Method for protecting or maintaining cardiovascular health, and composition
By administering a dehydrogingerone composition to subjects, the expression of VCAM-1 and ICAM-1 was inhibited or the content of nitric oxide was increased, which solved the problem of the lack of effective cardiovascular health protection in the prior art and achieved the effects of preventing atherosclerosis and improving vascular function.
Patent Information
- Authority / Receiving Office
- WO · WO
- Patent Type
- Applications
- Current Assignee / Owner
- NANJING NUTRABUILDING BIO TECH CO LTD
- Filing Date
- 2025-12-01
- Publication Date
- 2026-06-11
Smart Images
Figure CN2025138891_11062026_PF_FP_ABST
Abstract
Description
Methods and compositions for protecting or maintaining cardiovascular health Technical Field
[0001] This invention belongs to the technical field of health food and dietary supplements, specifically relating to compositions and methods for protecting or maintaining cardiovascular health, and their related applications in nutritional products, dietary supplements, food, beverages or animal feed. Background Technology
[0002] Cardiovascular health is a major public health issue globally, causing millions of deaths annually, with coronary heart disease and stroke being the most common causes. While some developed countries have seen declines in cardiovascular disease incidence and mortality through lifestyle improvements and medical interventions, in many developing countries, these rates continue to rise due to population aging and the prevalence of unhealthy lifestyles. In China, the prevalence of cardiovascular disease continues to rise, with estimated numbers reaching hundreds of millions, and the increase is more pronounced in rural areas. An increasing number of people are using dietary supplements to prevent and improve cardiovascular health, aiming to clear blood vessels, lower blood pressure, cleanse and quickly eliminate toxins from blood vessels, and improve blood cell activity. Simultaneously, it is hoped that these supplements can break down intravascular fat, accelerate vascular metabolism, reduce the viscosity of intravascular lipids, and effectively prevent cardiovascular and cerebrovascular diseases.
[0003] Dehydrozingerone (DHZ), also known as feruloylmethane, is isolated from turmeric and is a structural analogue of curcumin. It possesses various biological activities, such as potent anti-inflammatory effects and the ability to scavenge oxygen free radicals, but there are no reports of its use in protecting or maintaining cardiovascular health. Summary of the Invention
[0004] One aspect of the present invention relates to a method for protecting or maintaining cardiovascular health, the method comprising administering to a subject a composition containing dehydrogingerone or its salts, acids, esters or derivatives thereof.
[0005] In some implementation schemes, protecting or maintaining cardiovascular health includes preventing atherosclerosis, regulating the function of vascular endothelial cells, and regulating vasomotor activity and permeability.
[0006] In some implementations, the method is achieved by inhibiting the expression of vascular cell adhesion molecule-1 (VCAM-1) or intercellular adhesion molecule-1 (ICAM-1), or by increasing the content of nitric oxide.
[0007] In some embodiments, compositions containing dehydrogingerone or its salts, acids, esters or derivatives are formulated as nutritional products, dietary supplements, foods, beverages or animal feed.
[0008] In some implementations, the subjects are humans or mammals.
[0009] In some embodiments, the composition containing dehydrogingerone or its salts, acids, esters or derivatives is in the form of suppositories, tablets, pills, granules, powders, films, capsules, beverages, aerosols, liniments, tinctures, tonics, liquid suspensions or syrups.
[0010] In some embodiments, the composition containing dehydrogingerone or its salts, acids, esters or derivatives is administered to the subject at a dose of 1-1500 mg.
[0011] In some implementations, administration is carried out via a route selected from: oral, intravenous, intramuscular, intraperitoneal, or sublingual administration.
[0012] In some embodiments, the composition is administered to a subject by a single dose or multiple fractions, such that the daily intake of dehydroshogaol or its salts, acids, esters, or derivatives is about 5-1200 mg, 10-1000 mg, 12-1500 mg, 15-1200 mg, 20-1000 mg, 25-800 mg, or about 3-500 mg, 5-400 mg, 8-300 mg, 10-200 mg, 12-150 mg, or about 100-1500 mg, 200-1200 mg, 300-1000 mg; or about 10 μM to 1 M, for example about 100 μM to 500 mM, 1 mM to 100 mM, 2 mM to 50 mM, 5 mM to 20 mM, or about 50 μM to 500 mM, 100 μM to 100 mM, 500 mM to 20 mM, or about 50 μM to 500 mM, 100 μM to 100 mM, 500 mM to 20 mM. μM to 50 mM, 1 mM to 10 mM, or approximately 100 μM to 1 M, 1 mM to 800 mM, 2 mM to 500 mM, 5 mM to 300 mM, 10 mM to 100 mM.
[0013] In some embodiments, the composition may be applied once daily or every other day for a period of time, such as 3 days to 1 week, 1 week to 7 weeks, 2 weeks to 7 weeks, 3 weeks to 7 weeks, 4 weeks to 7 weeks, 1 week to 14 weeks, 2 weeks to 14 weeks, 3 weeks to 14 weeks, or 4 weeks to 14 weeks. For example, it may be taken for a period of time according to the above time periods.
[0014] Another aspect of the invention relates to the use of a composition containing dehydrogingerone or its salts, acids, esters or derivatives in the preparation of nutritional products, dietary supplements, foods, beverages or animal feed for the protection or maintenance of cardiovascular health.
[0015] In some implementation schemes, protecting or maintaining cardiovascular health includes preventing atherosclerosis, regulating the function of vascular endothelial cells, and regulating vasomotor activity and permeability.
[0016] In some implementations, protecting or maintaining cardiovascular health is achieved by inhibiting the expression of vascular cell adhesion molecule-1 (VCAM-1) or intercellular adhesion molecule-1 (ICAM-1), or by increasing nitric oxide levels.
[0017] In some embodiments, the dosage of the composition is 1-1500 mg.
[0018] In some embodiments, the composition is administered to a subject by a single dose or multiple fractions, such that the daily intake of dehydroshogaol or its salts, acids, esters, or derivatives is about 5-1200 mg, 10-1000 mg, 12-1500 mg, 15-1200 mg, 20-1000 mg, 25-800 mg, or about 3-500 mg, 5-400 mg, 8-300 mg, 10-200 mg, 12-150 mg, or about 100-1500 mg, 200-1200 mg, 300-1000 mg; or about 10 μM to 1 M, for example about 100 μM to 500 mM, 1 mM to 100 mM, 2 mM to 50 mM, 5 mM to 20 mM, or about 50 μM to 500 mM, 100 μM to 100 mM, 500 mM to 20 mM, or about 50 μM to 500 mM, 100 μM to 100 mM, 500 mM to 20 mM. μM to 50 mM, 1 mM to 10 mM, or approximately 100 μM to 1 M, 1 mM to 800 mM, 2 mM to 500 mM, 5 mM to 300 mM, 10 mM to 100 mM.
[0019] In some embodiments, the composition may be applied once daily or every other day for a period of time, such as 3 days to 1 week, 1 week to 7 weeks, 2 weeks to 7 weeks, 3 weeks to 7 weeks, 4 weeks to 7 weeks, 1 week to 14 weeks, 2 weeks to 14 weeks, 3 weeks to 14 weeks, or 4 weeks to 14 weeks. For example, it may be taken for a period of time according to the above time periods.
[0020] In some embodiments, the composition containing dehydrogingerone or its salts, acids, esters or derivatives is in the form of suppositories, tablets, pills, granules, powders, films, capsules, beverages, aerosols, liniments, tinctures, tonics, liquid suspensions or syrups.
[0021] Another aspect of the present invention relates to a composition containing dehydrogingerone or its salts, acids, esters or derivatives thereof, for the protection or maintenance of cardiovascular health.
[0022] In some implementation schemes, protecting or maintaining cardiovascular health includes preventing atherosclerosis, regulating the function of vascular endothelial cells, and regulating vasomotor activity and permeability.
[0023] In some implementations, protecting or maintaining cardiovascular health is achieved by inhibiting the expression of vascular cell adhesion molecule-1 (VCAM-1) or intercellular adhesion molecule-1 (ICAM-1), or by increasing nitric oxide levels.
[0024] In some embodiments, compositions containing dehydrogingerone or its salts, acids, esters or derivatives are formulated as nutritional products, dietary supplements, foods, beverages or animal feed.
[0025] In some embodiments, the composition containing dehydrogingerone or its salts, acids, esters or derivatives is in the form of suppositories, tablets, pills, granules, powders, films, capsules, beverages, aerosols, liniments, tinctures, tonics, liquid suspensions or syrups.
[0026] In some embodiments, the dosage of the composition is 1-1500 mg. Attached Figure Description
[0027] Figure 1 shows the effect of 10 mM DHZ on VCAM-1 secretion induced by ox-LDL damage.
[0028] Figure 2 shows the effect of 10 mM DHZ on ICAM-1 secretion induced by ox-LDL damage.
[0029] Figure 3 shows the effect of 10 mM DHZ on NO secretion induced by ox-LDL damage. Detailed Implementation
[0030] The present invention will now be further described with reference to preferred embodiments thereof. While the invention will be described in conjunction with preferred embodiments, it should be understood that they are not intended to limit the invention to these embodiments. Rather, the invention is intended to cover alternatives, modifications, and equivalents that may be included within the spirit and scope of the invention as defined in the claims. Furthermore, numerous specific details are set forth in the detailed description of the invention to provide a thorough understanding of the invention. However, it will be apparent to those skilled in the art that the invention may be practiced without these specific details. In other instances, well-known methods, procedures, components, and other features have not been described in detail to avoid unnecessarily obscuring aspects of the invention.
[0031] As used in this article, the term “or” is intended to include both “and” and “or”. In other words, the term “or” can also be replaced by “and / or”.
[0032] As used herein, unless the context clearly indicates otherwise, the singular forms “a / an” and “the” are intended to include the plural forms as well.
[0033] As used herein, the terms “subject” and “individual” are used interchangeably to refer to any subject to whom the methods and compositions of this disclosure may be applied or administered. A subject may have a disease or condition, but does not need to be ill to benefit from the methods and compositions of this disclosure. A subject may need to protect or maintain cardiovascular health, or may have generally healthy cardiovascular health and wish to maintain or further protect their cardiovascular and / or overall health. Therefore, any subject may take the disclosed compositions or become a recipient of the disclosed methods. In this document, the term “subject” refers to an animal (e.g., birds, reptiles, and mammals). In some embodiments, the subject may be a mammal including non-primates (e.g., camels, donkeys, zebras, cows, horses, cats, dogs, rats, and mice) and primates (e.g., monkeys, chimpanzees, and humans). In some embodiments, the subject may be a non-human mammal. In other embodiments, the subject may be a human.
[0034] As used in this invention, the term "administration" refers to the direct administration of a compound or a pharmaceutically acceptable salt or composition of a compound to a subject, or the administration of a prodrug derivative or analogue of a compound or a pharmaceutically acceptable salt or composition of a compound to a subject, which may form an equivalent amount of the active compound in the subject's body.
[0035] The intended method involves administering at least 1 mg of dehydroshogaol or a dehydroshogaol alternative daily, depending on the specific dehydroshogaol-containing formulation and form. This daily dose can be administered once or multiple times. Typically, the effective amount of dehydroshogaol or a dehydroshogaol derivative in a dehydroshogaol-containing composition administered once or multiple times daily is between 1 mg and 1500 mg, or between 1 mg and 1500 mg. One or more doses can be administered once daily at any time. For example, an effective dose can be administered daily for one day, several days, multiple days, or indefinitely. Dehydroshogaol can be taken for 7 days or more in a cycle, depending on the desired effect. More typically, the daily dose of dehydroshogaol or its derivatives is approximately 2 mg, 5 mg, 10 mg, 25 mg, 250 mg, 100 mg, 200 mg, 300 mg, 400 mg, 500 mg, 600 mg, 700 mg, 800 mg, 900 mg, 1000 mg, 1100 mg, 1200 mg, 1300 mg, 1400 mg, or 1500 mg. More typically, the daily dose of dehydroshogaol or its derivatives ranges from approximately 10 mg to 1000 mg. Most typically, the daily dose of dehydroshogaol or its derivatives is approximately 50 mg, 100 mg, 300 mg, or 500 mg.
[0036] Various forms and formulations of compositions containing dehydroshogaol are considered for the protection or maintenance of cardiovascular health. These compositions will be formulated as nutritional supplements or dietary supplements, (medical) foods, or animal feeds, in liquid or solid form, and may optionally include a nutritionally or pharmaceutically acceptable carrier. For example, when the composition is in solid form, it can be formulated as a snack bar, yogurt, lozenge, tablet, or capsule, or it can be coated onto cereal products, including baked goods. On the other hand, when the supplement is in liquid form, the composition can be formulated as a tincture, soft gel capsule, liquid capsule, syrup, carbonated beverage, brewed beverage (e.g., coffee or tea), juice, energy drink, sports drink, or flavored water. While specific consideration has been given to nutritional, food, and pharmaceutical compositions intended for human use, it should be understood that compositions and formulations containing dehydroshogaol may also be used for veterinary purposes (e.g., animal feed for domestic companion animals (“pets”) or for farm animals. In other considerations, compositions containing dehydroshogaol may also be provided in bulk form (e.g., in quantities equal to or greater than 100 g, equal to or greater than 1000 g, or equal to or greater than 10 kg) for the production of nutritional supplements, (medical) foods, and animal feed. Example
[0037] Cell culture: Human umbilical vein endothelial cells (HUVECs) were cultured in a humid environment (95% air and 5% carbon dioxide, 37°C) on endothelial cell basal medium supplemented with 10% heat-inactivated fetal bovine serum (FBS), 1% endothelial cell culture additive, and 1% penicillin / streptomycin. Cultures were harvested, and cell morphology was examined under a microscope. Cell counts were performed on the cell suspension using a hemocytometer (Marienfeld, Germany) to monitor cell number.
[0038] Preparation of DHZ test solution: Weigh 19.22 mg DHZ, dissolve it in 10 mL of complete endothelial cell culture medium, and filter it through a 0.22 μm filter membrane to obtain a 10 mM sample solution.
[0039] DHZ stimulation and ox-LDL (oxidized low-density lipoprotein) damage: HUVECs were seeded in 24-well plates (1×10⁻⁶). 4 Cells were cultured at a concentration of 10 mM DHZ (cells / mL) until ~80% confluence. The old culture medium was removed. The ox-LDL damage + DHZ group was treated with freshly prepared medium containing 10 mM DHZ, while the control and ox-LDL damage groups were treated with freshly prepared medium without DHZ. After 1 hour, the ox-LDL damage + DHZ group and the ox-LDL damage group were treated with 100 µg / mL ox-LDL for 24 hours; the control group was left untreated for 24 hours. After 24 hours, the cell supernatant was collected, and the levels of VCAM-1, ICAM-1, and NO were measured. VCAM-1 and ICAM-1 could be detected directly using an ELISA kit; NO detection required incubation of the supernatant overnight at 4°C.
[0040] VCAM-1 and ICAM-1 detection: According to the kit manufacturer's instructions, soluble VCAM-1 and ICAM-1 were measured in the culture medium supernatant using an ELISA (Shanghai Enzyme-Linked Biotechnology, China). The absorbance was obtained at 450 nm using a microplate reader, and the VCAM-1 and ICAM-1 content in the supernatant was calculated based on the standard curve.
[0041] NO detection: The NO content is directly detected using a kit. NO is readily oxidized to NO2 in vivo and in aqueous solutions. - Under acidic conditions, NO2 - A diazonium compound is formed from diazonium sulfonate amine, which is then coupled with naphthylvinyldiamine. The product has a characteristic peak at 550 nm. Its absorbance is measured, and the NO content is calculated.
[0042] As shown in the table below, sample solution, reagent 1, and reagent 2 were added sequentially to a 96-well plate. After mixing, the plate was allowed to stand at room temperature for 15 minutes, and the absorbance was measured at 550 nm. Data were collected and analyzed.
[0043]
[0044] The absorbance value of the blank tube is A (blank), and the absorbance value of the test tube is A (test). The NO content is calculated using the following formula: NO content (μmol / L) = (△A + 0.0103) ÷ 0.008 × Vtotalreaction ÷ Vsample = 250 × (△A + 0.0103), where Vtotalreaction: total reaction volume, 0.2 mL; Vsample: sample volume in the reaction, 0.1 mL; Vtotalsample: volume of extract added, 1 mL.
[0045] Figure 1 shows the effect of 10 mM DHZ on VCAM-1 secretion induced by ox-LDL damage. As shown in Figure 1, compared with the ox-LDL group, DHZ significantly reduced VCAM-1 secretion levels by 61.9%. Statistical analysis showed no significant difference between the ox-LDL damage group and the ox-LDL damage + DHZ group (p < 0.05). Figure 2 shows the effect of 10 mM DHZ on ICAM-1 secretion induced by ox-LDL damage. As shown in Figure 2, compared with the ox-LDL group, DHZ significantly reduced ICAM-1 secretion levels by 95%. Statistical analysis showed no significant difference between the ox-LDL damage group and the ox-LDL damage + DHZ group (p < 0.0001). Figure 3 shows the effect of 10 mM DHZ on NO secretion induced by ox-LDL damage. As shown in Figure 3, compared with the ox-LDL group, DHZ significantly increased the NO secretion level by 60%. Statistical analysis showed that the ox-LDL damage group and the ox-LDL damage + DHZ group had a p-value < 0.01.
[0046] The inventors have discovered that the DHZ-containing compositions and methods of this invention have a positive regulatory effect on cardiovascular health. They can regulate or improve cardiovascular health by inhibiting the expression of vascular cell adhesion molecule-1 (VCAM-1) or intercellular adhesion molecule-1 (ICAM-1), thereby reducing the accumulation of inflammatory cells on the blood vessel wall at its source, thus delaying or even preventing the formation and development of atherosclerotic plaques. Alternatively, they can increase nitric oxide levels, which is beneficial for relaxing vascular smooth muscle and causing vasodilation. This further regulates the function of vascular endothelial cells, affecting vascular contraction and permeability, preventing arteriosclerosis, and further influencing the stability of the cardiovascular system, reducing the risk of various cardiovascular diseases such as hypertension, coronary heart disease, myocardial infarction, and stroke.
[0047] The above description is merely a preferred embodiment of the present invention and is not intended to limit the present invention. Any person skilled in the art can make various changes, modifications, substitutions and variations to these embodiments without departing from the principles and spirit of the present invention. The scope of the present invention is defined by the claims and their equivalents.
Claims
1. A method for protecting or maintaining cardiovascular health, characterized in that, The method includes administering to a subject a composition containing dehydrogingerone or its salts, acids, esters or derivatives.
2. The method according to claim 1, characterized in that, The protection or maintenance of cardiovascular health includes preventing atherosclerosis, regulating the function of vascular endothelial cells, and regulating vasomotor activity and permeability.
3. The method according to claim 1 or 2, characterized in that, The method is achieved by inhibiting the expression of vascular cell adhesion molecule-1 (VCAM-1) or intercellular adhesion molecule-1 (ICAM-1), or by increasing the content of nitric oxide.
4. The method according to any one of claims 1-3, characterized in that, The composition containing dehydrogingerone or its salts, acids, esters or derivatives is formulated into nutritional products, dietary supplements, foods, beverages or animal feed.
5. The method according to any one of claims 1-4, characterized in that, The subjects are humans or mammals.
6. The method according to any one of claims 1-5, characterized in that, The composition containing dehydrogingerone or its salts, acids, esters or derivatives is in the form of suppositories, tablets, pills, granules, powders, films, capsules, beverages, aerosols, liniments, tinctures, tonics, liquid suspensions or syrups.
7. The method according to any one of claims 1-6, characterized in that, The composition containing dehydrogingerone or its salts, acids, esters or derivatives was administered to the subject at a dose of 1-1500 mg.
8. The method according to any one of claims 1-7, characterized in that, The administration is carried out via a route selected from the following: oral, intravenous, intramuscular, intraperitoneal, or sublingual administration.
9. Use of a composition containing dehydrogingerone or its salts, acids, esters or derivatives in the preparation of nutritional products, dietary supplements, foods, beverages or animal feed for the protection or maintenance of cardiovascular health.
10. The use according to claim 9, characterized in that, The protection or maintenance of cardiovascular health includes preventing atherosclerosis, regulating the function of vascular endothelial cells, and regulating vasomotor activity and permeability.
11. The use according to claim 9 or 10, characterized in that, The protection or maintenance of cardiovascular health is achieved by inhibiting the expression of vascular cell adhesion molecule-1 (VCAM-1) or intercellular adhesion molecule-1 (ICAM-1), or by increasing the content of nitric oxide.
12. The use according to any one of claims 9-11, characterized in that, The dosage of the composition is 1-1500 mg.
13. The use according to any one of claims 9-12, characterized in that, The composition containing dehydrogingerone or its salts, acids, esters or derivatives is in the form of suppositories, tablets, pills, granules, powders, films, capsules, beverages, aerosols, liniments, tinctures, tonics, liquid suspensions or syrups.
14. A composition containing dehydroshogaol or its salts, acids, esters or derivatives, characterized in that, The composition is used to protect or maintain cardiovascular health.
15. The composition according to claim 14, characterized in that, The protection or maintenance of cardiovascular health includes preventing atherosclerosis, regulating the function of vascular endothelial cells, and regulating vasomotor activity and permeability.
16. The composition according to claim 14 or 15, characterized in that, The protection or maintenance of cardiovascular health is achieved by inhibiting the expression of vascular cell adhesion molecule-1 (VCAM-1) or intercellular adhesion molecule-1 (ICAM-1), or by increasing the content of nitric oxide.
17. The composition according to any one of claims 14-16, characterized in that, The composition containing dehydrogingerone or its salts, acids, esters or derivatives is formulated into nutritional products, dietary supplements, foods, beverages or animal feed.
18. The composition according to any one of claims 14-17, characterized in that, The composition containing dehydrogingerone or its salts, acids, esters or derivatives is in the form of suppositories, tablets, pills, granules, powders, films, capsules, beverages, aerosols, liniments, tinctures, tonics, liquid suspensions or syrups.
19. The composition according to any one of claims 14-18, characterized in that, The dosage of the composition is 1-1500 mg.