KR20240067803A - Composition for preventing or treating Parkinson's disease comprising shogaol and levodopa as active ingredients - Google Patents

Abstract

The present invention relates to a composition for the prevention or treatment of Parkinson's disease containing shogaol and levodopa as active ingredients. Shogaol of the present invention, when administered in combination with levodopa in an animal model of Parkinson's disease, enhances the efficacy of levodopa. It was confirmed that the intestinal motility disorder induced by levodopa was improved while maintaining the effect. In addition, it was confirmed that it can suppress the expression of TH (tyrosine hydroxylase) and DAT (dopamine transporter) in the striatum and the aggregation of α-syn in the DMV, the brain stem. In addition, the increase in the amount of dopamine in plasma induced by levodopa is further increased by the combined use of shogaol, so it can be usefully used in related industries.

Description

Composition for preventing or treating Parkinson's disease comprising shogaol and levodopa as active ingredients}

The present invention relates to a composition for preventing or treating Parkinson's disease containing shogaol and levodopa as active ingredients.

Parkinson's disease is a chronic progressive neurological disease and is one of the representative incurable diseases. Parkinson's disease occurs when cells that produce the neurotransmitter dopamine suddenly degenerate or greatly decrease in number in the substantia nigra area of the midbrain. The cause has not yet been specifically identified, but it is known to be involved in cerebral arteriosclerosis, carbon monoxide poisoning, drugs, metabolic aftereffects of traumatic encephalitis caused by hypoparathyroidism, etc. As the neurotransmitter dopamine decreases, the balance of the entire neurotransmitter system is disrupted, resulting in tremor, rigidity, bradykinesia, and postural instability, which are typical symptoms of Parkinson's disease. Symptoms such as:

As drugs for the treatment of Parkinson's disease, L-DOPA preparations, dopamine receptor agonists, anticholinergic drugs, Eldepryl (Eldepryl=depreyl), etc. are known, and most of these drugs control symptoms rather than treating the cause. It plays a role, and therefore requires constant and continuous administration of the drug. However, long-term administration of these drugs causes problems with drug side effects. For example, anticholinergic drugs have limitations in continuously administering them to elderly patients because they may cause abnormalities in the autonomic nervous system or mental function. In addition, in the case of L-dopa preparations, the effectiveness gradually decreases when taken over a long period of time, and side effects such as body distortion and abnormal movement of hands or feet occur on their own. In particular, dopamine-induced dyskinesia induced by dopamine therapy such as L-dopa preparations is a symptom that appears in 90% of Parkinson's disease patients treated with dopamine therapy, and it can be used to suppress or suppress Parkinson's disease while reducing the side effects of taking L-dopa preparations. There is a need for effective therapy for treatment.

Meanwhile, shogaol, one of the ingredients that gives ginger its spicy taste, has the chemical formula C ₁₇ H ₂₄ O ₃ and has been reported to have anticancer and antioxidant effects and inhibit the growth of nervous system tumor cells. In particular, the two ingredients gingerol and shogaol remove free radicals before genes are damaged by free radicals. In other words, ginger has an excellent antioxidant effect that removes free radicals, has an anticancer effect by blocking gene damage caused by free radicals, and has antipyretic, analgesic, and strong anti-inflammatory effects. In addition, gingerol and shogaol have the function of calming the central nervous system and stimulating the gastric mucosa to increase gastric juice secretion, promote digestion, and suppress vomiting. Shogaol has a stronger anti-inflammatory and analgesic effect than gingerol, making it effective for arthritis. Additionally, ginger ingredients such as gingerol and shogaol are known to have a strong bactericidal effect.

Accordingly, the present inventors confirmed that shogaol can increase the anti-Parkinsonian effect of levodopa when administered in combination with levodopa, and completed the present invention.

The purpose of the present invention is to provide a pharmaceutical composition for the prevention or treatment of Parkinson's disease, comprising a compound represented by the following formula (1) or a pharmaceutically acceptable salt thereof and levodopa as active ingredients: .

[Formula 1]

Another object of the present invention is to provide a food composition for preventing or improving Parkinson's disease, comprising the compound represented by Formula 1 or a pharmaceutically acceptable salt thereof and levodopa as active ingredients.

In order to achieve the above object, the present invention provides a pharmaceutical for the prevention or treatment of Parkinson's disease, comprising a compound represented by the following formula (1) or a pharmaceutically acceptable salt thereof and levodopa as active ingredients. A composition is provided.

[Formula 1]

Additionally, the present invention provides a food composition for preventing or improving Parkinson's disease, comprising the compound represented by Formula 1 or a pharmaceutically acceptable salt thereof and levodopa as active ingredients.

The present invention relates to a composition for the prevention or treatment of Parkinson's disease containing shogaol and levodopa as active ingredients. Shogaol of the present invention, when administered in combination with levodopa in an animal model of Parkinson's disease, enhances the efficacy of levodopa. It was confirmed that the intestinal motility disorder induced by levodopa was improved while maintaining the effect. In addition, it was confirmed that it can suppress the expression of TH (tyrosine hydroxylase) and DAT (dopamine transporter) in the striatum and the aggregation of α-syn in the DMV, the brain stem. In addition, the increase in the amount of dopamine in plasma induced by levodopa is further increased by the combined use of shogaol, so it can be usefully used in related industries.

Figure 1 schematically illustrates the experimental process to confirm the effect of the combined use of shogaol and levodopa of the present invention.

Hereinafter, embodiments of the present invention will be described in detail with reference to the attached drawings. In the following description, detailed descriptions of techniques well known to those skilled in the art may be omitted. Additionally, when describing the present invention, if it is determined that a detailed description of a related known function or configuration may unnecessarily obscure the gist of the present invention, the detailed description may be omitted. In addition, the terminology used in this specification is a term used to appropriately express preferred embodiments of the present invention, and may vary depending on the intention of the user or operator or the customs of the field to which the present invention belongs.

Therefore, definitions of these terms should be made based on the content throughout this specification. Throughout the specification, when a part is said to “include” a certain element, this means that it may further include other elements rather than excluding other elements, unless specifically stated to the contrary.

The present invention provides a pharmaceutical composition for preventing or treating Parkinson's disease, comprising a compound represented by the following formula (1) or a pharmaceutically acceptable salt thereof and levodopa as active ingredients.

[Formula 1]

The term "pharmaceutically acceptable salt" means that, within the scope of sound medical judgment, it is intended for use in contact with the tissues of humans and lower animals without undue toxicity, irritation, allergic reactions and the like, and in a reasonable advantage/disadvantage ratio. These salts are meant to be proportional. For example, S. M. Berge et al. describe pharmaceutically acceptable salts in detail in J. Pharmaceutical Sciences, 1977, 66, 1-19, which is incorporated herein by reference. Pharmaceutically acceptable salts of the compounds of the present invention include those derived from suitable inorganic and organic acids and bases. Examples of pharmaceutically acceptable, non-toxic acid addition salts include those formed with inorganic acids such as hydrochloric acid, hydrobromic acid, phosphoric acid, sulfuric acid and perchloric acid, or organic acids such as acetic acid, oxalic acid, maleic acid, tartaric acid, citric acid, succinic acid or malonic acid, or It is a salt of an amino group formed using other methods used in the art, such as ion exchange. Other pharmaceutically acceptable salts include adipate, alginate, ascorbate, aspartate, benzenesulfonate, benzoate, bisulfate, borate, butyrate, camphorate, camphorsulfonate, citrate, and cyclopentaneprop. Cypionate, digluconate, dodecyl sulfate, ethanesulfonate, formate, fumarate, glucoheptonate, glycerophosphate, gluconate, hemisulfate, heptanoate, hexanoate, hydroiodide, 2- Hydroxy-ethanesulfonate, lactobionate, lactate, laurate, lauryl sulfate, malate, maleate, malonate, methanesulfonate, 2-naphthalenesulfonate, nicotinate, nitrate, oleate, Oxalate, palmitate, pamoate, pectinate, persulfate, 3-phenylpropionate, phosphate, pivalate, propionate, stearate, succinate, sulfate, tartrate, thiocyanate, p-toluene sulfo. nate, undecanoate, valerate salt, and the like.

Salts derived from suitable bases include alkali metal, alkaline earth metal, ammonium and N ⁺ (C _1-4 alkyl) ₄ salts. Representative alkali or alkaline earth metal salts include sodium, lithium, potassium, calcium, magnesium, and the like. In addition, pharmaceutically acceptable salts include, when appropriate, non-toxic ammoniums, quaternary ammoniums, and counterions such as halides, hydroxides, carboxylates, sulfates, phosphates, nitrates, lower alkyl sulfonates, and aryl sulfonates. Contains amine cations formed using.

The term “prevention” used in the present invention refers to all actions that suppress the symptoms or delay the progression of a specific disease by administering the composition of the present invention.

The term “treatment” used in the present invention refers to any action that improves or beneficially changes the symptoms of a specific disease by administering the composition of the present invention.

The pharmaceutical composition of the present invention may further include adjuvants in addition to the active ingredients. The auxiliary agent may be any one known in the art without limitation, but the effect may be increased by further including, for example, Freund's complete auxiliary agent or incomplete auxiliary agent.

The pharmaceutical composition according to the present invention can be prepared by incorporating the active ingredient into a pharmaceutically acceptable carrier. Here, pharmaceutically acceptable carriers include carriers, excipients, and diluents commonly used in the pharmaceutical field. Pharmaceutically acceptable carriers that can be used in the pharmaceutical composition of the present invention include, but are not limited to, lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, gum acacia, alginate, gelatin, Examples include calcium phosphate, calcium silicate, cellulose, methyl cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil.

The pharmaceutical composition of the present invention can be formulated and used in the form of oral dosage forms such as powders, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols, external preparations, suppositories, or sterile injection solutions according to conventional methods. .

When formulated, it can be prepared using diluents or excipients such as commonly used fillers, extenders, binders, wetting agents, disintegrants, and surfactants. Solid preparations for oral administration include tablets, pills, powders, granules, capsules, etc., and such solid preparations contain the active ingredient plus at least one excipient, such as starch, calcium carbonate, sucrose, lactose, and gelatin. It can be prepared by mixing etc. Additionally, in addition to simple excipients, lubricants such as magnesium stearate and talc can also be used. Liquid preparations for oral administration include suspensions, oral solutions, emulsions, and syrups. In addition to the commonly used diluents such as water and liquid paraffin, they contain various excipients such as wetting agents, sweeteners, fragrances, and preservatives. You can. Preparations for parenteral administration include sterile aqueous solutions, non-aqueous solutions, suspensions, emulsions, lyophilized preparations, and suppositories. Non-aqueous solvents and suspensions include propylene glycol, polyethylene glycol, vegetable oil such as olive oil, and injectable ester such as ethyl oleate. As a base for suppositories, witepsol, tween 61, cacao, laurel, glycerogelatin, etc. can be used.

The pharmaceutical composition according to the present invention can be administered to an individual through various routes. All modes of administration are contemplated, for example, by oral, intravenous, intramuscular, subcutaneous, or intraperitoneal injection.

The dosage of the pharmaceutical composition according to the present invention is selected taking into account the age, weight, gender, physical condition, etc. of the individual. It is obvious that the concentration of the active ingredient included in the pharmaceutical composition can be selected in various ways depending on the target, and is preferably included in the pharmaceutical composition at a concentration of 0.01 to 5,000 μg/ml. If the concentration is less than 0.01 ㎍/ml, pharmaceutical activity may not appear, and if it exceeds 5,000 ㎍/ml, it may be toxic to the human body.

The compound of Formula 1 is also called shogaol or 6-shogaol, and its chemical name is (E)-1-(4-hydroxy-3-methoxyphenyl)dec-4-en-3-one. [(E)-1-(4-hydroxy-3-methoxyphenyl)dec-4-en-3-one] has the structure of Formula 1 above.

The shogaol can be isolated from ginger or ginger, and various synthetic methods are known, including, for example, European Patent No. EP1506958.

According to one embodiment of the present invention, the composition may maintain the anti-Parkinsonian effect of levodopa.

According to one embodiment of the present invention, the composition may regulate the expression of factors in the brain related to Parkinson's disease, and regulating the expression of the factors in the brain may inhibit the expression of TH or DAT in the striatum. The expression of TH or DAT in the striatum may be induced by levodopa.

According to one embodiment of the present invention, the composition may inhibit aggregation of alpha-synuclein (α-syn), and the aggregation of alpha-synuclein may occur in the brain or intestine. It may be, and the brain may be the brainstem.

According to one embodiment of the present invention, the composition may increase the amount of dopamine in plasma.

Additionally, the present invention provides a food composition for preventing or improving Parkinson's disease, comprising the compound represented by Formula 1 or a pharmaceutically acceptable salt thereof and levodopa as active ingredients.

As used herein, the term “improvement” refers to any action that reduces at least the severity of a parameter, such as a symptom, related to the condition being treated.

In addition to containing the active ingredient of the present invention, the food composition of the present invention may contain various flavoring agents or natural carbohydrates as additional ingredients like a typical food composition.

Examples of the above-mentioned natural carbohydrates include monosaccharides such as glucose, fructose, etc.; Disaccharides such as maltose, sucrose, etc.; and polysaccharides, such as common sugars such as dextrin and cyclodextrin, and sugar alcohols such as xylitol, sorbitol, and erythritol. The above-described flavoring agents include natural flavoring agents (thaumatin), stevia extracts (e.g. rebaudioside A, glycyrrhizin, etc.) and synthetic flavoring agents (saccharin, aspartame, etc.). The food composition of the present invention can be formulated in the same way as the pharmaceutical composition and used as a functional food or added to various foods. Foods to which the composition of the present invention can be added include, for example, beverages, meat, chocolate, foods, confectionery, pizza, ramen, other noodles, gum, candy, ice cream, alcoholic beverages, vitamin complexes, health supplements, etc. There is.

In addition, the food composition contains, in addition to the extract as an active ingredient, various nutrients, vitamins, minerals (electrolytes), flavoring agents such as synthetic and natural flavors, colorants and thickening agents (cheese, chocolate, etc.), pectic acid and its salts, It may contain alginic acid and its salts, organic acids, protective colloidal thickeners, pH adjusters, stabilizers, preservatives, glycerin, alcohol, carbonating agents used in carbonated beverages, etc. In addition, the food composition of the present invention may contain pulp for the production of natural fruit juice, fruit juice beverages, and vegetable beverages.

The functional food composition of the present invention can be manufactured and processed in the form of tablets, capsules, powders, granules, liquids, pills, etc. for the purpose of preventing or treating Parkinson's disease. In the present invention, 'health functional food composition' refers to food manufactured and processed using raw materials or ingredients with functionality useful to the human body in accordance with Act No. 6727 on Health Functional Food, and refers to food that is related to the structure and function of the human body. It means taking it for the purpose of controlling nutrients or obtaining useful health effects such as physiological effects. The health functional food of the present invention may contain common food additives, and its suitability as a food additive is determined in accordance with the general provisions and general test methods of the food additive code approved by the Food and Drug Administration, unless otherwise specified. Judgment is made according to specifications and standards. Items listed in the 'Food Additive Code' include, for example, chemical compounds such as ketones, glycine, calcium citrate, nicotinic acid, and cinnamic acid; Natural additives such as dark pigment, licorice extract, crystalline cellulose, kaoliang pigment, and guar gum; Examples include mixed preparations such as sodium L-glutamate preparations, noodle additive alkaline preparations, preservative preparations, and tar coloring preparations. For example, the health functional food in the form of a tablet is made by granulating a mixture of the active ingredient of the present invention with excipients, binders, disintegrants and other additives in a conventional manner, and then adding a lubricant and compression molding, or The mixture can be directly compression molded. Additionally, the health functional food in the form of tablets may contain flavoring agents, etc., if necessary. Among capsule-type health functional foods, hard capsules can be manufactured by filling a regular hard capsule with a mixture of the active ingredient of the present invention mixed with additives such as excipients, and soft capsules can be prepared by mixing the active ingredient of the present invention with additives such as excipients. It can be manufactured by filling the mixture with a capsule base such as gelatin. The soft capsule may contain plasticizers such as glycerin or sorbitol, colorants, preservatives, etc., if necessary. The health functional food in the form of a pill can be prepared by molding a mixture of the active ingredient of the present invention, excipients, binders, disintegrants, etc., by a known method. If necessary, it can be coated with white sugar or another coating agent. Alternatively, the surface can be coated with substances such as starch or talc. The health functional food in the form of granules can be manufactured into granules by mixing a mixture of excipients, binders, disintegrants, etc. of the active ingredients of the present invention by a known method, and may contain flavoring agents, flavoring agents, etc., if necessary. You can.

Hereinafter, the present invention will be described in more detail through examples. These examples are merely for illustrating the present invention in more detail, and it will be apparent to those skilled in the art that the scope of the present invention is not limited to these examples.

<Example 1> Production of an animal model to confirm the effect of combined use of shogaol and levodopa

In order to confirm the effect of the combined use of shogaol and levodopa of the present invention, an animal model of Parkinson's disease was created. Specifically, to a mouse model in which Parkinson's disease was induced with 6-hydroxydopamine, levodopa (L-DOPA) was administered at a concentration of 80 mg/kg, and shogaol (Selleckchem, USA) was administered at a dose of 10 mg/kg for 4 weeks. It was administered at a concentration of ml. The control group included 1) SHAM group, normal mice; 2) PD group, Parkinson's disease-induced mice; and 3) L-DOPA group in which levodopa was administered to Parkinson's disease mice. The specific experimental process is shown in Figure 1, and information about each experimental group is shown in Table 1.

group name explanation SHAM normal mouse P.D. Parkinson's disease-inducing mice L-DOPA Parkinson's disease-inducing mouse + levodopa L-DOPA + 6-shogaol Parkinson's disease-inducing mouse + levodopa + shogaol

<Example 2> Confirmation of the effect of shogaol on the anti-Parkinsonian effect of combined use of levodopa

It was confirmed whether shogaol of the present invention, when administered in combination with levodopa, affects the anti-Parkinsonian effect of levodopa. Specifically, the combined effect of shogaol on the anti-parkinsonian effect of levodopa was confirmed using the pole test and cylinder test, and the pole test and cylinder test were performed following 2 weeks of shogaol administration. Pole test and cylinder results are shown in Tables 2 and 3 below.

Pole test
(% of SHAM) SHAM P.D. L-DOPA L-DOPA + 6-shogaol average 100.00 126.11 90.59 90.65 standard error 12.63 19.23 11.33 7.26

Cylinder trst
(% of SHAM) SHAM P.D. L-DOPA L-DOPA + 6-shogaol average 100.00 91.58 104.99 102.84 standard error 1.60 1.40 6.20 5.26

As a result, as shown in Table 2, in the pole test, compared to the SHAM group, the pole test index increased in the PD group, but significantly decreased in the L-DOPA group. group, the index decreased to a significant level compared to the L-DOPA group, confirming that shogaol maintains the anti-Parkinsonian effect of levodopa.

In addition, as shown in Table 3, in the cylinder test, compared to the SHAM group, the cylinder test index significantly decreased in the PD group, but significantly increased in the L-DOPA group, and in the group administered shogaol In , the index increased to a level similar to that of the L-DOPA group, confirming that shogaol maintains the anti-Parkinsonian effect of levodopa.

<Example 3> Confirmation of the effect of shogaol on improving levodopa-induced intestinal motility disorder

<3-1> Check the control of moisture content in feces

It was confirmed whether shogaol of the present invention improves intestinal dysmotility induced by levodopa. Specifically, mice from each group in Example 1 were humanely sacrificed, intestinal tissue was obtained, and intestinal fecal matter was obtained. Afterwards, the water content in the feces was measured to confirm the effect of improving intestinal motility following Shogaol administration.

Fecal water content (% in feces) SHAM P.D. L-DOPA L-DOPA + 6-shogaol Water content in feces (%) 68.94 61.28 57.31 69.54 standard error 1.62 1.39 2.46 1.51

As a result, as shown in Table 4, compared to the SHAM group, the water content in the feces was significantly reduced in the L-DOPA group, but when shogaol was administered, the reduced water content in the feces increased, It was confirmed that bowel movements were improved.

<3-2> Confirmation of inhibition of alpha-synuclein aggregation in intestine

It was confirmed whether shogaol of the present invention inhibits the aggregation of alpha-synuclein (α-syn) in the intestine induced by levodopa. Specifically, in the intestinal tissue obtained in Example 3-1, the aggregation of α-syn was analyzed by Western blot.

Aggregated α-syn in jejunum (% of SHAM) SHAM P.D. L-DOPA L-DOPA + 6-shogaol average 100.00 117.90 243.40 94.64 standard error 24.67 30.55 57.26 16.98

As a result, as shown in Table 5 above, it was confirmed that the aggregation of α-syn was significantly increased in the L-DOPA group compared to the SHAM group. When shogaol was administered, the increased aggregation of α-syn was significant. It was confirmed that Shogaol of the present invention improves intestinal motility.

<Example 4> Confirmation of regulation of factors in the brain during combined administration of shogaol and levodopa

It was confirmed whether shogaol of the present invention restores the expression of TH (tyrosine hydroxylase) and DAT (dopamine transporter), factors in the striatum that decrease when administered with levodopa. In addition, it was confirmed whether it inhibits the aggregation of α-syn within the DMV in the brainstem region. Mice from each group in Example 1 were humanely sacrificed, and striatal tissue and DMV tissue within the brain were obtained. Afterwards, the expression of TH and DAT factors in the striatum was analyzed by Western blot, and the aggregation of α-syn in DMV tissue was analyzed by Western blot. The results are shown in Tables 6 to 8 below.

TH in ST
(% of SHAM) SHAM P.D. L-DOPA L-DOPA + 6-shogaol average 100.00 50.07 39.43 55.84 standard error 9.99 7.48 5.29 9.28

DAT in ST
(% of SHAM) SHAM P.D. L-DOPA L-DOPA + 6-shogaol average 100.00 46.82 40.82 62.24 standard error 11.44 8.20 6.07 10.45

Aggregated α-syn in DMV (% of SHAM) SHAM P.D. L-DOPA L-DOPA + 6-shogaol average 100.00 71.47 116.53 70.23 standard error 31.45 20.77 40.41 19.17

As a result, as shown in Tables 6 and 7, compared to the SHAM group, the expression of TH and DAT factors in the striatum was significantly reduced in the L-DOPA group, but with the administration of shogaol, the decreased TH and DAT It was confirmed that the expression of the factor significantly increased.

In addition, as shown in Table 8, compared to the SHAM group, the aggregation of α-syn in the DMV of the brainstem increased significantly in the L-DOPA group, but with the administration of shogaol, the aggregation of α-syn was significant. It was confirmed that shogaol can regulate factors in the brain.

<Example 5> Confirmation of the effect of increasing dopamine in the blood following combined administration of shogaol and levodopa

It was confirmed whether shogaol of the present invention increases dopamine in the blood when administered in combination with levodopa. Specifically, blood was obtained from the sacrificed mouse in Example 3, the obtained blood was treated with ethylene diamine tetra acetic acid (EDTA), and then placed in a tube to separate plasma. Afterwards, the amount of dopamine in the separated plasma was analyzed using the Dopamine Assat kit (novus, USA). The results are shown in Table 9 below.

Dopamine levels in Plasma
(ng/ml) SHAM P.D. L-DOPA L-DOPA + 6-shogaol average 8.62 5.47 64.43 106.56 standard error 1.64 2.30 10.67 48.25

As a result, as shown in Table 9, compared to the SHAM group, the amount of dopamine in plasma was significantly increased in the L-DOPA group, and in the group administered shogaol in combination with levodopa, dopamine in plasma was higher than that in the L-DOPA group. By confirming that the amount was further increased, it was confirmed that shogaol has a synergistic effect on the effect of levodopa on increasing dopamine in plasma.

Therefore, it was confirmed that shogaol of the present invention, when administered in combination with levodopa in an animal model of Parkinson's disease, improves intestinal dysmotility induced by levodopa while maintaining the efficacy of levodopa. In addition, it was confirmed that it can suppress the expression of TH (tyrosine hydroxylase) and DAT (dopamine transporter) in the striatum and the aggregation of α-syn in the DMV, the brain stem. In addition, it was confirmed that the increase in the amount of dopamine in plasma induced by levodopa further increased with the combined use of shogaol.

Claims (10)

A pharmaceutical composition for the prevention or treatment of Parkinson's disease, comprising a compound represented by the following formula (1) or a pharmaceutically acceptable salt thereof and levodopa as active ingredients:
[Formula 1]
. According to clause 1,
The composition maintains the anti-Parkinsonian effect of levodopa. According to clause 1,
The composition is a composition that regulates the expression of factors in the brain related to Parkinson's disease. According to clause 3,
A composition that regulates the expression of the factor in the brain by suppressing the expression of TH (tyrosine hydroxylase) or DAT (dopamine transporter) in the striatum. According to clause 4,
The composition, wherein the expression of TH or DAT in the striatum is induced by levodopa. According to clause 1,
The composition is a composition that inhibits aggregation of alpha-synuclein (α-syn). According to clause 6,
A composition wherein the aggregation of alpha-synuclein is in the brain or intestine. According to clause 7,
The composition, wherein the brain is the brainstem. According to clause 1,
The composition is a composition that increases the amount of dopamine in plasma. A food composition for preventing or improving Parkinson's disease, comprising a compound represented by the following formula (1) or a pharmaceutically acceptable salt thereof and levodopa as active ingredients:
[Formula 1]
.