Compounds, compositions and methods for protecting brain health in neurodegenerative disorders

Abstract

Aspects of the invention relate to compounds, extracts and compositions thereof, and methods of using of the same, to treat neurodegenerative disorders and/or improve brain health. In certain embodiments, said compounds are pomegranate flavonoids.

We claim: 
     
         1 . A method comprising the step of administering to a subject an amount of Punicalin, Punicalagin, Pedunculagin, Tellimagrandin, Corilagin, Granatine A, Granatine B, Terminalin, Gallagyldilactone, Compound A or a compound of Formula I: 
       
         
           
           
               
               
           
         
       
       or pharmaceutically acceptable salt, biologically active metabolite, solvate, hydrate, prodrug, enantiomer or stereoisomer thereof; wherein, independently for each occurrence,
 X is 
 
       
         
           
           
               
               
           
         
          and 
         R 1 , R 2  and R 3  are each independently hydrogen, alkyl, aralkyl, alkylcarboxy, or a sugar; or 
         R 1  is hydrogen, alkyl, aralkyl, alkylcarboxy, 
       
       
         
           
           
               
               
           
         
          or a sugar, R 2  is hydrogen or 
       
       
         
           
           
               
               
           
         
          and R 3  is 
       
       
         
           
           
               
               
           
         
          or 
         R 1  is hydrogen, alkyl, aralkyl, alkylcarboxy, or a sugar, and R 2  and R 3  taken together are 
       
       
         
           
           
               
               
           
         
       
     
     
         2 . The method of  claim 1 , wherein the compound of the invention is pure and isolated. 
     
     
         3 . The method of  claim 1 , wherein the compound is administered as part of a nutraceutical composition, pharmaceutical composition, functional food, functional nutrition product, medical food, medical nutrition product, dietary supplement or botanical drug. 
     
     
         4 . The method of  claim 1 , wherein the subject is a human. 
     
     
         5 . The method of  claim 1 , wherein the general cognition of the subject is improved. 
     
     
         6 . The method of  claim 1 , wherein the method treats or prevents a cognitive disorder, a neurodegenerative disorder, a metabolic syndrome, type-II diabetes, dislipidemia, or obesity. 
     
     
         7 . The method of  claim 1 , wherein the method treats or prevents an amyloidosis-related condition in said subject. 
     
     
         8 . The method of  claim 1 , wherein the method treats or prevents ALS, Huntington's disease, Parkinson's disease, or Down syndrome. 
     
     
         9 . The method of  claim 1 , wherein the method treats or prevents Alzheimer's disease, 
     
     
         10 . The method of  claim 1 , wherein the method treats a cognitive impairment in a human. 
     
     
         11 . The method of  claim 10 , wherein memory is improved in the human following said administration. 
     
     
         12 . The method of  claim 10 , wherein the improvement in memory is an improvement in at least one measure selected from the group consisting of an improvement in short-term memory, long-term memory, memory consolidation, procedural memory and declarative memory. 
     
     
         13 . The method of  claim 10 , wherein attention is improved in the human following said administration. 
     
     
         14 . The method of  claim 10 , wherein reaction time is improved in the human following said administration. 
     
     
         15 . The method of  claim 10 , wherein learning is improved in the human following said administration. 
     
     
         16 . A method comprising the step of administering to a subject an amount of a pomegranate extract; wherein
 the extract contains an active fraction comprising at least one polyphenol; and   the extract has been prepared by:   a juicing and manufacturing process, optionally followed by fractionalization by centrifugation and/or ultrafiltration, before being dried;   a juicing and manufacturing process, optionally followed by fractionalization by centrifugation and/or ultrafiltration, before being adsorbed into the polymeric chromatographic resin, washed with water, and eluted with a solvent; or   a juicing and manufacturing process, optionally followed by fractionalization by centrifugation and/or ultrafiltration, before being adsorbed into the polymeric chromatographic resin, washed with water, eluted with a solvent, and subsequently dried.   
     
     
         17 . A method of inhibiting aggregation of a peptide or protein, comprising the step of contacting the peptide or protein with an effective amount of Punicalin, Punicalagin, Pedunculagin, Tellimagrandin, Corilagin, Granatine A, Granatine B, Terminalin, Gallagyldilactone, Compound A or a compound of Formula I: 
       
         
           
           
               
               
           
         
         or pharmaceutically acceptable salt, biologically active metabolite, solvate, hydrate, prodrug, enantiomer or stereoisomer thereof; wherein, independently for each occurrence, 
         X is 
       
       
         
           
           
               
               
           
         
          and 
         R 1 , R 2  and R 3  are each independently hydrogen, alkyl, aralkyl, alkylcarboxy, or a sugar; or 
         R 1  is hydrogen, alkyl, aralkyl, alkylcarboxy, 
       
       
         
           
           
               
               
           
         
          or a sugar, R 2  is hydrogen or 
       
       
         
           
           
               
               
           
         
          and R 3  is 
       
       
         
           
           
               
               
           
         
          or 
         R 1  is hydrogen, alkyl, aralkyl, alkylcarboxy, or a sugar, and R 2  and R 3  taken together are 
       
       
         
           
           
               
               
           
         
       
     
     
         18 . A pure and isolated compound, or a pharmaceutically acceptable salt, biologically active metabolite, solvate, hydrate, prodrug, enantiomer or stereoisomer thereof;
 wherein the compound is represented by formula I:   
       
         
           
           
               
               
           
         
         wherein independently for each occurrence 
         X is 
       
       
         
           
           
               
               
           
         
          and 
         R 1 , R 2  and R 3  are each independently hydrogen, alkyl, aralkyl, alkylcarboxy, or a sugar; or 
         R 1  is hydrogen, alkyl, aralkyl, alkylcarboxy, 
       
       
         
           
           
               
               
           
         
          or a sugar, R 2  is hydrogen or 
       
       
         
           
           
               
               
           
         
          and R 3  is 
       
       
         
           
           
               
               
           
         
          or 
         R 1  is hydrogen, alkyl, aralkyl, alkylcarboxy, or a sugar, and R 2  and R 3  taken together are 
       
       
         
           
           
               
               
           
         
       
     
     
         19 . The compound of  claim 18 , wherein the compound is Compound A, or a pharmaceutically acceptable salt, biologically active metabolite, solvate, hydrate, prodrug, enantiomer or stereoisomer thereof.