk at mRNA and protein levels. And with the help of HcoEpiC cell model intervened by conjugated bile acids， simulating the UC state， and according to the different modes of intervention， they were divided into the blank group， conjugated bile acid group， Olibanum group， vinegar-processed Olibanum group and 3-O-acetyl-9，11-dehydro-β-boswellic acid（ADHBA） group. The effect of Olibanum before and after processing with vinegar and the main differential component ADHBA on the mRNA expression of FXR and FGF19 were explored by Real-time PCR. ResultCompared with the normal group， the levels of conjugated bile acids in the model group increased significantly（P<0.01）， and the mRNA and protein expressions of "gut-liver" crosstalk factors FXR， FGF15 and FGFR4 decreased significantly（P<0.05， P<0.01）. Compared with the model group， the content of conjugated bile acids in the Olibanum group and vinegar-processed Olibanum group was significantly decreased（P<0.01）， the mRNA and protein expressions of FXR， FGF15 and FGFR4 were significantly elevated（P<0.05， P<0.01）， and vinegar-processed Olibanum exhibited superior effects than Olibanum. In cellular experiments， a significant decrease in mRNA expression of FXR and FGF19 was observed in the conjugated bile acid group when compared with the blank group（P<0.01）. Compared with the conjugated bile acid group， the mRNA expressions of FXR and FGF19 were significantly higher in the Olibanum， vinegar-processed Olibanum and ADHBA groups（P<0.05， P<0.01）， and the effect of vinegar-processed Olibanum was more favorable. ConclusionVinegar-processed Olibanum may enhance the ameliorating effect on UC by enhancing the down-regulation of conjugated bile acids in the colon and the up-regulation of FXR-FGF15/19-FGFR4 "gut-liver" crosstalk pathway， and ADHBA may be the main material basis for the synergy.