Rosmarinic acid attenuates hepatic fibrogenesis via suppression of hepatic stellate cell activation/proliferation and induction of apoptosis 
	    		
		   		
		   			
		   		
	    	
    	 
    	10.1016/j.apjtm.2017.05.012
   		
        
        	
        	
        	
        		- Author:
	        		
		        		
		        		
			        		Naglaa M. EL-LAKKANY
			        		
			        		
			        		
			        			1
			        			
			        		
			        		
			        		
			        		
			        		;
		        		
		        		
		        		
			        		Walaa H. EL-MAADAWY
			        		
			        		
			        		
			        			1
			        			
			        		
			        		
			        		
			        		
			        		;
		        		
		        		
		        		
			        		Sayed H. SEIF EL-DIN
			        		
			        		
			        		
			        			1
			        			
			        		
			        		
			        		
			        		
			        		;
		        		
		        		
		        		
			        		Olfat A. HAMMAM
			        		
			        		
			        		
			        			2
			        			
			        		
			        		
			        		
			        		
			        		;
		        		
		        		
		        		
			        		Salwa H. MOHAMED
			        		
			        		
			        		
			        			3
			        			
			        		
			        		
			        		
			        		
			        		;
		        		
		        		
		        		
			        		Shahira M. EZZAT
			        		
			        		
			        		
			        			4
			        			
			        		
			        		
			        		
			        		
			        		;
		        		
		        		
		        		
			        		Marwa M. SAFAR
			        		
			        		
			        		
			        			5
			        			
			        		
			        		
			        		
			        		
			        		;
		        		
		        		
		        		
			        		Samira SALEH
			        		
			        		
			        		
			        			5
			        			
			        		
			        		
			        		
			        		
			        		
		        		
		        		
		        		
		        		
		        			
			        		
			        		Author Information
			        		
		        		
		        		
			        		
			        		
			        			1. Department of Pharmacology, Theodor Bilharz Research Institute, Warak El-Hadar
			        		
			        			2. Department of Pathology, Theodor Bilharz Research Institute, Warak El-Hadar
			        		
			        			3. Department of Immunology, Theodor Bilharz Research Institute, Warak El-Hadar
			        		
			        			4. Department of Pharmacognosy, Faculty of Pharmacy, Cairo University
			        		
			        			5. Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University
			        		
		        		
	        		
        		 
        	
        	
        	
        		- Publication Type:Journal Article
 
        	
        	
        		- Keywords:
        			
	        			
	        				
	        				
			        		
				        		Apoptosis;
			        		
			        		
			        		
				        		Hepatic fibrosis;
			        		
			        		
			        		
				        		Hepatic stellate cells;
			        		
			        		
			        		
				        		Profibrogenic markers;
			        		
			        		
			        		
				        		Proliferation;
			        		
			        		
			        		
				        		Rosmarinic acid
			        		
			        		
	        			
        			
        		
 
        	
            
            
            	- From:
	            		
	            			Asian Pacific Journal of Tropical Medicine
	            		
	            		 2017;10(5):444-453
	            	
            	
 
            
            
            	- CountryChina
 
            
            
            	- Language:Chinese
 
            
            
            	- 
		        	Abstract:
			       	
			       		
				        
				        	 Objective To investigate the antifibrotic role of rosmarinic acid (RA), a natural polyphenolic compound, on HSCs activation/proliferation and apoptosis in vitro and in vivo. Methods The impact of RA on stellate cell line (HSC-T6) proliferation, activation and apoptosis was assessed along with its safety on primary hepatocytes. In vivo, rats were divided into: (i) normal; (ii) thioacetamide (TAA)-intoxicated rats for 12 weeks; (iii) TAA + silymarin or (iv) TAA + RA. At the end of experiment, liver functions, oxidative stress, inflammatory and profibrogenic markers, tissue inhibitor metalloproteinases type-1 (TIMP-1) and hydroxyproline (HP) levels were evaluated. Additionally, liver histopathology and immunohistochemical examinations of alpha-smooth muscle actin (α-SMA), caspase-3 and proliferation cellular nuclear antigen (PCNA) were determined. Results RA exhibited anti-proliferative effects on cultured HSCs in a time and concentration dependent manner showing an IC