KR20130081675A - Compositions for improving memory power and learning ability comprising at least one selected from curcuma xanthorrhizae extracts, curcumin, demethoxycurcumin, xanthorrhizol - Google Patents

Abstract

The present invention relates to a composition for enhancing memory and learning ability comprising at least one selected from the group consisting of extracts of Curcuma xanthorrhizae , curcumin, dimethoxycurcumin and xanthorrhizol , The composition of the present invention has the effect of inhibiting the damage of nerve cells, especially nerve cells in the base of the cerebrum through inhibiting the activity of acetylcholinesterase. In addition, the present invention not only enhances memory and learning ability through protecting and protecting nerve cells, but also exerts effects of preventing and treating diseases with cognitive impairment.

Description

Compositions for Improving Memory Power and Learning Ability Comprising at least one selected from Curcuma Xanthorrhizae Extracts, Curcumin , Demethoxycurcumin, Xanthorrhizol}

The present invention relates to a composition for enhancing memory and learning ability comprising at least one selected from the group consisting of extracts of curcuma, curcumin, dimethoxycurcumin and naxazole.

In the human brain, there are 100 billion neurons, each of which is connected to other nerve cells around each other by an area of about 10,000 synapses, forming a network. Through these synapses, the close communication between the neurons is achieved, and the mediator plays a role in the neurotransmitter (neurotransmitter). Neurons release neurotransmitters to stimulate receptors and thereby exchange information with each other. The way that the human brain stores memory is the process of strengthening synaptic connection strength through continuous chemical and electrical stimulation. This is called long-term potentiation (LPT). Synaptic plasticity is called synaptic plasticity. The fact that neurotransmitters chemically communicate information at synapses was experimentally demonstrated in the early 20th century. Currently known neurotransmitters include acetylcholine (ACh), norepinephrine, dopamine (DA), gamma-amonobutyric acid (GABA), glycine and glutamic acid. Cognitive impairment, such as loss of memory and learning, caused by Alzheimer's disease, which is a type of senile dementia, is caused by damage to acetylcholine neurons in the base of the cerebral base. Drugs that can enhance the function of acetylcholine neurons have been developed according to various mechanisms of action such as agonists, acetylcholine production promoters, and acetylcholinesterase inhibitors. Currently, tacrine has been developed as an acetylcholinesterase inhibitor, but there are some side effects such as gastrointestinal disorder. Therefore, it is necessary to search and utilize inhibitory active material from natural plant material.

Flavonoids are a component of foods that affect human memory and learning. Flavonoids that have a positive effect on the human brain include isoflavones found in soybeans, flavonols and anthocyanins found in tea and cocoa and red wine. Isoflavones mimic the action of estrogens in the brain, while flavanols and ansocyanins are mitogen-activated protein kinase (MAPK) pathways and PI3 kinase (PI3 kinase / Akt) signaling. Interact with signaling pathways in neurons such as step responses. Both MAPK and PI3 kinase pathways are known to have memory storage functions in the hippocampus and cortex of the brain. It has the potential to enhance memory and learning by activating kinases in these pathways. It is also known to promote the activation of proteins such as cAMP Response Element Binding (CREB), which is involved in the expression of genes associated with memory. According to the King's College London team in England, the ingredients found in broccoli, potatoes, oranges, apples and radishes work the same way as Alzheimer's disease drugs, and these are enzymes that destroy the neurotransmitter acetylcholine. It was found that it inhibits acetylcholinesterase.

Numerous papers and patent documents are referenced and cited throughout this specification. The disclosures of the cited papers and patent documents are incorporated herein by reference in their entirety to better understand the state of the art to which the present invention pertains and the content of the present invention.

The present inventors have made diligent research efforts to develop a safe material, especially plant-derived materials, which can effectively improve memory and learning ability, and as a result, curcumin derived from Java turmeric and Java turmeric, which are conventionally used as herbal medicines. The present invention was completed by declaring that dimethoxycurcumin and xanthorrhizol are very effective for enhancing memory and learning ability.

Accordingly, an object of the present invention is to provide a composition for memory and learning promotion.

Another object of the present invention to provide a composition for preventing or treating cognitive dysfunction.

Still another object of the present invention is to provide a food composition for improving memory and learning ability.

Another object of the present invention to provide a pharmaceutical composition for preventing or treating cognitive dysfunction.

Another object of the present invention to provide a food composition for preventing or improving cognitive dysfunction.

Other objects and advantages of the present invention will become more apparent from the following detailed description of the invention, claims and drawings.

According to an aspect of the present invention, the present invention provides a memory including at least one selected from the group consisting of extracts of Curcuma xanthorrhizae , curcumin, demethoxycurcumin and xanthorrhizol It provides a composition for improving learning ability.

The present inventors have made diligent research efforts to develop a memory-safe substance, especially a plant-derived substance, which can effectively improve memory and learning ability, and as a result, the curcumin derived from the Java medicinal herb, curcumin, dime, which are conventionally used as herbal medicine, Toxicurcumin and naxazole were found to be very effective in enhancing memory and learning ability.

Java turmeric extract used in the composition of the present invention, when obtained by treating the extraction solvent to Java turmeric, various extraction solvents may be used. According to one embodiment of the present invention, a polar solvent or a non-polar solvent can be used. Suitable polar solvents include (i) water, (ii) alcohols (according to one embodiment of the invention methanol, ethanol, propanol, butanol, normal-propanol, iso-propanol, normal-butanol, 1-pentanol, 2-butoxyethanol or ethylene glycol), (iii) acetic acid, (iv) dimethyl-formamide (DMFO) and (v) dimethyl sulfoxide (DMSO). Suitable nonpolar solvents are acetone, acetonitrile, ethyl acetate, methyl acetate, fluoroalkane, pentane, hexane, 2,2,4-trimethylpentane, decane, cyclohexane, cyclopentane, diisobutylene, 1- But are not limited to, pentane, 1-chlorobutane, 1-chloropentane, o -xylene, diisopropyl ether, 2- chloropropane, toluene, 1- chloropropane, chlorobenzene, benzene, diethyl ether, diethylsulfide, Methane, 1,2-dichloroethane, aniline, diethylamine, ether, carbon tetrachloride, and THF.

According to another embodiment of the present invention, the extraction solvent used in the present invention may be selected from the group consisting of (a) water, (b) an anhydrous or hydric alcohol having 1 to 4 carbon atoms (methanol, ethanol, propanol, butanol, (E) ethyl acetate, (f) chloroform, (g) butyl acetate, (h) 1,3-butylene glycol, (i) hexane, and (j) Diethyl ether. According to certain embodiments of the present invention, the extract of the present invention is obtained by treating Java turmeric with water, ethanol or a combination thereof.

As used herein, the term " extract " means that it is used in the art as a crude extract as described above, but broadly includes fractions obtained by further fractionating the extract. That is, the Java turmeric extract includes not only one obtained by using the aforementioned extraction solvent, but also one obtained by additionally applying a purification process thereto. For example, fractions obtained by passing the extract through an ultrafiltration membrane having a constant molecular weight cut-off value, separation by various chromatography (manufactured for separation according to size, charge, hydrophobicity or affinity), etc. The fraction obtained through the purification method is also included in the Java turmeric extract of the present invention.

Java turmeric extract used in the present invention may be prepared in a powder state by an additional process such as distillation under reduced pressure and freeze drying or spray drying.

According to a particular embodiment of the present invention, the Java turmeric extract used in the present invention was used by concentration under reduced pressure.

According to another aspect of the present invention, the present invention provides a composition for preventing or treating cognitive disorders comprising at least one selected from the group consisting of extracts of curcuma, curcumin, dimethoxycurcumin and naxazole.

The effects of the present invention are exerted by inhibiting the protection and damage of neurons, acetylcholinergic neurons in the base of the cerebrum, according to certain embodiments.

Acetylcholine is a neurotransmitter that is secreted at the nerve endings and delivers nerve stimuli to muscles.

According to one embodiment of the present invention, the present invention can inhibit the degradation of acetylcholine by acetylcholinesterase by inhibiting the activity of acetylcholinesterase can inhibit the protection and damage of nerve cells.

'Cognitive dysfunction' in the specification of the present invention refers to a disease that does not exhibit cognitive functions such as memory processing, perception and problem solving.

The present invention is a composition capable of preventing and / or treating cognitive dysfunction. More specifically, the present invention inhibits the activity of Acetylcholinesterase, prevents cognitive dysfunction through the combination of antioxidant activity (eg, reactive oxygen species) and NMDA (N-methyl-D-aspartate) receptor and And / or a curable composition.

According to one embodiment of the present invention, the cognitive impairment in the present invention is dementia, learning disorder, agnosia, amnesia, aphasia, apraxia or Delirium, and according to another embodiment of the present invention, AIDS-induced dementia (AIDS dementia complex), Binswanger's disease, dementia with Lewy Bodies, frontotemporal dementia dementia, mild cognitive impairment, multi-infarct dementia, Pick's disease, semantic dementia, Alzheimer's dementia or vascular dementia Means.

The composition of the present invention may be prepared as a pharmaceutical composition.

According to a particular embodiment of the present invention, the composition of the present invention comprises (a) a pharmaceutically effective amount of the above-described Java turmeric extract of the present invention; And (b) a pharmaceutically acceptable carrier. As used herein, the term " pharmaceutically effective amount " means an amount sufficient to achieve efficacy or activity of the above-described Java turmeric extract.

When the composition of the present invention is manufactured from a pharmaceutical composition, the pharmaceutical composition of the present invention includes a pharmaceutically acceptable carrier. Pharmaceutically acceptable carriers included in the pharmaceutical compositions of the present invention are those commonly used in the preparation, such as lactose, dextrose, sucrose, sorbitol, mannitol, starch, acacia rubber, calcium phosphate, alginate, gelatin, Calcium silicate, microcrystalline cellulose, polyvinylpyrrolidone, cellulose, water, syrup, methyl cellulose, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil, and the like It doesn't happen. In addition to the above components, the pharmaceutical composition of the present invention may further include a lubricant, a humectant, a sweetener, a flavoring agent, an emulsifier, a suspending agent, a preservative, and the like. Suitable pharmaceutically acceptable carriers and formulations are described in detail in Remington ' s Pharmaceutical Sciences (19th ed., 1995).

The pharmaceutical composition of the present invention may be administered orally or parenterally, and may be administered orally in accordance with an embodiment of the present invention.

The appropriate dosage of the pharmaceutical composition of the present invention may vary depending on factors such as the formulation method, administration method, age, body weight, sex, pathological condition, food, administration time, administration route, excretion rate, . Typical dosages of the pharmaceutical compositions of the invention are in the range of 0.001-100 mg / kg on an adult basis.

The pharmaceutical compositions of the present invention may be prepared in unit dose form by formulating with a pharmaceutically acceptable carrier and / or excipient according to methods which can be easily carried out by those skilled in the art. Or may be prepared by incorporation into a multi-dose container. The formulations may be in the form of solutions, suspensions, syrups or emulsions in oils or aqueous media, or in the form of excipients, powders, powders, granules, tablets or capsules, and may additionally contain dispersing or stabilizing agents.

The composition of the present invention can be provided as a food composition.

When the composition of the present invention is prepared as a food composition, it contains not only the extract of Java as an active ingredient but also a component which is ordinarily added in the production of food, for example, a protein, a carbohydrate, a fat, a nutrient, And flavoring agents. Examples of the above carbohydrates include monosaccharides such as glucose, fructose and the like; Disaccharides such as maltose, sucrose, oligosaccharides and the like; And sugars such as conventional sugars such as polysaccharides such as dextrin, cyclodextrin and the like and xylitol, sorbitol, erythritol. As flavoring agents, natural flavoring agents (tauumatin, stevia extract (for example rebaudioside A, glycyrrhizin, etc.)) and synthetic flavoring agents (saccharin, aspartame, etc.) can be used. For example, when the food composition of the present invention is prepared as a drink, it may further contain citric acid, liquid fructose, sugar, glucose, acetic acid, malic acid, juice, mulberry extract, jujube extract, licorice extract, .

The features and advantages of the present invention are summarized as follows:

(A) The present invention is a composition for enhancing memory and learning ability comprising at least one selected from the group consisting of extract of Curcuma xanthorrhizae, curcumin, demethoxycurcumin and xanthorrhizol And it provides a composition for preventing and treating cognitive dysfunction.

(b) The present invention has the effect of inhibiting the damage of nerve cells, especially nerve cells in the base of the cerebrum through inhibiting the activity of acetylcholinesterase.

(c) The present invention not only enhances memory and learning ability through protecting and preventing neurons, but also exerts effects of preventing and treating diseases with cognitive impairment.

Figure 1 shows a schematic of the passive avoidance experiment of the mouse.
Figure 2 shows a passive avoidance system (GEMINI avoidance system, SD instrument, USA) for measuring the memory capacity of the experimental animal.
Figure 3 is a schematic diagram of the Morris underwater maze experiment for measuring the spatial learning and memory capacity of the experimental animals.
4 is Curcuma xanthorrhiza ) is a graph showing the inhibitory activity of acetylcholinesterase over time and concentration of the extract.
5 is a graph showing the acetylcholinesterase inhibitory activity with concentration and time of octagonal fennel ( Ilicium verum Hook f.).
Figure 6 shows a graph comparing the acetylcholinesterase inhibitory activity of Java turmeric and octagonal fennel.
Figure 7 shows the results of passive avoidance test of the control group, scopolamine group, rivastigmine group and experimental group treated with Java turmeric extract by concentration. The letters 'a', 'b' or 'c' on each bar indicate a significant difference between the alphabets as a result of Duncan's multiple range test.
Figure 8 is a graph showing the results of the experiment in water maze of the control group, scopolamine group, rivastigmine group and experimental group treated with Java turmeric extract by concentration. The 'a' or 'b' alphabet above each bar indicates that there is a significant difference between the alphabets as a result of Duncan's multiple test.
Figure 9 is a graph showing the results of the experiment in water maze of the control group, scopolamine group, rivastigmine group and experimental group treated with Java turmeric extract by concentration. The 'a' or 'b' alphabet above each bar indicates that there is a significant difference between the alphabets as a result of Duncan's multiple test.
Figure 10 shows the results confirming the NMDA (N-methyl-D-aspartate) receptor affinity of the turmeric and turmeric extract.
11 is a graph showing the effect of increasing the concentration of acetylcholine in thalamus by ethanol extract and rivastigmine of Java turmeric and turmeric.
12 shows Nano-SPECT images treated with a control group (10% DMSO in saline).
FIG. 13 shows a CT image injected with ¹²³ I-A85380 and a single-photon emission computed tomography (SPECT) image.
14A and 14B show the location of the probe insertion and the microdialysis process. FIG. 14A shows the stratum (stereolocation coordinates: AP 1.2 L-2.6 for bregma, H-4.2 for dura mater), and FIG. 14B shows a photograph of sample collection using a microfraction collector connected to the probe outlet. .
Fig. 15 shows a schematic diagram of ¹⁸ F-CP118954 synthetic image evaluation using a Nano-SPECT imaging apparatus.
FIG. 16 is a graph showing the results of experiments as a latency time of Morris aquatic mice of mice treated with the control group, scopolamine, rivastigmine, curcumin, dimethoxycurcumin, and naxazole.
FIG. 17 shows the effect of curcumin, dimethoxycurcumin and naxazole on probe demonstration in Morris underwater maze experiment. Represents the number of crossings of the shelters during the demonstration (n = 4).
FIG. 18 shows the effects of curcumin, dimethoxycurcumin and naxazoles on memory damage induced by scopolamine by passive avoidance experiments. Results were expressed as mean ± SEM (n = 4).
19 shows the results of nano-SPECT imaging experiments to confirm the binding to acetylcholine esterase.

Hereinafter, the present invention will be described in more detail with reference to Examples. It is to be understood by those skilled in the art that these embodiments are only for describing the present invention in more detail and that the scope of the present invention is not limited by these embodiments in accordance with the gist of the present invention .

Example 1: Effect of Java Turmeric Extract

Materials and Experiments

Java Turmeric ( Curcuma xanthorrhiza ) And Octagonal Fennel (Illicium verum Hook f.)  extraction

Curcuma xanthorrhiza powder samples were supplied from S & D. 80% EtOH was added to the dry pulverized powdered Java turmeric and octagonal fennel samples at a ratio of 1:10 and extracted at 78.3 ° C. for 6 hours in a COSMOS-660 ultrafast vacuum low temperature extractor (Kyungseo, Korea). The extract was concentrated under reduced pressure at 75 ℃ was used as a test sample for AChE inhibitory activity.

Yield calculation

The yield of the sample was expressed by the solid content (%) with respect to the dry weight of the raw material used to prepare the extract after freeze-drying the extract.

Determination of In vitro Inhibitory Activity of Acetylcholinesterase (AChE)

AChE inhibitory activity is that 5,5'-dithio bis is reacted with thiocholine, a reaction product produced when AChE hydrolyzes acetylthiocholine. (-2-nitrobenzoic acid); reacted with DTNB to produce yellow 2-nitrobenzoic acid (NTB), and thus the ACBE inhibitory activity was measured by measuring the absorbance at 412 nm. Determination of acetylcholinesterase inhibitory activity of plant extracts was used by modifying the method of Ellman et al, Dohi et al, Hammond and Forster.

That is, the 50 ㎕ phosphate buffer (phosphate bufer, 0.1 M, pH 8.0) and 25 ㎕ AChE (2.36 U / ㎖ , phosphate buffer in Java turmeric (crucuma xanthorrhiza) dissolved in 10% tween 80 in 25 ㎕ a 96-well plate In a dissolved state) and reacted at 37 ° C. for 15 minutes. After the reaction, 125 μl of DTNB (3 mM, dissolved in phosphate buffer) and 25 μl of acetylcholine iodine (15 mM, dissolved in phosphate buffer) were added, followed by stirring at room temperature for 1 minute and then again. The reaction was carried out at room temperature for 30 minutes. Absorbance was measured at 412 nm. 1,2,3,4-tetrahydroacridin-9-amine (1,2,3,4-tetrahydroacridin-9-amine, Tacrine, sigma, USA) was used as a positive control and AChE inhibitory activity of plant extracts The effect was measured by the same method using the same amount of 0.1 M phosphate buffer (pH 8.0) instead of the sample to obtain a result. A _sample of the following formula is the absorbance of the Java turmeric treated sample, A _control is the absorbance of the tacrine treated sample.

% Suppression = 100-(A _sample / A _control ) × 100

Experimental Animal and Experimental Group

The rats used in the passive avoidance and labyrinth experiments were Sprague-Dawley system and 66 males, weighing 180 g to 200 g at 5 weeks of age, were sold from Nara Biotech (Chungcheongbuk-do, Korea) for 7 days in the nursery. During the period of adaptation. Two experimental animals were raised per cage, and the environment of the cage was maintained at a temperature of 21 ± 2 ° C. and a relative humidity of 55 ± 10%. Contrast was kept constant over a 12 hour period (from 08:00 am to 08:00 pm). Solid feed and water were freely ingested during the experiment. After the adaptation period, it was divided into 6 groups by the lump method. Animal experiments were the control group, Scopolamine group, positive control group Rivastigmine group, Curcuma Xanthorrhiza (CX) 125 mg / kg group, Java turmeric 250 mg / kg group and Java turmeric 500 mg Separation into groups / kg was performed for 3 weeks.

Oral Administration of Experimental Samples

Java turmeric extract powder used in this experiment was supplied from S & D Co., Ltd. in the form of lyophilized powder of 80% ethanol extract. The experimental group fed the Java turmeric extract was orally administered at each concentration at about 10 AM, which was a constant time every day, and the control group and the scopolamine group were orally administered the same amount of distilled water for 3 weeks. At around 10 am on the day of the experiment, the experimental group used the extract of the corresponding concentration, the control group, the scopolamine group, distilled water, and the rivastigmine group, the positive control group, to rivastigmine (ethyl [methyl-carbamic acid 3-[(1S) -1-) Dimethylamino) ethyl] phenyl ester (Ethylmethyl-carbamic acid 3-[(1S) -1- (Dimethylamino) ethyl] phenyl Ester); Toronto Research Chemicals, Canada) orally administered in distilled water at a concentration of 1.5 mg / kg It was. In order to cause memory damage in experimental animals, scopolamine hydrobromide (Sigma, USA) was used by dissolving in physiological saline at a concentration of 1 mg / kg. Thirty minutes after oral administration, the group was intraperitoneally administered, and the control group received the same amount of saline.

Manual Evasion Experiment Passive avoidance test Memory measurement by

A manual avoidance system (GEMINI avoidance system, SD instrument, USA) was used to measure the memory capacity of experimental animals. In the middle of the device was a chamber of 24 × 20 × 20 cm on both sides with a guillotine door, and a grid was installed at the bottom of each chamber to set current to flow in a dark room. The experiment was carried out by applying a step-down format to the acquisition trial and retention trial. Acquisition experiment was carried out one day before the regeneration experiment. The animals are placed in the left box and after 20 seconds of acclimation, the left chamber is lit and at the same time the guillotine door opens. At this time, due to the instinct to move to the dark part of the rat to move to a dark place, the rat was measured the latency time (latency time) into the dark box. As soon as the rat enters the dark room, the guillotine door closes and the electric shock is applied to the rat into the dark room by flowing a current of 0.5 mA into the grid for 2 seconds. When the rats were taken out and moved to the cage and left open in a bright room after 24 hours, the guillotine door was opened. Around 10 am on the day of the acquisition experiment, the CX group was orally administered extracts of Java turmeric at each concentration, and the control group was orally administered with 1.5 mg / kg of the rivastigmine group, a positive control group, with distilled water. After 30 minutes, the experimental group was injected with scopolamine (1 mg / kg, dissolved in saline), and the control group was intraperitoneally injected with saline. After 1 hour of intraperitoneal injection, the mice were placed in a bright chamber, and the time of staying in the bright area (maximum 300 seconds, cut off time) was measured (n = 36, 6 rats × 6 groups). After 24 hours, the rats were placed in the bright chamber again, and the regeneration experiment was performed to measure the length of time that the animals stayed in the bright chamber as an index of memory.

Morris Underwater maze  Measure( Morris water maze test )

Morris's underwater maze is widely used to evaluate spatial learning and memory abilities in rats. Fill a circular water tank (100 cm in diameter and 35 cm in height) where light does not shine in the water, with water at a temperature of 22 ° C-25 ° C to about 1 cm above the sheath and add black food coloring to make the bottom invisible. The circular water tank was divided into quarters and a marker was recognized at each location. The experiment began by placing the mice in water at the wall in the middle of any one quadrant. At this time, the eyes of the animal are directed toward the underwater wall so that the inside of the tank is not visible, and the distance and time from this time until the rat swims and finds the evacuation zone are measured. SMATR polyvalent video tracking system, Panlap (Spain) was used to measure and record the learning outcomes of the trial. On the first day of the experiment, they were allowed to swim freely in the tank for 60 seconds without the evacuation pad. When rats climbed up the shelter, they gave a 10 second interval. If the rat could not find the escape after 120 seconds, the experimenter guided the mouse to the escape and allowed him to stay there for 1 minute to remember the location of the escape. On day 7 of the experiment, the shelters were removed to measure working memory and the time and distance to the shelters were measured (n = 30, group 6 x 5 rats).

NMDA  Receptor affinity test

Recently, a study to control dementia by preventing damage to brain cells by various excitatory amino acids such as glutamic acid and N-methyl-D-aspartate (NMDA) has attracted attention. NMDA receptors act as the most important Ca ⁺⁺ channel in neurons and induce apoptosis of neurons by promoting the introduction of Ca ⁺⁺ into neurons by various NMDA agonists such as NMDA. Therefore, the antagonists of NMDA receptors with excellent efficacy by measuring the affinity between plant extracts and NMDA receptors were investigated.

Plant extracts were used as target samples, indicating that these samples inhibit the binding of NMDA receptors isolated from the rat brain and [ ³ H] -glycine, which is known as a selective ligand for glycine binding sites. We explored the affinity for the NMDA receptor.

Microdialysis to Analyze Brain Function Improvement Efficacy

Rats (male, Sprague-Dawley rats, 250-300 g) were anesthetized with zoletin (50 mg / kg, IP) and rumpen and then aseptically treated with Paxinos and Watson. A guide tube was inserted into the thalamus according to Atlas (1986) and fixed using microscrews and dental cement. After the procedure, the rats received a 24 mm recovery period and inserted a 2 mm vertical microdialysis probe (CMA-12, Carnegie-Medicin, Sweden) through an induction tube. The inlet of the microdialysis probe is connected to a syringe mounted in a perfusion pump via a double-ring rotator ring through which Ringer's solution (147 mM NaCl, 1.2 mM CaCl ₂ , 2.7 mM KCl and 1.0 mM MgCl ₂ , 3 basal dialysates and 6 samples after drug administration were collected at 30 minute intervals using a Carnegie-Medicin connected to the probe exit with a pH of 7.4) injected at 1.0 μl / min. . Data analysis calculated the mean value (control) of three basal dialysates as 100 and expressed the change values (% control) for them.

Natural products extracted with ethanol were dissolved in physiological saline containing 10% DMSO (Dimethyl Sulfoxide), and then single dosed intraperitoneally to SD rats (n = 3) at a concentration of 25 mg / kg, followed by microdialysis. In addition, the effects of natural products were evaluated using rivastigmine (1.5 mg / kg), an acetylcholinesterase inhibitor (ACHI), which was previously used. The concentration of acetylcholine in the microdialysis sample was analyzed using a liquid chromatography (Acquity UPLC, waters, USA) -mass spectrometer (Quattro Premier XE, waters, USA) system. The dialysate was separated using a reversed-phase Waters UPLC BEH HILIC column (1.7 μm, 2.1 × 50 mm). The mobile phase used 20% ACN (Acetonitrile) and 80% 20 mM ammonium formate (total volume), and the flow rate of the system was 1.0 ml / min.

MicroSPECT  Efficacy evaluation using imaging device

Nano-SPECT (Single-Photon Emission Computed Tomography) imaging experiments were conducted to determine whether ethanol extracts of Java and turmeric ethanol increase acetylcholine concentration. Figure 12 is an image showing when the control group (10% DMSO in saline) treated. Stratum, Colliculi, and Thalamus were clearly visible through the image, and the thalamus was clearly distinguished from other brain regions. This image was also consistent with the existing autoradiogram (left of FIG. 12). The results of microdialysis confirmed the increase of acetylcholine by natural products in the thalamus, and the distinction of this region was clearly shown in the image, which was designated as the subject area of the experiment. In addition, the combination of ¹²³ I-A85380 in the cerebellum did not appear, which was determined as the reference region for standardizing the image.

Thirty minutes before the injection of ¹²³ I-A85380, the ethanol extracts of Java turmeric and turmeric were lyophilized, dissolved in DMSO, and diluted in physiological saline so that the concentration was 10% of the total volume. As a control material, saline containing 10% DMSO was used. ¹²³ I-A85380 after the injection time to start the image acquisition was performed to analyze the acquired image for half an hour.

Experimental Results and Discussion

Acetylcholinesterase  Inhibitory activity

Cognitive impairments such as memory loss and decreased learning ability caused by senile dementia have been reported to be due to acetylcholinergic neuronal damage at the base of the cerebral base. The world's most active research and development and FDA-approved dementia enhancer is an inhibitor of acetylcholinesterase (AChE), which breaks down acetylcholine. Curcuma xanthorrhiza ; Measurement results of AChE inhibitory activity of CX) is shown in Figure 4 and shows the inhibitory activity of AChE with concentration and time of Java turmeric extract. FIG. 5 shows that Jaw turmeric showed an inhibitory effect of 97.93% when the absorbance was measured immediately after the reaction when compared with the inhibitory activity of octagonal fennel ( Ilicium verum Hook f.), But the octagonal fennel was 26.69. The inhibitory effect of% showed that AChE inhibitory activity of Java turmeric was much higher. When comparing the inhibition rate over time, the Java turmeric did not significantly decrease the inhibitory activity over time, while the AChE inhibitory activity of the octagonal fennel was greatly reduced (FIGS. 4 and 5). The AChE inhibitory activity of the Java turmeric at concentrations of 1.25, 0.63, 0.32, 0.16 and 0.08 mg / ml was 97.93%, 85.02%, 37.51%, 21.40% and 9.30%, respectively. Figure 6 is a chart comparing the AChE inhibitory activity of Java turmeric and octagonal fennel after comparing the AChE inhibitory activity immediately after the treatment according to the concentration of the extract, it was confirmed that the greater activity in the Java activity showed an excellent AChE inhibitory activity.

Manual Evasion

Manual evacuation experiments were conducted to evaluate the effect of extract of turmeric java on the memory of experimental animals. Acquisitional trials showed no significant difference in the range of 21-40 seconds in each group. In the retention trial conducted after 24 hours, the control group remembered the electric shock received 24 hours ago, and the average time to enter the dark box was 300 seconds, so the electric shock received the previous day did not enter the dark box. Scopolamine group, a negative control group, was found to have lost 19.15 seconds of electric shock and moved to a dark box according to the instinct. The positive control group, rivastigmine group, showed a significant increase in the acquisition test compared with the scopolamine group, which induced memory impairment at 85.88 seconds. The acquisition test of the CX-125 group was 63.06 seconds, which was significantly increased compared to scopolamine, indicating that it was effective in memory impairment. On the other hand, there was no significant difference in the CX-250 and CX-500 groups. The residence time in the bright box in the group fed with Java turmeric extract for 6 weeks showed the effect of restoring impaired memory when supplied with 125 mg / kg compared to the scopolamine group, but 250 mg / kg and 500 At high concentrations of mg / kg, the same effect could not be expected (FIG. 7).

Underwater maze  Memory recovery effect

Morris water maze test (Morris water maze test) to determine the effect of the extract of Java turmeric on the spatial learning of scopolamine-induced memory loss rats are shown in FIGS. 8 and 9.

Animals treated with scopolamine increased their travel distance and settling time compared to the control group looking for escapes by remembering where they swam through a relatively different path due to temporary memory impairment. On the other hand, after 3 weeks of administration of Java turmeric extract, the distance and settling time decreased in the scopolamine-treated animals. It was confirmed that the Java turmeric extract administration group recognized the location of the escape zone on the aquatic labyrinth during the cognitive training for 7 days and remembered the spatial perception power through repeated continuous training. Java turmeric extract was found to be effective in improving long-term memory in scopolamine-induced dementia rats.

Nervous systems related to memory are known as cholinergic nervous system, glutamatergic nervous system, GABAergic nervous system, serototonic nervous system, and adrenergic nervous system, but cholinergic nervous system is mainly related to memory It is known. Scopolamine is a drug that blocks muscarinic receptors, one of the subtypes of cholinergic nerves, and prevents acetylcholine from binding to the receptor in the synaptic gap without changing the amount of acetylcholine. This is similar to the memory loss caused by damage to the central nervous system cholinergic nerves, and the drug that works in this model would be effective through the cholinergic nervous system. Therefore, the oral ingestion of Java turmeric extract may improve memory and cognitive abilities in scopolamine-induced memory impaired animal models.

NMDA  Receptor affinity test

Java and turmeric diluted to 0.01, 0.1, 1 and 10 mg / ㎖ concentrations to search for affinity for the NMDA receptor is shown in Figure 10. Curcuma Curcuma for xanthorrhizae extract longae ) showed higher NMDA receptor affinity at all concentration ranges.

Microdialysis to Analyze Brain Function Improvement Efficacy

As a result of confirming the effect of increasing the concentration of acetylcholine in the thalamus by ethanol extract of japonic and turmeric and rivastigmine, thalassemia was administered by single administration of 1.5 mg / kg of rivastigmine as an intraperitoneal injection (ip). The change of acetylcholine in water was increased from 30 minutes immediately after administration to an increase of 147% compared with baseline, and continued to 129% until 60 minutes. Changes in the concentrations of acetylcholine administered in a single dose of 25 mg / kg of ethanol extract of Java turmeric and turmeric are shown in FIG. 11. Comparison of the ethanol extracts of Java turmeric and turmeric showed up to 110.9% and 189% increase in basal value, respectively. Java turmeric extract was higher than rivastigmine, an acetylcholinesterase inhibitor used as a positive control. It has been shown to maintain the concentration of acetylcholine. These results indicate that the Java turmeric has a significant effect on memory improvement.

MicroSPECT  Efficacy evaluation using imaging device

The CT and SPECT images were used to determine the region of the thalamus and cerebellum, and then normalized to the cerebellum. Comparison of the binding ratio of ¹²³ I-A85380 resulted in a decrease of 93.77% for turmeric extract and 75.2% for Java turmeric extract compared to the control, which showed statistical significance at 0.05 level. The decrease in binding of ¹²³ I-A85380 in this thalamus means an increase in the concentration of extracellular acetylcholine induced by natural products, and Java turmeric extract was shown to be more effective than turmeric extract.

This result can also be confirmed by the image of ¹²³ I-A85380. In Figure 13, the image of turmeric and Java turmeric extract was confirmed that the binding of the ¹²³ I-A85380 was reduced compared to the control (control), the case of Java turmeric showed a large decrease. Table 1 shows the binding of ¹²³ I-A85380 in the thalamus of the natural product treated group to the control group.

- Control group curcuma Java Turmeric Average
(% Control) 100.00 93.77 75.2 Standard Deviation 0.00 3.25 2.80

Example  2: three single substances ( Curcumin , Dimethoxycurcumin  And Nagging ) Effect

Materials and Experiments

In the Java  Separated single substance AChE  In vitro inhibitory activity assay

AChE inhibitory activity is yellow 2-nitrobenzoic acid (NTB) when thiocholine, a reaction product generated when AChE hydrolyzes acetylcholine, reacts with 5,5'-dithiobis (-2-nitrobenzoic acid) (DTNB). ), The ACBE inhibitory activity was measured by measuring the absorbance of the resulting NTB at 412 nm. Determination of AChE inhibitory activity of single turmeric isolates was carried out using a modified method of Ellman et al., (1961) and Dohi et al. (2009). Ie, 25 μl of Java turmeric fraction (in ethanol dissolved form), 50 μl of phosphate buffer (0.1 M, pH 8.0), 25 μl of AChE (2.36 U / ml phosphate buffer), 0.1 M, in a 96 well plate. pH 8.0) was added and reacted at 37 ° C. for 15 minutes. After the reaction, 125 μl of DTNB (3 mM, dissolved in phosphate buffer, 0.1 M, pH 8.0) and 25 μl of acetylcholine iodine (15 mM, dissolved in phosphate buffer, 0.1 M, pH 8.0) were added at room temperature. After reacting for minutes, absorbance was measured at 412 nm. 1,2,3,4-tetrahydroacridin-9-amine (Tacrine; sigma, USA) was used as a positive control, and the effect of plant extracts on AChE inhibition activity was the same as that of ethanol instead of the sample. Measurements resulted.

Animal testing of three single substances

36 6-week-old ICR mice (25-30 g) were sold at NARA biotech. (Seoul, South Korea) and used for the experiment. After one week of adaptation, one animal was bred in each cage, and the environment was maintained at a temperature of 21 ± 2 ℃ and a relative humidity of 55 ± 10%. Contrast was kept constant over a 12 hour period (from 8 am to 8 pm). Solid feed and water were freely consumed during the experiment.

Oral Administration of Experimental Samples

Curcumin and dimethoxycurcumin used in this experiment were purchased from Sigma (USA), and were supplied by S & D Co., Ltd., xanthorrihzol (55% naxolisol in oil).

The experimental group was separated into a control group, a memory impairment control group, scopolamine group, a positive control tacrine group, a curcumin group, a dimethoxycurcumin group, and a nagging sol group. Turmeric single substance is curcumin (50 mg / kg, dissolved in corn oil), dimethoxycurcumin (10 mg / kg, dissolved in corn oil) and naxazole (100 mg / kg Dissolved in corn oil) orally, and the control group, the scopolamine group and the tacrine group were orally administered the same amount of corn oil for 4 weeks. Oral administration From week 4, the tacrine group was orally administered for 10 days at a concentration of 10 mg / kg (dissolved in distilled water).

Morris Underwater maze  Measure

Training began in aquatic life from the start of week 4 of oral administration. Fill a circular water tank (100 cm in diameter, 35 cm in height) where light does not shine in the water and fill the water with a temperature of 22-25 ° C. up to 1 cm above the evacuation table, and put the non-toxic black food coloring (squid ink) so that the bottom is not visible. made. The circular water tank was divided into quarters and markers were recognized at each location (N, W, E and S). The training was conducted for a total of seven days, beginning with a sign of water on the wall of the other quadrant each day. At this time, the eyes of the animal are directed toward the underwater wall so that the inside of the tank is not visible, and then the distance and time from when the rat swims to find the evacuation zone is measured using the SMATR multi-function video tracking system (Panlap, Spain). It was measured and recorded as the learning grade of the trial. On the first day of the experiment, they were allowed to swim freely in the tank for 60 seconds without the escape pad. When the rats went up to find the escape, they gave a 30-second interval to learn the environment. If the rat could not find the escape after 120 seconds, the experimenter guided the mouse to the escape and allowed him to stay there for 30 seconds to remember the location of the escape. On day 7 of the experiment, the sheath was removed and the time and distance to stay in the quadrant containing the sheath was measured to determine working memory (n = 24, group 6 × 4 mice). At around 11 am on the 8th day of training, the experimental group received the same amount of corn, the positive control tacrine group (10 mg / kg, dissolved in saline), the control group and the scopolamine group orally administered the same amount of corn oil. In order to induce memory impairment, scopolamine (dissolved in 0.8 mg / kg saline, ip) was administered to the control group one hour after the injection of the same amount of saline.

Manual Evasion Experiment Passive avoidance test Memory measurement by

A manual avoidance system (GEMINI avoidance system, SD instrument, USA) was used to measure the memory capacity of experimental animals. In the middle of the device, there were chambers of 24 × 20 × 20 cm on both sides with guillotine doors between them, and the bottom of each chamber was set with a grid to allow current to flow in a dark room. The experiment was conducted by dividing the acquisition type (acquisitional trial) and the retention trial (retention trial). Acquisition experiments were conducted one day before the regeneration experiment. When the animal is placed in the left chamber, after 20 seconds of acclimatization, the left chamber is lit and at the same time the guillotine door is opened. At this time, due to the instinct to move to the dark part of the rat to move to the dark place, the rat (latency time) was measured in the dark box. As soon as the rat enters the dark room, the guillotine door closes, and a 1.0 ㎃ current flows through the bottom grid for 2 seconds to give an electric shock to the rat. When the white mouse is taken out and moved to the cage and after 24 hours, it is placed in a bright room again and the guillotine door is opened. Acquisition of the experimental animals after the probe test in water maze at about 11 am on the experimental day, the experimental group was a single substance of the corresponding concentration, the positive control tacrine group (soluble in 10 mg / kg saline), and the control group and the scopolamine group were the same amount of corn. After 30 minutes, oral milk was administered. In order to cause memory impairment, scopolamine (dissolved in 0.8 mg / kg saline, ip) was administered to the control group one hour after the injection of the same amount of saline. After 1 hour of intraperitoneal injection, the mice were placed in a bright chamber, and the time of staying in the bright area (maximum 300 seconds, cut off time) was measured (n = 24, group 6 × 4 mice). After 24 hours, the rats were placed in the bright chamber again, and the regeneration experiment was performed to measure the length of time that the animals stayed in the bright chamber as an index of memory.

Microdialysis , Nano - SPECT  Evaluation of Memory Enhancement Efficacy of Three Single Substances Using Image in vivo )

The rats used in this experiment were Sprague-Dauri and 6-week-old males (weight 190-210 g) were purchased from Orient (Gyeonggi-do, South Korea) and had a period of acclimation for 7 days in the nursery. Two experimental animals were raised per cage, and the environment of the cage was maintained at a temperature of 21 ± 2 ℃ and a relative humidity of 55 ± 10%. Contrast was kept constant over a 12 hour period (from 8 am to 8 pm). Solid feed and water were freely consumed during the experiment. After the adaptation period, each group was separated into experimental and control groups by the ingot method.

Microdialysis Microdialysis in vivo )

Experimental animals (male Sprague-Dawley rats, 250-300 g) were anesthetized with zoletin (50 mg / kg, ip) and lumps, and then sterile in accordance with the atlas of Paxinos and Watson (1986) by aseptic methods. (striatume, stereotactic coordinates: AP 1.2 L -2.6 for bregma, H 4.2 for the dural, Fig. 14a) was inserted into the guide tube and fixed using a microscrew and dental cement. After 24 hours of recovery, the experimental animals were inserted with a 3 mm vertical microdialysis probe (CMA-12, Carnegie-Medicin, Stockholm, Sweden) through an induction tube. The inlet of the microdialysis probe is connected to a syringe mounted in a perfusion pump via a double liquid rotary ring, through which Ringer's solution (147 mM NaCl, 1.2 mM CaCl ₂ , 2.7 mM KCL, 1.0 mM MgCl ₂ ; pH 7.4) is introduced. Three basal dialysates and six samples after drug administration were collected at 30-minute intervals using a Carnegie-Medicin connected to the probe outlet while injecting at 1.0 μl / min (FIG. 14B). Data analysis calculated the average value (control) of three basal dialysates as 100 and then presented the change values (% control) for them in graphs and tables.

After the experiment, deep anesthesia was induced with pentobarbital, and the brain was removed after perfusing the experimental animals with saline and 10% formalin solution through the heart. The removed brain was stored in a 10% formalin solution for at least 2 weeks, and then the tissue at the site of the microdialysis probe was cut to a thickness of 50 μm to confirm the position of the probe by hematoxylin staining.

Treatment of three single substances and control drugs

Three single substances were dissolved in physiological saline containing DMSO and administered intraperitoneally to SD rats (n = 3) at a concentration of 50 mg / kg curcumin, 20 mg / kg dimethoxycurcumin and 100 mg / kg naxazole. After that, microdialysis was performed. In addition, the effects of natural products were evaluated using rivastigmine (1.5 mg / kg), an acetylcholinesterase inhibitor (ACHI), which was previously used.

Chromatography Separation

The concentration of acetylcholine in the microdialysis sample was analyzed using a liquid chromatography (Acquity UPLC, waters, USA) -mass spectrometer (Quattro Premier XE, waters, USA): LC / MS / MS system. The dialysate was separated using a reversed-phase Waters UPLC BEH HILIC column (1.7 μm, 2.1 × 50 mm). The mobile phase used 20% ACN and 80% 20 mM ammonium formate over the total volume, and the flow rate of the system was 1.0 ml / min. For accurate analysis, 50 μl of acetylmethylcholine of 25 nM of internal standard was added to 30 μl of dialysate and analyzed by injection of a total of 80 μl of analyte.

Nano - SPECT  Using imaging equipment ¹⁸ F- CP118954  Habitat Image Evaluation

Image evaluation using Nano-SPECT (Bio-Scan) was performed using ¹⁸ F-CP118954. Each subject was injected intravenously in an amount of 0.5-0.8 mCi of isotope ( ¹⁸ F-CP118954). A simple image acquisition model is shown in FIG. 15. Before injection the ¹⁸ F-CP118954 30 minutes, to injection through intraperitoneal a single substance or a control substance. ¹⁸ F-CP118954 Images are taken for one hour immediately after injection. Acquired images were analyzed using PMOD software (PMOD Technologies Ltd) and normalized using the cerebellar ¹⁸ F-CP118954 binding in the background.

Results and Discussion

In the Java  Separated single substance AChE  In vitro inhibitory activity assay

The evaluation of AChE inhibitory activity of six substances, extracts and fractions isolated from Java turmeric was presented in Tables 2 and 3. Inhibitory activity was best in dimethoxycurcumin and curcumin, and activity was not detected in zedoarondol and zedoalacton B. Xanthorrizoside A and 1,5-bis (4-hydroxy-3-methoxyphenyl) -1,4-pentadiene-3-one (1,5-bis (4-hydroxy-3- Inhibitory activity of methoxyphenyl) -1,4-pentadien-3-one) was insignificant. Based on the AChE activity analysis results of the first single substance, animal behavior experiments of curcumin, dimethoxycurcumin, and naxazole were determined.

 % AChE inhibition Curcumin Deoxycurcumin Islands Aaron Dior IslandsAlacton B Nagging Research A AChE inhibitory activity
IC ₅₀ ([mu] g / ml) 316.38 194.00 NA NA 2630.11

AChE inhibition rate (%) 1,5-bis (4-hydroxy-3-methoxyphenyl) -1,4-pentadiene-3-one MeOH Extract The EtOAc fraction BuOH fraction H ₂ O fraction AChE inhibitory activity
IC ₅₀ ([mu] g / ml) 1313.22 396.82 459.69 754.28 NA

Morris Underwater maze  Measure

The results of the three experiments with Morris underwater maze are shown in FIGS. 16 to 17. The training period for finding the targets of the experimental animals was carried out for a total of 7 days, and four times a day, they were obtained from different areas and trained to find the targets. The test was performed on the 8th day of training and on the 7th day of the training, only the test animals that were less than 30 seconds for the test animals to visit the target were selected for the probe test.

The number of crossings of the shelters is shown in FIG. 17. Although the evacuation zone was removed, the number of times that the existing location was remembered and crossed was the control group (8.75), the scopolamine group (4), the tacrine group (4.75), the curcumin group (9), and the dimethoxycurcumin group (6.25). And the nagging sol group (8.5), remembering the location of the existing shelter of the scopolamine group, the smallest number of crossings (4), and the number of curcumin and nagging sol among the single substances was similar to the control group, but there was no significant difference. Did.

In the model that induced memory impairment with scopolamine, we tested the effect of memory improvement through the experiment with Morris underwater maze, and the curcumin and naxorisol administration group recognized and repeated the position of the escape zone on the underwater maze during the 7 days cognitive training. Although the tendency to remember spatial perception was confirmed through continuous training, the lack of dog breeding of experimental animals did not show any significant result. In the future, an experiment is underway to increase the number of dogs.

Manual Evasion Experiment Passive avoidance test Memory measurement by

Manual evacuation experiments were performed to evaluate the efficacy of scavenging amines to alleviate memory impairment in the three isolates of single turmeric. The average crossing time of the experimental animals in the acquisition test was about 16 seconds, and when the chamber was turned on, it was confirmed that the animals moved quickly to the dark chamber. Regeneration test was performed 24 hours after the 1 mA electric shock. The crossover time of each group was control group (156.25 seconds), scopolamine group (12.6 seconds), tacrine group (52.05 seconds), curcumin group (44.8 seconds), dimethoxycurcumin group (35.48 seconds), and naxolizol group (41.45 seconds). ). Compared with the control group, the crossover time was significantly reduced in the scopolamine group in which memory impairment was induced, resulting in memory impairment caused by scopolamine. In the oxycurcumin group and the nagging sol group, the crossover time was longer than that of the scopolamine group, and alleviation of memory impairment was confirmed. However, no significant difference was shown, and the number of dogs was increased in the future (Fig. 18).

Analysis of Increased Acetylcholine Concentration Using Microdialysis

Microdialysis was performed in thalamus to measure changes in acetylcholine. Changes in acetylcholine by the drug are expressed as a percentage of baseline (baselinel: 100%) of the mean value of acetylcholine concentrations in the last three samples collected immediately before the experimental treatment. The results showed that 1.5 mg / kg of rivastigmine was administered as a single intraperitoneal injection (ip) to measure changes in acetylcholine in thalamic dialysate. The value was increased and lasted 129% until 60 minutes (Table 4). In addition, curcumin was increased by 122.5% compared to the base value when 50 mg / kg treatment was administered, the dimethoxy curcumin 20 mg / kg 161.1%, nagging sol 100 mg / kg treatment showed an increase of 131.1%.

- Time (minutes) -60 -30 0 30 60 90 120 150 180 Ribastigin
(+) Control 103.3 ± 4.7 101.6 ± 7.8 96.1 ± 10.4 147.8 ± 45.5 129.1 ± 13.8 80.6 ± 19.6 86.7 ± 5.7 96.7 ± 4.7 80.0 ± 4.9 Curcumin 98.8 ± 30.5 98.8 ± 10.9 103.2 ± 20.8 122.5 ± 6.3 97.0 ± 17.6 100.3 ± 26.6 89.5 ± 23.2 73.9 ± 24.1 - Dimethoxycurcumin 107.3 ± 9.4 92.7 ± 6.5 88.9 ± 15.7 161.2 ± 83.9 109.6 ± 9.7 103.2 ± 17.4 126.0 ± 31.3 125.5 ± 75.9 109.1 ± 25.6 Nagging 93.6 ± 10.1 99.9 ± 17.0 123.1 ± 7.8 131.7 ± 27.3 117.8 ± 12.5 113.0 ± 17.7 131.2 ± 19.9 122.1 ± 9.9 90.3 ± 43.2

Nano - SPECT  3 kinds of single substance using image Acetylcholine esterase  Binding inhibition effect

Nano-SPECT imaging experiments were performed to confirm the binding of two single substances to acetylcholine esterase. 19 is an image showing when the control (salin containing 10% DMSO) was treated. It was confirmed that the stratum (arrow) is clearly seen through the image, and the results of microdialysis confirmed the increase of acetylcholine by three single substances in the stratum, and the distinction of this region was clearly shown in the image. Designated as an area. In addition, the combination of ¹⁸ F-CP118954 in the cerebellum did not appear, so this area was determined as the reference area.

¹⁸ F-CP118954 30 minutes prior to the injection curcumin is 50 ㎎ / ㎏, dimethoxy tokki curcumin is 20 ㎎ / ㎏, xanthorrhizol was diluted with intraperitoneal injection of physiological saline dissolving 100 ㎎ / ㎏ in DMSO. ¹⁸ F-CP118954 Implants were acquired for 1 hour and analyzed for 60 minutes. The CT and PET images were used to determine the stratum and cerebellar regions, and then normalized to the cerebellum. The results were shown in FIG. 19. In the case of 50 mg / kg curcumin, 20 mg / kg dimethoxycurcumin and 100 mg / kg naxazole, the binding of ¹²³ I-A85380 was reduced by 30% compared to the control group, which was statistically significant at 0.05 level. Showed. The reduction in binding of ¹⁸ F-CP118954 at this stratum can indirectly demonstrate that the three single materials bind to acetylcholine esterase. This can be explained through the image that the inhibition of acetylcholine esterase finally increases the concentration of acetylcholine at the synapse by interfering with the decomposition of acetylcholine.

While the present invention has been particularly shown and described with reference to exemplary embodiments thereof, it is to be understood that the invention is not limited to the disclosed exemplary embodiments. Therefore, the substantial scope of the present invention will be defined by the appended claims and equivalents thereof.

Claims (8)

A composition for improving memory and learning ability, comprising at least one selected from the group consisting of extracts of Curcuma xanthorrhizae , curcumin, demethoxycurcumin, and xanthorrhizol.
A composition for preventing or treating cognitive disorders comprising at least one selected from the group consisting of extracts of Curcuma xanthorrhizae , curcumin, demethoxycurcumin, and xanthorrhizol.
The composition of claim 1 or 2, wherein the composition inhibits the activity of acetylcholinesterase.
The composition of claim 2, wherein the cognitive impairment is dementia, learning disability, blindness, forgetfulness, aphasia, executive or delirium.
The method of claim 2, wherein the cognitive dysfunction is AIDS-induced dementia, Vincewanger disease, Lewy body dementia, frontal temporal dementia, mild cognitive impairment, multiple infarct dementia, PEEK disease, semantic dementia, Alzheimer's dementia or vascular dementia Characterized by a composition.
A food composition for improving memory and learning ability, comprising at least one selected from the group consisting of extracts of Curcuma xanthorrhizae , curcumin, demethoxycurcumin, and xanthorrhizol.
(a) a therapeutically effective amount of the composition of any one of claims 1 to 2; And (b) pharmaceutical composition for preventing or treating cognitive dysfunction comprising a pharmaceutically acceptable carrier.
Food composition for preventing or improving cognitive dysfunction, including one or more selected from the group consisting of extract of Curcuma xanthorrhizae , curcumin, demethoxycurcumin and xanthorrhizol.

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