Sinensetin improves intestinal mucosal dysfunction in mice with ulcerative colitis by inhibiting iron death pathway
	    		
		   		
		   			
		   		
	    	
    	 
    	10.13699/j.cnki.1001-6821.2024.07.019
   		
        
        	
        		- VernacularTitle:甜橙黄酮通过抑制铁死亡途径改善溃疡性结肠炎小鼠肠道黏膜功能障碍的研究
 
        	
        	
        	
        		- Author:
	        		
		        		
		        		
			        		Li-Ping YU
			        		
			        		
			        		
			        			1
			        			
			        		
			        		
			        		
			        		
			        		;
		        		
		        		
		        		
			        		Liang-Pan SHI
			        		
			        		
		        		
		        		
		        		
		        		
		        			
			        		
			        		Author Information
			        		
		        		
		        		
			        		
			        		
			        			1. 福建医科大学附属泉州市第一医院,痔疮科,福建泉州 362000
			        		
		        		
	        		
        		 
        	
        	
        	
        	
        		- Keywords:
        			
	        			
	        				
	        				
			        		
				        		sinensetin;
			        		
			        		
			        		
				        		iron death pathway;
			        		
			        		
			        		
				        		ulcerative colitis;
			        		
			        		
			        		
				        		intestinal mucosal function
			        		
			        		
	        			
        			
        		
 
        	
            
            
            	- From:
	            		
	            			The Chinese Journal of Clinical Pharmacology
	            		
	            		 2024;40(7):1024-1028
	            	
            	
 
            
            
            	- CountryChina
 
            
            
            	- Language:Chinese
 
            
            
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		        	Abstract:
			       	
			       		
				        
				        	Objective To investigate the effects of Sinensetin on intestinal mucosal dysfunction in mice with ulcerative colitis by inhibiting iron death pathway.Methods C57BL/6 mice were randomly divided into control group,model group,positive group and low,medium,high dose experimental groups.UC model was established in all groups except control group.At the same time,control group and model group were given the same amount of 0.9%NaCl by intragastric administration;low,medium and high dose experimental groups were given intragastric administration of 10,20 and 40 mg·kg-1 sinensetin;positive group was given intragastric administration of 50 mg·kg-1mesalazine,once a day,for 14 days.The general condition,colon length,intestinal weight index,disease activity index(DAI)and mucosal damage index(CMDI)scores of mice were observed.D-lactic acid content(D-LA),diamine oxidase(DAO),interleukin-1 β(IL-1 β),interleukin-10(IL-10)and tumor necrosis factor-α(TNF-α)were detected by the kit.The expression of compact connecting closure protein(Occludin),tight junction protein-1(Claudin-1),non-glycosylated xCT(SLC7A11)and glutathione peroxidase 4(GPX4)were detected by Western blot.Results The serum DAO of control group,model group and low,medium,high dose experimental groups were(9.23±1.28),(34.61±3.95),(29.36±3.34),(23.41±2.74)and(16.75±2.57)U·mL-1,respectively;serum D-LA were(7.04±1.71),(18.25±1.05),(15.14±1.56),(11.43±1.70)and(8.93±1.56)ng·mL-1,respectively;the expression of Occludin protein were 0.89±0.08,0.25±0.05,0.37±0.03,0.48±0.05 and 0.66±0.07,respectively;the expression of Claudin-1 protein were 0.83±0.09,0.33±0.05,0.47±0.05,0.59±0.06 and 0.72±0.07,respectively;GPX4 protein expression were 0.85±0.06,0.23±0.05,0.36±0.04,0.53±0.06 and 0.72±0.08,respectively;SLC7A11 protein expressions were 0.95±0.06,0.30±0.04,0.42±0.05,0.65±0.05 and 0.84±0.05,respectively.There was statistical significance between control group and model group(all P<0.05).There were significant differences in the above indexes between model group and low,medium,high dose experimental groups(all P<0.05).Conclusion Sinensetin can inhibit iron death pathway and improve intestinal mucosal dysfunction in mice with ulcerative colitis.