JP2018002631A - Oph active enhancer - Google Patents
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- JP2018002631A JP2018002631A JP2016130042A JP2016130042A JP2018002631A JP 2018002631 A JP2018002631 A JP 2018002631A JP 2016130042 A JP2016130042 A JP 2016130042A JP 2016130042 A JP2016130042 A JP 2016130042A JP 2018002631 A JP2018002631 A JP 2018002631A
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Abstract
Description
本発明は、酸化蛋白質を分解する生体内酵素である酸化蛋白質分解酵素（ｏｘｉｄｉｚｅｄ ｐｒｏｔｅｉｎ ｈｙｄｒｏｌａｓｅ：ＯＰＨ）の活性を増強させるＯＰＨ活性増強剤、及び、当該ＯＰＨ活性増強剤を含有する飲食品や医薬品などに関する。 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は、蛋白のＮ末端アシル化アミノ酸を遊離するセリンプロテアーゼの一種で、アシルアミノ酸遊離酵素（ａｃｙｌａｍｉｎｏ−Ａｃｉｄ Ｒｅｌｅａｓｉｎｇ Ｅｎｚｙｍｅ：ＡＡＲＥ）、アシル化ペプチド分解酵素（ａｃｙｌｐｅｐｔｉｄｅ ｈｙｄｒｏｌａｓｅ：ＡＰＨ）などとも言われている。また、ＯＰＨは、アシル化だけでなく、ホルミル化（Ｆｏｒｍｙｌ）、アセチル化（Ａｃｅｔｙｌ）、ブチル化（Ｂｕｔｙｌ）、プロピル化（Ｐｒｏｐｙｌ）された蛋白質のＮ末端アミノ酸に対しても作用する。 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 hydrolase (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はブタ肝臓、ラット脳、ヒト血液、角層などの生体組織に広く存在している。ＯＰＨは酸化蛋白質や糖化蛋白質を優先的に分解するとともにプロテアソームと協働して老化蛋白質を分解すること、アルツハイマー病の原因であるアミロイドβ蛋白質を減少させることが報告されている。またＯＰＨがＡＧＥｓ（終末糖化産物）を分解することも確認されている。これらのことから生体中のＯＰＨの活性を増強させることは、老化蛋白質の分解を促進し、老化や疾患を予防・治療できる可能性がある。 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 prevent or treat aging and diseases.
上記の事情を鑑み、本発明は、ＯＰＨの活性を増強させるＯＰＨ活性増強剤を提供することを課題とする。 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.
上記課題を解決するための手段として、以下の発明などを提供する。すなわち、ルブソシド、没食子酸のいずれかを含有するＯＰＨ活性増強剤を提供する。また、前記ＯＰＨ活性増強剤を含有する食品、食品添加物、医薬品、医薬部外品及び化粧品を提供する。 As means for solving the above problems, the following inventions and the like are provided. That is, the OPH activity enhancer containing either rubusoside or gallic acid is provided. Also provided are foods, food additives, pharmaceuticals, quasi drugs and cosmetics containing the OPH activity enhancer.
本発明により、酸化蛋白質を分解する生体内酵素であるＯＰＨの活性を増強させるＯＰＨ活性増強剤などを提供することができる。 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.
以下、本発明の実施例について説明する。なお、本発明は、これらの実施例に何ら限定されるべきものではなく、その要旨を逸脱しない範囲において、種々なる態様で実施し得る。
＜実施例＞
＜構成＞
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.
<Example>
<Configuration>
本実施例に係るＯＰＨ活性増強剤は、ルブソシド、没食子酸のいずれかを有効成分として含有するＯＰＨ活性増強剤である。「ＯＰＨ活性増強剤」とは、酸化蛋白質の分解酵素であるＯＰＨの酸化蛋白質分解活性（以下、単にＯＰＨ活性）を増強させる剤を意味する。 The OPH activity enhancer according to this example is an OPH activity enhancer containing either rubusoside or gallic acid as an active ingredient. 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.
「ルブソシド（Ｒｕｂｕｓｏｓｉｄｅ）」（Ｃ３２Ｈ５０Ｏ１３）は、甜茶の原料であるバラ科キイチゴ属のテンヨウケンコウシに含まれる物質であり、甘味成分として知られている。図１は、ルブソシドの構造を示す図である。 “Rubusoside” (C 32 H 50 O 13 ) is a substance contained in the moss of the genus Rosaceae, which is a raw material of strawberry tea, and is known as a sweetening ingredient. FIG. 1 is a diagram showing the structure of rubusoside.
「没食子酸」（Ｃ６Ｈ２（ＯＨ）３ＣＯ２Ｈ）は、テンヨウケンコウシに含まれる物質である。また、茶、没食子やそのほかの虫?に存在することが知られており、タンニンを加水分解しても得られる。 “Gallic acid” (C 6 H 2 (OH) 3 CO 2 H) is a substance contained in the calendula. It is also known to exist in tea, gallic and other insects, and can be obtained by hydrolyzing tannins.
本実施例におけるＯＰＨ活性増強剤は、さらに既知の方法を用いることにより、当該ＯＰＨ活性増強剤を含有する食品、食品添加物、医薬品、医薬部外品、化粧品などとして提供することが可能である。 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. .
例えば、医薬品とする場合には、本実施例のＯＰＨ活性増強剤を粉体や粒体としカプセルに充填したり、あるいは、賦形剤、結合剤、崩壊剤などを添加して打錠機等を用いて製造することができる。また、食品とする場合には、各植物を適宜乾燥や破砕等を湯で煮出すことで提供できる。また、医薬品のようにカプセルや錠剤のような形態で提供してもよいし、他の飲料、調味料、菓子等の各種の食品にＯＰＨ活性増強剤を添加した態様で提供することもできる。 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 simmering each plant suitably with a hot water such as drying or crushing. Moreover, you may provide in the form like a capsule and a tablet like a pharmaceutical, and can also provide in the aspect which added OPH activity enhancer to various foodstuffs, such as another drink, a seasoning, and confectionery.
また、美容液、クリーム、ローションなどの化粧品とすることもできる。例えば、美容液とする場合には、本実施例のＯＰＨ活性増強剤の他、水、コメヌカ油、ペンチレングリコール、グリセリン、スクワラン、パルミチン酸セチル、ダイマージリノール酸などを主成分とし、ヒアルロン酸Ｎａ、水添ナタネ油アルコール、カルボマー、キサンタンガム、水酸化カリウム、ジメチコン、ポリソルベート−６０、ステアリン酸グリセリル、水添ヒマシ油、フェノキシエタノール、尿素、アルギニン、アルブチン、クエン酸などを添加剤とする。そして、各成分を水溶性原料・油溶性原料に分けて溶解してから、それらを加熱して混合・乳化する。これを冷却しながらエキスなどの添加物を配合し、さらに低温になったところで精油や香料などの揮発性の高いものを添加する。その後、所定の安全性の検査（菌、ｐＨ、温度安定性、粘度等）を行い、瓶などに充填して製品として提供することができる。
＜試験＞
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>
本試験において、ルブソシドと没食子酸のＯＰＨ活性の増強作用について測定する。本測定ではＯＰＨとその反応基質であるＮ−ａｃｅｔｙｌ−Ｌ−ａｌａｎｉｎｅ ｐ−ｎｉｔｒｏ−ａｎｉｌｉｄｅ（ＡＡＰＡ）との反応系に試料溶液を添加し、ＯＰＨの酵素反応への影響を評価した。試料には、ルブソシドと没食子酸の他に比較対象として、テンヨウケンコウシに含まれる成分であるルチン及びエラグ酸をサンプルに含めた。
＜測定方法＞
In this test, the effect of enhancing the OPH activity of rubusoside and gallic acid 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. In addition to rubusoside and gallic acid, the sample contained rutin and ellagic acid, which are components contained in the calcareous cow, for comparison.
<Measurement method>
ＯＰＨとしてａｃｙｌａｍｉｎｏ−ａｃｉｄ ｒｅｌｅａｓｉｎｇ ｅｎｚｙｍｅ（ＡＡＲＥ）、ＯＰＨの反応基質としてＡＡＰＡ溶液を使用した。測定にはＯＰＨを０．０１Ｕ／ｍＬ、０．００５Ｕ／ｍＬ、０．００１Ｕ／ｍＬに調製して使用した。 Acylamino-acid releasing enzyme (AARE) was used as OPH, and AAPA solution was used as a reaction substrate for OPH. For the measurement, OPH was adjusted to 0.01 U / mL, 0.005 U / mL, and 0.001 U / mL.
９６ウェルマイクロプレートの各ｗｅｌｌにＯＰＨ、ＡＡＰＡ、試料溶液（ジメチルスルホキシドを溶媒）を混合添加し、３７℃に設定したインキュベーター内で４時間反応させた反応液の４０５ｎｍにおける吸光度をマイクロプレートリーダーで測定した。ＯＰＨの酵素活性は１時間当たりの吸光度変化量（反応速度）を求めた。同時にｒｅｆｅｒｅｎｃｅ（Ｒｅｆ）として試料無添加時の反応速度を求め、下式に従ってＲｅｆの反応速度を１００％とした時の活性増強作用を算出した。ＯＰＨ活性増強作用のネガティブコントロールにはエピガロカテキンガレート（ＥＧＣｇ）を使用した。
（式）ＯＰＨ活性増強作用（％）＝（試料のＯＰＨ反応速度／ＲｅｆのＯＰＨ反応速度）×１００
＜測定結果＞
Absorbance at 405 nm of the reaction solution obtained by mixing and adding OPH, AAPA, and sample solution (dimethyl sulfoxide as a solvent) to each well of a 96-well microplate for 4 hours in an incubator set at 37 ° C. was measured with a microplate reader. did. For the enzyme activity of OPH, the amount of change in absorbance per hour (reaction rate) was determined. At the same time, the reaction rate when no sample was added was determined as reference (Ref), and the activity enhancing action when the reaction rate of Ref was 100% was calculated according to the following formula. Epigallocatechin gallate (EGCg) was used as a negative control for enhancing the OPH activity.
(Expression) OPH activity enhancing action (%) = (OPH reaction rate of sample / OPH reaction rate of Ref) × 100
<Measurement results>
測定結果を表１に示す。
表に示すように、ルブソシドと没食子酸にＯＰＨ活性増強作用があることが分かった。とくにルブソシドは、テンヨウケンコウシに含まれる他の成分と比べて顕著に優れたＯＰＨ活性増強作用を有することが分かった。
＜効果＞
As shown in the table, it was found that rubusoside and gallic acid have an effect of enhancing OPH activity. In particular, it was found that rubusoside has a significantly superior effect of enhancing OPH activity as compared with other components contained in the hen.
<Effect>
本実施形態により、優れたＯＰＨ活性増強作用を有するルブソシド、没食子酸のいずれかを含有するＯＰＨ活性増強剤を提供することができる。 According to the present embodiment, an OPH activity enhancer containing either rubusoside or gallic acid having an excellent effect of enhancing OPH activity can be provided.
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2019187354A (en) * | 2018-04-27 | 2019-10-31 | 株式会社アンチエイジングコミュニケーション | OPH activity enhancer |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2008024600A (en) * | 2006-07-18 | 2008-02-07 | Naris Cosmetics Co Ltd | Inhibitor for acrolein adduct formation, skin anti-aging external preparation and anti-aging food and beverage containing the same |
| JP2011126795A (en) * | 2009-12-16 | 2011-06-30 | Maruzen Pharmaceut Co Ltd | Type i collagen production promoter |
| JP2014076957A (en) * | 2012-10-10 | 2014-05-01 | Noevir Co Ltd | Desaccharification agent and skin external preparation |
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Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2008024600A (en) * | 2006-07-18 | 2008-02-07 | Naris Cosmetics Co Ltd | Inhibitor for acrolein adduct formation, skin anti-aging external preparation and anti-aging food and beverage containing the same |
| JP2011126795A (en) * | 2009-12-16 | 2011-06-30 | Maruzen Pharmaceut Co Ltd | Type i collagen production promoter |
| JP2014076957A (en) * | 2012-10-10 | 2014-05-01 | Noevir Co Ltd | Desaccharification agent and skin external preparation |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2019187354A (en) * | 2018-04-27 | 2019-10-31 | 株式会社アンチエイジングコミュニケーション | OPH activity enhancer |
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