Autophagy activator

Abstract

The present invention relates to an autophagy activator that contains an Alpinia zerumbet extract and / or a Dioscorea nipponica extract.

Description

Autophagy activators

[0001] The present invention relates to an autophagy activator and a food or beverage composition for activating autophagy.

[0002] Autophagy is known as an intracellular purification and recycling system present in all eukaryotic organisms, including yeast and plants, and research into this system has been progressing in recent years. As an intracellular purification system, autophagy functions as a defense system to protect the body from various diseases by degrading and purifying cytoplasmic components such as intracellular proteins, intracellular organelles such as mitochondria, and pathogenic bacteria that have invaded the cell. Furthermore, as an intracellular recycling system, autophagy has the function of breaking down excess proteins and other substances under conditions of starvation to supply amino acids. As described above, autophagy plays an important role in maintaining the normal function of the body.

[0003] In recent years, it has become clear that a decrease in the activity of autophagy, which plays an important role in maintaining biological functions, has a wide range of effects, including various diseases, dysfunction of various organs in the body, and even aging (Non-Patent Document 1).

[0004] Cell Reports 38, 110444, March 1, 2022

[0005] The problem to be solved by the present invention is to provide a novel component capable of activating autophagy.

[0006] As a result of intensive research conducted by the present inventors to solve the above-mentioned problems, they discovered that shell ginger extract and / or senzanryu extract activate autophagy, and thus completed the present invention.

[0007] The present application is as follows: [1] An autophagy activator containing a shell ginger extract and / or a senzanryu extract. [2] A food or beverage composition for activating autophagy containing a shell ginger extract and / or a senzanryu extract. [3] A food or beverage composition containing a shell ginger extract and / or a senzanryu extract for at least one effect selected from the group consisting of regulating gastrointestinal condition, maintaining intestinal function, rejuvenating the intestines, improving cognitive function, enhancing memory, removing waste products from the brain, maintaining healthy liver function, improving motor function, maintaining skin moisture and elasticity, reducing skin blemishes, wrinkles, and / or dullness, improving hair color, moisture, and / or luster, extending healthy lifespan, and improving germ cell quality. [4] The food or beverage composition according to [3], wherein the activation of autophagy by the shell ginger extract and / or the sanshanlong extract exhibits at least one effect selected from the group consisting of regulating gastric condition, maintaining intestinal function, rejuvenating the intestines, improving cognitive function, enhancing memory, removing waste products from the brain, maintaining healthy liver function, improving motor function, maintaining skin moisture and elasticity, improving skin blemishes, wrinkles and / or dullness, improving hair color, moisture and / or luster, extending healthy lifespan, and improving the quality of germ cells. [5] The food or beverage composition according to [3] or [4], wherein the LC3-II activation of the shell ginger extract and / or the lancet ginger extract exhibits at least one effect selected from the group consisting of regulating gastric condition, maintaining intestinal function, rejuvenating the intestines, improving cognitive function, enhancing memory, removing waste products from the brain, maintaining healthy liver function, improving motor function, maintaining skin moisture and elasticity, improving skin blemishes, wrinkles and / or dullness, improving hair color, moisture and / or luster, extending healthy lifespan, and improving the quality of germ cells. [6] The autophagy activator according to [1], which is used for at least one purpose selected from the group consisting of regulating gastric condition, maintaining intestinal function, rejuvenating the intestines, improving cognitive function, improving memory, removing waste products from the brain, maintaining healthy liver function, improving motor function, maintaining skin moisture and elasticity, improving skin blemishes, wrinkles, and / or dullness, improving hair color, moisture, and / or luster, extending healthy lifespan, and improving the quality of germ cells.

[0008] [A1] A method for activating autophagy using a shell ginger extract and / or a senzanryu extract. [A2] A method for activating autophagy using a food or beverage composition containing a shell ginger extract and / or a senzanryu extract. [A3] A method for achieving at least one effect selected from the group consisting of regulating gastric condition, maintaining intestinal function, rejuvenating the intestine, improving cognitive function, improving memory, removing waste products from the brain, maintaining healthy liver function, improving motor function, maintaining skin moisture and elasticity, improving skin blemishes, wrinkles, and / or dullness, improving hair color, moisture, and / or luster, extending healthy lifespan, and improving germ cell quality, using a food or beverage composition containing a shell ginger extract and / or a senzanryu extract. [A4] A method for activating autophagy using a food or beverage composition containing shell ginger extract and / or tsutsumi-ryu extract, thereby achieving at least one effect selected from the group consisting of regulating stomach condition, maintaining intestinal function, rejuvenating the intestines, improving cognitive function, enhancing memory, removing waste products from the brain, maintaining healthy liver function, improving motor function, maintaining skin moisture and elasticity, improving skin blemishes, wrinkles and / or dullness, improving hair color, moisture and / or luster, extending healthy lifespan, and improving the quality of germ cells. [A5] The method according to [A3] or [A4], using a food or beverage composition containing shell ginger extract and / or tsutsumi-ryu extract, which activates LC3-II to bring about at least one effect selected from the group consisting of regulating gastric condition, maintaining intestinal function, rejuvenating the intestines, improving cognitive function, enhancing memory, removing waste products from the brain, maintaining healthy liver function, improving motor function, maintaining skin moisture and elasticity, improving skin blemishes, wrinkles and / or dullness, improving hair color, moisture and / or luster, extending healthy lifespan, and improving the quality of germ cells. [A6] The method for activating autophagy described in [A1], which exhibits at least one effect selected from the group consisting of regulating gastric condition, maintaining intestinal function, rejuvenating the intestines, improving cognitive function, improving memory, removing waste products from the brain, maintaining healthy liver function, improving motor function, maintaining skin moisture and elasticity, improving skin blemishes, wrinkles, and / or dullness, improving hair color, moisture, and / or luster, extending healthy lifespan, and improving the quality of germ cells.

[0009] [B1] Use of Alpinia zerumbet extract and / or Senzanryu extract for activating autophagy. [B2] Use of a food or beverage composition containing Alpinia zerumbet extract and / or Senzanryu extract for activating autophagy. [B3] Use of a food or beverage composition containing Alpinia zerumbet extract and / or Senzanryu extract for at least one effect selected from the group consisting of regulating gastric condition, maintaining intestinal function, rejuvenating the intestines, improving cognitive function, enhancing memory, removing waste products from the brain, maintaining healthy liver function, improving motor function, maintaining skin moisture and elasticity, reducing skin blemishes, wrinkles, and / or dullness, improving hair color, moisture, and / or luster, extending healthy lifespan, and improving germ cell quality. [B4] Use of a food or beverage composition that exhibits at least one effect selected from the group consisting of regulating stomach condition, maintaining intestinal function, rejuvenating the intestines, improving cognitive function, enhancing memory, removing waste products from the brain, maintaining healthy liver function, improving motor function, maintaining skin moisture and elasticity, improving skin blemishes, wrinkles and / or dullness, improving hair color, moisture and / or luster, extending healthy lifespan, and improving the quality of germ cells, by activating autophagy with shell ginger extract and / or sanshanlong extract. [B5] The use according to [B3] or [B4], wherein the activation of LC3-II by the shell ginger extract and / or the lancet ginseng extract exhibits at least one effect selected from the group consisting of regulating gastric condition, maintaining intestinal function, rejuvenating the intestines, improving cognitive function, enhancing memory, removing waste products from the brain, maintaining healthy liver function, improving motor function, maintaining skin moisture and elasticity, improving skin blemishes, wrinkles and / or dullness, improving hair color, moisture and / or luster, extending healthy lifespan, and improving the quality of germ cells. [B6] The use according to [B1] for activating autophagy for at least one application selected from the group consisting of regulating gastric condition, maintaining intestinal function, rejuvenating the intestines, improving cognitive function, enhancing memory, removing waste products from the brain, maintaining healthy liver function, improving motor function, maintaining skin moisture and elasticity, reducing skin blemishes, wrinkles, and / or dullness, improving hair color, moisture, and / or luster, extending healthy lifespan, and improving the quality of germ cells.

[0010] [C1] Use of Alpinia zerumbet extract and / or Senzanryu extract for the manufacture of an autophagy activator. [C2] Use of Alpinia zerumbet extract and / or Senzanryu extract for the manufacture of a food or beverage composition for activating autophagy. [C3] Use of Alpinia zerumbet extract and / or Senzanryu extract for the manufacture of a food or beverage composition for at least one effect selected from the group consisting of regulating stomach condition, maintaining intestinal function, rejuvenating the intestines, improving cognitive function, improving memory, removing waste products from the brain, maintaining healthy liver function, improving motor function, maintaining skin moisture and elasticity, reducing skin blemishes, wrinkles, and / or dullness, improving hair color, moisture, and / or luster, extending healthy lifespan, and improving germ cell quality. [C4] Use of shell ginger extract and / or sanshanlong extract in the production of a food or beverage composition that exhibits at least one effect selected from the group consisting of regulating stomach condition, maintaining intestinal function, rejuvenating the intestines, improving cognitive function, enhancing memory, removing waste products from the brain, maintaining healthy liver function, improving motor function, maintaining skin moisture and elasticity, improving skin blemishes, wrinkles and / or dullness, improving hair color, moisture and / or luster, extending healthy lifespan, and improving the quality of germ cells, by activating autophagy. [C5] Use according to [C3] or [C4] for the production of a food or beverage composition, which exhibits at least one effect selected from the group consisting of regulating gastric condition, maintaining intestinal function, rejuvenating the intestines, improving cognitive function, enhancing memory, removing waste products from the brain, maintaining healthy liver function, improving motor function, maintaining skin moisture and elasticity, improving skin blemishes, wrinkles and / or dullness, improving hair color, moisture and / or luster, extending healthy lifespan, and improving the quality of germ cells, by activating LC3-II with shell ginger extract and / or tsutsumi extract. [C6] The use according to [C1] for the production of an autophagy activator that activates autophagy for at least one application selected from the group consisting of regulating gastric condition, maintaining intestinal function, rejuvenating the intestines, improving cognitive function, enhancing memory, removing waste products from the brain, maintaining healthy liver function, improving motor function, maintaining skin moisture and elasticity, reducing skin blemishes, wrinkles, and / or dullness, improving hair color, moisture, and / or luster, extending healthy lifespan, and improving the quality of germ cells.

[0011] [D1] Alpinia zerumbet extract and / or Senzanryu extract used to activate autophagy. [D2] A food or beverage composition containing Alpinia zerumbet extract and / or Senzanryu extract used to activate autophagy. [D3] A food or beverage composition containing Alpinia zerumbet extract and / or Senzanryu extract used for at least one purpose selected from the group consisting of regulating stomach condition, maintaining intestinal function, rejuvenating the intestines, improving cognitive function, enhancing memory, removing waste products from the brain, maintaining healthy liver function, improving motor function, maintaining skin moisture and elasticity, reducing skin blemishes, wrinkles, and / or dullness, improving hair color, moisture, and / or luster, extending healthy lifespan, and improving germ cell quality. [D4] A food or beverage composition used to bring about at least one effect selected from the group consisting of regulating stomach condition, maintaining intestinal function, rejuvenating the intestines, improving cognitive function, enhancing memory, removing waste products from the brain, maintaining healthy liver function, improving motor function, maintaining skin moisture and elasticity, improving skin blemishes, wrinkles and / or dullness, improving hair color, moisture and / or luster, extending healthy lifespan, and improving the quality of germ cells, by activating autophagy with shell ginger extract and / or sanshanlong extract. [D5] The food or beverage composition according to [D3] or [D4], which is used to bring about at least one effect selected from the group consisting of regulating stomach condition, maintaining intestinal function, rejuvenating the intestines, improving cognitive function, enhancing memory, removing waste products from the brain, maintaining healthy liver function, improving motor function, maintaining skin moisture and elasticity, improving skin blemishes, wrinkles and / or dullness, improving hair color, moisture and / or luster, extending healthy lifespan, and improving the quality of germ cells, by activating LC3-II with the shell ginger extract and / or the lancet ginger extract. [D6] The shell ginger extract and / or shuanshanlong extract according to [D1], which is used to activate autophagy for at least one application selected from the group consisting of regulating stomach condition, maintaining intestinal function, rejuvenating the intestines, improving cognitive function, enhancing memory, removing waste products from the brain, maintaining healthy liver function, improving motor function, maintaining skin moisture and elasticity, reducing skin blemishes, wrinkles and / or dullness, improving hair color, moisture and / or luster, extending healthy lifespan, and improving the quality of germ cells.

[0012] In the present invention, particularly in the above [A1] to [D6], the inventions may be therapeutic or non-therapeutic. That is, they may be inventions of therapeutic or non-therapeutic methods, inventions of therapeutic or non-therapeutic uses, or inventions of therapeutic or non-therapeutic products. Furthermore, in the present invention, a "non-therapeutic invention" means an invention that does not involve medical practice when administered to a subject or ingested by a subject, i.e., an invention that does not involve methods of surgery, treatment, or diagnosis of a subject, particularly a human. In some cases, the subject may also include non-human animals. More specifically, a "non-therapeutic invention" means an invention that does not involve methods of surgery, treatment, or diagnosis performed on a human by a physician or a person under the physician's supervision. Examples of "non-therapeutic inventions" include inventions aimed at health promotion or cosmetic purposes. Furthermore, a "non-therapeutic invention" may also be a "prophylactic invention" as long as it does not fall under the category of a "therapeutic invention."

[0013] The present invention makes it possible to provide a novel component capable of activating autophagy.

[0014] The results of evaluating autophagy activity are shown. Western blotting shows that LC3-I or LC3-II is increased upon treatment with Shuanshanryu extract. Western blotting shows that LC3-I or LC3-II is increased upon treatment with Shell Ginger extract.

[0015] Hereinafter, an embodiment of the present invention (hereinafter referred to as "the present embodiment") will be described, but the scope of the present invention should not be interpreted as being limited to the following embodiment.

[0016] One embodiment of the present invention relates to an autophagy activator containing an extract of Shell Ginger and / or Shuanshan Long as an active ingredient.

[0017] In this embodiment, activation of autophagy may involve, for example, the activation of an intracellular protein recycling system by inducing or promoting autophagy within cells. Furthermore, activation of an intracellular purification system that degrades cytoplasmic components, intracellular organelles, pathogenic bacteria, and the like may also involve the induction or promotion of at least one of the processes of isolation membrane formation, isolation membrane elongation, autophagosome formation, and fusion between autophagosomes and lysosomes. Furthermore, activation of autophagy may specifically involve the function of degrading proteins to supply amino acids under starvation conditions or the function of degrading intracellular waste products, abnormal proteins, and the like. The autophagy activator may be an agent for degrading proteins to supply amino acids under starvation conditions and / or an agent for degrading intracellular waste products, abnormal proteins, and the like. Autophagy plays an important role in maintaining normal biological functions. Abnormalities in autophagy can cause various diseases and aging conditions. Therefore, it is believed that activating autophagy can treat and improve various diseases and aging conditions.

[0018] The autophagy activator of this embodiment can be used for at least one selected from the group consisting of regulating gastric condition, maintaining intestinal function, rejuvenating the intestines, improving cognitive function, improving memory, removing waste products from the brain, maintaining healthy liver function, improving motor function, maintaining skin moisture and elasticity, reducing skin blemishes, wrinkles, and / or dullness, improving hair color, moisture, and / or luster, extending healthy lifespan, and improving the quality of germ cells. Specifically, the autophagy activator of this embodiment or the food or beverage composition of this embodiment contains at least one of the extracts, thereby enabling autophagy activation, and can be used for the applications listed in Table 1.

[0019] In this embodiment, activation of autophagy may be assessed by methods known to those skilled in the art. Examples include assessing autophagy activity when autophagosomes are formed, when autophagosomes fuse with lysosomes, and assessing these activities using immunofluorescence or electron microscopy. Furthermore, autophagy activity may be measured by measuring the gene expression levels or protein expression levels of autophagy-related proteins.

[0020] Specific techniques for measuring autophagy activity include, for example, observing cells under a microscope, expressing a fluorescently labeled autophagy-related marker and then observing under a fluorescence microscope or measuring with an instrument (e.g., a flow cytometer, a fluorescent plate reader, etc.), and measuring autophagy-related markers by Western blotting, etc. More specifically, autophagy activity can be detected by methods such as RT-PCR, real-time RT-PCR, and immunological assays (e.g., chemiluminescence assay, immunohistochemistry, ELISA, Western blotting, immunoprecipitation, etc.).

[0021] Autophagy can be evaluated as activated when the chemiluminescence intensity in an immunological assay is greater when the autophagy activator of this embodiment is administered compared to when the autophagy activator of this embodiment is not administered. Furthermore, autophagy can be evaluated as activated when the chemiluminescence intensity is increased by, for example, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100%, 200%, 300%, 400%, or 500% or more. Preferably, autophagy can be evaluated as activated when the chemiluminescence intensity is increased by 30% or more.

[0022] An example of an autophagy marker protein is LC3. LC3 (MAP1LC3: Microtubule-associated protein 1 light chain 3) is a ubiquitin-like molecule and the mammalian homolog of the molecule encoded by yeast Atg8 (Autophagy-related protein 8). The cytosolic form of LC3 (LC3-I) is known to be conjugated with phosphatidylethanolamine (PE) upstream of autophagy signaling, attracted to the autophagosome membrane, and converted to LC3-II. LC3 specifically localizes to autophagy structures throughout the process from the isolation membrane to lysosomal degradation, and is used as a marker for autophagosomes.

[0023] Because LC3-II is in a lipidated form, it binds to both the outer and inner membranes of autophagosomes, and its amount is known to correlate with the number of autophagosomes. Therefore, measuring the amount of LC3-II can measure the amount of autophagosomes, and thus the activation of autophagy. LC-3 is then degraded after fusing with lysosomes, so the amount of LC3-II degradation can also be measured as an indicator of the activation of the autophagy recycling system.

[0024] The autophagy activator of this embodiment can be used in pharmaceuticals, foods, beverages, etc. It can also be used as a research reagent.

[0025] In this specification, "Shell ginger" in the shell ginger extract means an evergreen perennial plant belonging to the genus Alpinia. Examples of shell ginger include A. bilamellata, A. boninensis, A. flabellata, A. formosana, A. intermedia, A. japonica, A. nakaiana, A. speciosa, A. albplineata, A. chinensis, A. conchigera, A. galanga, A. officinarum, A. yakuchi, A. Examples of suitable species include Alpinia oxyphylla, Red ginger (A. purpurata), Alpinia sanderae, and Alpinia zerumbet. The shell ginger may be Alpinia zerumbet or Alpinia speciosa, or may be Alpinia zerumbet.

[0026] In this embodiment, only one type of shell ginger may be used as the shell ginger extract, or two or more types may be used in combination.

[0027] As used herein, the term "Chuanshanlong" in the "Chuanshanlong extract" refers to a perennial vine plant belonging to the genus Dioscorea. Examples of the "Chuanshanlong" include water yam (D. alata), Dioscorea kamoonensis (D. kamoonensis), and Prickly Pear (D. nipponica). The "Chuanshanlong" may be D. nipponica.

[0028] In this embodiment, the Chuanshanlong extract may be used alone or in combination of two or more kinds.

[0029] In this embodiment, as the active ingredient of the autophagy activator, only one of the shell ginger extract and the chinshanlong extract may be used, or the shell ginger extract and the chinshanlong extract may be used in combination. When using either the shell ginger extract or the chinshanlong extract, two or more types of shell ginger extract may be used, or two or more types of chinshanlong extract may be used. When using the shell ginger extract and the chinshanlong extract in combination, two or more types of shell ginger extract may be used, or two or more types of chinshanlong extract may be used, or two or more types of both may be used.

[0030] In this embodiment, the part of the shell ginger or senzanryu used to obtain the shell ginger extract or senzanryu extract may be, for example, the whole plant, or at least one part selected from the leaves, stems, flowers, fruits, and roots. As the shell ginger part, the leaves or stems are preferred. As the senzanryu part, the roots are preferred. Furthermore, the shell ginger or senzanryu may be used for extraction as is after harvesting, or may be processed, such as by rubbing, drying, heating (baking, boiling, steaming, frying, etc.), or crushing (including pulverization), before being used for extraction. These processing steps may be repeated multiple times, or different steps may be combined. The shell ginger or senzanryu may be sun-dried or hot-air-dried before being used to obtain the shell ginger extract or senzanryu extract.

[0031] Fine pieces of shell ginger or senzanryu can be obtained by crushing to an appropriate size according to a conventional method. Powder of shell ginger or senzanryu can be obtained by crushing and pulverizing according to a conventional method. These processes may be carried out once or twice or more times, but it is preferable to combine a coarse crushing process with a more finely crushed powdering process.

[0032] In this embodiment, any method or apparatus known to those skilled in the art may be used to prepare the shell ginger extract or the chinshanlong extract. Examples of such preparation methods include solvent extraction, supercritical extraction, steam distillation, and compression. Further extracts (including fractions, hereinafter the same) may be prepared from the extract obtained by compression (which may be fractions (including compressed products, hereinafter the same)). When preparing the extract, particularly in solvent extraction, an appropriate solvent may be used depending on the raw material and the specific components to be obtained. Examples of such solvents include water, acetic acid, ethanol, methanol, acetone, hexane, benzene, and diethyl ether. The obtained extract may be in any form, such as liquid, solid, or powder. In the case of a liquid, the extract may be in the solvent used for extraction, or may be a liquid concentrate obtained by concentration. Alternatively, the extract may be a suspension in which a portion of the extract or fraction precipitates during the concentration process. A liquid extract may be subjected to a drying process, such as freeze-drying, to obtain a solid extract or fraction.

[0033] Extraction may be performed by adding a solvent to pieces or powder of Alpinia zerumbet or Senzanryu and stirring as necessary, with the temperature, extraction time, and solid-liquid ratio being appropriately set. When water is used as the solvent, extraction may be performed with hot water. The resulting extract may be freeze-dried or spray-dried as is or together with an excipient, or may be freeze-dried or spray-dried after vacuum concentration. The resulting extract may be in various forms, such as an extract, solution, powder, concentrated liquid, or paste. Alpinia zerumbet extract or Senzanryu extract may be obtained by purifying an extract extracted by a predetermined method. Purification may be performed using known purification methods. Alpinia zerumbet extract or Senzanryu extract may be obtained by concentrating an extract extracted by a predetermined method. Concentration may be performed using known concentration methods.

[0034] In this embodiment, commercially available shell ginger extract or chuanshanlong extract may be used.

[0035] Autophagy activators can exert their functions, for example, by being administered directly or indirectly to organs or cells of the body.

[0036] The autophagy activator may be administered in any dosage form as long as it can exert its function, for example, in oral dosage forms such as tablets, capsules, granules, fine granules, powders, liquids, syrups, chewable tablets, and lozenges, as well as ointments, gels, creams, injections, sublingual preparations, inhalants, and suppositories. These dosage forms can be prepared using conventionally known additives, and may include, but are not limited to, excipients, binders, diluents, disintegrants, buffers, thickeners, stabilizers, emulsifiers, dispersants, suspending agents, and / or preservatives known in the art, as needed.

[0037] The dosage and frequency of administration of the autophagy activator may be appropriately determined depending on various conditions, such as the route of administration and the age, weight, and symptoms of the subject.

[0038] The subjects to which the autophagy activator is administered are preferably mammals, more preferably humans, monkeys, cats, pigs, horses, cows, mice, rats, guinea pigs, dogs, and rabbits, and even more preferably humans.

[0039] One embodiment of the present invention provides a food, beverage, feed, cosmetic, pharmaceutical, or quasi-drug product, etc., containing the autophagy activator of this embodiment. The food, beverage, feed, cosmetic, pharmaceutical, or quasi-drug product may have the same dosage form as that described for the autophagy activator.

[0040] The present invention may be a therapeutic invention or a non-therapeutic invention. That is, it may be an invention of a therapeutic or non-therapeutic method, an invention of a therapeutic or non-therapeutic use, or an invention of a therapeutic or non-therapeutic product. In the case of a non-therapeutic invention, it may be used in food or beverage applications, and the use aspect of the present invention means that it is used in a non-therapeutic manner.

[0041] In another embodiment of the present invention, there is provided a food or beverage composition for activating autophagy, which contains an extract of Alpinia zerumbet and / or an extract of Ch'ien Sanlong.

[0042] Food or beverage compositions can be in a form suitable for the intended use, including, but not limited to, oral preparations such as tablets, capsules, granules, fine granules, powders, liquids, syrups, chewable tablets, and lozenges, as well as ointments, gels, creams, injections, sublingual preparations, inhalants, and suppositories. Food or beverage compositions can be in an edible form, including, but not limited to, solids, liquids, granules, powders, capsules, creams, pastes, and jellies. For example, capsules may be coated with one or more layers as needed. These dosage forms and shapes can be achieved using conventionally known additives, including, but not limited to, excipients, binders, diluents, disintegrants, buffers, thickeners, stabilizers, emulsifiers, dispersants, suspending agents, and / or preservatives known in the food industry. The food or beverage composition is not particularly limited, and may be, for example, a health food, a functional food, a food for specified health uses, a nutrient-functional food, a health supplement, or a supplement. Examples of the food or beverage composition include food, beverages, seasonings, and food additives. Specific examples of foods include confectioneries, dairy products, breads, noodles, rice, soups, and prepared dishes. Specific examples of beverages include milk drinks, soft drinks, fruit juice drinks, carbonated drinks, sports drinks, energy drinks, and alcoholic beverages.

[0043] If necessary, coloring agents, flavoring agents, sweeteners, bittering agents, acidulants, preservatives, antioxidants, pH adjusters, and / or thickening stabilizers may be added to the food or beverage composition.

[0044] The food or beverage composition may be provided after heat sterilization, or may be provided in a sealed form in a bag or container. When provided, it may be labeled with at least one claim selected from the group consisting of "regulating stomach condition," "maintaining intestinal function," "rejuvenating the intestines," "improving cognitive function," "improving memory," "removing waste products from the brain," "maintaining healthy liver function," "improving motor function," "maintaining skin moisture and elasticity," "improving skin blemishes, wrinkles, and / or dullness," "improving hair color, moisture, and / or luster," "extending healthy lifespan," and "improving germ cell quality."

[0045] The food or beverage composition in this embodiment contains shell ginger extract and / or tsutsumi-ryu extract, which activates autophagy and provides at least one effect selected from the group consisting of regulating stomach condition, maintaining intestinal function, rejuvenating the intestines, improving cognitive function, improving memory, removing waste products from the brain, maintaining healthy liver function, improving motor function, maintaining skin moisture and elasticity, improving skin blemishes, wrinkles and / or dullness, improving hair color, moisture and / or luster, extending healthy lifespan, and improving the quality of germ cells. Therefore, in this embodiment, we also provide a food or beverage composition containing shell ginger extract and / or sanshanlong extract, for at least one selected from the group consisting of regulating stomach condition, maintaining intestinal function, rejuvenating the intestines, improving cognitive function, improving memory, removing waste products from the brain, maintaining healthy liver function, improving motor function, maintaining skin moisture and elasticity, improving skin blemishes, wrinkles and / or dullness, improving hair color, moisture and / or luster, extending healthy lifespan, and improving the quality of germ cells. The food or beverage composition of this embodiment may exhibit at least one effect selected from the group consisting of regulating stomach condition, maintaining intestinal function, rejuvenating the intestine, improving cognitive function, enhancing memory, removing waste products from the brain, maintaining healthy liver function, improving motor function, maintaining skin moisture and elasticity, improving skin blemishes, wrinkles and / or dullness, improving hair color, moisture and / or luster, extending healthy lifespan, and improving germ cell quality, by activating autophagy with the shell ginger extract and / or the lancet extract, or by activating LC3-II, or by activating autophagy through LC3-II activation.

[0046] In another embodiment of the present invention, the food or beverage composition of this embodiment may be a food or beverage composition that activates autophagy by activating LC3-II. Furthermore, by including at least one of the extracts in the food or beverage composition of this embodiment, it becomes possible to activate autophagy, thereby providing the effects described in Table 1 above. Therefore, this embodiment also provides a food or beverage composition that provides the effects described in Table 1 above.

[0047] The present invention will be described in more detail below using examples, but the technical scope of the present invention is not limited to these examples.

[0048] 1. Sample preparation: Shell ginger extract. Whole dried shell ginger (Ryuka Shoji) was crushed into powder, and 3.0 g of this powder was added to 30 mL of 99.5% ethanol and stirred at room temperature for 30 minutes to perform extraction. After that, the residue was removed by a conventional method, and the mixture was dried to obtain 0.186 g of dried product.

[0049] Chuanshanlong Extract: Whole dried Chuanshanlong (Shingi) was crushed into powder, and 3.0 g of this powder was added to 30 mL of 99.5% ethanol and stirred at room temperature for 30 minutes to extract. After that, the residue was removed by a conventional method, and the mixture was dried to obtain 0.161 g of a dried product.

[0050] 2. Test in cultured cells Mizushima, N. et al. Dissection of autophagosome formation using Apg5-deficient mouse embryonic stem cells. J. Cell Biol. 152, 657-668 (2001). Mouse embryonic fibroblasts (MEFs) established from wild-type C57 / B6J mice at embryonic day 14.5, which were prepared by the method described in, were immortalized by introducing a gene expressing SV40 T antigen into them by electroporation using the Nucleofector system (Amaxa).

[0051] DMEM medium (Sigma Aldrich) containing 10% FBS (Sigma Aldrich), 1 mM sodium pyruvate solution (Nacalai Tesque), 1 mM HEPES buffer (Nacalai Tesque), 0.1 mM non-essential amino acid solution (Fujifilm Wako Pure Chemical Industries, Ltd.), 0.1 mM MEM Vitamin solution (Invitrogen), 100 U / mL penicillin (Nacalai Tesque), 100 μg / mL streptomycin (Nacalai Tesque), and 0.05 mM 2-mercaptoethanol (Bio-Rad) was used.

[0052] 3 x 10 cells ５ The cells were seeded into a 6-well plate (Corning) at a concentration of 1000 cells / mL and incubated at 37°C, 5% CO ２ The cells were cultured for 24 hours in an incubator. Alpinia zerumbet extract and Sanzanryu extract were diluted in DMSO (Fujifilm Wako Pure Chemical Industries, Ltd.) and added to the cells to final concentrations of 13 and 40 μg / mL, respectively. After 5 hours, the cells were washed with 2 mL of PBS (Nacalai Tesque), and then 200 μL of RIPA buffer containing a protease inhibitor (ThermoFisher Scientific, Halt™ Protease and Phosphatase Inhibitor Cocktail (100X)) was added to each well, and the cell extract was collected.

[0053] After protein quantification using a BCA assay kit (Bio-Rad), the cell extract was adjusted to a certain protein concentration, and 4x Laemmil Sample buffer (Bio-Rad) was added and heated at 95°C for 5 minutes. The extract was loaded onto a TGX gel (Bio-Rad) and subjected to electrophoresis. After that, blotting was performed using iBlot™ 2 (Thermo Fisher Scientific) with iBlot™ 2 Transfer Stacks, PVDF, regular size (Thermo Fisher Scientific). Antigen-antibody reactions were carried out using the iBindFlex Solution Kit (Thermo Fisher Scientific). The antibodies used were anti-LC3 antibody (Cosmo Bio, 1 / 500 dilution), anti-actin antibody (Chemicon International, 1 / 10,000 dilution), and anti-mouse IgG, HRP-linked antibody (Cell Signaling Technology, 1 / 200).

[0054] The membrane was chemiluminesced using Chemiluminescent One Super (Nacalai Tesque) and photographed using an LAS4000 mini (Fujifilm). The image analysis function of the LAS4000 mini was then used to output the integrated values ​​(signal intensity) of the band intensities and areas. The integrated values ​​of each band were divided by the integrated value of the Vehicle band (Figure 1, Table 2).

[0055] Test Results As shown in Figure 1, an increase in LC3-I and LC3-II was confirmed by the addition of Alpinia zerumbet extract or Senzanryu extract. A summary of the analyzed values ​​is shown in Table 1. These proteins are widely used as markers of autophagy, and it is known that LC3-II increases when autophagy is promoted. In this example, an increase in LC3-II was also confirmed by the known autophagy-inducing compounds raloxifene and rapamycin (Figures 2 and 3). Similar changes were confirmed by the addition of Alpinia zerumbet extract or Senzanryu extract, confirming that Alpinia zerumbet extract or Senzanryu extract has the ability to activate autophagy.

[0056]

[0057] The results in Table 2 and Figures 1 to 3 confirmed that the shell ginger extract or the chuanshanryu extract has the function of activating autophagy.

Claims

1. An autophagy activator containing Alpinia zerumbet extract and / or Dioscorea nipponica extract.

2. A food or beverage composition for activating autophagy, containing Alpinia zerumbet extract and / or Dioscorea nipponica extract.

3. A food or beverage composition containing Alpinia zerumbet extract and / or Dioscorea nipponica extract for at least one selected from the group consisting of regulating stomach condition, maintaining intestinal function, rejuvenating the intestine, improving cognitive function, enhancing memory, removing brain waste, maintaining healthy liver function, improving motor function, maintaining skin moisture and elasticity, improving skin spots, wrinkles and / or dullness, improving hair color, moisture and / or gloss, extending healthy lifespan, and improving the quality of germ cells.

4. The food or beverage composition according to claim 3, which shows at least one selected from the group consisting of regulating stomach condition, maintaining intestinal function, rejuvenating the intestine, improving cognitive function, enhancing memory, removing brain waste, maintaining healthy liver function, improving motor function, maintaining skin moisture and elasticity, improving skin spots, wrinkles and / or dullness, improving hair color, moisture and / or gloss, extending healthy lifespan, and improving the quality of germ cells by activating autophagy of Alpinia zerumbet extract and / or Dioscorea nipponica extract.

5. The food or beverage composition according to claim 3 or 4, which shows at least one selected from the group consisting of regulating stomach condition, maintaining intestinal function, rejuvenating the intestine, improving cognitive function, enhancing memory, removing brain waste, maintaining healthy liver function, improving motor function, maintaining skin moisture and elasticity, improving skin spots, wrinkles and / or dullness, improving hair color, moisture and / or gloss, extending healthy lifespan, and improving the quality of germ cells by activating LC3-II of Alpinia zerumbet extract and / or Dioscorea nipponica extract.

6. The autophagy activator according to claim 1, which is used for at least one selected from the group consisting of regulating stomach condition, maintaining intestinal function, rejuvenating the intestine, improving cognitive function, enhancing memory, removing brain waste, maintaining healthy liver function, improving motor function, maintaining skin moisture and elasticity, improving skin spots, wrinkles and / or dullness, improving hair color, moisture and / or gloss, extending healthy lifespan, and improving the quality of germ cells.

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