Explore The Molecular Mechanism Of Berberine In The Treatment Of Ulcerative Colitis Based On TAS2R38

Background and objective:Traditional Chinese medicine has its own rule in the treatment of ulcerative colitis,which can be widely applied to the lesion site in many ways and targets.It has unique advantages in improving clinical symptoms,promoting ulcer healing,preventing and delaying the recurrence of ulcerative colitis,and hindering the process of "inflammation-cancer transformation".Through database analysis,we found that bitter traditional Chinese medicine is mainly used in the treatment of ulcerative colitis,and the reception of bitter in the body depends on the role of bitter taste receptor.Therefore,the purpose of this study is to explore whether bitter traditional Chinese medicine/compounds play a role in the treatment of ulcerative colitis through bitter taste receptor.Methods:Molecular docking,MTT and intracellular calcium concentration detection were used to screen bitter compounds;colon length measurement,spleen weight measurement,in vivo imaging and HE staining were used to detect the effect of berberine on UC colon injury;WESTERN BLOT,IHC and IF were used to detect the expression of TAS2R38,PLC β 2,IP3R3,ZO-1 and E-cadherin.PCR was used to detect inflammatory factors in colon tissue,and ELISA was used to detect the level of inflammatory factors in the supernatant.Results:1)The subtype of bitter taste receptor used in the screening experiment is TAS2R38,and the bitter compound is berberine;2)Berberine can significantly improve the stool characteristics of UC mice,reverse the shortening of colon length,the decrease of HE score and the damage of intestinal barrier.3)Berberine can up-regulate the expression of TAS2R38 and its downstream proteins,and berberine can up-regulate the level of tight junction protein and decrease the level of pro-inflammatory factors.4)Berberine and TAS2R38 agonists can up-regulate the expression of TAS2R38 and its downstream proteins,while TAS2R38 agonists can promote the expression of ZO-1 and E-cadherin and reduce the secretion of inflammatory factors.5)TAS2R38 inhibitors down-regulate the expression of TAS2R38 and its downstream proteins,while TAS2R38 inhibitors can reduce the expression of ZO-1 and E-cadherin,reversing the trend of berberine reducing the secretion of inflammatory factors.Conclusion and significance:Berberine may regulate the expression of tight junction protein and the secretion of inflammatory factors in colonic epithelial cells through TAS2R38/PLC β2/IP3R3 signal axis,and play a role in the treatment of UC.This experimental study found that TAS2R38 can be used as a potential target for the treatment of UC,revealed the specific mechanism of berberine,the main active component of Coptis chinensis,in the treatment of UC,provided a new strategy for the treatment of UC,and verified the potential of berberine in the treatment of UC by acting on TAS2R38.