Orally bioavailable stilbenoids- compositions and therapeutic applications thereof

Abstract

A novel, bioavailable and safe stilbenoid 3,5-dimethoxy-3,4′-dihydroxystilbene represented by STR#1 with an unexpected enhanced ability to prevent the accumulation of lipids accompanying the terminal differentiation of adipocytes, thereby inhibiting adipogenesis, and nutraceutical and cosmeceutical compositions comprising 3,5-dimethoxy-3,4′-dihydroxystilbene useful for anti-obesity and anti-cellulite therapy, are disclosed. Further the enhanced SIRT-1 activation ability of 3,5-dimethoxy-3,4′-dihydroxystilbene represented by STR#1 and 2,3′,5′,6-tetrahydroxy-trans-stilbene represented by STR#II are disclosed. The enhancement of SIRT-1 polypeptide activity of the said compounds is unexpectedly much higher than resveratrol or its natural analog pterostilbene. Sirtuin modulating compositions comprising an orally bioavailable SIRT-1 enhancing compounds (i) 3,5-dimethoxy-3,4′-dihydroxystilbene represented by STR#I and (ii) 2,3′,5′,6-tetrahydroxy-trans-stilbene represented by STR#II are also disclosed. An additional embodiment, also discloses the enhanced anti-Propionibacterium acnes activity of 3,5-dimethoxy-3,4′-dihydroxystilbenes represented by STR#I and compositions thereof.

1 . A novel, orally bioavailable and safe stilbenoid 3,5-dimethoxy-3,4′-dihydroxystilbene represented by STR#1, said stilbenoid useful with an unexpected enhanced ability to inhibit the accumulation of lipids accompanying the terminal differentiation of adipocytes and thereby inhibiting adipogenesis. 
       
         
           
           
               
               
           
         
       
     
     
         2 . Compositions comprising the novel, orally bioavailable and safe stilbenoid of  claim 1 . 
     
     
         3 . The compositions according to  claim 2  wherein said compositions are nutraceutical compositions. 
     
     
         4 . The compositions according to  claim 2  wherein said compositions are pharmaceutical compositions. 
     
     
         5 . The compositions according to  claim 2  wherein said compositions are cosmeceutical compositions. 
     
     
         6 . The compositions according  claim 5 , wherein said compositions comprise from about 0.3% w/v to about 5% w/v of 3,5-dimethoxy-3,4′-dihydroxystilbene represented by STR#1. 
       
         
           
           
               
               
           
         
       
     
     
         7 . An enhanced sirtuin modulating stilbenoid represented by STR#1. 
       
         
           
           
               
               
           
         
       
     
     
         8 . An enhanced sirtuin modulating stilbenoid represented by STR#2 
       
         
           
           
               
               
           
         
       
     
     
         9 . A stilbenoid inhibiting the growth of  Propionibacterium acnes  in an enhanced manner, said stilbenoid represented by STR#1 
       
         
           
           
               
               
           
         
       
     
     
         10 . Cosmeceutical formulations comprising from about 0.3% w/v to about 5% w/v of the stilbenoid of  claim 9 . 
     
     
         11 . Nutraceutical formulations comprising the stilbenoid of  claim 7 . 
     
     
         12 . Nutraceutical formulations comprising the stilbenoid of  claim 8 . 
     
     
         13 . Pharmaceutical formulations comprising the stilbenoid of  claim 7 . 
     
     
         14 . Pharmaceutical formulations comprising the stilbenoid of  claim 8 . 
     
     
         15 . Adipogenesis inhibitors represented by the general structure STR#III, wherein R1=R 2  are aliphatic or aromatic side chains and the resulting ether linkages thereof form primary, secondary or tertiary ethers. 
       
         
           
           
               
               
           
         
       
     
     
         16 . Nutraceutical compositions comprising the inhibitors of  claim 15 . 
     
     
         17 . Pharmaceutical compositions comprising the inhibitors of  claim 15 . 
     
     
         18 . Cosmeceutical compositions comprising the inhibitors of  claim 15 .