Natural extracts for modulating pp2a methylation, and providing antioxidant and anti inflammatory activity

Abstract

Compositions containing natural and botanical extracts for use in inhibiting one, two, or three of (a)-(c): (a) demethylation of PP2A by PME-1 methylesterase; (b) formation of free radicals and reactive oxygen species; and/or (c) inflammation. These compositions include an extract of one or more botanicals selected from the group consisting of: juniper berry fruit, schisandra fruit, strawberry fruit, avocado seeds, black raspberry seeds, blueberry seeds, celery seeds, cranberry seeds, fennel seeds, grape seeds, guarana seeds, red raspberry seeds, maca root, goldenseal root, turmeric root, magnolia bark, pygeum bark, red raspberry leaf, almond, cocoa powder, Echinacea angustifolia, prickly pear cactus and walnut.

1 . A composition for use in for inhibiting demethylation of PP2A by PME-1 methylesterase comprising an extract of one or more botanicals selected from the group consisting of juniper berry fruit, schisandra fruit, strawberry fruit, avocado seeds, black raspberry seeds, blueberry seeds, celery seeds, cranberry seeds, fennel seeds, guarana seeds, red raspberry seeds, maca root, goldenseal root, turmeric root, magnolia bark, pygeum bark, red raspberry leaf, almond, cocoa powder, Echinacea angustifolia, prickly pear cactus and walnut. 
     
     
         2 . The composition of  claim 1 , wherein the one or more botanicals is selected from the group consisting of guarana seed, red raspberry seed, prickly pear cactus, and turmeric root. 
     
     
         3 . The composition of any one of  claim 1  or  2 , wherein the composition further includes an extract of grape seed. 
     
     
         4 . The composition of  claim 1 , wherein the extract is obtained from a solvent selected from solvents having a dielectric constant ranging from about 2.3 to about 25. 
     
     
         5 . The composition of  claim 4 , wherein the extract is obtained from one or more of isopropyl alcohol, toluene, and ethyl acetate. 
     
     
         6 . The composition of  claim 4 , wherein the extract is substantially free of polar components soluble in solvents with a dielectric constant no less than 30. 
     
     
         7 . The composition of  claim 6 , wherein the solvent with a dielectric constant no less than 30 is water. 
     
     
         8 . The composition of  claim 6 , wherein the extract is substantially free of non-polar components soluble in solvents with a dielectric constant no more than 2.0. 
     
     
         9 . The composition of  claim 8 , wherein the solvent with a dielectric constant no more than 2.0 is selected from cyclohexane, hexane, heptane or isooctane. 
     
     
         10 . A composition for use in for inhibiting the formation of free radicals and reactive oxygen species comprising an extract of one or more botanicals selected from the group consisting of grape seed, guarana seed, red raspberry seed, prickly pear cactus, and turmeric root. 
     
     
         11 . The composition of  claim 10  wherein the extract is obtained from a solvent selected from solvents having a dielectric constant ranging from about 2.3 to about 25. 
     
     
         12 . The composition of  claim 11 , wherein the extract is obtained from one or more of isopropyl alcohol, toluene, and ethyl acetate. 
     
     
         13 . The composition of  claim 11 , wherein the extract is substantially free of polar components soluble in solvents with a dielectric constant no less than 30. 
     
     
         14 . The composition of  claim 13 , wherein the solvent with a dielectric constant no less than 30 is water. 
     
     
         15 . The composition of  claim 11 , wherein the extract is substantially free of non-polar components soluble in solvents with a dielectric constant no more than 2.0. 
     
     
         16 . The composition of  claim 15 , wherein the solvent with a dielectric constant no more than 2.0 is selected from cyclohexane, hexane, heptane or isooctane. 
     
     
         17 . A composition for use in for inhibiting inflammation comprising an extract of one or more botanicals selected from the group consisting of grape seed, guarana seed, red raspberry seed, prickly pear cactus, and turmeric root. 
     
     
         18 . The composition of  claim 17  wherein the extract is obtained from a solvent selected from solvents with a dielectric constant ranging from about 2.3 to about 25. 
     
     
         19 . The composition of  claim 18 , wherein the extract is obtained from one or more of isopropyl alcohol, toluene, and ethyl acetate. 
     
     
         20 . The composition of  claim 18 , wherein the extract is substantially free of polar components soluble in solvents with a dielectric constant no less than 30. 
     
     
         21 . The composition of  claim 20 , wherein the solvent with a dielectric constant no less than 30 is water. 
     
     
         22 . The composition of  claim 20 , wherein the extract is substantially free of non-polar components soluble in solvents with a dielectric constant no more than 2.0. 
     
     
         23 . The composition of  claim 22 , wherein the solvent with a dielectric constant no more than 2.0 is selected from cyclohexane, hexane, heptane or isooctane. 
     
     
         24 . A composition for use in for inhibiting demethylation of PP2A by PME-1 methylesterase, inhibiting the formation of free radicals and reactive oxygen species, and inhibiting inflammation comprising an extract of one or more botanicals selected from the group consisting of grape seed, guarana seed, red raspberry seed, prickly pear cactus, and turmeric root. 
     
     
         25 . The composition of  claim 24 , wherein the composition comprises comprising an extract of two or more botanicals selected from the group consisting of grape seed, guarana seed, red raspberry seed, prickly pear cactus, and turmeric root. 
     
     
         26 . The composition of  claim 25 , wherein the composition comprises comprising an extract of three or more botanicals selected from the group consisting of grape seed, guarana seed, red raspberry seed, prickly pear cactus, and turmeric root. 
     
     
         27 . The composition of  claim 26 , wherein the composition comprises comprising an extract of four or more botanicals selected from the group consisting of grape seed, guarana seed, red raspberry seed, prickly pear cactus, and turmeric root. 
     
     
         28 . The composition of  claim 27 , wherein the composition comprises an extract of grape seed, an extract of guarana seed, an extract of red raspberry seed, an extract of prickly pear cactus, and an extract of turmeric root. 
     
     
         29 . A method of preparing a botanical extract comprising:
 (a) introducing a raw botanical to a solvent having a dielectric constant ranging from about 2.3 to about 25 and allowing the mixture to reside for a sufficient time to obtain a crude extract;   (b) filtering out remaining raw botanical and evaporating the solvent from the crude extract under reduced pressure to obtain a dried crude extract;   (c) washing the dried crude extract with a polar solvent having a dielectric constant of no less than 30, heating the resulting mixture, and allowing to cool to ambient;   (d) collecting a filtrate from the cooled mixture from step (c); and   (e) washing the collected filtrate with a non-polar solvent having a dielectric constant of no more than 2.0; and   (f) filtering and drying the mixture from step (e) to obtain the botanical extract.   
     
     
         30 . The method of  claim 29 , wherein the solvent having a dielectric constant ranging from about 2.3 to about 25 is selected from isopropyl alcohol, toluene and ethyl acetate. 
     
     
         31 . The method of  claim 29 , wherein the solvent having a dielectric constant ranging from about 2.3 to about 25 is evaporated from the crude extract by a rotary evaporator. 
     
     
         32 . The method of  claim 29 , wherein the polar solvent having a dielectric constant of no less than 30 is water. 
     
     
         33 . The method of  claim 29 , wherein the non-polar solvent having a dielectric constant of no more than 2.0 is selected from cyclohexane, hexane, heptane and isooctane. 
     
     
         34 . A composition comprising an extract prepared by the process of any one of  claims 29 - 33 . 
     
     
         35 . A method for inhibiting demethylation of PP2A by PME-1 methylesterase comprising administering to a subject in need thereof an effective amount of a botanical extract. 
     
     
         36 . The method of  claim 35 , wherein the subject exhibits, or is at risk for exhibiting, Tau hyper-phosphorylation. 
     
     
         37 . The method of  claim 35 , wherein the subject exhibits, or is at risk for exhibiting, α-synculein hyper-phosphorylation. 
     
     
         38 . The method of  claim 35 , wherein the subject exhibits, or is at risk for exhibiting, abnormally elevated homocysteine levels. 
     
     
         39 . The method of  claim 35 , wherein the subject has been diagnosed with, or is at risk for developing, Alzheimer's Disease. 
     
     
         40 . The method of  claim 35 , wherein the subject has been diagnosed with, or is at risk for developing, Parkinson's Disease. 
     
     
         41 . The method of  claim 35 , wherein the subject is a healthy subject. 
     
     
         42 . The method of any one of  claims 35 - 41 , wherein the subject desires to prevent cognitive and/or motor function decline. 
     
     
         43 . The method of  claim 35 , wherein the subject exhibits, or is at risk for exhibiting, a skin disorder, medical condition or disease. 
     
     
         44 . The method of any one of  claims 35 , wherein the subject desires to maintain healthy skin and prevent skin aging. 
     
     
         45 . The method of  claim 35 , wherein the botanical extract is obtained from at least one fruit source selected from the group consisting of: juniper berry, schisandra, and strawberry. 
     
     
         46 . The method of  claim 35 , wherein the botanical extract is obtained from at least one seed source. 
     
     
         47 . The method of  claim 46 , wherein the seed source is selected from the group consisting of: avocado, black raspberry, blueberry, celery, cranberry, fennel, grape, guarana and red raspberry. 
     
     
         48 . The method of  claim 47 , wherein the seed source is selected from grape, guarana and red raspberry. 
     
     
         49 . The method of  claim 35 , wherein the botanical extract is obtained from a least one root, bark or leaf source. 
     
     
         50 . The method of  claim 49 , wherein the root, bark or leaf source is selected from the group consisting of maca root, goldenseal root, turmeric root, magnolia bark, pygeum bark, red raspberry leaf. 
     
     
         51 . The method of  claim 50 , wherein the root, bark or leaf source is turmeric root. 
     
     
         52 . The method of  claim 35 , wherein the botanical extract is obtained from at least one natural source selected from the group consisting of: almond, cocoa powder, Echinacea angustifolia, prickly pear cactus and walnut. 
     
     
         53 . The method of  claim 52 , wherein the natural source is prickly pear cactus. 
     
     
         54 . The method of  claim 35 , wherein the botanical extract is a botanical extract obtained by the method of any one of  claims 29 - 33 . 
     
     
         55 . The method of any one of  claims 35 - 54 , wherein the botanical extract is topically administered as a cream, lotion, cleanser, ointment or other pharmaceutically acceptable topical dosage form. 
     
     
         56 . The method of any one of  claims 35 - 54 , wherein the botanical extract is orally administered as a pill, tablet, capsule, syrup or a drink or other pharmaceutically acceptable oral dosage form. 
     
     
         57 . The method of any one of  claims 35 - 54 , wherein the botanical extract is administered together with other botanicals and vitamins. 
     
     
         58 . A method for treating or preventing a sleep disorder comprising administering to a subject in need thereof an effective amount of a botanical extract. 
     
     
         59 . The method of  claim 58 , wherein the sleep disorder is selected from insomnia, narcolepsy, familial advanced sleep-phase syndrome (FASPS) and disruption to the circadian rhythm. 
     
     
         60 . The method of  claim 58 , wherein the botanical extract is selected from one or more of grape seed, juniper berry fruit, schisandra fruit, strawberry fruit, avocado seeds, black raspberry seeds, blueberry seeds, celery seeds, cranberry seeds, fennel seeds, guarana seeds, red raspberry seeds, maca root, goldenseal root, turmeric root, magnolia bark, pygeum bark, red raspberry leaf, almond, cocoa powder, Echinacea angustifolia, prickly pear cactus and walnut. 
     
     
         61 . The method of  claim 60 , wherein the botanical extract is selected from grape seed, guarana seed, red raspberry seed, prickly pear cactus, and turmeric root. 
     
     
         62 . A method for treating or preventing an eye or vision disorder comprising administering to a subject in need thereof an effective amount of a botanical extract. 
     
     
         63 . The method of  claim 62 , wherein the botanical extract is selected from one or more of grape seed, juniper berry fruit, schisandra fruit, strawberry fruit, avocado seeds, black raspberry seeds, blueberry seeds, celery seeds, cranberry seeds, fennel seeds, guarana seeds, red raspberry seeds, maca root, goldenseal root, turmeric root, magnolia bark, pygeum bark, red raspberry leaf, almond, cocoa powder, Echinacea angustifolia, prickly pear cactus and walnut. 
     
     
         64 . The method of  claim 63 , wherein the botanical extract is selected from grape seed, guarana seed, red raspberry seed, prickly pear cactus, and turmeric root. 
     
     
         65 . A method for treating or preventing a metabolic disease or disorder comprising administering to a subject in need thereof an effective amount of a botanical extract. 
     
     
         66 . The method of  claim 65 , wherein the metabolic disease or disorder is selected from metabolic syndrome, insulin resistance, glucose intolerance, hyperglycemia, type I diabetes, type II diabetes, hyperlipidemia, hypertriglyceridemia, hypercholesterolemia, dyslipidemia, and polycystic ovary syndrome (PCOS). 
     
     
         67 . The method of  claim 65 , wherein the botanical extract is selected from one or more of grape seed, juniper berry fruit, schisandra fruit, strawberry fruit, avocado seeds, black raspberry seeds, blueberry seeds, celery seeds, cranberry seeds, fennel seeds, guarana seeds, red raspberry seeds, maca root, goldenseal root, turmeric root, magnolia bark, pygeum bark, red raspberry leaf, almond, cocoa powder, Echinacea angustifolia, prickly pear cactus and walnut. 
     
     
         68 . The method of  claim 67 , wherein the botanical extract is selected from grape seed, guarana seed, red raspberry seed, prickly pear cactus, and turmeric root. 
     
     
         69 . A method for treating or preventing a mental disorder comprising administering to a subject in need thereof an effective amount of a botanical extract. 
     
     
         70 . The method of  claim 69 , wherein the mental disorder is selected from a mood disorder, a psychotic disorder, an anxiety disorder, a childhood disorder, an eating disorder, a personality disorder, an adjustment disorder, an autistic disorder, delirium, dementia, multi-infarct dementia and a Tourette's disorder. 
     
     
         71 . The method of  claim 70 , wherein the mental disorder is an autistic disorder. 
     
     
         72 . The method of  claim 69 , wherein the botanical extract is selected from one or more of grape seed, juniper berry fruit, schisandra fruit, strawberry fruit, avocado seeds, black raspberry seeds, blueberry seeds, celery seeds, cranberry seeds, fennel seeds, guarana seeds, red raspberry seeds, maca root, goldenseal root, turmeric root, magnolia bark, pygeum bark, red raspberry leaf, almond, cocoa powder, Echinacea angustifolia, prickly pear cactus and walnut. 
     
     
         73 . The method of  claim 72 , wherein the botanical extract is selected from grape seed, guarana seed, red raspberry seed, prickly pear cactus, and turmeric root. 
     
     
         74 . A method for treating a traumatic brain injury comprising administering to a subject in need thereof an effective amount of a botanical extract. 
     
     
         75 . The method of  claim 74 , wherein the botanical extract is selected from one or more of grape seed, juniper berry fruit, schisandra fruit, strawberry fruit, avocado seeds, black raspberry seeds, blueberry seeds, celery seeds, cranberry seeds, fennel seeds, guarana seeds, red raspberry seeds, maca root, goldenseal root, turmeric root, magnolia bark, pygeum bark, red raspberry leaf, almond, cocoa powder, Echinacea angustifolia, prickly pear cactus and walnut. 
     
     
         76 . The method of  claim 75 , wherein the botanical extract is selected from grape seed, guarana seed, red raspberry seed, prickly pear cactus, and turmeric root. 
     
     
         77 . A method for inhibiting inflammation in a subject comprising administering to a subject an effective amount of a botanical extract obtained from at least one source selected from the group consisting of grape seed, guarana seed, red raspberry seed, prickly pear cactus and turmeric root. 
     
     
         78 . The method of  claim 77  wherein the botanical extract is a botanical extract obtained by the process of any one of  claims 29 - 33 . 
     
     
         79 . The method of any one of  claims 77 - 78 , wherein the botanical extract is topically administered as a cream, lotion, cleanser, ointment or any generally accepted topical dosage form. 
     
     
         80 . The method of any one of  claims 77 - 78  wherein the botanical extract is orally administered as a pill, tablet, capsule, syrup or a drink or other pharmaceutically acceptable oral dosage form. 
     
     
         81 . The method of any one of  claims 77 - 78 , wherein the botanical extract is administered together with other botanicals and vitamins. 
     
     
         82 . A method for inhibiting demethylation of PP2A by PME-1 methylesterase, inhibiting the formation of free radicals and reactive oxygen species, and inhibiting inflammation in a subject comprising administering to a subject in need thereof a composition comprising one or more botanical extracts obtained from at least one source selected from the group consisting of grape seed, guarana seed, red raspberry seed, prickly pear cactus and turmeric root. 
     
     
         83 . The method of  claim 82 , wherein the composition comprises comprising an extract of two or more botanicals selected from the group consisting of grape seed, guarana seed, red raspberry seed, prickly pear cactus, and turmeric root. 
     
     
         84 . The method of  claim 83 , wherein the composition comprises comprising an extract of three or more botanicals selected from the group consisting of grape seed, guarana seed, red raspberry seed, prickly pear cactus, and turmeric root. 
     
     
         85 . The method of  claim 84 , wherein the composition comprises comprising an extract of four or more botanicals selected from the group consisting of grape seed, guarana seed, red raspberry seed, prickly pear cactus, and turmeric root. 
     
     
         86 . The method of  claim 85 , wherein the composition comprises an extract of grape seed, an extract of guarana seed, an extract of red raspberry seed, an extract of prickly pear cactus, and an extract of turmeric root. 
     
     
         87 . The method of any of  claims 82 - 86 , wherein said extracts are administered in a single composition. 
     
     
         88 . The method of  claim 87 , wherein said extracts are orally administered. 
     
     
         89 . The method of  claim 87 , wherein said extracts are topically administered.