Investigation of the improvement effect of Dihuang yinzi on neurological function of APP/PS1 double transgenic positive mice based on gut-brain axis and its mechanism
	    		
		   		
	    	
    	
    	
   		
        
        	
        		- VernacularTitle:基于肠脑轴探讨地黄饮子对APP/PS1转基因阳性小鼠神经功能的改善作用及机制
 
        	
        	
        	
        		- Author:
	        		
		        		
		        		
			        		Jing CHEN
			        		
			        		
			        		
			        			1
			        			
			        		
			        		
			        		
			        		
			        		;
		        		
		        		
		        		
			        		Xicai LIANG
			        		
			        		
			        		
			        			2
			        			
			        		
			        		
			        		
			        		
			        		;
		        		
		        		
		        		
			        		Jian WANG
			        		
			        		
			        		
			        			2
			        			
			        		
			        		
			        		
			        		
			        		;
		        		
		        		
		        		
			        		Shenghua WANG
			        		
			        		
			        		
			        			2
			        			
			        		
			        		
			        		
			        		
			        		;
		        		
		        		
		        		
			        		Tianyi NING
			        		
			        		
			        		
			        			2
			        			
			        		
			        		
			        		
			        		
			        		
		        		
		        		
		        		
		        		
		        			
			        		
			        		Author Information
			        		
		        		
		        		
			        		
			        		
			        			1. Teaching Experiment Center of Liaoning University of Traditional Chinese Medicine,Shenyang 110847,China
			        		
			        			2. Experimental Animal Center of Liaoning University of Traditional Chinese Medicine,Shenyang 110847,China
			        		
		        		
	        		
        		 
        	
        	
        	
        		- Publication Type:Journal Article
 
        	
        	
        		- Keywords:
        			
	        			
	        				
	        				
			        		
				        		Dihuang yinzi;
			        		
			        		
			        		
				        		gut-brain axis;
			        		
			        		
			        		
				        		neurological
			        		
			        		
	        			
        			
        		
 
        	
            
            
            	- From:
	            		
	            			China Pharmacy
	            		
	            		 2022;33(24):2978-2984
	            	
            	
 
            
            
            	- CountryChina
 
            
            
            	- Language:Chinese
 
            
            
            	- 
		        	Abstract:
			       	
			       		
				        
				        	OBJECTIVE To investigate the improvement effect of Dihuang yinzi on neurological function of APP/PS1 double transgenic positive mice and its possible mechanism. METHODS APP/PS1 double transgenic positive mice were randomly divided into APP/PS1 positive model group, Dihuang yinzi low-dose, medium-dose and high-dose groups (12, 24, 48 g/kg,by the amount of crude drug), western medicine group (donepezil hydrochloride 0.8 mg/kg); APP/PS1 transgenic negative mice were included in as APP/PS1 negative normal group, with 6 mice in each group. Administration groups were given relevant medicine intragastrically; APP/PS1 positive model group and APP/PS1 negative normal group were given constant volume of normal saline intragastrically, once a day, for consecutive 28 d. After the last medication, the ability of learning and memory, intestinal flora diversity (only medium-dose group of Dihuang yinzi), pathological changes of neural cells in hippocampus, and the expressions of Bcl-2, Bax and brain-derived neurotrophic factor (BDNF) in mice of each group were investigated. RESULTS Compared with APP/PS1 positive model group, escape latency of mice was shortened significantly in Dihuang yinzi medium-dose and high-dose groups, while the times of crossing the platform significantly increased (P<0.05). Compared with APP/PS1 positive model group, Chao1 index of Dihuang yinzi medium-dose group was lower, while Shannon index was higher (P<0.05); OTU abundance of microbial flora was decreased to some extent; dominant flora was Clostridia o_ Clostridia_ vadinBB60_ Group, verruca G_ UCG_ 005. Compared with the APP/PS1 positive model group, the pathological changes of the nerve cells in the hippocampal CA1 area of mice were improved in the medium-dose and high-dose groups of Dihuang yinzi; the protein expressions of Bcl-2 and BDNF in the hippocampal tissue were significantly increased, while the protein expression of Bax was significantly decreased (P<0.05). CONCLUSIONS Dihuang yinzi can enhance the diversity of flora, change the type of dominant flora, and can inhibit the apoptosis of brain neurons, and increase the level of BDNF; its mechanism may be to protect nerve cells by means of gut-brain axis, thereby improving the learning and memory ability of APP/PS1 positive model mice.