MAO inhibitors

Abstract

The present invention provides an MAO inhibitor for preventing or treating a disease in which the inactivation of a monoamine neurotransmitter is involved in the onset or progression of symptoms. SOLUTION: The active ingredient is an extract of at least one plant selected from mulberry and saxifrage.

Description

[Technical field]

[0001] The present invention relates to MAO inhibitors. [Background technology]

[0002] MAO (monoamine oxidase) is an enzyme that catalyzes the oxidation of monoamines in the body. It has the function of removing amines from monoamines using oxygen, and is known to play a major role in the inactivation of monoamine neurotransmitters such as serotonin, melatonin, noradrenaline, adrenaline, phenethylamine, and dopamine. There are two subtypes of MAO, MAO-A and MAO-B, the former of which is mainly expressed in the brain, intestine, liver, placenta, skin, etc., and the latter of which is mainly expressed in the brain, platelets, lymphocytes, etc. For this reason, in recent years, there has been an active search for ingredients that inhibit the inactivation of monoamine neurotransmitters by inhibiting MAO, thereby preventing or treating diseases in which the inactivation of monoamine neurotransmitters is involved in the onset or progression of symptoms. For example, Patent Document 1 describes that xanthone derivatives have MAO inhibitory effects. However, the search for ingredients that have MAO inhibitory effects is still in a significant state. [Prior art documents] [Patent documents]

[0003] [Patent Document 1] Japanese Patent Application Publication No. 8-119959 Summary of the Invention [Problem to be solved by the invention]

[0004] Therefore, an object of the present invention is to provide an MAO inhibitor for preventing or treating diseases in which inactivation of monoamine neurotransmitters is involved in the onset or progression of symptoms. [Means for solving the problem]

[0005] In view of the above, the present inventors have conducted extensive research and have found that an extract of mulberry (Morus) and an extract of saxifragaceae (Saxifraga stoloniferaz) have MAO inhibitory activity.

[0006] The inhibitor against the enzyme activity of MAO-A of the present invention, which has been made based on the above findings, is as described in claim 1, The extraction solvent is alcohol, which may contain water. Contains saxifrage extract as an active ingredient (However, when used as a skin whitening agent, this does not include the cases where it is used in combination with tranexamic acid or in combination with a hydrolysate of rice bran extract.) . Effect of the Invention

[0007] According to the present invention, it is possible to provide an MAO inhibitor for preventing or treating diseases in which inactivation of monoamine neurotransmitters is involved in the onset or progression of symptoms. [Brief description of the drawings]

[0008] [Figure 1] 1 is a graph showing the inhibitory effect of mulberry extract and saxifrage extract on the enzyme activity of MAO-A in an example. [Diagram 2] 11 is a graph showing the inhibitory effect on the enzyme activity of MAO-B. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0009] The MAO inhibitor of the present invention contains as an active ingredient an extract of at least one plant selected from mulberry and saxifrage.

[0010] The mulberry used in the present invention may be Yamaguwa, Muguwa, Logua, etc., which belong to the genus Mulberry of the family Mulberry. The dried root bark is known as Sohakuhi (white bark of mulberry), the dried leaves as Soyou (mulberry leaf), the dried branches as Soushi (mulberry branch), and the dried fruit as Soujin (mulberry sapling), and these herbal medicines may be used. Saxifrage is a plant of the genus Saxifrage of the family Saxifragaceae, and is used as food and medicinal herb. However, there have been no reports of any of the extracts having MAO inhibitory activity. In addition, both mulberry and saxifrage may be naturally grown or cultivated by producers.

[0011] In the present invention, the extract of mulberry can be obtained as a filtrate by, for example, adding water or an organic solvent (monoalcohols such as methanol, ethanol, and isopropanol, polyhydric alcohols such as 1,3-butylene glycol, ether, hexane, ethyl acetate, acetonitrile, etc., which may contain water) as an extraction solvent to the root bark (which may be chopped, dried, or crushed), leaving it at room temperature for 1 hour to 1 week to extract the components, or refluxing it to extract the components, and then filtering it. The extraction solvent may be a single solvent or a mixture of multiple solvents. The extract of saxifrage can be obtained as a filtrate by the same method as above using the whole plant (all parts such as flowers, leaves, stems, and roots). The obtained filtrate may be used as a liquid extract as it is, or may be used as a solid or powder by vacuum concentration or freeze-drying. The filtrate may be further purified by ammonium sulfate fractionation, gel filtration, ion chromatography, etc., and the obtained fraction may be used as a liquid extract. Alternatively, for example, an extraction operation may be performed first using hexane, and then extraction operations may be performed successively using solvents with gradually increasing polarity, such as ethyl acetate, acetone, and water, and the filtrate obtained by using any of the solvents may be used as the liquid extract.

[0012] The MAO inhibitor of the present invention can be formulated into various formulations and can be taken or ingested as a medicine or health food by itself, and can also be incorporated into various foods and drinks and ingested.The MAO inhibitor of the present invention can also be applied to the skin in the form of an external preparation such as an ointment, cream, or lotion.The dosage, intake, or application amount can be appropriately determined based on the age, sex, weight, and severity of symptoms of the subject, and by taking, taking, or applying an appropriate amount, the MAO inhibitor can be expected to have a preventive effect or treatment effect (including skin beautifying effect and whitening effect) on depression, Parkinson's disease, skin disorders, aging, and other diseases in which the inactivation of monoamine neurotransmitters is involved in the onset or progression of symptoms. EXAMPLES

[0013] The present invention will be described in detail below with reference to examples, but the present invention should not be construed as being limited to the following description.

[0014] Experimental Example 1: MAO inhibitory effect of mulberry extract and saxifrage extract (Experimental Method) The inhibitory effects of mulberry extract and saxifrage extract on the enzyme activity of MAO-A and MAO-B were evaluated using MAO-Glo Assay Systems (Promega). Specifically, 12.5 μL of the test sample prepared using the reaction buffer included in the kit was added to 25 μL of 100 nM solutions of MAO-A and MAO-B (both from Active Motif) prepared using the reaction buffer included in the kit so that the final concentrations of the mulberry extract and saxifrage extract were 0.3% and 1%, respectively, and incubated at 25°C for 30 minutes. After that, 12.5 μL of the solutions prepared using the reaction buffer included in the kit so that the final concentrations of the MAO-A reaction substrate and the MAO-B reaction substrate included in the kit were added to the reaction buffer included in the kit so that the final concentrations of the former were 160 μM and the latter were 16 μM, and further incubated at 25°C for 60 minutes. After incubation, 50 μL of luciferin detection reagent included in the kit was added, and the mixture was incubated at 25°C for 30 minutes. The luminescence intensity was then measured to evaluate the MAO inhibitory effects of the mulberry extract and saxifrage extract. Both the mulberry extract and saxifrage extract used as samples were commercially available products, and the composition (weight %) of the mulberry extract was magua root bark extract (extraction solvent was 30% water-containing 1,3-butylene glycol): 1.2, 1,3-butylene glycol: 69.16, water: 29.64. The composition (weight %) of the saxifrage extract was whole plant extract (extraction solvent was ethanol): 1.4, ethanol: 49.3, water: 49.3.

[0015] (Experimental Results) The inhibitory effects of mulberry extract and saxifrage extract on the enzyme activity of MAO-A and MAO-B are shown in Figures 1 and 2, respectively. For the mulberry extract, 12.5 μL of a sample prepared using the reaction buffer provided in the kit to make the final concentration of 70% 1,3-butylene glycol aqueous solution 1% was added to 25 μL of the reaction buffer provided in the kit. The luminescence intensity was measured in the same manner, except that 12.5 μL of a sample prepared using the reaction buffer provided in the kit to make the final concentration of 50% ethanol ... inhibitory effects of the mulberry extract and saxifrage extract on the enzyme activity of MAO-A and MAO-B are shown in Figures 1 and 2, respectively. The luminescence intensity was measured in the same manner, except that 12.5 μL of a sample prepared using the reaction buffer provided in the kit to make the final concentration of 50% ethanol aqueous solution 1% was added to 25 μL of the reaction buffer provided in the kit. The inhibitory effects of the mulberry extract and saxifrage extract on the enzyme activity of MAO-A and MAO-B are shown in Figures 1 and 2. In addition, Figures 1 and 2 show the results of measuring the luminescence intensity in the same manner except that a test sample with a final concentration of mulberry extract of 0% was prepared using the reaction buffer included in the kit so that the final concentration of 70% 1,3-butylene glycol aqueous solution was 1%. Also, a test sample with a final concentration of saxifrage extract of 0% was prepared using the reaction buffer included in the kit so that the final concentration of 50% ethanol aqueous solution was 1%. As is clear from Figures 1 and 2, both the mulberry extract (Saxifrage extract) and the saxifrage extract showed concentration-dependent inhibitory effects on the enzyme activity of MAO-A and MAO-B. From the above results, the MAO inhibitory effects of mulberry extract and saxifrage extract could be confirmed.

[0016] Formulation Example 1: Tablets Tablets having MAO inhibitory activity and consisting of the following component composition were produced by a method known per se (unit: weight %). Mulberry extract powder used in Experimental Example 1 1 lactose 80 Magnesium stearate 19

[0017] Formulation example 2: Biscuits Biscuits having MAO inhibitory activity and consisting of the following component composition were produced by a method known per se (unit: weight %). Saxifrage extract used in Experimental Example 1 1 32g plain flour Whole eggs 16 Butter 16 Sugar 24 water 10 1 teaspoon baking powder

[0018] Formulation example 3: Jelly A jelly having an MAO inhibitory effect and consisting of the following component composition was produced by a method known per se (unit: weight %). Mulberry extract used in Experimental Example 1 0.01 Gelling agent 1.3 Sugar 20 pH adjuster 2.5 Wednesday 76.19

[0019] Formulation Example 4: Ointment An ointment having an MAO inhibitory effect and consisting of the following component composition was produced by a method known per se (unit: weight %). Powder of Saxifrage extract used in Experimental Example 1 5 White Vaseline 95

[0020] Formulation Example 5: Cream A cream having an MAO inhibitory effect and consisting of the following component composition was produced by a method known per se (unit: weight %). Powder of mulberry extract used in Experimental Example 1 5 White Vaseline 30 Cetanol 15 Sodium Lauryl Sulfate 1 Ethyl parahydroxybenzoate 0.1 Butyl paraoxybenzoate 0.1 Water 48.8

[0021] Formulation Example 6: Lotion A lotion having an MAO inhibitory effect and consisting of the following component composition was produced by a method known per se (unit: weight %). Saxifrage extract used in Experimental Example 1 10 Polyoxyethylene (40) hydrogenated castor oil 0.5 Ethanol 5 Paraben: 0.2 Water 84.3 [Industrial Applicability]

[0022] INDUSTRIAL APPLICABILITY The present invention has industrial applicability in that it can provide an MAO inhibitor for preventing or treating diseases in which inactivation of monoamine neurotransmitters is involved in the onset or progression of symptoms.

Claims

[Claim 1] An inhibitor of the enzyme activity of MAO-A, the active ingredient being an extract of Saxifrage using an alcohol which may contain water as the extraction solvent (however, when used as a skin whitening agent, this does not include the case where it is used in combination with tranexamic acid or in combination with a hydrolysate of a rice bran extract).

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