Composition for treating atherosclerosis and a preparation method thereof

Abstract

Disclosed are a composition for preventing and treating atherosclerosis which includes chalcone compound. In particular, the chalcone compound bound with 2-hydroxyl in ring A and 4′-methyoxy in ring B has versatile therapeutic potentials on anti-atherosclerosis by acting as PPARγ inducer, p44/42 MAPK inhibitor and cell cycle blocker and does not show toxicity to human aortic smooth muscle cells (HASMCs). In addition, the chalcone compound exhibits synergistic effect with the PPARγ ligand (rosiglitazone) to inhibit cell proliferation and the upregulation of cyclin D1, cyclin D3, interleukin-1β (IL-1β) and interleukin-6 (IL-6) induced by oxidized low density lipoprotein (Ox-LDL).

1 . A composition for one of a prevention and a treatment of an atherosclerosis, comprising a chalcone compound represented by Formula I: 
       
         
           
           
               
               
           
         
         wherein R1 is a first hydrogen, each of R2 to R5 is selected from a group consisting of a second hydrogen, a first hydroxide and a halogen, each of R6, R7, R9 and R10 is selected from a group consisting of a third hydrogen, a second hydroxide, a C 1  to C 20  alkoxy group and a benzyloxy group, and R8 is selected from a group consisting of a fourth hydrogen, a C 1  to C 20  alkyl group and a benzyl group. 
       
     
     
         2 . The composition according to  claim 1  being effective in regulating a pathway by one of inhibiting a p44/42 mitogen-activated protein kinase (MAPK) phosphorylation and activating a peroxisome proliferator activated receptor gamma (PPARγ). 
     
     
         3 . The composition according to  claim 2 , wherein the p44/42 MAPK phosphorylation is effective in promoting an expression of at least one of an interleukin-6 (IL-6) and an interleukin-1beta (IL-1β). 
     
     
         4 . The composition according to  claim 2 , wherein the PPARγ is effective in inhibiting an expression of at least one of an interleukin-6 (IL-6) and an interleukin-1beta (IL-1β). 
     
     
         5 . The composition according to  claim 2 , wherein the PPARγ is effective in inhibiting an expression of at least one of a cyclin D1 and a cyclin D3. 
     
     
         6 . A composition for increasing a reproduction of a peroxisome proliferator activated receptor gamma (PPARγ), comprising a chalcone compound represented by Formula I: 
       
         
           
           
               
               
           
         
         wherein R1 is a first hydrogen, each of R2 to R5 is selected from a group consisting of a second hydrogen, a first hydroxide and a halogen, each of R6, R7, R9 and R10 is selected from a group consisting of a third hydrogen, a second hydroxide, a C 1  to C 20  alkoxy group and a benzyloxy group, and R8 is selected from a group consisting of a fourth hydrogen, a C 1  to C 20  alkyl group and a benzyl group. 
       
     
     
         7 . The composition according to  claim 6 , wherein the PPARγ is translated from a messenger RNA, and the composition is effective in increasing an expression of the messenger RNA. 
     
     
         8 . A pharmaceutical composition for inhibiting at least one of a cell proliferation of human aortic smooth muscle cells and an inflammation thereof, comprising a chalcone compound represented by Formula I and a ligand of a peroxisome proliferator activated receptor gamma (PPARγ): 
       
         
           
           
               
               
           
         
         wherein R1 is a first hydrogen, each of R2 to R5 is selected from a group consisting of a second hydrogen, a first hydroxide and a halogen, each of R6, R7, R9 and R10 is selected from a group consisting of a third hydrogen, a second hydroxide, a C 1  to C 20  alkoxy group and a benzyloxy group, and R8 is selected from a group consisting of a fourth hydrogen, a C 1  to C 20  alkyl group and a benzyl group. 
       
     
     
         9 . A pharmaceutical composition inhibiting an inflammation, comprising:
 a first effective amount of a chalcone compound represented by formula II:   
       
         
           
           
               
               
           
         
       
       and
 a second effective amount of an (RS)-5-[4-(2-[methyl(pyridin-2-yl)-amino]ethoxy)benzyl]thiazolidine-2,4-dione (rosiglitazone). 
 
     
     
         10 . The pharmaceutical composition according to  claim 9 , wherein the inflammation is a symptom of an atherosclerosis. 
     
     
         11 . A pharmaceutical composition inhibiting a proliferation of a smooth muscle cell, comprising:
 a first effective amount of a chalcone compound represented by formula II:   
       
         
           
           
               
               
           
         
       
       and
 a second effective amount of a 2-(2-amino-3-methoxyphenyl)-chromen-4-one (PD98059).