Method for improving digestive health

Abstract

Disclosed herein are methods for improving digestive health by providing a consumable composition. Some embodiments provided include, for example, administering a compound of Formula (I) or compound of Formula (II). Some embodiments provide the composition is formulated as a dietary supplement, food ingredient or additive, a medical food, nutraceutical or pharmaceutical composition.

What is claimed is: 
     
         1 . A method for improving digestive health comprising providing a consumable composition comprising at least one carrier and an effective amount of an extract comprising a compound of Formula (I), or an isomer, salt, homodimer, heterodimer, or conjugate thereof: 
       
         
           
           
               
               
           
         
       
       wherein
 R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , and R 9  are each independently selected from hydrogen, deuterium, hydroxyl, halogen, cyano, nitro, optionally substituted amino, optionally substituted C-amido, optionally substituted N-amido, optionally substituted ester, optionally substituted —(O)C 1-6 alkyl, optionally substituted —(O)C 1-6 alkenyl, optionally substituted —(O)C 1-6 alkynl, optionally substituted, —(O)C 4-12 cycloalkyl, optionally substituted —(O)C 1-6 alkylC 4-12 cycloalkyl, optionally substituted —(O)C 4-12 heterocyclyl, optionally substituted —(O)C 1-6 alkylC 4-12 heterocyclyl, optionally substituted —(O)C 4-12 aryl, optionally substituted —(O)C 1-6 alkylC 5-12 aryl, optionally substituted —(O)C 1-12 heteroaryl, and optionally substituted —(O)C 1-6 alkylC 1-12 heteroaryl; the dashed bond is present or absent; 
 X is CH 2  or O; 
 Z is CHR a , NR a , or O; and 
 R a  is selected from hydrogen, deuterium, hydroxyl, halogen, cyano, nitro, optionally substituted amino, optionally substituted C-amido, optionally substituted N-amido, optionally substituted ester, optionally substituted —(O)C 1-6 alkyl, optionally substituted —(O)C 1-6 alkenyl, optionally substituted —(O)C 1-6 alkynl, optionally substituted, —(O)C 4-12 cycloalkyl, optionally substituted —(O)C 1-6 alkylC 4-12 cycloalkyl, optionally substituted —(O)C 4-12 heterocyclyl, optionally substituted —(O)C 1-6 alkylC 4-12 heterocyclyl, optionally substituted —(O)C 4-12 aryl, optionally substituted —(O)C 1-6 alkylC 5-12 aryl, optionally substituted —(O)C 1-12 heteroaryl, and optionally substituted —(O)C 1-6 alkylC 1-12 heteroaryl,
 thereby improving digestive health. 
 
 
     
     
         2 . The method of  claim 1 , wherein said compound has the structure of Formula II: 
       
         
           
           
               
               
           
         
       
       wherein:
 R 1 , R 2 , R 3 , and R 4  are each independently selected from hydrogen, deuterium, hydroxyl, halogen, cyano, nitro, optionally substituted amino, optionally substituted C-amido, optionally substituted N-amido, optionally substituted ester, optionally substituted —(O)C 1-6 alkyl, optionally substituted —(O)C 1-6 alkenyl, optionally substituted —(O)C 1-6 alkynl, optionally substituted, —(O)C 4-12 cycloalkyl, optionally substituted —(O)C 1-6 alkylC 4-12 cycloalkyl, optionally substituted —(O)C 4-12 heterocyclyl, optionally substituted —(O)C 1-6 alkylC 4-12 heterocyclyl, optionally substituted —(O)C 4-12 aryl, optionally substituted —(O)C 1-6 alkylC 5-12 aryl, optionally substituted —(O)C 1-12 heteroaryl, and optionally substituted —(O)C 1-6 alkylC 1-12 heteroaryl; 
 the dashed bond is present or absent; 
 Z is CHR a , NR a , or O; and 
 R a  is selected from hydrogen, deuterium, hydroxyl, halogen, cyano, nitro, optionally substituted amino, optionally substituted C-amido, optionally substituted N-amido, optionally substituted ester, optionally substituted —(O)C 1-6 alkyl, optionally substituted —(O)C 1-6 alkenyl, optionally substituted —(O)C 1-6 alkynl, optionally substituted, —(O)C 4-12 cycloalkyl, optionally substituted —(O)C 1-6 alkylC 4-12 cycloalkyl, optionally substituted —(O)C 4-12 heterocyclyl, optionally substituted —(O)C 1-6 alkylC 4-12 heterocyclyl, optionally substituted —(O)C 4-12 aryl, optionally substituted —(O)C 1-6 alkylC 5-12 aryl, optionally substituted —(O)C 1-12 heteroaryl, and optionally substituted —(O)C 1-6 alkylC 1-12 heteroaryl. 
 
     
     
         3 . The method of  claim 1 , wherein said extract is an ethanol extract of a member of the genus  Allium, Amoracia, Chenopodium, Spinacia, Fagopyrum, Annona, Jatropha, Hibiscus, Piper, Eragrostis, Zea, Nelumbo, Cannabis, Ziziphus, Zanthoxylum, Ipomea, Capsicum, Lycium, Solanum , or  Tribulus.    
     
     
         4 . The method of  claim 1 , wherein the composition is formulated as a dietary supplement, food ingredient or additive, a medical food, nutraceutical or pharmaceutical composition. 
     
     
         5 . The method of  claim 1 , wherein R 1 , R 2 , R 3 , and R 8  are each independently selected from hydrogen, deuterium, hydroxyl, halogen, cyano, nitro, optionally substituted amino, optionally substituted C-amido, optionally substituted N-amido, optionally substituted ester, optionally substituted —(O)C 1-6 alkyl, optionally substituted —(O)C 1-6 alkenyl, optionally substituted —(O)C 1-6 alkynl, optionally substituted, —(O)C 4-12 cycloalkyl, optionally substituted —(O)C 1-6 alkylC 4-12 cycloalkyl, optionally substituted —(O)C 4-12 heterocyclyl, optionally substituted —(O)C 1-6 alkylC 4-12 heterocyclyl, optionally substituted —(O)C 4-12 aryl, optionally substituted —(O)C 1-6 alkylC 5-12 aryl, optionally substituted —(O)C 1-12 heteroaryl, and optionally substituted —(O)C 1-6 alkylC 1-12 heteroaryl;
 R 4 , R 5 , R 6 , R 7 , and R 9  are each independently hydrogen, deuterium, hydroxyl, or halogen; 
 dashed bond is present; 
 X is O; 
 Z is CHR a , NR a , or O; and 
 R a  is selected from hydrogen, deuterium, hydroxyl, halogen, cyano, nitro, optionally substituted amino, optionally substituted C-amido, optionally substituted N-amido, optionally substituted ester, optionally substituted —(O)C 1-6 alkyl, optionally substituted —(O)C 1-6 alkenyl, optionally substituted —(O)C 1-6 alkynl, optionally substituted, —(O)C 4-12 cycloalkyl, optionally substituted —(O)C 1-6 alkylC 4-12 cycloalkyl, optionally substituted —(O)C 4-12 heterocyclyl, optionally substituted —(O)C 1-6 alkylC 4-12 heterocyclyl, optionally substituted —(O)C 4-12 aryl, optionally substituted —(O)C 1-6 alkylC 5-12 aryl, optionally substituted —(O)C 1-12 heteroaryl, and optionally substituted —(O)C 1-6 alkylC 1-12 heteroaryl. 
 
     
     
         6 . The method of  claim 1 , wherein R 1 , R 2 , and R 8  are each independently selected from hydrogen, deuterium, hydroxyl, halogen, cyano, nitro, optionally substituted amino, optionally substituted C-amido, optionally substituted N-amido, optionally substituted ester, optionally substituted —(O)C 1-6 alkyl, optionally substituted —(O)C 1-6 alkenyl, optionally substituted —(O)C 1-6 alkynl, optionally substituted, —(O)C 4-12 cycloalkyl, optionally substituted —(O)C 1-6 alkylC 4-12 cycloalkyl, optionally substituted —(O)C 4-12 heterocyclyl, optionally substituted —(O)C 1-6 alkylC 4-12 heterocyclyl, optionally substituted —(O)C 4-12 aryl, optionally substituted —(O)C 1-6 alkylC 5-12 aryl, optionally substituted —(O)C 1-12 heteroaryl, and optionally substituted —(O)C 1-6 alkylC 1-12 heteroaryl;
 R 3 , R 4 , R 5 , R 6 , R 7 , and R 9  are each independently hydrogen, deuterium, hydroxyl, or halogen; 
 the dashed bond is present; 
 X is CH 2  or O; 
 Z is CHR a , NR a , or O; and 
 R a  is selected from hydrogen, deuterium, hydroxyl, halogen, cyano, nitro, optionally substituted amino, optionally substituted C-amido, optionally substituted N-amido, optionally substituted ester, optionally substituted —(O)C 1-6 alkyl, optionally substituted —(O)C 1-6 alkenyl, optionally substituted —(O)C 1-6 alkynl, optionally substituted, —(O)C 4-12 cycloalkyl, optionally substituted —(O)C 1-6 alkylC 4-12 cycloalkyl, optionally substituted —(O)C 4-12 heterocyclyl, optionally substituted —(O)C 1-6 alkylC 4-12 heterocyclyl, optionally substituted —(O)C 4-12 aryl, optionally substituted —(O)C 1-6 alkylC 5-12 aryl, optionally substituted —(O)C 1-12 heteroaryl, and optionally substituted —(O)C 1-6 alkylC 1-12 heteroaryl. 
 
     
     
         7 . The method of  claim 2 , wherein R 4  is selected from hydrogen, deuterium, hydroxyl, halogen, cyano, nitro, optionally substituted amino, optionally substituted C-amido, optionally substituted N-amido, optionally substituted ester, optionally substituted —(O)C 1-6 alkyl, optionally substituted —(O)C 1-6 alkenyl, optionally substituted —(O)C 1-6 alkynl, optionally substituted, —(O)C 4-12 cycloalkyl, optionally substituted —(O)C 1-6 alkylC 4-12 cycloalkyl, optionally substituted —(O)C 4-12 heterocyclyl, optionally substituted —(O)C 1-6 alkylC 4-12 heterocyclyl, optionally substituted —(O)C 4-12 aryl, optionally substituted —(O)C 1-6 alkylC 5-12 aryl, optionally substituted —(O)C 1-12 heteroaryl, and optionally substituted —(O)C 1-6 alkylC 1-12 heteroaryl;
 R 1  and R 2  are —OH; 
 R 3  is H; 
 the dashed bond is present; 
 Z is CHR a , NR a , or O; and 
 R a  is selected from hydrogen, deuterium, hydroxyl, halogen, cyano, nitro, optionally substituted amino, optionally substituted C-amido, optionally substituted N-amido, optionally substituted ester, optionally substituted —(O)C 1-6 alkyl, optionally substituted —(O)C 1-6 alkenyl, optionally substituted —(O)C 1-6 alkynl, optionally substituted, —(O)C 4-12 cycloalkyl, optionally substituted —(O)C 1-6 alkylC 4-12 cycloalkyl, optionally substituted —(O)C 4-12 heterocyclyl, optionally substituted —(O)C 1-6 alkylC 4-12 heterocyclyl, optionally substituted —(O)C 4-12 aryl, optionally substituted —(O)C 1-6 alkylC 5-12 aryl, optionally substituted —(O)C 1-12 heteroaryl, and optionally substituted —(O)C 1-6 alkylC 1-12 heteroaryl. 
 
     
     
         8 . The method of  claim 2 , wherein R 2  and R 4  is selected from hydrogen, deuterium, hydroxyl, halogen, cyano, nitro, optionally substituted amino, optionally substituted C-amido, optionally substituted N-amido, optionally substituted ester, optionally substituted —(O)C 1-6 alkyl, optionally substituted —(O)C 1-6 alkenyl, optionally substituted —(O)C 1-6 alkynl, optionally substituted, —(O)C 4-12 cycloalkyl, optionally substituted —(O)C 1-6 alkylC 4-12 cycloalkyl, optionally substituted —(O)C 4-12 heterocyclyl, optionally substituted —(O)C 1-6 alkylC 4-12 heterocyclyl, optionally substituted —(O)C 4-12 aryl, optionally substituted —(O)C 1-6 alkylC 5-12 aryl, optionally substituted —(O)C 1-12 heteroaryl, and optionally substituted —(O)C 1-6 alkylC 1-12 heteroaryl;
 R 1  is —OH; 
 R 3  is H; 
 the dashed bond is present; 
 Z is CHR a , NR a , or O; and 
 R a  is selected from hydrogen, deuterium, hydroxyl, halogen, cyano, nitro, optionally substituted amino, optionally substituted C-amido, optionally substituted N-amido, optionally substituted ester, optionally substituted —(O)C 1-6 alkyl, optionally substituted —(O)C 1-6 alkenyl, optionally substituted —(O)C 1-6 alkynl, optionally substituted, —(O)C 4-12 cycloalkyl, optionally substituted —(O)C 1-6 alkylC 4-12 cycloalkyl, optionally substituted —(O)C 4-12 heterocyclyl, optionally substituted —(O)C 1-6 alkylC 4-12 heterocyclyl, optionally substituted —(O)C 4-12 aryl, optionally substituted —(O)C 1-6 alkylC 5-12 aryl, optionally substituted —(O)C 1-12 heteroaryl, and optionally substituted —(O)C 1-6 alkylC 1-12 heteroaryl. 
 
     
     
         9 . The method of  claim 2 , R 1 , R 2 , and R 4  are —OH;
 R 3  is H; 
 the dashed bond is present; 
 Z is CHR a , NR a , or O; and 
 R a  is selected from hydrogen, deuterium, hydroxyl, halogen, cyano, nitro, optionally substituted amino, optionally substituted C-amido, optionally substituted N-amido, optionally substituted ester, optionally substituted —(O)C 1-6 alkyl, optionally substituted —(O)C 1-6 alkenyl, optionally substituted —(O)C 1-6 alkynl, optionally substituted, —(O)C 4-12 cycloalkyl, optionally substituted —(O)C 1-6 alkylC 4-12 cycloalkyl, optionally substituted —(O)C 4-12 heterocyclyl, optionally substituted —(O)C 1-6 alkylC 4-12 heterocyclyl, optionally substituted —(O)C 4-12 aryl, optionally substituted —(O)C 1-6 alkylC 5-12 aryl, optionally substituted —(O)C 1-12 heteroaryl, and optionally substituted —(O)C 1-6 alkylC 1-12 heteroaryl. 
 
     
     
         10 . The method of  claim 1  or  2 , wherein the compound of Formula (I) or Formula (II) is selected from the group consisting of: N-trans-caffeoyltyramine, N-cis-caffeoyltyramine, N-trans-feruloyltyramine, N-cis-feruloyltyramine, p-coumaroyltyramine, cinnamoyltyramine, sinapoyltyramine, and 5-hydroxyferuloyltyramine, or a pharmaceutically acceptable salt, solvates, and combinations of the foregoing. 
     
     
         11 . The method of  claim 1  or  2 , wherein the compound of Formula (I) or Formula (II) is selected from the group consisting of: a compound of Formula (II) is selected from (E)-3-(3,4-dihydroxyphenyl)-N-(4-ethoxyphenethyl)acrylamide, (E)-3-(3,4-dihydroxyphenyl)-N-(4-(2-methoxyethoxy)phenethyl)acrylamide, (E)-3-(3,4-dihydroxyphenyl)-N-(4-(2-(methylsulfonyl)ethoxy)phenethyl)acrylamide, (E)-2-(4-(2-(3-(3,4-dihydroxyphenyl)acrylamido)ethyl)phenoxy)acetic acid, ethyl (E)-2-(4-(2-(3-(3,4-dihydroxyphenyl)acrylamido)ethyl)phenoxy)acetate, (E)-N-(4-(cyclopropylmethoxy)phenethyl)-3-(3,4-dihydroxyphenyl)acrylamide, (E)-3-(3,4-dihydroxyphenyl)-N-(4-(3,3,3-trifluoropropoxy)phenethyl)acrylamide, (E)-3-(3,4-dihydroxyphenyl)-N-(4-((tetrahydro-2H-pyran-4-yl)methoxy)phenethyl)acrylamide, (E)-3-(3,4-dihydroxyphenyl)-N-(4-((4-fluorobenzyl)oxy)phenethyl)acrylamide, (E)-N-(4-(cyanomethoxy)phenethyl)-3-(3,4-dihydroxyphenyl)acrylamide, (E)-3-(3,4-dihydroxyphenyl)-N-(4-(pyridin-3-ylmethoxy)phenethyl)acrylamide, (E)-3-(3,4-dihydroxyphenyl)-N-(4-(pyridin-2-ylmethoxy)phenethyl)acrylamide, (E)-3-(3,4-dihydroxyphenyl)-N-(4-(2-(dimethylamino)ethoxy)phenethyl)acrylamide, (E)-3-(3,4-dihydroxyphenyl)-N-(4-isobutoxyphenethyl)acrylamide, (E)-3-(3,4-dihydroxyphenyl)-N-(4-(pyridin-4-ylmethoxy)phenethyl)acrylamide, (E)-3-(3,4-dihydroxyphenyl)-N-(4-((4-methoxybenzyl)oxy)phenethyl)acrylamide, (E)-3-(3,4-dihydroxyphenyl)-N-(4-(oxetan-3-ylmethoxy)phenethyl)acrylamide, (E)-3-(3,4-dihydroxyphenyl)-N-(4-((tetrahydro-2H-pyran-2-yl)methoxy)phenethyl)acrylamide, (E)-3-(3,4-dihydroxyphenyl)-N-(4-((tetrahydrofuran-2-yl)methoxy)phenethyl)acrylamide, (E)-3-(3,4-dihydroxyphenyl)-N-(4-(thiophen-2-yloxy)phenethyl)acrylamide, (E)-3-(3,4-dihydroxyphenyl)-N-(4-(3,3-dimethylbutoxy)phenethyl)acrylamide, (E)-3-(3,4-dihydroxyphenyl)-N-(4-(2-hydroxyethoxy)phenethyl)acrylamide, (E)-N-(4-((1H-tetrazol-5-yl)methoxy)phenethyl)-3-(3,4-dihydroxyphenyl)acrylamide, (E)-3-(3,4-dihydroxyphenyl)-N-(4-((1-methylpyrrolidin-2-yl)methoxy)phenethyl)acrylamide, (E)-2-hydroxy-5-(3-((4-hydroxyphenethyl)amino)-3-oxoprop-1-en-1-yl)phenyl hydrogen carbonate, (E)-3-(4-hydroxy-3-(pyridin-4-yloxy)phenyl)-N-(4-hydroxyphenethyl)acrylamide, (E)-3-(4-hydroxy-3-isobutoxyphenyl)-N-(4-hydroxyphenethyl)acrylamide, (E)-3-(3-(4-fluorophenoxy)-4-hydroxyphenyl)-N-(4-hydroxyphenethyl)acrylamide, (E)-3-(3-(cyanomethoxy)-4-hydroxyphenyl)-N-(4-hydroxyphenethyl)acrylamide, (E)-2-(2-hydroxy-4-(3-((4-hydroxyphenethyl)amino)-3-oxoprop-1-en-1-yl)phenoxy)acetic acid, (E)-3-(3-hydroxy-4-(pyridin-4-ylmethoxy)phenyl)-N-(4-hydroxyphenethyl)acrylamide, (E)-3-(4-((4-fluorobenzyl)oxy)-3-hydroxyphenyl)-N-(4-hydroxyphenethyl)acrylamide, (E)-3-(3-hydroxy-4-isobutoxyphenyl)-N-(4-hydroxyphenethyl)acrylamide, (E)-3-(4-(cyanomethoxy)-3-hydroxyphenyl)-N-(4-hydroxyphenethyl)acrylamide, (E)-N-(3-(3,4-dihydroxyphenyl)acryloyl)-N-(4-hydroxyphenethyl)glycine, (E)-3-(3,4-dihydroxyphenyl)-N-(4-hydroxyphenethyl)-N-(pyridin-4-ylmethyl)acrylamide, (E)-3-(3,4-dihydroxyphenyl)-N-(4-hydroxyphenethyl)-N-isobutylacrylamide, (E)-N-(cyanomethyl)-3-(3,4-dihydroxyphenyl)-N-(4-hydroxyphenethyl)acrylamide, 3-(3,4-dihydroxyphenyl)-N-(4-hydroxyphenethyl)propanamide, 3-(3,4-dihydroxyphenyl)-N-(4-(methylsulfonamido)phenethyl)propanamide, or pharmaceutical salts, solvates, and combination of the foregoing. 
     
     
         12 . The method of  claim 1  or  2 , wherein the compound of Formula (I) or Formula (II) is in the form of a pharmaceutically acceptable salt. 
     
     
         13 . The method of  claim 1  or  2 , wherein the composition of Formula (I) or Formula (II) is in a unit dosage form and is configured for administration between 0.1 and 100 mg/kg of the body weight of the subject of Formula (I) or Formula (II) per administration. 
     
     
         14 . The method of  claim 1  or  2 , wherein administering the compound of Formula (I) or Formula (II) increases HNF4α expression. 
     
     
         15 . The method of  claim 1  or  2 , wherein administering the compound of Formula (I) or Formula (II) reverses the loss of Paneth cells that occur from a high fat diet. 
     
     
         16 . The method of  claim 1  or  2 , wherein improving digestive health is treating or ameliorating digestive health in the subject. 
     
     
         17 . The method of  claim 1  or  2 , wherein improving digestive health is treating or ameliorating inflammation. 
     
     
         18 . The method of  claim 1  or  2 , wherein improving digestive health is increasing HNF4α expression in the subject. 
     
     
         19 . The method of  claim 1  or  2 , wherein improving digestive health reverses the loss of Paneth cells. 
     
     
         20 . The method of  claim 1  or  2 , wherein improving digestive health improves digestive health in a subject by at least 30%. 
     
     
         21 . The method of  claim 1  or  2 , wherein improving digestive health reduces a disease or condition by about 30%. 
     
     
         22 . The method of  claim 1  or  2 , wherein improving digestive health improves intestinal villus levels. 
     
     
         23 . A method of treating or preventing a disease or disorder in a subject, comprising:
 administering a therapeutically effective amount of a compound of Formula I, or a pharmaceutically acceptable salt, to a subject in need thereof,   
       
         
           
           
               
               
           
         
       
       wherein
 R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , and R 9  are each independently selected from hydrogen, deuterium, hydroxyl, halogen, cyano, nitro, optionally substituted amino, optionally substituted C-amido, optionally substituted N-amido, optionally substituted ester, optionally substituted —(O)C 1-6 alkyl, optionally substituted —(O)C 1-6 alkenyl, optionally substituted —(O)C 1-6 alkynl, optionally substituted, —(O)C 4-12 cycloalkyl, optionally substituted —(O)C 1-6 alkylC 4-12 cycloalkyl, optionally substituted —(O)C 4-12 heterocyclyl, optionally substituted —(O)C 1-6 alkylC 4-12 heterocyclyl, optionally substituted —(O)C 4-12 aryl, optionally substituted —(O)C 1-6 alkylC 5-12 aryl, optionally substituted —(O)C 1-12 heteroaryl, and optionally substituted —(O)C 1-6 alkylC 1-12 heteroaryl; the dashed bond is present or absent; 
 X is CH 2  or O; 
 Z is CHR a , NR a , or O; and 
 R a  is selected from hydrogen, deuterium, hydroxyl, halogen, cyano, nitro, optionally substituted amino, optionally substituted C-amido, optionally substituted N-amido, optionally substituted ester, optionally substituted —(O)C 1-6 alkyl, optionally substituted —(O)C 1-6 alkenyl, optionally substituted —(O)C 1-6 alkynl, optionally substituted, —(O)C 4-12 cycloalkyl, optionally substituted —(O)C 1-6 alkylC 4-12 cycloalkyl, optionally substituted —(O)C 4-12 heterocyclyl, optionally substituted —(O)C 1-6 alkylC 4-12 heterocyclyl, optionally substituted —(O)C 4-12 aryl, optionally substituted —(O)C 1-6 alkylC 5-12 aryl, optionally substituted —(O)C 1-12 heteroaryl, and optionally substituted —(O)C 1-6 alkylC 1-12 heteroaryl; 
 wherein the disease or disorder is associated with the intestines. 
 
     
     
         24 . The method of  claim 23 , wherein administering the compound of Formula (I) induces a large increase in HNF4α. 
     
     
         25 . The method of  claim 23  or  24 , wherein administering the compound of Formula (I) increases intestinal villus. 
     
     
         26 . The method of any one of  claims 23  to  25 , wherein administering the compound of Formula (I) increases Paneth cell formation. 
     
     
         27 . The method of any one of  claims 23  to  26 , wherein the disease or disorder associated with the intestines is inflammation. 
     
     
         28 . The method of any one of  claims 23  to  27 , wherein the disease or disorder associated with the intestines is a condition associated with an allergic response. 
     
     
         29 . The method of any one of  claims 23  to  28 , wherein the composition is formulated as a dietary supplement, food ingredient or additive, a medical food, nutraceutical or pharmaceutical composition. 
     
     
         30 . The method of any one of  claims 23  to  29 , wherein R 1 , R 2 , R 3 , and R 8  are each independently selected from hydrogen, deuterium, hydroxyl, halogen, cyano, nitro, optionally substituted amino, optionally substituted C-amido, optionally substituted N-amido, optionally substituted ester, optionally substituted —(O)C 1-6 alkyl, optionally substituted —(O)C 1-6 alkenyl, optionally substituted —(O)C 1-6 alkynl, optionally substituted, —(O)C 4-12 cycloalkyl, optionally substituted —(O)C 1-6 alkylC 4-12 cycloalkyl, optionally substituted —(O)C 4-12 heterocyclyl, optionally substituted —(O)C 1-6 alkylC 4-12 heterocyclyl, optionally substituted —(O)C 4-12 aryl, optionally substituted —(O)C 1-6 alkylC 5-12 aryl, optionally substituted —(O)C 1-12 heteroaryl, and optionally substituted —(O)C 1-6 alkylC 1-12 heteroaryl;
 R 4 , R 5 , R 6 , R 7 , and R 9  are each independently hydrogen, deuterium, hydroxyl, or halogen; 
 dashed bond is present; 
 X is O; 
 Z is CHR a , NR a , or O; and 
 R a  is selected from hydrogen, deuterium, hydroxyl, halogen, cyano, nitro, optionally substituted amino, optionally substituted C-amido, optionally substituted N-amido, optionally substituted ester, optionally substituted —(O)C 1-6 alkyl, optionally substituted —(O)C 1-6 alkenyl, optionally substituted —(O)C 1-6 alkynl, optionally substituted, —(O)C 4-12 cycloalkyl, optionally substituted —(O)C 1-6 alkylC 4-12 cycloalkyl, optionally substituted —(O)C 4-12 heterocyclyl, optionally substituted —(O)C 1-6 alkylC 4-12 heterocyclyl, optionally substituted —(O)C 4-12 aryl, optionally substituted —(O)C 1-6 alkylC 5-12 aryl, optionally substituted —(O)C 1-12 heteroaryl, and optionally substituted —(O)C 1-6 alkylC 1-12 heteroaryl. 
 
     
     
         31 . The method of any one of  claims 23  to  30 , wherein R 1 , R 2 , and R 8  are each independently selected from hydrogen, deuterium, hydroxyl, halogen, cyano, nitro, optionally substituted amino, optionally substituted C-amido, optionally substituted N-amido, optionally substituted ester, optionally substituted —(O)C 1-6 alkyl, optionally substituted —(O)C 1-6 alkenyl, optionally substituted —(O)C 1-6 alkynl, optionally substituted, —(O)C 4-12 cycloalkyl, optionally substituted —(O)C 1-6 alkylC 4-12 cycloalkyl, optionally substituted —(O)C 4-12 heterocyclyl, optionally substituted —(O)C 1-6 alkylC 4-12 heterocyclyl, optionally substituted —(O)C 4-12 aryl, optionally substituted —(O)C 1-6 alkylC 5-12 aryl, optionally substituted —(O)C 1-12 heteroaryl, and optionally substituted —(O)C 1-6 alkylC 1-12 heteroaryl;
 R 3 , R 4 , R 5 , R 6 , R 7 , and R 9  are each independently hydrogen, deuterium, hydroxyl, or halogen; 
 the dashed bond is present; 
 X is CH 2  or O; 
 Z is CHR a , NR a , or O; and 
 R a  is selected from hydrogen, deuterium, hydroxyl, halogen, cyano, nitro, optionally substituted amino, optionally substituted C-amido, optionally substituted N-amido, optionally substituted ester, optionally substituted —(O)C 1-6 alkyl, optionally substituted —(O)C 1-6 alkenyl, optionally substituted —(O)C 1-6 alkynl, optionally substituted, —(O)C 4-12 cycloalkyl, optionally substituted —(O)C 1-6 alkylC 4-12 cycloalkyl, optionally substituted —(O)C 4-12 heterocyclyl, optionally substituted —(O)C 1-6 alkylC 4-12 heterocyclyl, optionally substituted —(O)C 4-12 aryl, optionally substituted —(O)C 1-6 alkylC 5-12 aryl, optionally substituted —(O)C 1-12 heteroaryl, and optionally substituted —(O)C 1-6 alkylC 1-12 heteroaryl. 
 
     
     
         32 . The method of any one of  claims 23  to  31 , wherein the compound of Formula (I) is selected compound is selected from the group consisting of: N-trans-caffeoyltyramine, N-cis-caffeoyltyramine, N-trans-feruloyltyramine, N-cis-feruloyltyramine, p-coumaroyltyramine, cinnamoyltyramine, sinapoyltyramine, and 5-hydroxyferuloyltyramine. 
     
     
         33 . The method of any one of  claims 23  to  32 , wherein the compound of Formula (I) is in the form of a pharmaceutically acceptable salt.