JP2019193620A - OPH activity enhancer - Google Patents

Abstract

To provide, as enhancing the activity of OPH (oxidized proteolytic enzyme) in the living body may promote the degradation of oxidized proteins and glycated proteins, so-called aging proteins, and may prevent and treat aging and disease, and therefore an OPH activity enhancer that enhances the activity of OPH.SOLUTION: In order to solve the above-mentioned problems, an OPH activity enhancer containing at least any one of an extract of Yukinoshita (Saxifraga stolonifera ), Ume (Plum), Toki (Anjelica), Unshumikan (Cirtus unshiu), Mandarin orange, Hirami lemon, Tachibana (Citrus tachibana), Kawaraketsumei (Cassia nomame), Tougeshiba (Huperzia serrata), Rakanka (Momordicae grosvenori) as an active ingredient is provided. Also provided are foods, food additives, pharmaceuticals, quasi-drugs, cosmetics, etc. for enhancing OPH activity characterized by containing said OPH activity enhancer.SELECTED DRAWING: Figure 1

Description

  The present invention relates to an OPH activity enhancer that enhances the activity of oxidized protein hydrolase (OPH), which is an in vivo enzyme that degrades oxidized protein, and foods and beverages and pharmaceuticals containing the OPH activity enhancer. About.

  OPH is a kind of serine protease that liberates N-terminal acylated amino acids of proteins, and is also referred to as acyl amino acid releasing enzyme (AARE), acylated peptide degrading enzyme (APH) and the like. . Further, OPH acts not only on acylation but also on the N-terminal amino acid of a protein that has been formylated (Formyl), acetylated (Acetyl), butylated (Butyl), or propylated (Propyl).

  OPH is widely present in living tissues such as pig liver, rat brain, human blood, and stratum corneum. It has been reported that OPH preferentially degrades oxidized proteins and glycated proteins, degrades aging proteins in cooperation with the proteasome, and reduces amyloid β protein that causes Alzheimer's disease. It has also been confirmed that OPH degrades AGEs (terminal glycation products). From these facts, enhancing the activity of OPH in the living body promotes the degradation of aging proteins, and may possibly prevent or treat aging and diseases (Patent Document 1).

  In addition, OPH has an action of decomposing organophosphorus pesticides in blood (Non-Patent Document 1), an effect of suppressing prostate cancer (Non-Patent Document 2), and an inhibitory action of crystallin, which is an eye lens lens substance (Non-Patent Document 1) Reference 3), myeloma inhibitory action (Non-patent document 4), suppression of cell death by pesticide (chlorphyrifos) (Non-patent document 5), and the like have also been reported.

International Publication Number WO2011 / 004733

Gary B. Quistad, Rebecka Klintenberg, and John E. Casida, Blood acylpeptide hydrolase activity is a sensitive marker for exposure to some organophosphate toxicants.TOXICOLOGICAL SCIENCES 86 (2), 291-299 (2005) Christopher A McGoldrick1, Yu-Lin Jiang, Victor Paromov, Marianne Brannon, Koyamangalath Krishnan and William L Stone, Identification of oxidized protein hydrolase as apotential prodrug target in prostate cancer.http: //www.biomedcentral.com/1471-2407/14 / 77 R. Senthilkumar, P. Neelakanta Reddy AND K. Krishna Sharma, Studies on trypsin-modified bovine and human lens acylpeptide hydrolase. Exp. Eye Res. (2001) 72, 301 ± 310 Rosanna Palumbo, Marta Gogliettino, Ennio Cocca, Roberta Iannitti, Annamaria Sandomenico, Menotti Ruvo, Marco Balestrieri, Mose Rossi and Gianna Palmieri, APEH inhibition affects osteosarcoma cell viability via downregulation of the proteasome.Int.J. Mol. Sci. 2016, 17 , 1614 The Journal of Toxicological Sciences Vol. 38 , No.2, 193-203, 2013

  In view of the above circumstances, an object of the present invention is to provide an OPH activity enhancer that enhances the activity of OPH.

  As means for solving the above problems, the following inventions and the like are provided. That is, the present invention provides an OPH activity enhancer containing any one or more of Yukinoshita, Ume, Touki, Kawaraketsumei, Unshimikan, Mandarin Orange, Hiramemon, Tachibana, Togeshiba and Rakanka as an active ingredient.

  Further, an OPH activity enhancing food, an OPH activity enhancing food additive, an OPH activity enhancing pharmaceutical, an OPH activity enhancing quasi-drug, and an OPH, comprising any one of the above OPH activity enhancing agents Provide cosmetics for enhancing activity.

  The present invention can provide an OPH activity enhancer that enhances the activity of OPH, which is an in vivo enzyme that degrades oxidized protein.

Table showing OPH activity enhancing effect of each sample

Examples of the present invention will be described below. In addition, this invention should not be limited at all to these Examples, and can be implemented with various aspects in the range which does not deviate from the summary.
<Embodiment>
<Configuration>

  The OPH activity enhancer according to this example is an OPH activity enhancer containing any one or more of Yukinoshita, Ume, Toki, Kawaraketsumei, Unshimikan, Mandarin Orange, Hiramemon, Tachibana, Togeshiba, Lacanca as active ingredients. It is an agent. The “OPH activity enhancer” means an agent that enhances the oxidized proteolytic activity (hereinafter simply referred to as OPH activity) of OPH, which is an enzyme that degrades oxidized protein.

  The plant extract in this embodiment may be extracted from any part of the plant, for example, extracted from whole grass, flowers, seeds, fruits, pericarp, branches, stems, leaves, bark, roots, etc. It may be a thing. Moreover, the property of the extract is not limited. Below, each plant in this embodiment is demonstrated.

  Moreover, the extraction method is not particularly limited, and known methods such as solvent extraction, distillation, and pressing can be employed. As the solvent, ethanol, methanol, butylene glycol, etc. can be used in addition to water and hot water.

  “Saxifraga stolonifera” is a plant belonging to the genus Yukinoshita. The extract of Yukinoshita may be extracted from whole grass, flowers, seeds, fruits, fruit skin, branches, stems, leaves, bark, and roots.

  “Prunus mume” is a plant of the genus Rosaceae. The extract of ume may be extracted from any of whole grass, flowers, seeds, fruits, peels, branches, stems, leaves, bark, and roots.

  “Angelica acutiloba” is a plant belonging to the genus Cericaceae. The extract of Toki may be extracted from whole grass, flowers, seeds, fruits, peels, branches, stems, leaves, bark, and roots.

  “Chamaecrista nome” is a plant belonging to the genus Kawaraketsumei. The extract of Kawaroketsumei may be extracted from whole grass, flowers, seeds, fruits, fruit skin, branches, stems, leaves, bark, and roots, but is preferably an extract from stems and leaves. Kawaraketsumei tea is also called Hama tea.

  “Citrus unshiu Markovich” is a plant belonging to the genus Citrus mandarin. The extract of Satsuma mandarin may be extracted from whole grass, flowers, seeds, fruits, fruit skin, branches, stems, leaves, bark, and roots.

  “Mandarin orange” is a plant belonging to the genus Citrus mandarin. The mandarin orange extract may be extracted from any of whole grass, flowers, seeds, fruits, pericarp, branches, stems, leaves, bark, and roots.

  “Cirrus depressa” is a plant belonging to the genus Citrus mandarin and is known by the name of “shikwasa”. The extract of hirami lemon may be extracted from whole grass, flowers, seeds, fruits, pericarp, branches, stems, leaves, bark, and roots.

  "Citrus tachibana" is a plant of the genus Citrus mandarin. The extract of Tachibana may be extracted from any of whole grass, flowers, seeds, fruits, peels, branches, stems, leaves, bark, and roots.

  “Huperzia serrata” is a plant of the genus Higangenokazura. The extract of Syringa may be extracted from whole grass, flowers, seeds, fruits, fruit skin, branches, stems, leaves, bark, and roots.

  “Shiraitia grosvenorii” is a plant of the genus Lacanca. The extract of Lacanca may be extracted from whole grass, flowers, seeds, fruits, peels, branches, stems, leaves, bark, and roots.

  The OPH activity enhancer in this example can be provided as a food, food additive, pharmaceutical, quasi-drug, cosmetic or the like containing the OPH activity enhancer by using a known method. .

  For example, in the case of a pharmaceutical product, the OPH activity enhancer of this example is filled with powder or granules, filled in a capsule, or added with an excipient, a binder, a disintegrant, etc. Can be used. Moreover, when setting it as a foodstuff, it can provide by drying or crushing each plant suitably and boiling out with hot water. Moreover, it may be provided as a food after being shaped into a capsule or a tablet like a pharmaceutical, or provided in a form in which an OPH activity enhancer is added to various foods such as other beverages, seasonings, and confectionery. You can also

Moreover, it can also be set as cosmetics, such as a cosmetic liquid, cream, and lotion. For example, when it is used as a cosmetic liquid, in addition to the OPH activity enhancer of this example, water, rice bran oil, pentylene glycol, glycerin, squalane, cetyl palmitate, dimer dilinoleic acid and the like as main components, hyaluronic acid Additives include Na, hydrogenated rapeseed oil alcohol, carbomer, xanthan gum, potassium hydroxide, dimethicone, polysorbate-60, glyceryl stearate, hydrogenated castor oil, phenoxyethanol, urea, arginine, arbutin and citric acid. Then, after each component is dissolved in a water-soluble raw material and an oil-soluble raw material, they are heated and mixed and emulsified. While cooling this, an additive such as an extract is blended, and a highly volatile substance such as essential oil or fragrance is added when the temperature becomes lower. Thereafter, a predetermined safety test (bacteria, pH, temperature stability, viscosity, etc.) is performed, and the product can be provided as a product after being filled into a bottle.
<Test>

  In this test, the effect of enhancing the OPH activity of each plant extract is measured. In this measurement, a sample solution was added to the reaction system of OPH and its reaction substrate, N-acetyl-L-alanine p-nitro-anilide (AAPA), and the influence of OPH on the enzyme reaction was evaluated.

As a sample of each plant extract in this test, an extract commercially available as a raw material for cosmetics, quasi drugs, food additives and the like was used. Specifically, as for the samples of Yukinoshita, Ume, Toki, Unshimikan, Mandarin orange, hirami lemon, Tachibana, Togeshiba, and Lacanca, raw materials marketed as concentrated extracts were used as samples. In addition, two types of samples (Togeshiba A and Togeshiba B) with different manufacturers were used as the spinach. In addition, for Kawaraketsumei, 2 g of a raw material obtained by pulverizing whole powdered Kawarakemei which is commercially available as a food material, weighed and extracted with 40 ml of hot water (80 ° C.) for 1 hour, cooled to room temperature, and then commercially available tea. The supernatant was recovered by filtration through a pack, and a liquid sample was obtained in the same manner as other samples. Moreover, about all the samples, it measured by each of undiluted | stock solution, 10 time dilution, and 100 time dilution.
<Measurement method>

  Acylamino-acid releasing enzyme (AARE) (Takara Bio Inc.) was prepared as OPH to 0.025 U / mL with 50 mmol / L phosphate buffer (pH 7.2). In addition, an AAPA solution (BACHEM) was prepared as a reaction substrate to 25 mmol / L with a 50% ethanol solution. Further, 120 mmol / L Tris-HCl (pH 7.4) was used as a reaction buffer. Further, 1 mg / mL rubusoside was used as a positive control, and 1 mg / mL EGCg (epigallocatechin gallate) was used as a negative control.

  Then, 10 uL of sample, 10 uL of 0.025 U / mL OPH, and 210 uL of reaction buffer were added to one well of the microplate, and pre-warmed (preincubation) for 60 minutes at 37 ° C. Once returned to room temperature, 20 uL of 25 mmol / L AAPA solution (substrate solution) was added and mixed well to initiate OPH reaction. The reaction was carried out in a constant temperature bath at 37 ° C.

  The microplate was taken out from the thermostatic chamber at intervals of 30 minutes or 60 minutes, the absorbance at 405 nm was measured with a microplate reader, and pNA (paranitroaniline) generated by the OPH reaction was measured.

The activity of enhancing the activity of OPH is to determine the amount of change in absorbance per hour (reaction rate) and to determine the reaction rate when no sample is added as reference (Ref). The activity enhancing action was calculated.
(Expression) OPH activity enhancing action (%) = (OPH reaction rate of sample / OPH reaction rate of Ref) × 100
<Measurement results>

FIG. 1 is a table showing the OPH activity enhancing action of each sample. As shown in the table, it has been found that all the extracts of Yukinoshita, Ume, Touki, Unshimikan, Mandarin orange, Hiramemon, Tachibana, Kawaraketsumei, Togeshiba, and Lacanca according to the present embodiment have an OPH activity enhancing action.
<Effect>

  As shown as a result of the test, according to the present embodiment, an OPH activity enhancer containing any one or more of Yukinoshita, Ume, Toki, Kawaraketsumei, Unshimikan, Mandarin Orange, Hiramemon, Tachibana, Togeshiba, Lacanca as an active ingredient Etc. can be provided.

Claims (6)

  An OPH activity enhancer containing as an active ingredient any one or more of an extract of Yukinoshita, Ume, Touki, Kawaraketsumei, Unshimikan, Mandarin Orange, Hiramemon, Tachibana, Togeshiba, and Lacanca.   A food for enhancing OPH activity, comprising the OPH activity enhancer according to claim 1.   A food additive for enhancing OPH activity, comprising the OPH activity enhancer according to claim 1.   A pharmaceutical product for enhancing OPH activity, comprising the OPH activity enhancer according to claim 1.   A quasi-drug for enhancing OPH activity, comprising the OPH activity enhancer according to claim 1.   A cosmetic for enhancing OPH activity, comprising the OPH activity enhancer according to claim 1.

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