Composition for neuroprotection from amyloid β
Cumin aldehyde or extract from Cuminum cyminum provides neuroprotection against amyloid β oligomers, addressing the lack of effective neuroprotective agents by reducing apoptosis induction.
Patent Information
- Application Number
- JP2023106778
- Authority / Receiving Office
- JP · JP
- Patent Type
- Applications
- Current Assignee / Owner
- Filing Date
- 2023-06-29
- Publication Date
- 2025-01-17
AI Technical Summary
Current technologies lack effective compositions for neuroprotection against amyloid β, particularly its oligomers, which induce apoptosis in nerve cells due to oxidative stress.
A composition comprising cumin aldehyde or cumin extract, derived from Cuminum cyminum, is developed to provide neuroprotection against amyloid β, specifically targeting amyloid β oligomers.
The composition exhibits a neuroprotective effect against amyloid β oligomers, reducing apoptosis induction and offering potential therapeutic benefits.
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Abstract
Description
[Technical field]
[0001] The present invention relates to a composition for neuroprotection from amyloid-β. [Background technology]
[0002] Amyloid beta is a type of protein produced in the brain. It has been reported that amyloid beta accumulates in the brain due to poor lifestyle habits, diabetes, lack of sleep, and other factors. The scientific name of cumin is Cuminum cyminum. Cumin is a type of spice that is mainly added to curry. In recent years, many reports have been published on the effects of cumin and its extracts or crushed products (Patent Documents 1 and 2). [Prior art documents] [Patent documents]
[0003] [Patent Document 1] JP 2017-160194 A [Patent Document 2] JP 2021-161088 A Summary of the Invention [Problem to be solved by the invention]
[0004] An object of the present invention is to provide a composition for neuroprotection from amyloid-β. [Means for solving the problem]
[0005] The present inventors have conducted extensive research into compositions for neuroprotection against amyloid β, and have found that cuminaldehyde has a neuroprotective effect against amyloid β. The present invention is based on these findings. Thus, the present invention provides [1] Cuminaldehyde, or Cumin (Cuminum cyminum) extract or ground material containing cuminaldehyde A composition for neuroprotection against amyloid beta, comprising: [2] The composition for neuroprotection against amyloid beta according to [1], wherein the extract or crushed product is an extract or crushed product of cumin seeds of cumin (Cuminum cyminum). [3] The composition for neuroprotection against amyloid beta according to [1] or [2], which is a food composition. [4] The composition for neuroprotection against amyloid β according to [1] or [2], wherein the neuroprotective effect against amyloid β is a neuroprotective effect against amyloid β oligomers; and [5] A composition for neuroprotection against amyloid beta according to [1] or [2], which is indicated to have a neuroprotective effect against amyloid beta. Regarding. Effect of the Invention
[0006] The composition for neuroprotection against amyloid β of the present invention is capable of exerting a neuroprotective effect against amyloid β, specifically against amyloid β oligomers. [Brief description of the drawings]
[0007] [Figure 1] These are the results of evaluating the neuroprotective effects of cumin essential oil using human neuronal-like SH-SY5Y cells. [Diagram 2] These are the results of evaluating the neuroprotective effects of cuminaldehyde using human neuronal-like SH-SY5Y cells. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
[0008] The present invention will be described in detail below. In this specification, unless otherwise specified, the expression "A to B" for a numerical value A and a numerical value B is equivalent to "A or more and B or less." In other words, the expression "A to B" includes the numerical values A and B at both ends. In such an expression, when a unit is added only to the numerical value B, the unit is also applied to the numerical value A. The expression "including A or B" includes an embodiment including both A and B.
[0009] (Cuminaldehyde) Cuminaldehyde is a compound having the following structure: [ka]
[0010] Cuminaldehyde is also called 4-isopropylbenzaldehyde, and has a CAS registration number of 122-03-2. Cuminaldehyde may be extracted from plants, particularly cumin, or may be commercially available. In addition, a derivative of cuminaldehyde or a salt of cuminaldehyde that has the effect of the present invention and produces cuminaldehyde after addition may be used.
[0011] (cumin) Cumin (Cuminum cyminum) is an annual or biennial herb of the Apiaceae family native to the eastern Mediterranean coast. Cumin seeds are oblong, narrow at both ends, about 6 mm long and 1.5 mm wide, and covered entirely with white bristles. In this specification, the term "cumin seed" refers to the part of cumin that is generally used as a spice and corresponds to the fruit in the botanical sense. The term "seed" refers to the part of cumin that corresponds to the seed in the botanical sense.
[0012] The part of cumin is not particularly limited, and may be the whole plant, roots, stems, leaves, flowers, cumin seeds (fruit), seeds, or a mixture of at least two of them, but preferably cumin seeds are used. When cumin seeds are used, other parts may be included. Cumin may be used raw or dried. In the present invention, the place of origin of cumin is not limited, and cumin from any place of origin may be used.
[0013] (extract) The cumin used to prepare the extract may be processed into a crushed or powdered state before extraction in order to improve the extraction efficiency. The extraction can be carried out by any conventional method for extracting plant-derived components, including, but not limited to, steam distillation, solvent extraction, pressing (direct, high temperature, or low temperature), or supercritical extraction, so long as the extract contains cuminaldehyde. A combination of these extraction methods, such as pressing followed by solvent extraction, may also be used. The extract can be in any form, such as oil, liquid, paste, or powder.
[0014] The cumin extract can be prepared using an aqueous solvent. The aqueous solvent is not limited as long as it contains water, and for example, water, physiological saline, or a buffer solution can be used. Examples of the buffer solution include phosphate buffer, sodium phosphate buffer, sodium carbonate buffer, citrate buffer, citrate phosphate buffer, acetate buffer, and Tris buffer. The pH of the aqueous solvent is not particularly limited. The cumin extract may be prepared by a mixture of an organic solvent and an aqueous solvent. The cumin extract may be prepared by an organic solvent. The organic solvent may be polar or non-polar.
[0015] When preparing a cumin extract by a solvent extraction method, the extraction temperature is not particularly limited, and is, for example, -50°C to 100°C, -25°C to 50°C, -25°C to 25°C, -10°C to 10°C, or 0°C to 10°C.
[0016] In addition, the extraction may be performed with stirring or shaking to improve the extraction efficiency. The extraction time may be appropriately determined depending on the part to be used, such as the root, stem, leaf, flower, fruit, or seed. The extraction time may be appropriately determined depending on the state of cumin, that is, when processed into a raw or dried product, or a crushed or powdered product, depending on the processed state. The extraction time is not particularly limited, and may be, for example, 1 minute to 72 hours, 1 hour to 48 hours, or 12 hours to 36 hours.
[0017] The cumin extract can be extracted by steam distillation. The steam distillation method is a method in which steam is passed through a raw material packed in a column, and the aroma components distilled along with the steam are condensed together with the steam. As the distillation method, any of pressurized steam distillation, normal pressure steam distillation, and reduced pressure steam distillation can be used.
[0018] (Crushed material) The ground material may be, for example, in the form of powder, granules, or paste. In addition, the powder may be molded or granulated into, for example, cubes, blocks, or granules. In the molding or granulation, raw materials other than the ground cumin, such as excipients, may be added. When the cumin included in the present invention is a ground material, the average longest diameter of the ground cumin is, for example, 0.01 to 2 mm, although this is not limited thereto.
[0019] The composition for neuroprotection from amyloid beta of the present invention may contain cumin, a cumin extract or a dried product thereof, or ground cumin, for example, as a dried product, in an amount of 90% by mass or more, 50% by mass or more, 10% by mass or more, or 1% by mass or more. In the composition for neuroprotection from amyloid beta of the present invention, "containing" cuminaldehyde, or an extract or crushed product of cumin (Cuminum cyminum) containing cuminaldehyde means that the final product contains cuminaldehyde, or an extract or crushed product of cumin (Cuminum cyminum) containing cuminaldehyde.
[0020] The dosage of the composition for neuroprotection from amyloid β of the present invention can be appropriately determined depending on the type of active ingredient, the subject's age, sex, weight, the presence or severity of symptoms, or the method of administration. The dosage, when administered to humans, is, for example, 1 to 200 mg / day, 5 to 150 mg / day, 10 to 100 mg / day, or 20 to 50 mg / day in terms of cuminaldehyde. The administration period can be, for example, 1, 2, 4, 8, or 12 weeks or longer when administered to a subject, preferably a human.
[0021] In the composition for neuroprotection from amyloid beta of the present invention, the concentration of the active ingredient, cuminaldehyde, is not limited as long as the effects of the present invention are obtained, but may be, for example, 0.01 to 500 mg / mL, 0.1 to 400 mg / mL, 0.5 to 300 mg / mL, 1 to 200 mg / mL, 2 to 150 mg / mL, or 1 to 100 mg / mL.
[0022] (Neuroprotection from amyloid beta) Amyloid beta is a type of protein produced in the brain. It is produced by peptide degradation of amyloid precursor proteins by beta- and gamma-secretases. Amyloid beta becomes oligomers, and these amyloid beta oligomers induce apoptosis in nerve cells due to oxidative stress. It is believed that the presence of cuminaldehyde suppresses apoptosis induction and exerts a neuroprotective effect, even when amyloid beta oligomers coexist with nerve cells.
[0023] (Composition for neuroprotection against amyloid beta) The composition for neuroprotection from amyloid β of the present invention may be used in vivo or in vitro. The composition for neuroprotection from amyloid β of the present invention may be, for example, a pharmaceutical composition or a food composition. The composition for neuroprotection from amyloid β of the present invention may contain all of cuminaldehyde and an extract or crushed product of cumin (Cuminum cyminum) containing cuminaldehyde, or may contain only one or two of them. The administration form of the composition for neuroprotection from amyloid β of the present invention is not limited, and either oral administration or parenteral administration (intravenous, intraarterial, subcutaneous, intramuscular, intraperitoneal injection, nasal, transdermal, etc.) may be selected, but oral administration is preferable. The composition for neuroprotection from amyloid β of the present invention is preferably a food composition. A composition for neuroprotection from amyloid β can also be referred to as a composition for protecting neurons from amyloid β or a composition for imparting a protective effect against amyloid β to neurons.
[0024] "For neuroprotection against amyloid-β" includes the display of such uses, actions, and / or properties. The above "display" includes all acts of informing consumers of the above uses, actions, and / or properties. The display may be on any medium, including packaging, containers, catalogs, pamphlets, and websites.
[0025] The composition for neuroprotection from amyloid β of the present invention can be a powder, granule, solid, liquid, capsule, gel, paste, or tablet.
[0026] (Food composition) The food compositions of the present invention include foods and beverages. Specific examples of foods include fresh foods such as salads; cooked foods such as steaks, pizzas, and hamburgers; fried foods such as stir-fried vegetables; vegetables such as tomatoes, peppers, celery, bitter melon, carrots, potatoes, and asparagus, and cooked foods made from these vegetables; confectioneries such as cookies, bread, biscuits, dry bread, cakes, rice crackers, yokan, puddings, jellies, ice creams, chewing gum, crackers, chips, chocolates, and candies; noodles such as udon, pasta, and soba; fish paste products such as kamaboko, ham, and fish sausages; dairy products such as cheese, cream, and butter; seasonings such as miso, soy sauce, dressing, ketchup, mayonnaise, soup base, noodle soup, curry powder, mirin, and roux; soy foods such as tofu; and konjac. The food is preferably a roux (for example, for curry or stew), a seasoning spice, or a supplement.
[0027] Examples of beverages include coffee beverages; cocoa beverages; vegetable juices obtained from the above-mentioned vegetables; fruit juice beverages such as grapefruit juice, orange juice, grape juice, and lemon juice; tea beverages such as green tea, black tea, sencha, and oolong tea; alcoholic beverages such as beer, wine (red wine, white wine, sparkling wine, etc.), sake, plum wine, sparkling wine, whiskey, brandy, shochu, rum, gin, and liqueurs; milk beverages; soy milk beverages; liquid foods, thickened beverages (aspiration prevention beverages); and sports drinks.
[0028] The food or beverage includes feed for animals, such as primates, cows, pigs, sheep, goats, horses, dogs, cats, rabbits, rats, or mice.
[0029] If desired, these foods or beverages may contain food additives and food ingredients, such as antioxidants, flavorings, acidulants, colorings, emulsifiers, preservatives, seasonings, sweeteners, spices, pH adjusters, stabilizers, vegetable oils, animal oils, sugars and sugar alcohols, vitamins, organic acids, fruit juice extracts, vegetable extracts, grains, beans, vegetables, meats, seafood, etc., either alone or in combination of two or more. The amounts of these food ingredients and food additives to be added may be appropriately determined within the range that does not impair the object of the present invention.
[0030] These foods or beverages can be subjected to common sterilization treatments, such as heat pressure sterilization using retort and autoclave, batch sterilization, plate sterilization, electric heating sterilization, microwave heating sterilization, and steam sterilization such as injection and infusion.
[0031] The food or beverage may be provided in packaging containers such as molded containers primarily made of polyethylene terephthalate (PET bottles), metal cans, paper containers combined with metal foil or plastic film, pouches such as aluminum pouches, plastic containers, vinyl containers, and bottles.
[0032] Foods and beverages include functional food (drinks) and health food (drinks). In this specification, "health food (drinks)" refers to food or beverage that has some effect on health or that can be expected to have such an effect, and "functional food (drinks)" refers to food or beverage that is designed and processed to fully exert a bioregulatory function among the above-mentioned "health foods (drinks)." EXAMPLES
[0033] The present invention will be described in detail below with reference to examples, but the scope of the present invention is not limited thereto. In addition, unless otherwise specified, "%" indicates % by mass.
[0034] Example 1: Evaluation of the neuroprotective effects of cuminaldehyde and cumin essential oil The neuroprotective effects of cuminaldehyde and cumin essential oil (containing 43% by mass of cuminaldehyde) as test samples were evaluated by the following procedure. Cumin essential oil is a cumin extract containing cuminaldehyde prepared by steam distillation. This cumin essential oil was added to a final concentration of 25 or 50 μg / mL. Cuminaldehyde was purchased from Sigma-Aldrich and added to a final concentration of 25 or 50 μM.
[0035] (procedure) 1. 2 x 10 SH-SY5Y cells 5 Dilute the medium to 2 × 10 cells / mL and seed 100 μL each into a 96-well microplate. 4 cells / well / 100 μL) and precultured for 24 hours. 2. After incubation, the medium was removed, and 100 μl of Opti-MEM medium containing the prepared test samples and comparative samples at various concentrations was added to each well. 3. The cells were cultured for 24 hours. 4. The medium was removed, and amyloid β42 (amyloid β oligomer) was added to each well to a concentration of 2.5 μM. 5. Cultured for 24 hours (37℃, 5% CO2, 95% air). 6. The medium was removed, and Opti-MEM and 5 mg / mL MTT reagent were mixed in a 1:10 ratio, and 100 μL of the mixture was added to each well. 7. Leave the sample standing for 24 hours (37℃, 5% CO2, 95% air). 8. 100 μL of 10% SDS solution was added to each well. 9. Leave the sample standing for 24 hours (37℃, 5% CO2, 95% air). 10. The absorbance was measured at 570 nm using a plate reader.
[0036] (result) The results for cumin essential oil are shown in Figure 1. A neuroprotective effect against amyloid β42 was observed in the 25 μg / mL and 50 μg / mL treatment groups. The results for cuminaldehyde are shown in Figure 2. A neuroprotective effect against amyloid β42 was observed in the 25 μM and 50 μM treatment groups. [Industrial Applicability]
[0037] According to the composition for neuroprotection from amyloid β of the present invention, it is possible to provide neuroprotection against amyloid β, specifically against amyloid β oligomers.
Claims
1. Cuminaldehyde, or Cumin (Cuminum cyminum) extract or ground product containing cuminaldehyde A composition for neuroprotection from amyloid beta comprising:
2. The composition for neuroprotection from amyloid beta according to claim 1 , wherein the extract or crushed product is an extract or crushed product of cumin seeds of Cuminum cyminum.
3. The composition for neuroprotection from amyloid β described in claim 1 or 2, which is a food composition.
4. The composition for neuroprotection from amyloid β according to claim 1 or 2, wherein the neuroprotective effect from amyloid β is a neuroprotective effect from amyloid β oligomers.
5. A composition for neuroprotection against amyloid β described in claim 1 or 2, which is indicated to have a neuroprotective effect against amyloid β.
Citation Information
Patent Citations
Immunostimulant and food composition for immunostimulation
JP2017160194A
Nitrogen monoxide production inhibitor, and food composition for inhibiting nitrogen monoxide production
JP2021161088A