KR102545313B1 - Pharmaceutical composition for preventing or treating of synucleinopathies containing 1,5-Dicaffeoyl quinic acid as an active ingredient - Google Patents

Abstract

The present invention relates to a composition for preventing or treating synucleinopathy, containing 1,5-dicaffeoylquinic acid, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof as an active ingredient. Specifically, using 10% w / v brain homogenate (BH) from a sample (brain tissue) of a patient with dementia with Lewy bodies (DLB) through real-time inductive conversion analysis (RT-QuIC), 1, 5 - As a result of application of decaffeoylquinic acid from 25 uM to 0.78 uM (780 nM), abnormal aggregation of alpha-synuclein (formation and accumulation of amyloid of alpha-synuclein) is induced to be prevented from occurring, 1 of the present invention , 5-decaffeoylquinic acid, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof as an active ingredient can be usefully used for the treatment of synucleinopathy.

Description

Composition for preventing or treating synucleinopathy containing 1,5-dicaffeoylquinic acid or a pharmaceutically acceptable salt thereof as an active ingredient an active ingredient}

The present invention relates to a pharmaceutical composition for preventing or treating synucleinopathy, containing 1,5-dicaffeoylquinic acid or a pharmaceutically acceptable salt thereof as an active ingredient.

Alpha-synuclein is a well-conserved, unstructured, soluble protein of 140 amino acids and a molecular weight of 19 kDa that is mainly expressed in nervous tissue. It is located in high concentration at presynaptic nerve terminals in the central nervous system where it plays a role in synaptic vesicle biology. Alpha-synucleinopathy is associated with other neurodegenerative diseases known as various synucleinopathies, such as Parkinson's disease (PD), Dementia with Lewy bodies (DLB), and multiple system atrophy. (multiple system atrophy: MSA). It is caused by the deposition of phosphorylated, insoluble alpha-synuclein aggregates within selective populations of nerve cells (neurons) and glial cells (Burre J. The Synaptic Function of alpha-Synuclein. J Parkinsons Dis. 2015;5:699- 713.).

These depositions are within neuronal cells as Lewy bodies (LB) or in dystrophic neurites in diseases such as Parkinson'disease (PD) or Dementia with Lewy bodies (DLB); or in glial cytoplasmic inclusion bodies in multiple system atrophy (MSA).

In the case of a family history of Parkinson's disease or dementia with Lewy bodies, missense mutations in the genetic coding of alpha-synuclein are known.

Fibrillar alpha-synuclein aggregates are known to replicate native alpha-synuclein by disease-associated structure. Alpha-synuclein aggregates replicate and diffuse along neuroanatomically connected regions, resulting in a typical form of Lewy pathology in the diseased human brain.

The proliferation of prion-like alpha-synuclein fibrils is known to play an important role in the development and spread of alpha-synucleinopathy. Alpha-synuclein protein, originally thought to help signal transmission between nerve cells, aggregates in a pathological state and accumulates in brain cells to form insoluble fibrils, resulting in loss of nerve cells, resulting in motor and cognitive impairment.

Real-time inductive conversion analysis (RT-QuIC) is a highly sensitive biochemical assay for detecting pathogenic prion protein (PrP ^Sc ) in brain tissue and cerebrospinal fluid (CSF), and is one of the recently developed techniques in the prion field. .

The RT-QuIC technique is a diagnostic technique based on prion protein conversion reaction. It uses a biological sample from a suspected patient and uses human recombinant prion protein or Bank Vole prion protein as a substrate to amplify prion protein aggregates intermittently in multi-wells. By shaking, thioflavin T (Th T), a fluorescent substance that binds specifically between β-sheet structures, reacts. When mixing the patient's sample and the reaction solution and inducing a stirring reaction while maintaining a constant temperature, Th T binds to the resulting β-sheet structure to obtain a fluorescence value, and the value is measured in real time to determine whether pathogenic prion protein is formed and its It is a detection method that measures the degree of level (Saijo E, Groveman BR, Kraus A, et al. Ultrasensitive

RT-QuIC seed amplification assays for disease-associated Tau, alpha-synuclein, and prion aggregates. Methods Mol Biol. 2019;1873:19-37.).

Recently, by several groups, a modified RT-QuIC method has been successfully allowed to detect alpha-synucleinopathy, similar to the prion protein detection technique, alpha-synuclein real-time induction assay (a-syn RT-QuIC ), it was possible to determine whether a suspected patient could have a disease associated with the presence of aggregates of alpha-synuclein in tissue samples or bodily fluids.

The exact mechanisms by which accumulation of alpha-synuclein results in the hallmarks of neurodegeneration in synucleinopathy are not fully understood, but recent studies suggest that the abnormal formation and accumulation of alpha-synuclein is the degeneration underlying synucleinopathy. imply that it is related to the process. In addition, since alpha-synuclein is a major component constituting the Lewy body, there is great interest in developing a therapeutic agent capable of controlling amyloid formation/accumulation of alpha-synuclein and suppressing abnormal aggregation reactions. Among the therapeutic strategies for synucleinopathy are compounds that inhibit the aggregation of alpha-synuclein. In particular, low-molecular-weight cuminaldehyde has been found to inhibit fibrosis of alpha-synuclein. However, nothing is known about the relationship of 1,5-decaffeoylquinic acid to alpha-synuclein.

Accordingly, the present inventors found that 1,5-Dicaffeoyl quinic acid inhibits the prion protein aggregation reaction through the latest RT-QuIC technique using the ability of prion protein to induce autocatalytic growth As a result of applying it to the a-syn RT-QuIC technique, the abnormal aggregation reaction of alpha-synuclein (formation/accumulation of amyloid of alpha-synuclein) did not occur, which could be useful for the treatment of synucleinopathy. The present invention was completed by confirming that there is.

An object of the present invention is to provide a pharmaceutical composition for preventing or treating synucleinopathy, containing 1,5-dicaffeoylquinic acid, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof as an active ingredient.

Another object of the present invention is to provide a health functional food for preventing or improving synucleinopathy, containing 1,5-dicaffeoylquinic acid, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof as an active ingredient.

In order to achieve the above object, the present invention provides prevention or treatment of synucleinopathy containing 1,5-dicaffeoylquinic acid, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof represented by the following formula (1) as an active ingredient. A pharmaceutical composition is provided for:

[Formula 1]

.

.

In addition, the present invention provides a health functional food for preventing or improving synucleinopathy containing 1,5-dicaffeoylquinic acid represented by Formula 1, a stereoisomer thereof or a pharmaceutically acceptable salt thereof as an active ingredient. to provide.

The present invention relates to a pharmaceutical composition for preventing or treating synucleinopathy containing 1,5-dicaffeoylquinic acid, a stereoisomer thereof or a pharmaceutically acceptable salt thereof as an active ingredient, 5-decaffeoylquinic acid can not only inhibit the formation and accumulation of alpha-synuclein in amyloid, but also induce abnormal aggregation of alpha-synuclein aggregates contained in biological samples, preventing synucleinopathy. And it can be usefully used for therapeutic purposes.

1 is a diagram analyzing the RT-QuIC reaction of a 1,5-dicaffeoylquinic acid compound to brain homogenate (BH) from animals with bovine spongiform encephalopathy (BSE).
Figure 2 is a diagram analyzing the a-syn RT-QuIC response to BH from patients with dementia with Lewy bodies (DLB) and patients without evidence of neuropathological disease as a control group.
Figure 3 shows the a-syn RT-QuIC reaction of alpha-synuclein aggregate inhibition according to natural product (A), natural product (B), and natural product (B) related compound treatment for BH from patients with dementia with Lewy bodies (DLB). It is also confirmed by
Figure 4 is a diagram analyzing the degree of amyloid inhibition of alpha-synuclein according to the 1,5-dicaffeoylquinic acid compound treatment by concentration by a-syn RT-QuIC reaction.

Hereinafter, the present invention will be described in detail.

The present invention provides a pharmaceutical composition for preventing or treating synucleinopathy, containing 1,5-dicaffeoylquinic acid, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof represented by Formula 1 below as an active ingredient. :

[Formula 1]

The 1,5-dicaffeoylquinic acid can inhibit the formation or accumulation of amyloid of alpha-synuclein or eliminate the deposition of fibrous aggregates of alpha-synuclein.

The synucleinopathy refers to diseases that form Lewy bodies, which are abnormal protein aggregates that develop in nerve cells of patients with Parkinson's disease (PD), Lewy body dementia, and other disorders, and synucleinopathy includes Parkinson's disease. It can include Parkinson's disease (PD), Dementia with Lewy bodies (DLB) or multiple system atrophy (MSA). The major protein aggregates in Lewy bodies are composed of alpha-synuclein.

Alpha-synuclein (a-syn) is a small, well-conserved acidic protein with 140 amino acids and a molecular weight of 19 kDa, encoded by the SNCA gene located on chromosome 4. It is a protein abundant in the human brain, and small amounts are also found in the heart, muscle and other tissues. In the brain, α-synuclein is mainly found at the end of nerve cells (neurons) with a special structure called presynaptic terminals. Within this structure, alpha-synuclein interacts with phospholipids and proteins.

The present invention may include 1,5-dicaffeoylquinic acid represented by Formula 1, a stereoisomer thereof or a pharmaceutically acceptable salt thereof, as well as possible solvates and hydrates that may be prepared therefrom. .

It can also be prepared by heating equal amounts of 1,5-decaffeoylquinic acid represented by Formula 1 and an acid or alcohol in water, then evaporating and drying the mixture, or suction filtering the precipitated salt.

In addition, a pharmaceutically acceptable metal salt may be prepared using a base. Alkali metal or alkaline earth metal salts are obtained, for example, by dissolving 1,5-decaffeoylquinic acid in an excess alkali metal hydroxide or alkaline earth metal hydroxide solution, filtering out the undissolved compound salt, and evaporating and drying the filtrate. . At this time, it is pharmaceutically suitable to prepare sodium, potassium or calcium salts as metal salts. In addition, the corresponding silver salt is obtained by reacting an alkali metal or alkaline earth metal salt with a suitable silver salt (eg, silver nitrate).

In a specific embodiment of the present invention, the present inventors screened 1,5-decaffeoylquinic acid and found that the compound was administered at a level of 12.5 uM to 4 uM in the brain lysate (BH) of animals with bovine spongiform encephalopathy (BSE). It was confirmed that the prion protein aggregate (RT-QuiC) reaction of the 5-dicaffeoylquinic acid compound did not occur (see FIG. 1). In addition, the a-syn RT-QuIC aggregation response to the brain lysate (BH) of patients with dementia with Lewy bodies (DLB) had a much lower and longer maximum induction period in the seeded reactions ranging from 10 ^-7 to 10 ^-8 , but 10 ^-8 diluted concentration gave a-syn positive reaction (see Fig. 2).

In addition, inhibition of aggregation was confirmed by applying a-syn RT-QuIC to 3 selected substances (2 natural products and 1 compound) inhibiting autocatalytic growth in vitro (see FIG. 3).

Finally, as a result of applying a-syn RT-QuIC from 25 uM to 0.78 uM (780 nM) of the compound 1,5-dicaffeoylquinic acid, which was confirmed to have an a-syn aggregation inhibitory reaction, It was confirmed that abnormal aggregation of alpha-synuclein did not occur in the brain lysate (BH) mixed seeding reaction (see FIG. 4).

Therefore, since 1,5-dicaffeoylquinic acid prevents abnormal aggregation of alpha-synuclein (formation and accumulation of amyloid of alpha-synuclein), 1,5-dicaffeoylquinic acid of the present invention or its A composition containing a pharmaceutically acceptable salt as an active ingredient can be usefully used for the treatment of synucleinopathy.

The pharmaceutical composition may contain 0.0001 to 10% by weight of 1,5-dicaffeoylquinic acid, a stereoisomer thereof or a pharmaceutically acceptable salt thereof according to the present invention, which is an active ingredient, based on the total weight of the pharmaceutical composition. there is. In addition, the pharmaceutical composition of the present invention may further contain at least one active ingredient exhibiting the same or similar function in addition to the above active ingredient.

The composition of the present invention may also include a carrier, diluent, excipient or a combination of two or more commonly used in biological preparations. The pharmaceutically acceptable carrier is not particularly limited as long as it is suitable for in vivo delivery of the composition, for example, Merck Index, 13th ed., Merck & Co. Inc., saline, sterile water, Ringer's solution, buffered saline, dextrose solution, maltodextrin solution, glycerol, ethanol, and one or more of these components may be mixed and used, and if necessary, an antioxidant, buffer or bacteriostatic agent Other conventional additives may be added.

When formulating the composition, it is prepared using diluents or excipients such as commonly used fillers, extenders, binders, wetting agents, disintegrants, and surfactants. Furthermore, it can be preferably formulated according to each disease or component by using an appropriate method in the art or by using a method disclosed in Remington's Pharmaceutical Science (Mack Publishing Company, Easton PA, 18th, 1990).

The composition of the present invention may be formulated as an oral preparation or parenteral preparation. Solid preparations for oral administration include tablets, pills, powders, granules and capsules, etc. These solid preparations contain at least one excipient such as starch, calcium carbonate, sucrose or lactose in one or more compounds. It can be prepared by mixing lactose, gelatin, etc. Lubricants such as magnesium stearate and talc may also be added. On the other hand, liquid formulations include suspensions, internal solutions, emulsions, syrups, and the like, which may include excipients such as wetting agents, sweeteners, aromatics, and preservatives.

Formulations for parenteral administration may include sterilized aqueous solutions, non-aqueous solutions, suspension solutions, emulsions, lyophilized formulations or suppositories. Propylene glycol, polyethylene glycol, vegetable oils such as olive oil, and injectable esters such as ethyl oleate may be used as non-aqueous solvents and suspending agents. As a base for the suppository, witepsol, macrogol, tween 61, cacao butter, laurin paper, glycerol or gelatin may be used.

The composition of the present invention may be administered orally or parenterally, depending on the desired method, and parenteral administration is external skin or intraperitoneal injection, rectal injection, subcutaneous injection, intravenous injection, intramuscular injection or intrathoracic injection injection method. can be selected from

A composition according to the present invention is administered in a pharmaceutically effective amount. This may vary depending on the type of disease, severity, activity of the drug, sensitivity to the drug, administration time, route of administration, excretion rate, duration of treatment, and concurrently used drugs. However, for desirable effects, the daily dosage of the pharmaceutical composition according to the present invention may be 0.0001 to 10 mg/ml, specifically 0.0001 to 5 mg/ml. The administration may be once a day, or may be divided into several times. The compositions of the present invention may be administered alone or in combination with other therapeutic agents. When administered in combination, administration can be sequential or simultaneous.

In addition, the present invention provides a health functional food for preventing or improving synucleinopathy, containing 1,5-dicaffeoylquinic acid, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof as an active ingredient.

1,5-dicaffeoylquinic acid, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof of the present invention may be added to food as it is or used together with other food or food ingredients. At this time, the content of the active ingredient added may be determined according to the purpose. In general, the content in the health functional food may be 0.01 to 90 parts by weight of the total food weight.

In addition, there is no particular limitation on the shape and type of the health functional food. The form of health functional food to which the above substances can be added may be tablets, capsules, powders, granules, liquids and pills.

The health functional food of the present invention may contain various flavoring agents or natural carbohydrates as additional components like normal health functional foods. The aforementioned natural carbohydrates include monosaccharides such as glucose and fructose, disaccharides such as maltose and sucrose, polysaccharides such as dextrin and cyclodextrin, and sugar alcohols such as xylitol, sorbitol, and erythritol. As the sweetener, natural sweeteners such as thaumatin and stevia extract, or synthetic sweeteners such as saccharin and aspartame may be used.

In addition to the above, the health functional food of the present invention includes various nutrients, vitamins, electrolytes, flavors, colorants, pectic acid and its salts, alginic acid and its salts, organic acids, protective colloidal thickeners, pH adjusters, stabilizers, preservatives, glycerin, It may contain alcohol and the like. These components may be used independently or in combination. The ratio of these additives may be selected in the range of 0.01 to 0.1 part by weight per 100 parts by weight of the composition of the present invention.

Hereinafter, the present invention will be described in detail by the following examples.

However, the following examples are merely illustrative of the present invention, and the content of the present invention is not limited thereto.

<Example 1> Preparation of 1,5-dicaffeoylquinic acid compound

A single compound, 1,5-dicaffeoylquinic acid, was dissolved in dimethyl sulfoxide (DMSO) at a concentration of 10 mM and stored at -20°C until use.

<Experimental Example 1> Prion protein aggregate (RT-QuIC) reaction of 1,5-dicaffeoylquinic acid compound to brain lysate (BH) of bovine spongiform encephalopathy (BSE) animals

Detection method of pathogenic prion protein in brain lysate (BH) of animals with Bovine spongiform encephalopathy (BSE) by RT-QuIC, reacting with recombinant Bank vole protein 0.1 mg/㎖ (Impact biologicals) 98 μl of the solution (5X PBS, 300 mM NaCl, 100 mM EDTA, 1 mM ThT) was dispensed into a black 96-well plate with a clean bottom, and 2 μl of BH was mixed therein, followed by seeding to a final reaction volume of 100 μl. Cover the plate with sealing tape and insert it into a FLUO star Omega plate reader (BMG Labtech) using an intermittent shaking cycle (1 minute shaking (700 rpm), 1 minute rest) for 61 hours and 50 minutes at 42℃. React for 250 cycles. ThT fluorescence values were measured in real time every 15 minutes at 440 nm (excitation) and 480 nm (emission) wavelengths. One negative control sample, one positive control and 4 concentrations of compound treated samples to be tested on one plate were allowed.

Specifically, 1,5-dicaffeoylquinic acid prepared in <Example 1> at a concentration of 4 uM, 5 uM, 6.25 uM or 12.5 uM was added to each well on a 96-well plate.

As a result, as shown in FIG. 1, the concentration of 1,5-dicaffeoylquinic acid compound from 12.5 uM to 4 uM level in the brain disruption fluid (BH) of animals suffering from bovine spongiform encephalopathy (BSE). It was confirmed that no prion protein aggregate (RT-QuIC) reaction occurred.

<Experimental Example 2> Alpha-synuclein real-time inductive conversion analysis (a-syn RT-QuIC) for brain lysate (BH) of patients with dementia with Lewy bodies (DLB)

Brain tissue from a patient with dementia with Lewy body (DLB) was provided by the Edinburgh Brain and Tissue Bank (EBTB, Edinburgh, UK). Additionally, brain tissues were also obtained from individuals without neurodegenerative diseases. Ethical approval for the use of brain samples from the Edinburgh Brain and Tissue Bank was guaranteed by the Research Ethics Committee of the Korea Brain Research Institute. An initial 10% w/v brain lysate was prepared using phosphate buffered saline (PBS) containing complete protease inhibitor and phosphatase inhibitor cocktails from Roche. It was centrifuged at 2000 x g for 2 minutes, and the supernatant was collected, stirred, and stored at -80°C prior to analysis.

RT-QuIC reaction buffer (RB) consisted of 100 mM phosphate buffer (pH 8.2), 10 uM ThT and 0.1 mg/ml human recombinant full length (1-140aa) alpha-synuclein (rPeptide). Each well of a clear-bottomed black 96-well plate contained 98 μl RB (depending on the volume of seeds added) and 4 glass beads 1.0-1.25 mm in diameter. Reactions were seeded with 2 μl of working strength brain lysate (BH) to a final reaction volume of 100 μl. Cover the plate with sealing tape, and insert it into a FLUO star Omega plate reader (BMG Labtech) using an intermittent shaking cycle (1 minute shaking (400 rpm), 2 orbits using 1 minute break) for 72 hours and 30 minutes at 37℃. Reacted for 250 cycles. ThT fluorescence values were measured in real time once every hour at 440 nm (excitation) and 480 nm (emission) wavelengths.

The alpha-synuclein real-time inductive conversion analysis (a-syn RT-QuIC) used above was designed and modified by Dr A. Green (2016) at the University of Edinburgh, UK, and Dr B, Caughey (2018) at the US National Institutes of Health. It is the most up-to-date technique.

As a result, as shown in FIG. 2, frontal lobe brain fragment (BH) from a patient with a clinical pathological diagnosis of dementia with Lewy body (DLB) and frontal lobe brain fragment from a patient without neuropathological evidence. (BH) was used as a control, and the study of a-syn RT-QuIC was performed. Brain lysate (BH) from patients with dementia with Lewy body (DLB) ranged from 10 ^-3 to 10 ^-6 The RT-QuIC reaction seeded at the diluted concentration had a plateau of 20 hours, after which the increase in ThT fluorescence signal appeared to be maximum at 70 hours. Reactants seeded in the 10 ^-7 to 10 ^-8 range of brain lysate (BH) from patients with dementia with Lewy body (DLB) have much lower and longer maximum induction periods, but up to 10 ^-8 diluted concentrations a -syn gave a positive reaction. Reactants seeded with brain lysate (BH) from patients with controls did not give a positive response under the same conditions.

<Experimental Example 3> Confirmation of inhibition of alpha-synuclein aggregation by treatment with 1,5-dicaffeoylquinic acid compound in brain lysate (BH) of patients with dementia with Lewy bodies (DLB)

<3-1> Confirmation of inhibition of aggregation through a-syn RT-QuIC using substances that inhibit autocatalytic growth in vitro

Using the alpha-synuclein real-time inductive conversion analysis (a-syn RT-QuIC) technique established in <Experimental Example 2>, the selected natural product (A), natural product (B), and natural product (B) related compounds were treated. In order to study whether or not it interferes with the a-syn aggregation reaction induced by , an experiment was performed using lysate (BH) of the frontal lobe brain of a patient with dementia with Lewy bodies (DLB) as follows.

Specifically, a brain emulsion (DLB BH; 10 ^-4 ) derived from a patient with Lewy body dementia and two natural products and one compound-treated sample to be tested on one plate were compared at a single concentration.

As a result, as shown in FIG. 3, the RT-QuIC reaction seeded with brain lysate (BH) from a patient with dementia with Lewy bodies (DLB) at a dilution concentration of 10 ^-4 has a plateau of 20 hours, after which ThT fluorescence The increase in signal was found to be maximum at 70 hours. It was confirmed that the a-syn aggregation reaction was hindered in the reaction mixture seeded by mixing brain lysate (BH) from a patient with dementia with Lewy bodies (DLB) and natural products A and B, respectively. In addition, in the case of the compound related to natural product B, no a-syn-positive reaction was provided in a mixed seeding reaction with brain lysate (BH) from a patient with dementia with Lewy bodies (DLB).

<3-2> Confirmation of interference with alpha-synuclein aggregation of 1,5-dicaffeoylquinic acid compounds

In order to determine whether the 1,5-dicaffeoylquinic acid compound interferes with alpha-synuclein aggregation, an experiment was conducted by applying 1,5-dicaffeoylquinic acid to a-syn RT-QuIC applied in <Experimental Example 2> performed. 1 negative control sample, 4 positive control samples (ranging from 10 ^-4 to 10 ^-7 of brain lysate (BH) from dementia with Lewy bodies (DLB)) samples and 5 concentrations of compound treatment to be performed on one plate. sample was used.

Specifically, 0.78 uM, 1.56 uM, 3.125 uM, 6.25 uM or 12.5 uM of 1,5-dicaffeoylquinic acid prepared in <Example 1> was added to each well on a 96-well plate.

As a result, as shown in FIG. 4, 1,5-dicaffeoylquinic acid was applied from 25 uM to 0.78 uM (780 nM) level, and brain disruption fluid (BH) mixed seeding reaction from patients with dementia with Lewy bodies (DLB) It was confirmed that abnormal aggregation of alpha-synuclein, that is, formation and accumulation of amyloid of alpha-synuclein did not occur.

As described above, since 1,5-dicaffeoylquinic acid prevents abnormal aggregation of alpha-synuclein (formation and accumulation of amyloid of alpha-synuclein), 1,5-dicaffeoylquinic acid of the present invention A composition containing nic acid or a pharmaceutically acceptable salt thereof as an active ingredient can be usefully used for the treatment of synucleinopathy.

Claims (8)

A pharmaceutical composition for the prevention or treatment of dementia with Lewy bodies containing 1,5-dicaffeoyl quinic acid represented by Formula 1 below or a pharmaceutically acceptable salt thereof as an active ingredient :
[Formula 1]

.
The pharmaceutical composition for preventing or treating dementia with Lewy bodies according to claim 1, wherein the compound inhibits amyloid formation or accumulation of alpha-synuclein.
The pharmaceutical composition for preventing or treating dementia with Lewy bodies according to claim 1, wherein the compound inhibits an abnormal aggregation reaction of alpha-synuclein.
delete Health functional food for preventing or improving dementia with Lewy bodies containing 1,5-Dicaffeoyl quinic acid represented by Formula 1 below or a pharmaceutically acceptable salt thereof as an active ingredient :
[Formula 1]

.
[Claim 6] The functional food for preventing or improving dementia of Lewy bodies according to claim 5, wherein the compound inhibits the formation or accumulation of amyloid of alpha-synuclein.
The health functional food for preventing or improving dementia of Lewy bodies according to claim 5, wherein the compound inhibits the abnormal aggregation reaction of alpha-synuclein.
The method of claim 5, wherein the synucleinopathy is Parkinson'disease (PD), Dementia with Lewy bodies (DLB) or multiple system atrophy (MSA), of Lewy body dementia. Health functional food for prevention or improvement.

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