Compositions and Methods for Treating Cardiovascular Diseases and Disorders
Disclosed herein are compounds and ligands, and compositions formed therewith, that modulate insulin secretion by activating endogenous receptors. Also disclosed herein are methods for using the compositions to treat cardiovascular disorders.
1 . A composition for treating atherosclerosis presented by a patient, comprising:
(i) at least a first receptor activating compound adapted to bind to and activate at least one first receptor selected from the group comprising olfactory receptor family 51 subfamily E member 1 OR51E1) and olfactory receptor family 1 subfamily A member 1 (OR1A1),
(ii) at least a second receptor activating compound adapted to bind to and activate at least one second receptor selected from the group comprising free fatty acid receptor 1 (FFAR1) and free fatty acid receptor 4(FFAR4), and
(iii) at least a third receptor activating compound adapted to bind to and activate olfactory receptor family 2 subfamily L member 13 (OR2L13),
said composition adapted to induce GLP-1 secretion, and, thereby, increased insulin secretion in vivo, whereby said atherosclerosis is treated when said composition is delivered to said patient.
2 . The composition of claim 1 , wherein said composition is further adapted to ameliorate at least one risk factor of said atherosclerosis when said composition is said delivered to said patient.
3 . The composition of claim 1 , wherein said composition is further adapted to ameliorate at least one pathophysiological effect induced by said atherosclerosis when said composition is said delivered to said patient.
4 . The composition of claim 1 , wherein said first receptor activating compound is selected from the group consisting of eugenol and 3-methylpentanoic acid.
5 . The composition of claim 4 , wherein said first receptor activating compound comprises said eugenol.
6 . The composition of claim 5 , wherein said eugenol comprises a first EC 50 concentration in said composition of at least 0.1 μM.
7 . The composition of claim 6 , wherein said first EC 50 concentration of said eugenol in said composition is in the range from about 1.0 μM to about 15.0 μM.
8 - 10 . (canceled)
11 . The composition of claim 1 , wherein said second receptor activating compound is selected from the group consisting of a medium-chain free fatty acid, a long-chain free fatty acid and an omega-3 polyunsaturated fatty acid.
12 . The composition of claim 11 , wherein said second receptor activating compound comprises a medium-chain free fatty acid.
13 . The composition of claim 11 , wherein said medium-chain free fatty acid comprises lauric acid.
14 . The composition of claim 13 , wherein said lauric acid comprises a second EC 50 concentration in said composition of at least 0.05 μM.
15 . The composition of claim 14 , wherein said second EC 50 concentration of said lauric acid in said composition is in the range from about 0.05 μM to about 50.0 μM.
16 . The composition of claim 1 , wherein said third receptor activating compound is selected from the group consisting of (−)-carvone and choline.
17 . The composition of claim 16 , wherein said third receptor activating compound comprises said (−)-carvone.
18 . The composition of claim 17 , wherein said (−)-carvone comprises a third EC 50 concentration in said composition of at least 0.1 μM.
19 . The composition of claim 18 , wherein said third EC 50 concentration of said (−)-carvone in said composition is in the range from about 0.01 μM to about 100.0 μM.
20 . The composition of claim 1 , wherein said composition further comprises at least a fourth receptor activating compound adapted to bind to and restrict 5-HT 2 serotonergic receptor activity.
21 . The composition of claim 20 , wherein said fourth receptor activating compound is selected from the group consisting of 3,3′,4′,5,6,7,8-heptamethoxyflavone (HMF), hesperidin and isoliquiritigenin (ISL).
22 . The composition of claim 21 , wherein said fourth receptor activating compound comprises said HMF.
23 . The composition of claim 22 , wherein said HMF comprises a fourth EC 50 concentration in said composition of at least approximately 0.01 μM.
24 . The composition of claim 23 , wherein said fourth EC 50 concentration of said HMF in said composition is in the range from about 0.01 μM to about 100.0 μM.
25 . The composition of claim 1 , wherein said first receptor activating compound is adapted to induce at least 50% activation of at least said olfactory receptor OR51E1 in vivo when said composition is said delivered to said patient.