WO2024040334A1 - Compositions et méthodes pour l'entretien et l'amélioration de la santé vasculaire - Google Patents

Compositions et méthodes pour l'entretien et l'amélioration de la santé vasculaire Download PDF

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Publication number
WO2024040334A1
WO2024040334A1 PCT/CA2023/051084 CA2023051084W WO2024040334A1 WO 2024040334 A1 WO2024040334 A1 WO 2024040334A1 CA 2023051084 W CA2023051084 W CA 2023051084W WO 2024040334 A1 WO2024040334 A1 WO 2024040334A1
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Prior art keywords
extract
fortified
aronia
juice
tart cherry
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PCT/CA2023/051084
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English (en)
Inventor
Sakwinder NARWAL
Miodrag ANDRIC
Maria GLIBETIC
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Vana Health Inc.
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Priority to PCT/CA2023/051104 priority Critical patent/WO2024040336A1/fr
Publication of WO2024040334A1 publication Critical patent/WO2024040334A1/fr

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/73—Rosaceae (Rose family), e.g. strawberry, chokeberry, blackberry, pear or firethorn
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/73—Rosaceae (Rose family), e.g. strawberry, chokeberry, blackberry, pear or firethorn
    • A61K36/736—Prunus, e.g. plum, cherry, peach, apricot or almond
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00—Preparations for care of the skin
    • A61Q19/06—Preparations for care of the skin for countering cellulitis

Definitions

  • the present invention relates to the field of nutraceuticals and dietary supplement compositions and, in particular, to compositions comprising Aronia juice fortified with Aronia extract, and tart cherry juice fortified with tart cherry extract, and methods for maintaining and improving vascular health.
  • BACKGROUND OF THE INVENTION [0002]
  • Heart and vascular, or cardiovascular, diseases include conditions such as arrhythmias, coronary heart disease, heart attack, high blood pressure, congenital heart defects, vascular dementia, and stroke. The World Health Organization has reported that cardiovascular diseases (CVDs) are the leading cause of death globally.
  • Atherosclerosis the pathological condition often underlying CVD, is a chronic inflammatory condition involved in the initiation and perpetuation of atherosclerotic lesions, which may erode or rupture leading to clinical events such as angina, myocardial infarction, or cerebrovascular attack. Modifiable CVD risk has been associated with poor quality diet, smoking, and physical inactivity.
  • bioavailability is dependent on the absorption of the micronutrients by the epithelial layer of the gut, and the chemical and biochemical transformations into epithelial cells. These processes are endogenous factors that greatly influence the bioavailability of bioactive compounds. Ensuring bioavailability is challenging due to the nature of both the bioactive compounds and the digestive tract of the consumer. As a result, the efficacy of bioactive compounds in nutraceuticals and dietary supplements, is limited at best, and unpredictable. [0006] New compositions and methods that address the shortcomings of existing nutraceuticals are, therefore, needed to realize the prophylactic and/or therapeutic effects of bioactive compounds on vascular health.
  • An object of the present invention is to provide compositions and methods for maintaining or improving vascular health in a subject, in particular.
  • a composition comprising Aronia juice fortified with Aronia extract in combination with tart cherry juice fortified with tart cherry extract. 2 Cardiovascular Protection.DOCX
  • the composition of the present invention further comprises one or more additional nutraceuticals.
  • compositions comprising Aronia juice fortified with Aronia extract in combination with tart cherry juice fortified with tart cherry extract, wherein said juices and extracts interact to enhance bioavailability of polyphenols and/or polyphenol gut metabolites from said extracts.
  • compositions comprising Aronia juice fortified with Aronia extract in combination with tart cherry juice fortified with tart cherry extract, wherein said juices and extracts interact synergistically to inhibit platelet aggregation and vascular inflammation.
  • a formulation for maintaining vascular health comprising Aronia juice fortified with Aronia extract, and tart cherry juice fortified with tart cherry extract, wherein said formulation inhibits platelet aggregation and vascular inflammation.
  • a method for preventing or treating, or to aid in preventing or treating, cardiovascular disease in a subject comprising administering a therapeutically effective amount of a composition comprising Aronia juice fortified with Aronia extract, and tart cherry juice fortified with tart cherry extract, wherein said composition enhances the bioavailability of polyphenols and/or polyphenol gut metabolites from said extracts.
  • Figure 2 is a graph presenting changes in diastolic blood pressure across three time points (baseline (T0), 3 weeks (T1) and 3 months (T2) of aronia (chokeberry)/tart cherry core formulation consumption).
  • the graph represents results of repeated measures ANOVA of normalized data, presented as relative change from T0. **p ⁇ 0.01, compared to T0; #, p ⁇ 0.05, compared to T1.
  • Figure 3 presents changes in total body water of right leg (A), left leg (B), Intracellular water of right leg (C), left leg (D), extracellular water of right leg (E) and left leg (F) across three time points (baseline (T0), 3 weeks (T1) and 3 months (T2) of aronia (chokeberry)/tart cherry core formulation consumption).
  • the graphs represent repeated measures ANOVA analysis of normalized data, presented as relative change from T0. **p ⁇ 0.01, compared to T0; #, p ⁇ 0.05, compared to T1.
  • Figure 4 presents the effect of 3-month long core formulation consumption on markers of endothelial dysfunction.
  • Results presented as median with 25-75 percentiles (box) and 10-90 percentile range (whiskers), before and after 3-month long core formulation consumption in subjects of both sexes at increased CVD risk. n 15-17 subjects; data analyzed by Wilcoxon signed-rank test for non-normal data distribution. ***, p ⁇ 0.001; ns, p>0.05.
  • Figure 9 are graphs presenting the acute effects of consuming core formulation (CF) and its components on markers of platelet aggregation with leukocytes after ex vivo stimulation with a suboptimal concentration (0.5 ⁇ M) of adenosine diphosphate (ADP):
  • Figure 9A is a graph presenting percentage of platelet-neutrophil aggregates (PNA) in the total population of neutrophils
  • Figure 9B is a graph presenting density of platelets in platelet-neutrophil aggregates
  • Figure 9C is a graph presenting percentage of platelet- monocyte aggregates (PMA) in the total population of monocytes
  • Figure 9D is a graph presenting density of platelets in platelet-monocyte aggregates
  • Figure 9E is a graph presenting relative number of platelets per platelet-monocyte aggregate (binding index, BI) calculated as % of aggregates in the total population of monocytes x mean fluorescence intensity (MFI)/100.
  • binding index, BI binding index
  • Figure 10 are graphs presenting the acute effects of consuming core formulation (CF) and its components on markers of platelet activation after ex vivo stimulation with a suboptimal concentration (0.5 ⁇ M) of adenosine diphosphate (ADP):
  • Figure 10A is a graph presenting percentage of GPIIbIIIa-positive platelets in the total number of collected platelets;
  • Figure 10B is a graph presenting relative number of GPIIbIIIa on the surface of antigen-positive platelets (platelet activation index, PAI, calculated as % of GPIIbIIIa- platelets x mean fluorescence intensity (MFI)/100
  • Figure 10C is a graph presenting percentage of P-selectin-positive platelets in the total number of collected platelets
  • Figure 10D is a graph presenting relative number of P-selectin on the surface of antigen-positive platelets.
  • Figure 11 are graphs presenting the acute effects of consuming core formulation (CF) and its components on markers of platelet aggregation with leukocytes in the basal state:
  • Figure 11A is a graph presenting percentage of platelet-neutrophil aggregates (PNA) in the total population of neutrophils
  • Figure 11B is a graph presenting density of platelets in platelet-neutrophil aggregates
  • Figure 11C is a graph presenting percentage of platelet- monocyte aggregates (PMA) in the total population of monocytes
  • Figure 11D is a graph presenting density of platelets in platelet-monocyte aggregates
  • Figure 11E is a graph presenting relative number of platelets per platelet-monocyte aggregate (binding index, BI) calculated as % of aggregates in the total population of monocytes x mean fluorescent intensity (MFI)/100.
  • binding index BI
  • Figure 12 are graphs presenting the acute effects of consuming core formulation (CF) and its components on markers of platelet activation in the basal state:
  • Figure 12A is a graph presenting percentage of GPIIbIIIa-positive platelets in the total number of collected platelets
  • Figure 12B is a graph presenting relative number of GPIIbIIIa on the surface of antigen-positive platelets (platelet activation index, PAI, calculated as % of GPIIbIIIa- platelets x mean fluorescence intensity (MFI)/100)
  • Figure 12C is a graph presenting percentage of P-selectin-positive platelets in the total number of collected platelets
  • Figure 12D is a graph presenting relative number of P-selectin on the surface of antigen-positive platelets.
  • Figure 13 are graphs presenting the effect of 3-month long core formulation consumption on markers of vascular inflammation and cell adhesion/migration.
  • Polyphenols are micronutrients found in a wide range of food sources that have gained particular attention for their antioxidant properties and their role in the prevention of various diseases associated with oxidative stress, such as cancer and cardiovascular and neurodegenerative diseases. Polyphenols, which constitute the active substances found in many medicinal plants, have also been found to modulate the activity of a wide range of enzymes and cell receptors. [0028] More than 8,000 types of polyphenols have been identified.
  • flavonoids which account for around 60% of all polyphenols and include quercetin, kaempferol, catechins, apigenin, fisetin, proanthocyanidins, and anthocyanins
  • phenolic acids which account for around 30% of 7 Cardiovascular Protection.DOCX all polyphenols and include stilbenes and lignans
  • polyphenolic amides which include capsaicinoids and avenanthramides
  • other polyphenols which include resveratrol, ellagic acid, ellagitannins, resveratrol, urolithin A, curcumin, and lignans.
  • nutraceutical compositions are described that unexpectedly enhance the bioavailability of polyphenols and the polyphenol gut metabolites.
  • the nutraceutical compositions of the present invention enhance antioxidant bioavailability in the gut by combining nutrient-rich and polyphenol- high Aronia and tart cherry juice.
  • the nutraceutical compositions comprise Aronia and tart cherry juices that are further fortified with Aronia and tart cherry extract which together enhance polyphenol bioavailability.
  • the nutraceutical compositions comprise a combination of Aronia juice fortified with Aronia extract in combination with tart cherry juice fortified with tart cherry extract.
  • Enhanced bioavailability of polyphenols leads to an increase in the final active metabolites produced by gut bacterial species and subsequent intestinal absorption of the polyphenol gut metabolites.
  • the nutraceutical compositions described herein alter the gut’s vascular wall to enhance absorption of micronutrients and bioactive phytochemicals.
  • the nutraceutical compositions result in an increase in n3 and a decrease in n6 polyunsaturated fatty acids (PUFAs) in endothelium and vascular wall cell membranes.
  • PUFAs polyunsaturated fatty acids
  • the components of the nutraceutical compositions interact synergistically to ultimately lead to increased cell membrane fluidity through phospholipid restructuring. According to certain embodiments, this restructuring of the vascular wall cell membrane further enhances the intestinal absorption of micronutrients and bioactive phytochemicals.
  • the nutraceutical compositions described herein result in stabilization of the permeability of the gut wall thereby reducing the loss of polyphenol gut metabolites, and thus increasing the amount of bioactive components to be absorbed by the gut epithelium and underlying vasculature.
  • the nutraceutical compositions result in the lowering of zonulin production that modulates the permeability of tight junctions between cells of the gut wall to stabilize gut wall permeability.
  • the compositions of the present invention are combined with additional nutraceuticals to enhance their absorption.
  • the compositions comprise Aronia juice fortified with Aronia extract in combination with tart cherry juice fortified with tart cherry extract, and further in combination with additional nutraceuticals. It is contemplated that the additional nutraceuticals can include any nutraceutical of interest.
  • the nutraceutical compositions comprise Aronia juice fortified with Aronia extract, and tart cherry juice fortified with tart cherry extract, in combination with one or more extracts.
  • the one or more extracts can include, for example, red beet extract, rosehip extract, chamomile extract, lemon balm extract, lion’s mane mushroom extract, reishi mushroom extract, resveratrol extract, quercetin extract, fisetin extract, berberine extract, urolithin A, NMN, Ca-AKG, spermidine extract, TMG, and/or cannabidiol (CBD).
  • the compositions comprise Aronia juice fortified with Aronia extract, and tart cherry juice fortified with tart cherry extract, in combination with, for example, red beet extract, lion’s mane mushroom extract, and/or 9 Cardiovascular Protection.DOCX rosehip extract.
  • compositions comprise Aronia juice fortified with Aronia extract, and tart cherry juice fortified with tart cherry extract, in combination with, for example, one or more of rosehip extract, chamomile extract, lemon balm extract, reishi mushroom extract, and/or cannabidiol (CBD).
  • Compositions of the present invention comprising Aronia juice fortified with Aronia extract in combination with tart cherry juice fortified with tart cherry extract, are therefore contemplated in certain embodiments for use as an absorption-enhancing carrier for micronutrients and bioactive phytochemicals derived from nutraceutical extracts.
  • the present invention provides for the use of the fortified Aronia and tart cherry juice composition prior to consumption of nutraceutical extracts.
  • the present invention provides for the use of the fortified Aronia and tart cherry juice composition as a carrier for additional nutraceutical extracts.
  • the enhanced bioavailability of the components of the nutraceutical composition comprising Aronia and tart cherry juices that are fortified with Aronia and tart cherry extract, unexpectedly interact to reduce the expression of cell adhesion molecules (CAMs) associated with vascular disorders and microvascular dysfunction, including one or more of E-selectin, L-selectin, P-selectin glycoprotein ligand- 1 (PSGL-1), ALCAM-1, ICAM-2, and ICAM-1.
  • CAMs cell adhesion molecules
  • compositions comprise components that synergistically interact to inhibit platelet aggregation and stabilize vascular endothelium by suppressing the expression of vascular inflammatory markers.
  • Definitions [0038] Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. 10 Cardiovascular Protection.DOCX [0039] As used herein, the term “about” refers to an approximately +/-10% variation from a given value. It is to be understood that such a variation is always included in any given value provided herein, whether or not it is specifically referred to.
  • the term “nutraceutical(s)” as used herein refers to a substance that is a food or a part of a food, such as an extract, and contains phytochemicals that are able to induce medical and health benefits.
  • the term “polyphenols” as used herein refers to the group of plant-derived phytochemicals that can be generally categorized into four main groups: flavonoids, phenolic acids, stilbenes, and lignans.
  • polyphenol gut metabolites refers to the polyphenol metabolites of the gut microbiota.
  • subject as used herein refers to both human and non-human animals.
  • the term “preventing” as used herein refers to reducing the risks associated with developing a disease, including reducing the onset of the disease.
  • the term “prevention” or “prophylaxis” may be used herein to refer to an individual known to be at high risk of 11 Cardiovascular Protection.DOCX developing a disease or in a population at large for maintaining good health, for example, maintaining vascular health.
  • vascular refers to the entire vascular system, including the heart, and the term “vascular health” is inclusive of the cardiovascular health and/or coronary health.
  • vascular health is inclusive of the cardiovascular health and/or coronary health.
  • FORTIFIED ARONIA AND TART CHERRY JUICE discloses a composition which comprises Aronia juice fortified with Aronia extract in combination with tart cherry juice fortified with tart cherry extract. According to embodiments, the combination of the extracts with the corresponding juice enhances the bioavailability of the polyphenol gut metabolites.
  • the combination of the extracts with the corresponding juice unexpectedly provides a synergistic effect to reduce the expression of cell adhesion molecules (CAMs) associated with vascular disorders and microvascular dysfunction, including one or more of E-selectin, L-selectin, P-selectin glycoprotein ligand-1 (PSGL-1), ALCAM-1, ICAM-2, and ICAM-1.
  • CAMs cell adhesion molecules
  • the compositions comprise components that interact to inhibit platelet aggregation and vascular inflammation.
  • the composition may also comprise additional nutraceutical extracts, wherein said composition enhances the absorption of micronutrients from the additional nutraceutical extracts.
  • Aronia also known as chokeberry, is known to contain very high concentrations of polyphenols having antioxidant and radical scavenging properties.
  • Aronia is a deciduous shrub which belongs to the plant family Rosaceae. Within the genus Aronia several species and hybrids are known, such as Aronia melanocarpa (black chokeberry), Aronia arbutifolia (red chokeberry), and Aronia x prunifolia (purple chokeberry). In certain embodiments, the 12 Cardiovascular Protection.DOCX Aronia extract and juice originate from an Aronia species which is pharmaceutically and nutraceutically acceptable or is a mixture of different pharmaceutically or nutraceutically acceptable Aronia species. Aronia species that may be used include, but are not limited to A.
  • the extract and juice are from Aronia melanocarpa.
  • the extract and juice are from Aronia melanocarpa rubinia.
  • the polyphenol content may vary depending on the maturity of the Aronia berries and the growing conditions of the plant.
  • the Aronia plant and fruit may be obtained from various parts of the world, including northern Europe and North America.
  • the Aronia extract and juice are derived from the fruit of A. melanocarpa, which may contain between 500 to 2000 mg of polyphenol per 100 mL of juice.
  • the polyphenol content is between 400 to 900 mg per 100 mL of juice. In further embodiments, the polyphenol content is between 600 to 900 mg per 100 mL of juice.
  • the Aronia extract may be derived from the whole fruit or from parts of the fruit. For example, according to embodiments, the extract may be produced from the pomace of the fruit, fresh fruit, dried fruit, or fruit juice.
  • the Aronia extract may be obtained according to any suitable extraction method.
  • the Aronia extract is prepared by ultrasound, microwave, and pressure assisted extraction.
  • the Aronia extract is prepared by solvent (ethanol) extraction and the solvent evaporated according to methods known in the art to produce a dry, water-soluble, extract.
  • the Aronia juice may be prepared from the whole fruit or from parts of the fruit.
  • the Aronia juice is prepared from the whole fruit in order to retain the full spectrum of fruit sugars, nutrients, vitamins and minerals found in the whole fruit juice.
  • the Aronia juice may be obtained according to any suitable juice extraction method.
  • the Aronia juice can be prepared by known methods of steam extraction, hot press extraction, cold press extraction, with or without macerating enzyme treatment.
  • the Aronia juice is prepared at low temperatures to maintain the integrity of 13 Cardiovascular Protection.DOCX the micronutrients and phytochemicals in the juice.
  • the Aronia juice is prepared by cold press extraction.
  • the whole Aronia fruit is pressed without heat to allow the release of polyphenols and other berry bioactives from the berry skin.
  • the Aronia juice is further pasteurized or sterilized at low temperatures.
  • the Aronia juice is fortified with Aronia extract.
  • the Aronia extract is a liquid concentrate and is combined with the Aronia juice.
  • the Aronia extract is a dry powder that is dissolved in the Aronia juice.
  • the fortified Aronia juice comprises from at least about 100 mg to about 4000 mg of Aronia extract per 100 mL of Aronia juice.
  • the fortified Aronia juice comprises from at least about 200 mg to about 3500 mg, from at least about 300 mg to about 3000 mg, from at least about 400 mg to about 2500 mg, from at least about 500 mg to about 2000 mg, from at least about 600 mg to about 1500 mg, and from at least about 700 mg to about 1000 mg of Aronia extract per 100 mL of Aronia juice.
  • the fortified Aronia juice comprises about 500 mg of Aronia extract per 100 ml of Aronia juice.
  • the fortified Aronia juice comprises about 1,000 mg to about 3,000 mg of Aronia extract per 100 ml of Aronia juice.
  • the fortified Aronia juice of the present invention comprises Aronia extract in a concentration from at least about 1 mg/mL to about 40 mg/mL, from about 2 mg/mL to about 35 mg/mL, from about 3 mg/mL to about 30 mg/mL, from about 4 mg/mL to about 25 mg/mL, and from about 6 mg/mL to about 15 mg/mL.
  • Aronia extract in a concentration from at least about 1 mg/mL to about 40 mg/mL, from about 2 mg/mL to about 35 mg/mL, from about 3 mg/mL to about 30 mg/mL, from about 4 mg/mL to about 25 mg/mL, and from about 6 mg/mL to about 15 mg/mL.
  • Tart Cherry Juice Tart cherry, sour cherry, or also referred to as dwarf cherry, is a species of Prunus in the subgenus Cerasus of the plant family Rosaceae.
  • Tart cherries have been shown to be a source of several beneficial micronutrients, particularly vitamin C, anthocyanins, and 14 Cardiovascular Protection.DOCX melatonin.
  • the Malawin Oblacinska variety of tart cherry is identified as a suitable variety of tart cherry juice and/or extract.
  • the tart cherry extract may be derived from the whole fruit or from parts of the fruit.
  • the extract may be produced from the pomace of the fruit, fresh fruit, dried fruit, or fruit juice.
  • the tart cherry extract may be obtained according to any suitable extraction method.
  • the tart cherry extract is prepared by ultrasound, microwave, and pressure assisted extraction.
  • the tart cherry extract is prepared by solvent (ethanol) extraction and the solvent evaporated according to methods known in the art to produce a dry, water-soluble, extract.
  • the tart cherry juice may be prepared from the whole fruit or from parts of the fruit.
  • the tart cherry juice is prepared from the whole fruit in order to retain the full spectrum of fruit sugars, nutrients, vitamins and minerals found in the whole fruit juice.
  • the tart cherry juice may be obtained according to any suitable juice extraction method.
  • the tart cherry juice can be prepared by known methods of steam extraction, hot press extraction, cold press extraction, with or without macerating enzyme treatment.
  • the tart cherry juice is prepared at low temperatures in order to maintain the integrity of the micronutrients and phytochemicals in the juice.
  • the tart cherry juice is prepared by cold press extraction. In further embodiments, the whole tart cherry fruit is pressed without heat to allow the release of polyphenols and other bioactives from the skin of the fruit. In further embodiments, the tart cherry juice is further pasteurized or sterilized at low temperatures. [0059] According to embodiments of the present invention, the tart cherry juice is fortified with tart cherry extract. In certain embodiments, the tart cherry extract is a liquid concentrate and is combined with the tart cherry juice. In other embodiments, the tart cherry extract is a dry powder that is dissolved in the tart cherry juice. In embodiments of the present invention, the fortified tart cherry juice comprises from at least about 100 mg to about 5000 mg of tart cherry extract per 100 mL of tart cherry juice.
  • the fortified tart cherry 15 Cardiovascular Protection.DOCX juice comprises from at least about 50 mg to about 4500 mg, from at least about 150 mg to about 3000 mg, from at least about 375 mg to about 2500 mg, from at least about 500 mg to about 2000 mg, from at least about 600 mg to about 1500 mg, and from at least about 700 mg to about 1000 mg of tart cherry extract per 100 mL of tart cherry juice.
  • the fortified tart cherry juice comprises about 1,000 mg to about 3,000 mg of tart cherry extract per 100 mL of tart cherry juice.
  • the fortified tart cherry juice of the present invention comprises tart cherry extract in a concentration from at least about 1 mg/mL to about 50 mg/mL, from about 0.5 mg/mL to about 25 mg/mL, from about 5 mg/mL to about 20 mg/mL, from about 6 mg/mL to about 15 mg/mL, and from about 7 mg/mL to about 10 mg/mL.
  • Fortified Aronia and Tart Cherry Juice [0061] According to embodiments, the composition of the present invention is prepared by combining the Aronia-extract-fortified Aronia juice and the tart cherry-extract-fortified tart cherry juice.
  • the composition comprises a volume ratio of fortified Aronia juice to fortified tart cherry juice in a 1:1, 2:1, 3:1, 4:1, 5:1, 6:1, 7:1, 8:1, 9:1, or 10:1 volume ratio.
  • the composition comprises a volume ratio of fortified Aronia juice to fortified tart cherry juice in a 1:1, 2:1, or 4:1 volume ratio.
  • the composition comprises a volume ratio of fortified tart cherry juice to fortified Aronia juice in a 1:1, 2:1, 3:1, 4:1, 5:1, 6:1, 7:1, 8:1, 9:1, or 10:1 volume ratio.
  • the composition comprises a volume ratio of fortified tart cherry juice to fortified Aronia juice in a 1:1, 2:1, or 4:1 volume ratio.
  • the composition of Aronia- extract-fortified Aronia juice and tart cherry-extract-fortified tart cherry juice comprises from at least about 100 mg to about 4000 mg of Aronia extract and from at least about 20 mg to about 5000 mg of tart cherry extract per 100 mL.
  • the composition comprises from at least about 200 mg to about 3500 mg, from at least about 16 Cardiovascular Protection.DOCX 300 mg to about 3000 mg, from at least about 400 mg to about 2500 mg, from at least about 500 mg to about 2000 mg, from at least about 600 mg to about 1500 mg, or from at least about 700 mg to about 1000 mg of Aronia extract per 100 mL, and from at least about 50 mg to about 4500 mg, from at least about 150 mg to about 3000 mg, from at least about 375 mg to about 2500 mg, from at least about 500 mg to about 2000 mg, from at least about 600 mg to about 1500 mg, or from at least about 700 mg to about 1000 mg of tart cherry extract per 100 mL.
  • DOCX 300 mg to about 3000 mg from at least about 400 mg to about 2500 mg, from at least about 500 mg to about 2000 mg, from at least about 600 mg to about 1500 mg, or from at least about 700 mg to about 1000 mg of Aronia extract per 100 mL
  • 50 mg to about 4500 mg from at least about 150 mg to about 3
  • the composition comprises about 2000 mg of Aronia extract and about 1500 mg of tart cherry extract per 100 mL.
  • ADDITIONAL MICRONUTRIENTS AND BIOACTIVE PHYTOCHEMICALS [0064] According to embodiments of the present invention, it is contemplated that the combination of Aronia and tart cherry extracts with the corresponding juice provides a synergistic effect that enhances the bioavailability of polyphenol and/or polyphenol gut metabolites, and enhances absorption of micronutrients and bioactive phytochemicals.
  • the composition of Aronia juice fortified with Aronia extract, and tart cherry juice fortified with tart cherry extract may also comprise additional nutraceutical extracts. In certain embodiments, the additional extracts comprise additional polyphenols.
  • the additional extracts comprise bioactive agents that further support vascular health. In other embodiments, the additional extracts comprise bioactive agents having activities that complement vascular health. It is contemplated that the increased absorption of the micronutrients and bioactive phytochemicals, when combined with the composition of fortified Aronia and tart cherry juice, results in an enhanced beneficial effect.
  • Additive Micronutrients and Bioactive Phytochemicals may be provided as one or more active compounds from the group of vitamins, minerals, and trace minerals.
  • the additional micronutrient and bioactive phytochemicals may be provided in synthetic or plant-derived form. In preferred embodiments, the additional micronutrients and bioactive phytochemicals comprise polyphenols.
  • the additional 17 Cardiovascular Protection.DOCX micronutrients and bioactive phytochemicals are provided as one or more nutraceutical extracts.
  • the additional micronutrients and bioactive phytochemicals may be provided as any one or more of the following nutraceutical extracts.
  • Beetroot Extract [0066] Beetroot extract has a high nitrate and antioxidant (betanin) content. Beetroot extract may increase in vivo nitric oxide (NO) bioavailability, enhance endothelial function, improve blood flow and enhance physical performance, as well as combat damaging reactive oxygen species.
  • NO nitrate and antioxidant
  • Rosehip Extract has a particularly high vitamin C, carotenoid (lycopene), and polyphenol content, which are all beneficial in fighting inflammation and protecting the immune system from viral and bacterial infection.
  • Chamomile Extract [0068] Chamomile extract is traditionally used for its calming effects and is thought to aid in combating depression and anxiety with its unique content of apigenin, an antioxidant that promotes sleepiness, improves sleep quality and reduces insomnia. In addition, chamomile extract is thought to improve gastrointestinal and cardiovascular health, and lower blood pressure.
  • Lemon Balm Extract [0069] Lemon balm (Melissa officinalis) is a powerful herb from the mint family that is thought to reduce stress and anxiety, and improve mood and sleep quality.
  • Lemon balm extract is high in flavonoids, phenolic compounds, as well as antioxidants such as rosmarinic and gallic acid, which all help to combat inflammation, promote gastrointestinal health and boost cognitive function. 18 Cardiovascular Protection.DOCX Lion’s Mane Mushroom Extract [0070] Lion’s mane mushroom is a medicinal mushroom believed to offer a range of health benefits, including reduced inflammation and improved cognitive and heart health. Reishi Mushroom Extract [0071] Reishi mushroom is a polypore fungus belonging to the genus Ganoderma (Ganoderma lucidum) and is considered to be a medicinal mushroom in many Asian cultures for its health-promoting effects. Reishi mushroom is thought to have immunomodulatory, renoprotective, anti-inflammatory, and hepatoprotective properties.
  • Natural Wild Species Parsley Extract [0072] The two main groups of parsley are curly leaf (i.e.,P. crispum crispum group; syn. P. crispum var. crispum) and Italian, or flat leaf (i.e., P. crispum neapolitanum group; syn. P. crispum var. neapolitanum). Of these, the neapolitanum group more closely resembles the natural wild species. It contains a variety of B vitamins including B-5 and B- 2. Parsley may also contain more vitamin K than any other herb since it has more than 1300 percent of the recommended daily intake. Parsley can be used to treat conditions like: water edema, high blood pressure, digestion.
  • CBD cannabidiol
  • CBD particularly from hemp, has a variety of vitamins and minerals such as vitamins A, C, E and B complex, as well as zinc, potassium, iron, calcium, essential amino acids, and omega 3 and 6 fatty acids.
  • CBD has been reported to reduce anxiety, stress and depression, as well as improve sleep quality, pain management and overall wellness.
  • the composition of Aronia- extract-fortified Aronia juice and tart cherry-extract-fortified tart cherry juice further includes one or more additional nutraceuticals selected from red beet extract, rosehip extract, chamomile extract, Melissa officinalis, lemon balm extract, lion’s mane mushroom extract, 19 Cardiovascular Protection.DOCX reishi mushroom extract, parlsley, cannabidiol (CBD), or any combination of these extracts.
  • additional nutraceuticals selected from red beet extract, rosehip extract, chamomile extract, Melissa officinalis, lemon balm extract, lion’s mane mushroom extract, 19 Cardiovascular Protection.DOCX reishi mushroom extract, parlsley, cannabidiol (CBD), or any combination of these extracts.
  • the one or more additional nutraceutical extracts are added to the Aronia-extract-fortified Aronia juice and tart cherry-extract-fortified tart cherry juice composition in the following ranges, from at least about 50 mg to 5000 mg of red beet extract, from at least about 20 mg to 5000 mg of rosehip extract, from at least about 10 mg to 2000 mg of chamomile extract, from at least about 10 mg to 3000 mg of Melissa officinalis, from at least about 10 mg to 4000 mg of lemon balm extract, from at least about 100 mg to 1500 mg of lion’s mane mushroom extract, from at least about 100 mg to 1500 mg of reishi mushroom extract, and/or from at least about 1 mg to 300 mg of cannabidiol (CBD) per 100 mL.
  • CBD cannabidiol
  • the composition includes one or both of the additional nutraceutical extracts selected from red beet extract, lion’s mane mushroom extract, and/or rosehip extract.
  • the composition includes from about 50 mg to 5000 mg of red beet extract, and/or from about 20 mg to 5000 mg of rosehip extract, and/or from about 100 mg to 1500 mg of lion’s mane mushroom extract per 100 mL.
  • the Aronia-extract-fortified Aronia juice and tart cherry-extract-fortified tart cherry juice composition further includes about 1000 mg of red beet extract, and/or about 1000 mg of rosehip extract, and/or about 1000 mg of lion’s mane mushroom extract, and/or about 300-1000 mg of wild form of parsley extract per 100 mL.
  • the Aronia-extract- fortified Aronia juice and tart cherry-extract-fortified tart cherry juice composition further includes one or more additional nutraceutical extracts that comprise one or more of rosehip extract, chamomile extract, reishi mushroom extract, and lemon balm extract.
  • the one or more additional nutraceutical extracts are added to the Aronia- extract-fortified Aronia juice and tart cherry-extract-fortified tart cherry juice composition in the following ranges, from at least about 20 mg to 5000 mg of rosehip extract, from at least about 10 mg to 2000 mg of chamomile extract, from at least about 100 mg to 1500 mg of reishi mushroom extract, and/or from at least about 10 mg to 4000 mg of lemon balm 20 Cardiovascular Protection.DOCX extract per 100 mL.
  • the Aronia-extract-fortified Aronia juice and tart cherry-extract-fortified tart cherry juice composition further includes about 1000 mg of rosehip extract, 700 mg of chamomile extract, 1000 mg of reishi mushroom extract, and/or 500 mg of lemon balm extract, and/or about 300-1000 mg of wild form of parsley extract per 100 mL.
  • the formulation comprises Aronia-extract-fortified Aronia juice, tart cherry-extract-fortified tart cherry juice, with at least about 50 mg to 5000 mg of red beet extract, about 20 mg to 5000 mg of rosehip extract, about 10 mg to 2000 mg of chamomile extract, and 100 mg to 1500 mg of lion’s mane mushroom extract per 100 mL.
  • the formulation comprises Aronia-extract-fortified Aronia juice, tart cherry-extract-fortified tart cherry juice, with at least about 10 mg to 2000 mg of chamomile extract, at least about 10 mg to 4000 mg of lemon balm extract, at least about 100 mg to 1500 mg of reishi mushroom extract per 100 mL.
  • the additional nutraceuticals added to the Aronia-extract-fortified Aronia juice and tart cherry-extract- fortified tart cherry juice composition further includes cannabidiol (CBD).
  • CBD cannabidiol
  • the CBD is added to the composition, according to certain embodiments, in an amount that ranges from at least about 1 mg to 300 mg per 100 mL.
  • the Aronia-extract-fortified Aronia juice and tart cherry- extract-fortified tart cherry juice composition includes one or more of from at least about 20 mg to 5000 mg of rosehip extract, from at least about 10 mg to 2000 mg of chamomile extract, from at least about 10 mg to 4000 mg of lemon balm extract, from at least about 100 to 1500 mg of reishi mushroom extract, from at least about 300 to1000 mg of wild form of parsley, and from at least about 1 mg to 300 mg of cannabidiol (CBD) per 100 mL.
  • CBD cannabidiol
  • the Aronia-extract-fortified Aronia juice and tart cherry- extract-fortified tart cherry juice composition further includes one or more additional nutraceuticals selected from about 100mg to 2,000mg of resveratrol extract, about 100mg to 21 Cardiovascular Protection.DOCX 1,000mg of quercetin extract, about 100mg to 1,000mg of fisetin extract, 100mg to 3,000mg of berberine extract, about 100mg to 3,000mg of urolithin A, about 100mg to 3,000mg of NMN, about 100mg to 3,000mg of Ca-AKG, about 10mg to 3,000mg of spermidine extract, and/or about 100mg to 3,000mg of TMG.
  • additional nutraceuticals selected from about 100mg to 2,000mg of resveratrol extract, about 100mg to 21 Cardiovascular Protection.DOCX 1,000mg of quercetin extract, about 100mg to 1,000mg of fisetin extract, 100mg to
  • the Aronia-extract-fortified Aronia juice and tart cherry-extract-fortified tart cherry juice composition can be formulated as a nutritional supplement for oral consumption.
  • the formulation comprises the Aronia- extract-fortified Aronia juice and tart cherry-extract-fortified tart cherry juice composition as described herein, formulated as an oral supplement.
  • the formulation comprises the Aronia-extract-fortified Aronia juice and tart cherry-extract- fortified tart cherry juice composition in combination with one or more additional nutraceutical extracts as described herein, formulated as an oral supplement.
  • the formulation comprises the Aronia-extract-fortified Aronia juice and tart cherry-extract-fortified tart cherry juice composition in combination with one or more additional polyphenol-containing extract.
  • the composition according to the present invention may be formulated in a liquid form, i.e., for example in the form of solutions, dispersions, emulsions and gels, or in a solid form.
  • the composition is formulated as a capsule, a tablet, a liquid concentrate, a liquid drink, or a powder.
  • the composition is formulated as a liquid drink, syrup, tonic, or jelly.
  • the composition is formulated as an edible solid or an edible semi-solid.
  • the formulation is a powder reconstituted into potable liquid (i.e. water, etc.).
  • additional components can be added to the formulation to provide colour, flavour, texture, scent, etc.
  • the formulation comprises additional components that act as preservatives or stabilize one or more of the ingredients. 22 Cardiovascular Protection.DOCX METHODS AND USE
  • Also within the scope of the invention are methods for treating and/or preventing and/or aiding the treatment and/or prevention of diseases and/or conditions associated with adhesive interactions modulated by cell adhesion molecules.
  • the methods comprise treating an existing medical condition, for example, high blood pressure or atherosclerosis, by affecting the pathology of the disease or the symptoms associated therewith.
  • the methods comprise preventing or reducing the risks associated with developing a disease, for example, high blood pressure or atherosclerosis.
  • the method comprises the prevention or prophylaxis of vascular health in an individual known to be at high risk of developing a disease.
  • the methods comprise maintaining good vascular health in a subject.
  • Diseases and/or conditions associated with adhesive interactions modulated by cell adhesion molecules include atherosclerosis, hypertension, coronary heart disease (CHD), cerebrovascular disease, heart attack, stroke, peripheral vascular disease and kidney failure. Also included are methods for inhibiting platelet aggregation, monocyte adhesion and proliferation of vascular smooth muscle, reducing blood pressure, reducing thrombosis, and modulating oxidative stress.
  • the methods comprise administering to a subject, an amount of the composition effective to treat, prevent, or aid in the treatment or prevention, or achieve at least the beneficial effect of inhibiting platelet aggregation.
  • the methods may further comprise determining the effectiveness of the treatment by, for example, determining plasma levels of CVD biomarkers, including cell adhesion molecules and/or platelet aggregation and/or platelet activation.
  • the composition may be administered to a healthy subject for prophylactic purposes or to a subject in need of a treatment or having at least one of the risk factors associated. Any individual having at least one of the risk factors associated with vascular health problems is a subject for administration of the compositions described herein.
  • a method of enhancing absorption of a polyphenol into the blood of a subject comprises administering to the subject an Aronia-extract- fortified Aronia juice and tart cherry-extract-fortified tart cherry juice composition.
  • the effective amount may be determined by a person skilled in the art using the guidance provided herein and the general knowledge in the art. It will be appreciated that the amount to be administered depends on the subject to be treated taking into account age, weight and other personal conditions.
  • the treatments/preventive administration may be continued as a regimen, e.g., daily, monthly, bimonthly, biannually, annually, or in some other regimen, as determined by the skilled medical practitioner for such time as is necessary.
  • the composition is administered daily, most preferably two or three times a day, for example, morning and evening to maintain the levels of the effective compounds in the body of the subject.
  • the composition may be administered for at least about 30 to about 60 days. These regimens may be repeated periodically.
  • the composition is taken at least once a day for 1 week to 12 months. In other embodiments, the composition is taken at least once a day for 1, 2, 3, or 4 weeks.
  • the composition is taken at least once a day for 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, or 12 months.
  • the formulation consisted of aronia also known as chokeberry (Aronia melanocarpa) and tart cherry (Prunus cerasus) mother juices combined in a 4:1 ratio (volume/volume) enriched with polyphenol-rich dry extracts from both of these fruits, total of 1000 mg od polyphenols.
  • the parameters observed in this preliminary study include: blood count parameters, markers of kidney and liver function, anthropometric parameters, blood pressure, metabolic parameters (blood lipid profiles, blood sugar), markers of cardiovascular risk, intestinal permeability, inflammatory biomarkers, antioxidant defense parameters and erythrocyte fatty acid profiles. These parameters were monitored to identify the systemic effects resulting from prolonged consumption of the core formulation which reflect the bioavailability and absorption of the polyphenols.
  • Study participants were not on special dietary regimens (e.g., vegan and vegetarian) and did not report allergy or intolerance to berries or chokeberry/tart cherry formulation components.
  • the study participants were instructed to consume a daily dose of 60 ml of core formulation after breakfast. During the study, participants were asked to maintain their habitual diet and physical activity but abstain from berries and berry-derived products other than the test drink and avoid excess amounts of other polyphenol rich-foods and alcohol.
  • trained staff conducted structured interviews with study subjects and collected data using a food frequency questionnaire and repeated 24-hour dietary recalls. Adherence to dietary restrictions was monitored by regular contact with members of the research team and unannounced 24-hour dietary recall checks.
  • Venous blood was drawn in the morning (8:00-9:00 a.m.) after an overnight fast, at three time points: before the consumption (Baseline, T0), after 3-weeks (short-term, T1), and after 3 months (long-term, T2) of core formulation consumption.
  • Blood was collected into the appropriate sample tubes and further processed to obtain serum and plasma samples. Biochemical parameters were determined in fresh serum samples using the clinical biochemistry analyzer. Plasma samples were used to evaluate intestinal permeability and inflammatory parameters by ELISA assays.
  • Whole blood was used to assess hematological parameters by the hematology analyzer and the antioxidant defense parameters by commercial kits. Erythrocyte fatty acid profiles in the total lipid pool were determined by gas chromatography.
  • Hematological parameters assessed include leukocyte count and differential, erythrocyte count, platelet count, hemoglobin concentration, hematocrit (packed cell volume), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC).
  • Kidney function was assessed for ability to perform normal functions like clearing waste products (serum urea (BUN), creatinine, uric acid levels) and maintaining the electrolyte balance (serum sodium, potassium, and chloride levels).
  • BUN serum urea
  • uric acid levels creatinine, uric acid levels
  • electrolyte balance sodium, potassium, and chloride levels.
  • liver function was assessed by observing how well the liver is performing its regular function like producing protein (serum albumin, total protein levels) and clearing bilirubin, as well as the measurement of enzymes that liver cells release in response to 29 Cardiovascular Protection.DOCX damage, including serum alanine transaminase (ALT), aspartate transaminase (AST) and lactate dehydrogenase (LDH).
  • ALT serum alanine transaminase
  • AST aspartate transaminase
  • LDH lactate dehydrogenase
  • VCAM-1 vascular cell adhesion protein 1
  • ICAM-1 intercellular adhesion molecule 1
  • ECM-1 endothelin-1
  • TNF ⁇ tumor necrosis factor alpha
  • IL-6 interleukin 6
  • Oxidative stress/antioxidant defense was evaluated as 1) activities of enzymes involved in antioxidant protection: glutathione peroxidase (GPx), superoxide dismutase (SOD), and catalase (CAT); and 2) index of lipid peroxidation determined as thiobarbituric acid-reactive substances (TBARS) expressed as malondialdehyde (MDA) equivalents.
  • GPx glutathione peroxidase
  • SOD superoxide dismutase
  • CAT catalase
  • MDA malondialdehyde
  • ICAM-1 a marker of endothelial dysfunction
  • plasma zonulin A significant reduction in junctional protein levels, ICAM-1 (a marker of endothelial dysfunction) and plasma zonulin, suggest that long-term consumption of the aronia/tart cherry core formulation improved intestinal permeability leading to tighter cell junctions and less water and nutrient loss. The resulting systemic effects of this were further shown by a significant effect on the total, intra and extracellular water in both legs and lowered diastolic blood pressure, suggesting potential anticellulite and blood pressure modulating effects of the studied formulation.
  • the test drink also showed increased variables associated with anemia and the health of the hemoglobin in the blood (MCH, MCHC) and reduced uric acid levels, a parameter associated with the development of hypertension, metabolic syndrome, and diabetes mellitus.
  • EXAMPLE 2 ACUTE EFFECT OF FORTIFIED ARONIA-TART CHERRY FORMULATION ON PLATELET FUNCTION
  • Platelets may interact with these cells directly through adhesion molecules such as P-selectin and GPIIbIIIa on the surface of activated platelets to form aggregates.
  • Disturbed platelet function has been shown to discriminate between healthy and individuals at high risk for CVD, and its major hallmarks are platelet hyperactivation (a higher number of activated platelets in basal state or in response to agonists ex vivo), and 35 Cardiovascular Protection.DOCX hyperreactivity (increased response to suboptimal concentrations of agonists).
  • increased platelet-leukocyte aggregates (neutrophil/monocytes) formation has been reported in subjects with hypertension, diabetes, metabolic syndrome, ischemic heart disease and stroke.
  • the objective of this study was to evaluate the potential acute effects of consuming core formulation and its components on platelet function, assessed as the expression of platelet activation markers (P-selectin and GPIIbIIIa) and platelet-monocyte and platelet- neutrophil aggregate formation in the whole blood of subjects in both basal state and after the ex vivo exposure to a suboptimal concentration of platelet agonist.
  • the core formulation consisted of chokeberry (Aronia melanocarpa) and tart cherry (Prunus cerasus) mother juices combined in a 4:1 ratio (volume/volume) and enriched with polyphenol-rich dry extracts from both fruits.
  • ii) Evaluated parameters included markers of: a) platelet activation — the expression of P-selectin and GPIIbIIIa activation markers on platelets b) platelet-leucocyte aggregation—platelet-neutrophil and platelet-monocyte aggregates in the population of neutrophils and monocytes, respectively [00128] These parameters were explored in the whole blood in the basal state and in response to suboptimal (0.5 ⁇ M) and optimal concentration (20 ⁇ M, maximal response) of agonist adenosine diphosphate (ADP), all assessed at two time points: before consuming each test drink (0h) and 2 hours after consumption (2h) (Figure 8).
  • ADP agonist adenosine diphosphate
  • Platelet activation markers were expressed as 1) the percentage and 2) mean fluorescence intensity (MFI) of P-selectin and GPIIbIIIa-positive platelets in the total number of collected platelets (20000).
  • the first parameter corresponds to the percentage of activated platelets in the total population of platelets and the latter is a measure of the density of P-selectin or GPIIbIIIa per platelet.
  • PAI platelet activation index
  • All data are presented relative to maximal platelet response (stimulation with 20 ⁇ M ADP).
  • Platelet aggregation with monocytes and neutrophils was expressed as a percentage of aggregates in the total population of monocytes (1000) and neutrophils (10000) as well as MFI in platelet-monocyte and platelet-neutrophil aggregates, which provided the relative 39 Cardiovascular Protection.DOCX measure of a density (average number per aggregate) of platelets in these aggregates. All data are presented relative to maximal platelet response (stimulation with 20 ⁇ M ADP). [00133] The effects of each study drink on evaluated markers of platelet function were evaluated by paired sample t-tests for normally distributed data, or Wilcoxon signed-rank tests for non-normal data distribution (0h vs. 2h time points).
  • Systolic and diastolic blood pressure values were within the higher normal blood pressure category (130-139 and/or 85-89mmHg) according to the European Society of Cardiology and the European Society of Hypertension. Assessed hematological and biochemical parameters of volunteers were within reference ranges for gender and age (Table 8). Table 8.
  • ALT Alanine transaminase
  • AST Aspartate transaminase
  • BMI Body mass index
  • HCT Hematocrit
  • HDL-c High-density lipoprotein cholesterol
  • HGB Hemoglobin
  • LDH Lactate dehydrogenase
  • LDL-c Low-density lipoprotein cholesterol
  • MCH Mean corpuscular hemoglobin
  • MCHC Mean corpuscular hemoglobin concentration
  • MCV Mean corpuscular volume
  • PLT Platelet count
  • RBC Red blood cells
  • TC Total cholesterol
  • WBC White blood cells.
  • the core formulation significantly reduced the percentage of GPIIbIIIa-positive platelets after responding to ADP.
  • individual core formulation components in addition to attenuating this parameter (AJ+AE), reduced the relative number of GPIIbIIIa on activated platelets (AJ+AE), the percentage of P-selectin positive platelets (AJ+AE, TCJ+TCE, TCE) and the relative number of P-selectin on activated platelets (TCJ+TCE, TCE).
  • GPIIbIIIa and P- selectin are markers of platelet activation that also directly mediate platelet interactions with other cells.
  • GPIIb/IIIa is a receptor for fibrinogen that mediates platelet-platelet and platelet-leukocyte aggregation.
  • the observed changes in these platelet activation parameters were more pronounced when fruit extracts were combined with their corresponding mother juices.
  • Individual core formulation components did not affect platelet activation, as the only significant reduction in the percentage of GPIIbIIIa-positive platelets was observed after consuming the core formulation itself.
  • EXAMPLE 3 EFFECT OF FORTIFIED ARONIA-TART CHERRY FORMULATION ON CELL ADHESION AND INFLAMMATION
  • This formulation consisted of chokeberry (Aronia melanocarpa) and tart cherry (Prunus cerasus) mother juices combined in a 4:1 ratio (volume/volume) and enriched with polyphenol-rich dry extracts from both of these fruits.
  • Study participants were not on special dietary regimens (e.g., vegan and vegetarian) and did not report allergy or intolerance to berries or chokeberry/tart cherry formulation components.
  • the study participants were instructed to consume a daily dose of 60 ml of core formulation (chokeberry and tart cherry mother juices (4:1, v/v) enriched with polyphenol- rich dry extracts from both fruits) after breakfast.
  • Study treatments were provided in dark 47 Cardiovascular Protection.DOCX bottles and participants were asked to keep them in the refrigerator to preserve polyphenol stability. Compliance with the study beverage supplementation was assessed by collecting empty bottles on the last day of the intervention.
  • MRP8/14 lipocalin A
  • NGAL matrix metallopeptidase 2
  • OPN osteopontin
  • MPO myeloperoxidase
  • DOCX 2 Cell adhesion molecules that mediate interactions between cells and cells and extracellular matrix and are essential in processes like cell adhesion, migration and inflammation. Assessed adhesion molecules included: platelet endothelial cell adhesion molecule (PECAM-1), activated leukocyte cell adhesion molecule (ALCAM-1), epithelial cellular adhesion molecule (EpCAM), neural cell adhesion molecule (NCAM), E-selectin, P-selectin, L-selectin, Intercellular Adhesion Molecule 1 (ICAM-1), ICAM-2, ICAM-3, P-selectin glycoprotein ligand-1 (PSGL- 1), and CD44.
  • PECAM-1 platelet endothelial cell adhesion molecule
  • ALCAM-1 activated leukocyte cell adhesion molecule
  • EpCAM epithelial cellular adhesion molecule
  • NCAM neural cell adhesion molecule
  • IAM-1 Intercellular Adhesion Molecule 1
  • ICAM-2
  • Core formulation ingredients are extensively metabolized by the gut microbiota and have increased bioavailability by crossing the gut/blood barrier. Moreover, these ingredients mediate the interaction between cells through cell adhesion molecules (CAMs), which are cell surface proteins that are involved in the binding of cells with other cells or with the extracellular matrix (ECM) and are broadly recognized as markers of inflammation and CVD risk. Increased CAM cell surface expression and plasma levels have been linked to cardiovascular disease. Our analysis showed the potency of chronic consumption of the chokeberry/tart cherry core formulation to significantly reduce the expression of several cell adhesion molecules (CAMs). [00155] These results suggest beneficial, anti-inflammatory and vessel-protective effects of long-term consumption of core formulation in preserving the CVH and in the subjects at increased CVD risk.
  • CAMs cell adhesion molecules

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Abstract

Une composition pour entretenir la santé vasculaire comprend une combinaison de jus d'Aronia enrichi avec un extrait d'Aronia, et un jus de cerise acide enrichi avec un extrait de cerise acide ainsi que des méthodes de prévention ou de traitement d'une maladie cardiovasculaire.
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