Pharmaceutical formulations of resveratrol and methods of use thereof for treating cell disorders
Described is a composition for preventing or treating an oxidative stress related disease or condition in a subject. The disease or condition is characterized by the presence of excess oxidative compounds in the subject, and the composition includes a synergistic combination of therapeutically effective amounts of resveratrol to promote NAD + synthesis in the subject; a chelating agent to reduce production of additional oxidative compounds in the subject; and an antioxidant to minimize the oxidative activity in the subject.
1. A method of treating a disease or condition associated with oxidative stress or DNA damage in a subject, wherein the disease or condition is characterized by the presence of excess oxidative compounds in the subject, the method consisting of:
administering to the subject a composition consisting of a synergistic composition of:
100 μM of resveratrol or a functionally equivalent analogue or derivative thereof effective to promote NAD+ synthesis in the subject;
10 μM of clioquinol to reduce production of additional oxidative compounds in the subject; and
5 μM of melatonin to minimize the oxidative activity in the subject.
2. The method according to claim 1 , wherein the disease or condition includes a neurodegenerative disorder, accelerated aging of the skin, and/or DNA damage.
3. The method according to claim 1 , wherein the neurodegenerative disorder is Alzheimer's disease or Parkinson's disease.
4. The method according to claim 2 , wherein the DNA damage includes UV-induced DNA damage in the subject's skin cells.
5. The method according to claim 4 , wherein the skin cells are keratinocytes and fibroblasts.
6. The method according to claim 2 , wherein the disease or condition is cancer.
7. The method according to claim 2 , wherein the disease or condition results from exposure to ultra-violet light, ionizing radiation, exposure to chemical agents, infection, inflammation, reduced mitochondrial efficiency, or a combination thereof.
8. The method according to claim 1 , wherein the resveratrol or functionally equivalent analogue or derivative is a functionally equivalent analogue selected from the group consisting of hydroxylated resveratrol analogues, methoxylated resveratrol analogues, cis-resveratrol glucoside (cis-piceid), and trans-resveratrol-3-O-β-glucoside (trans-piceid).
9. The method according to claim 1 , wherein the resveratrol or a functionally equivalent analogue or derivative thereof promotes NAD+ synthesis by upregulating nicotinamide mononucleotide adenylyl transferase (NMNAT) activity in the subject, thereby increasing the metabolism of nicotinamide (NAM).
10. The method according to claim 9 , wherein the increase in the metabolism NAD + increases PARP enzyme activity, thereby further promoting DNA repair in the subject, and also providing a correlated increase in mammalian sirtuin enzyme activity, thereby promoting cell viability and longevity in the subject.
11. The method according to claim 10 , wherein the PARP enzymes are selected from PARP-1 or PARP-2.
12. The method according to claim 10 , wherein the mammalian sirtuin enzyme family members are selected from the group consisting of SIRT1, SIRT2, SIRT3, SIRT4, SIRT5, SIRT6, and SIRT7.