JP5578822B2 - Acetylcholinesterase inhibitor - Google Patents

Description

The present invention relates to an inhibitor of acetylcholinesterase (hereinafter also referred to as “AChE”), which contains an essential oil of yellow batai ( Peltophorum dasyrachis ) as an active ingredient, and uses thereof.

  In recent years, an aging society has progressed, and the number of senile dementia patients has increased, and among them, Alzheimer-type dementia patients have increased. The cause of this Alzheimer-type dementia is unclear, but a decrease in the level of acetylcholine, a neurotransmitter in the patient's brain, is observed, which is caused by a decline in cholinergic nerve function. (Non-patent Document 1). Therefore, for Alzheimer-type dementia, treatment methods aiming at increasing the concentration of acetylcholine to prevent the function of cholinergic nerves from becoming mainstream have become mainstream.

  Acetylcholine is synthesized by acetylcholine transferase and maintained at a constant concentration by being decomposed by acetylcholinesterase. Therefore, it is a method of suppressing the reduction of acetylcholine by inhibiting the activity of acetylcholinesterase to suppress the degradation of acetylcholine. Although this method cannot completely treat symptoms, it has been found that symptoms can be improved or the progression of symptoms can be delayed.

  By the way, it is known that the scent of essential oils of plants exhibits antibacterial action, psychological action, and biological rhythm regulating action, and aromatherapy (aroma therapy) that heals the mind and body by the scent of plants has attracted attention.

  In recent years, it has been reported that aroma components of plants such as mint, lavender or grapefruit essential oils exhibit not only their aroma but also AChE inhibitory activity. In addition, ginkgo biloba extract is also said to have a brain dysfunction improving action and an Alzheimer-type dementia symptom improving action (Non-patent Document 2).

  It is of great interest that such naturally derived ingredients have been confirmed to have AChE inhibitory activity associated with the treatment of Alzheimer's dementia.

On the other hand, Yellow batai ( Peltophorum dasyrachis ) is one of Thai herbs and belongs to the leguminous family (Legminosae). Leguminous species are known to contain many phenolic compounds and flavonoids, and are expected to be used as active ingredients in functional foods, cosmetics, pharmaceuticals and the like. Regarding yellow batie, the present inventors have previously reported a compound having an antimutagenic effect contained in the extract (see Patent Document 1). In addition, the present inventors have reported that the ethanol extract has a whitening effect (see Patent Document 2). However, there has been no report so far that the essential oil component of Yellow Batai has AChE inhibitory activity.

JP 2006-151855 A Japanese Patent Laid-Open No. 2005-23036

Weinstock M .: Neurodegeneration, 4, pp.349-356, 1995 FOOD Style 21 2001.5 p67-72

  An object of this invention is to provide the novel AChE inhibitor which uses the essential oil of a plant as an active ingredient, and its use.

The inventors of the present invention have found that the essential oil component of Yellow batai ( Peltophorum dasyrachis ) exhibits a strong AChE inhibitory activity, and have further studied this to complete the present invention.

  That is, the present invention provides the following acetylcholinesterase inhibitors and the like.

Item 1. An acetylcholinesterase inhibitor containing an essential oil of yellow batai ( Peltophorum dasyrachis ) as an active ingredient.

  Item 2. The essential oil has the formula (I):

Ar-turmerone represented by the formula (II):

Item 2. The acetylcholinesterase inhibitor according to Item 1, comprising at least one sesquiterpene selected from the group consisting of dihydro-ar-turmerone represented by:

  Item 3. Said extract is of formula (Ia):

(+)-(S) -ar-turmerone ((+)-(S) -ar-turmerone) and / or formula (IIa):

Item 3. The acetylcholinesterase inhibitor according to Item 1 or 2, which comprises (+)-(S) -dihydro-ar-turmerone represented by (+)-(S) -dihydro-ar-turmerone).

  Item 4. Formula (Ia):

(+)-(S) -ar-turmerone and / or formula (IIa):

An acetylcholinesterase inhibitor comprising (+)-(S) -dihydro-ar-turmerone represented by the formula:

  Item 5. Item 5. A therapeutic or prophylactic agent for senile dementia, comprising the acetylcholinesterase inhibitor according to any one of Items 1 to 4.

  Item 6. Item 5. A brain dysfunction-improving drug comprising the acetylcholinesterase inhibitor according to any one of Items 1 to 4.

  Item 7. Item 5. A therapeutic or prophylactic agent for Alzheimer's dementia, comprising the acetylcholinesterase inhibitor according to any one of Items 1 to 4.

  Item 8. Item 5. A bath agent containing the acetylcholinesterase inhibitor according to any one of Items 1 to 4.

  Item 9. Item 5. A fragrance containing the acetylcholinesterase inhibitor according to any one of Items 1 to 4.

  Item 10. Item 5. An essential oil for aromatherapy containing the acetylcholinesterase inhibitor according to any one of Items 1 to 4.

  Since yellow batai essential oil and sesquiterpene contained in the essential oil have strong AChE inhibitory activity, they are used as AChE inhibitors and are used as AChE inhibitors, cerebral dysfunction improving drugs, senile dementia (especially Alzheimer-type dementia). It is useful as a therapeutic or prophylactic agent. In addition, the AChE inhibitor containing yellow batai essential oil or sesquiterpene is added to fragrances, bathing agents, aromatherapy essential oils, etc. due to its aroma and strong AChE inhibitory activity, and it can be used for relaxation and refreshing effects. The healing effect and the prevention / improvement effect of dementia can be achieved at the same time.

FIG. 3 is a graph showing the results of an AChE inhibitory activity test of yellow butterfly essential oil in Example 1. FIG. 3 is a graph showing the results of an AChE inhibitory activity test of the main component of yellow butterfly essential oil in Example 1. (A) is a figure which shows the result of the Dixon plot derived | led-out from the AChE inhibitory activity of (+)-(S) -ar-turmerone in Example 1, (B) is (+)-(S) -dihydro. -It is a figure which shows the result of the Dixon plot derived | led-out from the AChE inhibitory activity of ar-turmerone.

  Hereinafter, the present invention will be described in detail.

  The AChE inhibitor of the present invention contains an essential oil, which is an extract from yellow batie, as an active ingredient.

The yellow batai ( Peltophorum dasyrachis ) used in the present invention is a leguminosae plant planted in Southeast Asian countries such as Thailand, Cambodia, Laos, Vietnam, Malaysia, Sumatra and the like.

  The essential oil of yellow batai of the present invention means a component extracted from yellow bathai, and any oil extracted from the tree thereof is preferable, and one extracted from the bark is particularly preferable. Yellow batie can be used for extraction as it is, but after drying and pulverization, it may be used for extraction.

  As the extraction method of the essential oil of yellow and batai, since the boiling point of the essential oil component is low, known methods such as steam distillation method, pressing method, solvent extraction method, fat absorption method, volatile solvent extraction method, supercritical fluid extraction method, etc. The method is used. Of these, the steam distillation method is preferably employed.

  After the essential oil is obtained from yellow batie by the above method, the obtained extract can be used as it is as an AChE inhibitor in the present invention. Alternatively, if necessary, the essential oil can be obtained by solid-liquid separation from the residue by a conventional method such as filtration or centrifugation.

  Furthermore, if necessary, one or more suitable separation and purification means such as alumina column chromatography, silica gel chromatography, gel filtration chromatography, ion exchange chromatography, hydrophobic chromatography, and high performance liquid chromatography may be combined. Then, a fraction or compound having AChE inhibitory activity can be taken out and used as an AChE inhibitor. A known elution solvent may be used, but a nonpolar organic solvent having a low boiling point is preferably used as a main component. Thereby, the outstanding activity can be exhibited with a small amount of essential oil.

  Yellow Batai essential oil has strong AChE inhibitory activity by itself. The essential oil contains, as a main component, formula (I):

Ar-turmerone represented by the formula (II):

Sesquiterpenes such as dihydro-ar-turmerone represented by the formula (2) are included, and these sesquiterpenes also have strong AChE inhibitory activity. Here, since asymmetric carbon exists in ar-turmerone and dihydro-ar-turmerone, isomers related to configuration exist, and the present invention encompasses all of these isomers. One isomer may be sufficient and the isomer mixture in arbitrary ratios may be sufficient. As the absolute configuration of ar-turmerone and dihydro-ar-turmerone, both are preferably (S) isomers, and the optical rotation is preferably (+).

  That is, formula (Ia):

(+)-(S) -ar-turmerone represented by the formula (IIa):

(+)-(S) -dihydro-ar-turmerone represented by

  (+)-(S) -ar-turmerone and (+)-(S) -dihydro-ar-turmerone have strong AChE inhibitory activity, as shown in Examples described later. Among these, (+)-(S) -dihydro-ar-turmerone has particularly strong AChE inhibitory activity.

  The above yellow batai essential oil and its active compound sesquiterpenes ((+)-(S) -ar-turmerone and (+)-(S) -dihydro-ar-turmerone) have strong AChE inhibitory activity. Therefore, it can be widely used as an AChE inhibitor.

  When an AChE inhibitor containing, as an active ingredient, yellow batai essential oil or sesquiterpene, which is an active compound thereof, is used as a pharmaceutical, for example, a preventive or therapeutic agent for senile dementia in mammals (especially humans), particularly Used as a preventive or therapeutic agent for Alzheimer-type dementia. It is also effective as a remedy for brain dysfunction.

  Yellow Batay essential oil and sesquiterpene are prepared by conventional methods using tablets, powders, fine granules, granules, coated tablets, capsules, syrups, troches, inhalants, suppositories, injections, ointments , Eye ointments, eye drops, nasal drops, ear drops, poultices, lotions and the like.

  Excipients, binders, lubricants, coloring agents, flavoring agents, and if necessary stabilizers, emulsifiers, absorption promoters, surfactants, pH adjusters, preservatives, Antioxidants and the like can be used. In general, ingredients and blending amounts that are generally used as raw materials for pharmaceutical preparations are appropriately selected to prepare a preparation by a conventional method.

  When administering the pharmaceutical formulation of this invention, the form is not specifically limited, What is necessary is just the method used normally, and oral administration or parenteral administration may be sufficient. The pharmaceutical dosage according to the present invention can be appropriately selected from pharmaceutically effective doses according to the degree of symptoms, age, sex, body weight, dosage form / salt type, specific type of disease, etc. .

  In addition, AChE inhibitors containing yellow butterfly essential oil or sesquiterpene as an active ingredient have a strong AChE inhibitory activity and a pleasant fragrance. , Skin cleansing agents, deodorants, tranquilizers for pets, masking agents, and the like, or contained in them. The essential oil and sesquiterpene of yellow batai should be contained in an amount of usually about 0.001 to 100% by weight (preferably about 0.1 to 10% by weight) for each product. When used in the air, it may have a high concentration, for example, about 50 to 100% by weight.

  When yellow batai essential oil and sesquiterpene are used for such purposes, the healing effect of the mind and body is exhibited by the relaxation action of the scent of the essential oil in a stressful modern society. Furthermore, since the essential oil and sesquiterpene of the present invention have AChE inhibitory activity, they can improve senile dementia and improve the ability of daily life of the elderly by using it in an environment where the elderly and the sick live daily. It is also possible to make it.

  In particular, when yellow butterfly essential oil and sesquiterpene are used as essential oils for aromatherapy, they can be used in combination with other natural plant essential oils. Further, the essential oil for aromatherapy can be distributed in a predetermined place and used in a form that can be inhaled. As the distribution place, for example, it can be distributed in a room in a home, a hotel room, a conference room, a hospital room, an event hall where people gather, a break plaza, various relaxation facilities, and the like. Among them, when used in hospitals and facilities where patients with senile dementia live, an effect of improving dementia is expected.

  In addition, yellow and batai essential oils and sesquiterpenes can be blended in various foods and beverages such as soft drinks, dairy products (processed milk, yogurt), and confectionery (jelly, chocolate, biscuit, gum, tablet confectionery). it can. The blending amount is not particularly limited, but is usually about 0.01 to 10% by weight.

  Next, the present invention will be specifically described with reference to examples, but the present invention is not limited thereto.

Example 1
(1) Dried bark of yellow butterfly (manufactured by Picasso Chemical Research Laboratory) (4 kg) was subjected to steam distillation for 2 hours with a Linkens-Nickerson type apparatus. The obtained essential oil was dried over anhydrous sodium sulfate and filtered to obtain a pale yellow essential oil (0.04 g) (yield: 0.01% (v / w)).
(2) Isolation of Sesquiterpene from Yellow Batai Essential Oil Six fractions were obtained by subjecting the obtained yellow Batai essential oil (365 mg) to silica gel chromatography (eluent: n-hexane-CH ₂ Cl ₂ ). Fractionated into (fraction 1-6). Fraction 2 (150 mg) was subjected to silica gel chromatography (eluent: n-hexane-Et ₂ O) to give (+)-(S) -ar-turmerone (70.0 mg) and (+)-(S) -Dihydro-ar-turmerone (4.3 mg) was obtained.
(3) Analysis of isolated compound For the measurement of optical rotation, LTDDIP-1000 manufactured by JASCO Corporation was used. JASCO FT / IR-470 Plus Fourier Transform Infrared Spectrometer manufactured by JASCO Corporation was used for measurement of IR (infrared absorption) spectrum. ¹ H-NMR and ¹³ C-NMR, heteronuclear multi-quantum coherence (HMQC), heteronuclear multiple bond coherence (HMBC) spectrum is JEOL ECA spectrophotometer, TMS is used as an internal reference, and ¹ H-NMR is 400 And at 500 MHz, ¹³ C-NMR was measured at 100 and 125 MHz, respectively.
(+)-(S) -ar-turmerone; pale yellow oil; [α] ²⁹ _D + 63.7 ° (c = 0.995, CHCl ₃ ); HR-EIMS 216.1602 (M ⁺ , C ₁₅ H ₂₀ O, calcd 216.1582); EIMS m / z (relative intensity) 216 (M ⁺ 20%), 201 (7%), 132 (15%), 119 (100%), 105 (8%), 98 (3%), 91 (10%), 83 (98%), 77 (3%), 55 (17%); IR (film) cm ^-1 : 1685 (C = O), 1620 (C = C); ¹ H-NMR (CDCl ₃ , 400 MHz) δ7.10 (4H, brs, ArH), 6.02 (1H, brs, H-10), 3.29 (1H, ddd, J = 8.8, 7.6, 6.8 Hz, H-7), 2.71 (1H, dd, J = 16.4, 7.6 Hz, H-8), 2.61 (1H, dd, J = 16.4, 8.8 Hz, H-8), 2.31 (3H, s, H-15), 2.10 (3H, s, H-12), 1.86 (3H, s, H-13), 1.24 (3H, d, J = 6.8 Hz, H-14); ¹³ C-NMR (CDCl ₃ , 100 MHz) δ 200.0 (C- 9), 155.1 (C-11), 143.7 (C-4), 135.3 (C-1), 129.1 (C-3,5), 126.7 (C-2, 6), 124.1 (C-10), 52.7 (C-8), 35.3 (C-7), 27.6 (C-15), 22.0 (C-13), 21.0 (C-12), 20.7 (C-14).
(+)-(S) -dihydro-ar-turmerone; colorless oil; [α] ²⁹ _D + 15.4 ° (c = 0.15, CHCl ₃ ); HR-EIMS 218.1777 (M ⁺ , C ₁₅ H ₂₂ O, calcd.218.1741); EIMS m / z (relative intensity) 218 (M ⁺ 26%), 203 (18%), 161 (17%), 133 (10%), 119 (100%), 105 (8%) , 91 (6%), 85 (17%), 57 (22%); IR (film) cm ^-1 : 1712 (C = O), 1514 (C = C); ¹ H-NMR (CDCl ₃ , 500 MHz) δ 7.10 (4H, brs, ArH), 3.28 (1H, ddd, J = 8.0, 7.2, 6.3 Hz, H-7), 2.68 (1H, dd, J = 16.1, 6.3 Hz, H-8), 2.58 (1H, dd, J = 16.1, 8.0 Hz, H-8), 2.31 (3H, s, H-15), 2.19 (2H, m, H-10), 2.08 (1H, m, H-11) , 1.23 (3H, d, J = 7.2 Hz, H-14), 0.85 (6H, d, J = 4.6 Hz, H-12,13); ¹³ C-NMR (CDCl ₃ , 125 MHz) δ 209.9 (C -9), 143.3 (C-4), 135.7 (C-1), 129.1 (C-3,5), 126.6 (C-2, 6), 52.5 (C-10), 51.7 (C-8), 34.9 (C-7), 24.4 (C-11), 22.5 (C-12,13), 22.0 (C-14), 21.0 (C-15).

  In addition, these spectral data are Honwad, VK; Rao, AS Terpenoids-LXIX ABSOLUTE CONFIGURATION OF (-)-α-CURCUMENE *. Tetrahedron. 2004, 21, 2593-2604, Crawford, RJ; Erman, WF; Broaddus, CD Metalation of Limonene. A novel Method for the Synthesis of Bisabolene Sesquiterpens. J. Amer. Chem. Soc. 94 (12), 1972, 4298-4306), Zhang, A .; Rajanbabu, TV Chiral Benzyl Centers through Asymmetric Catalysis. A Three-Step Synthesis of (R)-(-)-α-Curcumene via Asymmetric Hydrovinilation. Org. Lett. 2004, 6 (18), 3159-3161, and Mori, K. Synthesis of (R) -ar-turmerone and its conversion to (R) -ar-himachalene, a pheromone component of the flea beetle: (R) -ar-himachalene is dextrorotary in hexane, while levorotatory in chloroform.Tetrahedron: Asymmetry. 2005, 16, 685-692 Compared to the data that has been.

  The structural formula of (+)-(S) -ar-turmerone is

And the structural formula of (+)-(S) -dihydro-ar-turmerone is

It is.
(4) A component search was performed on the obtained yellow-batai essential oil using GC-MS under the following conditions. As a result, 68 compounds occupying 88.0% of the total essential oil were identified (Table 1). ). Specifically, (+)-(S) -ar-turmerone (22.3%), caprylic acid (16.5%) and palmitic acid (6.58%) are included as main components. Furthermore, hydrocarbons such as alkenes classified as “others” constitute 3.9% of essential oils, followed by oxygenated sesquiterpenes (22.9%) and oxygenated monoterpenes (17.6%). . Yellow Batai essential oil also contained low amounts of sesquiterpene hydrocarbons (3.09%) and monoterpene hydrocarbons (0.52%).
GC / MS condition: GC / MS is any of two capillary columns (DB-WAX, 15 m × 0.25 mm, film thickness 0.25 μm, or HP-5MS, 30 m × 0.25 mm, film thickness 0.25 μm). A Hewlett Packard 6890-5933 system using the KA was used. DB-WAX was programmed to hold the column temperature at 40C to 240C, 240C for 5 minutes at 4C / min. For HP-5MS, the column temperature was programmed to hold at 40 ° C. to 260 ° C. at 260 ° C. for 5 minutes at 4 ° C./min. The injector and detector temperatures were 270 ° C. and 280 ° C., respectively. The flow rate of the carrier gas (He) was 1.4 ml / min and the split ratio was 1:10. The interface temperature of the detector was set at 280 ° C. The initial column temperature is held at 40 ° C. for 5 minutes, programmed to 280 ° C. at a rate of 4 ° C./minute (the actual temperature in the MS source reaches about 230 ° C.) and then constant at 260 ° C. for 5 minutes. Kept. The ionization voltage was 70 eV and the trapped mass range was 39-450 amu. The identification of essential oil components was done by comparing their relative retention times with those of standard samples or by comparing their retention indices (RI) for a series of n-hydrocarbons. Commercial programs (The NIST Mass Spectral Search Program for the NIST / EP / NIM Mass Spectral Library version 1.7, built 11/05/1999, and Terpenoids and Related Constituents of Essential oils; Library of MassFinder 3.1 .; Hamburg, Germany, 2001 ), And homemade libraries that collected mass spectra of pure and known oil components and literature MS data were also used for identification.

(5) The AChE inhibition test was performed using the 96-well microplate method previously reported by Bruhmann et al. (Bruhmann, C .; Marston, A .; Hostettmann, K .; Carrupt, PA .; Testa, B. Screening of Non- Alkaloidal Natural Compounds as Acetylcholinesterase Inhibitors. Chem. Biodiver. 2004, 1, 819-829). A brief description is given below. 20 μl of AChE solution (0.037 unit / mL, pH 7.4 in 0.01 M phosphate buffer), 200 μl of color former (5,5′-dithiobis (2-nitrobenzoic acid; DTNB) (0 0.15 mM, pH 7.4) in 1 M phosphate buffer, and 20 μl of an inhibitor (essential oil or terpenoid) methanol solution were added to the control wells. The contents in the mixture were mixed and preincubated for 15 minutes at room temperature, and then 30 μl of a substrate (acetylthiocholine iodide; ATC) aqueous solution (final concentration: 0.05-0.25 mM) was added and incubated for 15 minutes. Thereafter, a yellow colored anion (TNB) 405 generated by hydrolysis reaction of the substrate with AChE Absorbance at nm was measured using a microplate reader and the inhibition (percentage) of AChE activity was calculated using the formula:
I (%) = {(A _control− A _sample ) / A _control } × 100
(Where “A _sample ” is the absorbance of the reaction mixture containing the sample (inhibitor), and “A _control ” represents the absorbance of the reaction control mixture)). In addition, (+)-Pregon was used as a positive control. Each sample was measured at least three times, and the average value was shown. The results are shown in Table 2, FIG. 1 and FIG.

  As AChE, AChE of human erythrocytes manufactured by Sigma-Aldrich Corporation was used. DTNB and ATC were manufactured by Tokyo Chemical Industry Co. Ltd. (TCI). Terpenoids include l-menthol, (+)-camphor and eugenol (manufactured by Nacalai Tesque); anisole (manufactured by Wako Pure Chemical Industries, Ltd.); (+)-borneol (manufactured by Fluka Chemical Co., Ltd.); (+)-pregon (Manufactured by Kanto Chemical Co., Inc.) was used.

Yellow Batai essential oil showed strong AChE inhibition, with an IC ₅₀ value of 83.2 ± 2.8 μg / mL, a 50% inhibitory concentration (FIG. 1).

(+)-(S) -ar-turmerone and (+)-(S) -dihydro-ar-turmerone show stronger activity than essential oils, with IC ₅₀ values of 235.2 ± 0.16 μM and 81.5, respectively. ± 0.24 μM (Table 2 and FIG. 2). Since the positive control (+)-pregon has an IC ₅₀ value of 136 μM, (+)-(S) -dihydro-ar-turmerone has approximately 1.5 times stronger activity than (+)-pregon. You can see that On the other hand, both monoterpenes and aromatic compounds had low AChE inhibitory activity. This suggests that essential oils containing (+)-(S) -ar-turmerone and (+)-(S) -dihydro-ar-turmerone exhibit strong AChE inhibition. Conversely, the yellow batai essential oil contains sesquiterpenes ((+)-(S) -ar-turmerone and (+)-(S) -dihydro-ar-turmerone), which results in strong AChE inhibition. It can be said that it is obtained. To date, there have been several studies confirming that sesquiterpenes show moderate AChE inhibitory activity, but no sesquiterpenes have been reported that have stronger activity than essential oils. Therefore, it can be said that this result that the sesquiterpene contained in the essential oil shows a strong AChE inhibitory effect is very interesting.
(6) Next, the enzyme inhibition forms of (+)-(S) -ar-turmerone and (+)-(S) -dihydro-ar-turmerone were examined. The method used was the Dixon plot method, which is widely used in kinetic methods. In the Dixon plot method, the substrate concentration is fixed, and the reciprocal of the reaction rate is plotted against the inhibitor concentration. The result of (+)-(S) -ar-turmerone is shown in FIG. 3 (A), and the result of (+)-(S) -dihydro-ar-turmerone is shown in FIG. 3 (B). The results in FIG. 3 (A) indicated that (+)-(S) -ar-turmerone is a competitive inhibitor since the Dixon plot for each substrate concentration crossed in the second quadrant. The moderately active component (+)-(S) -ar-turmerone antagonizes the substrate for the active site of the enzyme. On the other hand, the result of FIG. 3 (B) shows that the Dixon plot for each substrate concentration is a parallel line, and (+)-(S) -dihydro-ar-turmerone showed a non-antagonistic form of inhibition. . The most active component, (+)-(S) -dihydro-ar-turmerone, binds to the enzyme-substrate complex rather than the enzyme and can therefore prevent product formation. From these results, it can be said that the presence of the C10-11 double bond plays an extremely important role in the AChE inhibitory effect.

As described above, the yellow Batai essential oil showed strong AChE inhibitory activity with an IC ₅₀ value of 83.2 ± 2.8 μg / mL. The sesquiterpenes (+)-(S) -ar-turmerone and (+)-(S) -dihydro-ar-turmerone contained in the essential oil showed stronger activity than the essential oil. In addition, (+)-(S) -ar-turmerone was found to be an antagonistic form of inhibition, and (+)-(S) -dihydro-ar-turmerone was found to be a non-antagonistic form of inhibition. .

Claims (6)

An acetylcholinesterase inhibitor containing yellow butterfly essential oil as an active ingredient. The essential oil has the formula (I):

Ar-turmerone represented by the formula (II):

The acetylcholinesterase inhibitor according to claim 1, comprising at least one sesquiterpene selected from the group consisting of dihydro-ar-turmerone represented by: Said essential oil is of formula (Ia):

(+)-(S) -ar-turmerone and / or formula (IIa):

The acetylcholinesterase inhibitor of Claim 1 or 2 containing the (+)-(S) -dihydro-ar-turmerone represented by these. A therapeutic or prophylactic agent for senile dementia, comprising the acetylcholinesterase inhibitor according to any one of claims 1 to 3. The brain dysfunction improving agent containing the acetylcholinesterase inhibitor in any one of Claims 1-3. A therapeutic or prophylactic agent for Alzheimer-type dementia, comprising the acetylcholinesterase inhibitor according to any one of claims 1 to 3.

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