JP6869712B2 - Composition for improving vascular endothelial function - Google Patents
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- JP6869712B2 JP6869712B2 JP2016244310A JP2016244310A JP6869712B2 JP 6869712 B2 JP6869712 B2 JP 6869712B2 JP 2016244310 A JP2016244310 A JP 2016244310A JP 2016244310 A JP2016244310 A JP 2016244310A JP 6869712 B2 JP6869712 B2 JP 6869712B2
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- Coloring Foods And Improving Nutritive Qualities (AREA)
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Description
本発明は、血管内皮機能改善用組成物に関する。より詳細には、本発明は米糠酵素処理物を含む血管内皮機能改善用組成物に関する。 The present invention relates to a composition for improving vascular endothelial function. More specifically, the present invention relates to a composition for improving vascular endothelial function, which comprises a rice bran enzyme-treated product.
血管内皮は血管の最内層に存在しており、血液成分などの血管透過性、血管の収縮や弛緩反応、凝固線溶系に関与することによる血液凝固性の調節、血小板機能の制御等、様々な機能を有している。これらの機能は、血管内皮細胞が様々な生理活性因子を産生することと深く関与している。 The vascular endothelium exists in the innermost layer of blood vessels, and has various vascular permeability such as blood components, contraction and relaxation reactions of blood vessels, regulation of blood coagulation by being involved in the coagulation / fibrinolytic system, control of platelet function, etc. It has a function. These functions are deeply involved in the production of various bioactive factors by vascular endothelial cells.
核因子赤血球2関連因子2(Nuclear factor erythroid 2−related factor 2;Nrf2)は、血管内皮を酸化ストレスから防御する上で重要な役割を担っている。Nrf2は、通常、抑制性因子であるKeap1と結合した状態で存在しており、細胞が酸化ストレスや親電子物質などにさらされるとKeap1による抑制が解除され、抗酸化酵素等を誘導することが知られている。また、Nrf2は、酸化ストレスだけでなく、一酸化窒素により、Nrf2−Keap1が刺激され、Nrf2が活性化することも知られている。さらに、Nrf2は、血管内皮でヘムオキシゲナーゼ(HO−1)を誘導することによって血管内皮機能が改善されることが知られている。 Nuclear factor Erythrocyte 2 related factor 2 (Nuclear factor erythroid 2-related factor 2; Nrf2) plays an important role in protecting the vascular endothelium from oxidative stress. Nrf2 normally exists in a state of being bound to the inhibitory factor Keap1, and when cells are exposed to oxidative stress or electrophiles, the inhibition by Keap1 is released, and antioxidant enzymes and the like can be induced. Are known. It is also known that Nrf2-Kep1 is stimulated by nitric oxide as well as oxidative stress, and Nrf2 is activated. Furthermore, Nrf2 is known to improve vascular endothelial function by inducing heme oxygenase (HO-1) in the vascular endothelium.
また、サーチュインは、カロリー制限による細胞老化の抑制、寿命の延長などに関与することが知られているが、血管内皮細胞において、サーチュインファミリーであるSirt1を過剰発現することにより、酸化ストレスによる細胞老化誘導を回避できることが知られている。 In addition, sirtuin is known to be involved in suppression of cell aging due to calorie restriction, prolongation of life span, etc., but cell aging due to oxidative stress is caused by overexpression of the sirtuin family Sirtu1 in vascular endothelial cells. It is known that induction can be avoided.
本出願人はこれまでに、圧搾米糠油を水蒸気蒸留処理して得られる圧搾精油米糠油(特許文献1)、セイヨウヤナギ抽出物(特許文献2)などが血管内皮機能の改善に有用であることを見出している。 The applicant has found that pressed refined rice bran oil (Patent Document 1), extract of Seiyoyanagi (Patent Document 2), etc. obtained by steam distillation of pressed rice bran oil are useful for improving vascular endothelial function. Is found.
本発明は、上記した従来技術の現状に鑑みてなされたものであり、Nrf2の発現促進作用を通じて血管内皮機能を改善することができる、新規な血管内皮機能改善用組成物を提供することを目的とする。 The present invention has been made in view of the above-mentioned current state of the prior art, and an object of the present invention is to provide a novel composition for improving vascular endothelial function capable of improving vascular endothelial function through the expression promoting action of Nrf2. And.
本発明者らは、上記した目的を達成すべき鋭意研究を重ねた結果、驚くべきことに、米糠酵素処理物が優れたNrf2発現促進作用を有することを見出した。さらに、本発明者らは、米糠酵素処理物が、Sirt1の発現促進作用を有することも見出した。本発明者らはかかる知見に基づきさらなる研究を重ねることにより、本発明を完成させるに至った。 As a result of repeated diligent studies to achieve the above-mentioned object, the present inventors have surprisingly found that the rice bran enzyme-treated product has an excellent Nrf2 expression promoting action. Furthermore, the present inventors have also found that the rice bran enzyme-treated product has an action of promoting the expression of Sirt1. The present inventors have completed the present invention by repeating further research based on such findings.
即ち、本発明は以下の項に記載の主題を包含する。
項1.
米糠酵素処理物を含む、血管内皮機能改善用組成物。
項2.
前記米糠酵素処理物が、米糠のプロテアーゼ処理物である、上記項1に記載の組成物。
項3.
前記米糠酵素処理物が、米糠のサーモリシン処理物である、上記項1又は2に記載の組成物。
項4.
経口組成物である、上記項1〜3のいずれかに記載の組成物。
項5.
食品組成物又は医薬組成物である、上記項1〜4のいずれかに記載の組成物。
That is, the present invention includes the subjects described in the following sections.
Item 1.
A composition for improving vascular endothelial function, which comprises a rice bran enzyme-treated product.
Item 2.
Item 2. The composition according to Item 1, wherein the rice bran enzyme-treated product is a rice bran protease-treated product.
Item 3.
Item 3. The composition according to Item 1 or 2, wherein the rice bran enzyme-treated product is a rice bran thermolysin-treated product.
Item 4.
The composition according to any one of Items 1 to 3 above, which is an oral composition.
Item 5.
The composition according to any one of Items 1 to 4, which is a food composition or a pharmaceutical composition.
本発明によれば、血管内皮機能を改善することができる。 According to the present invention, the vascular endothelial function can be improved.
以下、本発明について詳細に説明する。 Hereinafter, the present invention will be described in detail.
本発明は、血管内皮機能改善用組成物を包含する。本発明の血管内皮機能改善用組成物は、米糠酵素処理物を含む。なお、本明細書において、本発明の血管内皮機能改善用組成物を単に「本発明の組成物」と記載する場合がある。 The present invention includes a composition for improving vascular endothelial function. The composition for improving vascular endothelial function of the present invention contains a rice bran enzyme-treated product. In the present specification, the composition for improving vascular endothelial function of the present invention may be simply referred to as "the composition of the present invention".
本発明の組成物に含まれる米糠酵素処理物は、米糠を酵素により処理して得られるものである。 The rice bran enzyme-treated product contained in the composition of the present invention is obtained by treating rice bran with an enzyme.
米糠としては、特に限定されないが、脱脂米糠であることが好ましい。また、圧搾により脱脂された脱脂米糠(圧搾脱脂米糠)であることが好ましく、搗精後に得られた米糠(生米糠)を加熱することでリパーゼを失活させ、さらに圧搾処理することで得られる圧搾脱脂米糠がより好ましい。また、脂質含量が5〜20質量%の脱脂米糠が好ましい。この範囲の脂質含量の脱脂米糠が、圧搾脱脂(特に、リパーゼ失活処理後の圧搾脱脂)により好ましく得られる。 The rice bran is not particularly limited, but is preferably a defatted rice bran. Further, it is preferable that the degreased rice bran is degreased by squeezing (squeezed defatted rice bran), and the lipase is inactivated by heating the rice bran (raw rice bran) obtained after milling, and the squeezing obtained by further squeezing treatment. Solvent degreased rice bran is more preferable. Further, defatted rice bran having a lipid content of 5 to 20% by mass is preferable. A defatted rice bran having a lipid content in this range is preferably obtained by squeezing defatting (particularly, squeezing defatting after lipase deactivation treatment).
リパーゼ失活処理は、18〜20質量%程度の脂質を含有する米糠(生米糠)の酸化劣化を防ぐ目的で行われる。通常、生米糠を70〜130℃程度で加熱焙煎することにより行われる。圧搾処理は、公知の圧搾法、例えば加熱焙煎処理され100〜115℃程度になった米糠を低温連続圧搾機(例えば、テクノシグマ社より販売されているミラクルチャンバー)により圧搾することで行う。圧搾は、圧搾後の脱脂米糠中の脂質が5〜20重量%程度となるまで行うことが好ましい。また、リパーゼ失活処理前の米糠や搾油後の脱脂米糠の水分含量を低減させる等の目的で乾燥処理を行っても良い。更に、特に圧搾処理にて得られた脱脂米糠は、さらに公知の方法により粉砕、分級し、粉末状とすることが好ましい。この際、粉末の平均粒子径は、5〜200μmが好ましく、10〜150μmがより好ましく、40〜100μmが最も好ましい。なお、脱脂米糠中の脂質含量は、上述の通り5〜20重量%が好ましく、7〜15重量%がより好ましい。なお、市販されている、上記のような脱脂米糠を購入して用いることもできる。このような市販脱脂米糠としては、例えばヌカップ(株式会社東京ブレフ製)、ハイブレフ(サンブラン株式会社製)などを挙げることができる。 The lipase inactivation treatment is carried out for the purpose of preventing oxidative deterioration of rice bran (raw rice bran) containing about 18 to 20% by mass of lipid. Usually, it is carried out by heating and roasting raw rice bran at about 70 to 130 ° C. The squeezing treatment is carried out by a known squeezing method, for example, rice bran that has been heat roasted and has reached about 100 to 115 ° C. is squeezed by a low temperature continuous squeezing machine (for example, a miracle chamber sold by TechnoSigma). The squeezing is preferably carried out until the lipid content in the defatted rice bran after squeezing is about 5 to 20% by weight. Further, the drying treatment may be carried out for the purpose of reducing the water content of the rice bran before the lipase deactivation treatment and the degreased rice bran after the oil extraction. Further, it is preferable that the defatted rice bran obtained by the pressing treatment is further crushed and classified by a known method to be powdered. At this time, the average particle size of the powder is preferably 5 to 200 μm, more preferably 10 to 150 μm, and most preferably 40 to 100 μm. The lipid content in the defatted rice bran is preferably 5 to 20% by weight, more preferably 7 to 15% by weight, as described above. It is also possible to purchase and use a commercially available degreased rice bran as described above. Examples of such commercially available degreased rice bran include Nucup (manufactured by Tokyo Blef Co., Ltd.) and Hi-Bref (manufactured by Saint-Blanc Co., Ltd.).
また、本願における米糠としては、米糠の水抽出物も含まれる。米糠の水抽出物は、米糠を水で抽出して得られる。米糠の水抽出物は、好ましくは米糠を水で抽出処理して得られた液体組成物(水及び抽出された米糠成分からなる)である。当該米糠の水抽出物に対して、後述する酵素を加えて処理することで、米糠酵素処理物を得ることもできる。水抽出条件は特に制限されず、例えば、10〜50℃程度の水に米糠を1〜24時間程度浸漬(又は撹拌)する方法が挙げられる。 The rice bran in the present application also includes a water extract of rice bran. The water extract of rice bran is obtained by extracting the rice bran with water. The water extract of rice bran is preferably a liquid composition (composed of water and the extracted rice bran component) obtained by extracting the rice bran with water. A rice bran enzyme-treated product can also be obtained by treating the water extract of rice bran with an enzyme described later. The water extraction conditions are not particularly limited, and examples thereof include a method of immersing (or stirring) rice bran in water at about 10 to 50 ° C. for about 1 to 24 hours.
米糠酵素処理物の調製に用いる酵素としては、米糠に含まれるタンパク質やポリペプチドを分解することができるタンパク質分解酵素(プロテアーゼ:ペプチダーゼも含む)であれば特に限定的ではなく、公知の酵素を用いることができる。このような酵素としては、例えば、トリプシン(EC3.4.21.4)、パパイン(EC3.4.22.2)、サーモリシン(EC3.4.24.27)、キモトリプシン(EC3.4.21.1、EC3.4.21.2)などが挙げられる。なお、カッコ内の記載は、酵素番号(Enzyme Commission numbers)である。中でも、サーモリシンが好ましい。なお、本明細書において、米糠酵素処理物を、酵素処理に用いる酵素に応じて、例えば、米糠プロテアーゼ処理物、米糠サーモリシン処理物、米糠キモトリプシン処理物などと表記する場合がある。 The enzyme used for preparing the rice bran enzyme-treated product is not particularly limited as long as it is a proteolytic enzyme (protease: including peptidase) capable of degrading proteins and polypeptides contained in rice bran, and a known enzyme is used. be able to. Examples of such enzymes include trypsin (EC 3.4.21.4), papain (EC 3.4.22.2), thermolysin (EC 3.4.24.27), and chymotrypsin (EC 3.4.21.). 1, EC 3.4.21.2.) And the like. The description in parentheses is the enzyme number (Enzyme Commission numbers). Of these, thermolysin is preferred. In this specification, the rice bran enzyme-treated product may be referred to as, for example, a rice bran protease treated product, a rice bran thermolysin-treated product, a rice bran chymotrypsin-treated product, or the like, depending on the enzyme used for the enzyme treatment.
米糠の酵素処理に用いる酵素は、例えば、市販品を購入して用いることができる。例えば、サーモリシンは、株式会社ペプチド研究所、大和化成株式会社、ナカライテスク株式会社、天野エンザイム、和光純薬工業株式会社等から購入することができる。 As the enzyme used for the enzyme treatment of rice bran, for example, a commercially available product can be purchased and used. For example, thermolysin can be purchased from Peptide Institute, Ltd., Yamato Kasei Co., Ltd., Nacalai Tesque Co., Ltd., Amano Enzyme, Wako Pure Chemical Industries, Ltd., etc.
米糠酵素処理物を得るための酵素処理条件は、用いる酵素の活性が得られる条件であれば特に限定的ではなく、適宜決定することができる。例えば、酵素としてサーモリシンを用いる場合、米糠及びサーモリシンを水に混合したうえ、30℃〜70℃で穏やかに撹拌しながら1〜30時間程度反応させることで処理を行うことができる。反応温度や反応時間については、使用する製造機器の構造・機能や用いる酵素の純度などにより至適条件は相違する。例えば、サーモリシンの至適温度は約65℃付近であるが、工業的には35〜60℃(さらに好ましくは50〜60℃)付近で反応温度を決定することが好ましい。なお、当該処理後、品質を安定化させるなどの目的で酵素を失活させてもよい。酵素の失活処理は、例えば、加熱(使用する酵素により条件は異なるが、例えば、サーモリシンを3%程度含有する酵素製剤を使用する場合には、70〜100℃、1〜20分程度の処理を採用することが出来る)等により行うことが出来る。さらに、処理後にろ過や遠心分離などを行って濾液等を回収したり、得られた濾液等に対して濃縮、乾燥、カラム処理などの精製を行ってもよい。 The enzyme treatment conditions for obtaining the rice bran enzyme-treated product are not particularly limited as long as the activity of the enzyme to be used can be obtained, and can be appropriately determined. For example, when thermolysin is used as an enzyme, the treatment can be carried out by mixing rice bran and thermolysin with water and reacting them at 30 ° C. to 70 ° C. with gentle stirring for about 1 to 30 hours. The optimum conditions for the reaction temperature and reaction time differ depending on the structure and function of the manufacturing equipment used and the purity of the enzyme used. For example, the optimum temperature of thermolysin is around 65 ° C., but industrially, it is preferable to determine the reaction temperature around 35 to 60 ° C. (more preferably 50 to 60 ° C.). After the treatment, the enzyme may be inactivated for the purpose of stabilizing the quality. The enzyme inactivation treatment is performed by heating, for example (conditions differ depending on the enzyme used, but for example, when an enzyme preparation containing about 3% thermolysin is used, the treatment is performed at 70 to 100 ° C. for about 1 to 20 minutes. Can be adopted) and so on. Further, after the treatment, the filtrate or the like may be recovered by filtration, centrifugation or the like, or the obtained filtrate or the like may be purified by concentration, drying, column treatment or the like.
上記の通り、米糠酵素処理物は米糠を酵素処理することにより得られるものであり、米糠酵素処理物には、米糠に含まれるタンパク質やポリペプチドの酵素分解物が含まれる。 As described above, the rice bran enzyme-treated product is obtained by enzymatically treating rice bran, and the rice bran enzyme-treated product contains enzymatic decomposition products of proteins and polypeptides contained in rice bran.
本発明の組成物は、上記した米糠処理物そのものであってもよいし、当該米糠酵素処理物に加え、その他の成分を含んでいてもよい。その他の成分としては、薬学的又は食品衛生学的に許容され得る担体などが挙げられる。 The composition of the present invention may be the above-mentioned rice bran processed product itself, or may contain other components in addition to the rice bran enzyme treated product. Other ingredients include pharmaceutically or food hygiene-acceptable carriers and the like.
本発明の組成物は、経口組成物として利用することができる。経口組成物としては、例えば、食品組成物、医薬組成物(医薬部外品を含む)などとして利用することができる。また、本発明の組成物に含まれる米糠酵素処理物は、優れたNrf2発現促進作用を有するだけでなく、Sirt1の発現促進作用を有することから、血管内皮機能改善用組成物として好ましく利用することができる。さらに、本発明の組成物は、血管内皮機能を改善することができるため、血管内皮機能の低下に伴う疾患(例えば、高血圧症、動脈硬化症、脂質異常症、糖尿病、糖尿病合併症など)の予防及び/又は治療に好ましく用いることができる。また、これらの疾患の発症や症状を緩和させることを目的として、これらの疾患を発症している人や発症するリスクの高い人に対する用途においても好ましく用いることができる。 The composition of the present invention can be used as an oral composition. As the oral composition, for example, it can be used as a food composition, a pharmaceutical composition (including quasi-drugs), and the like. Further, the rice bran enzyme-treated product contained in the composition of the present invention not only has an excellent Nrf2 expression-promoting action, but also has a Sirtuin expression-promoting action, and therefore is preferably used as a composition for improving vascular endothelial function. Can be done. Furthermore, since the composition of the present invention can improve vascular endothelial function, it can be used for diseases associated with a decrease in vascular endothelial function (for example, hypertension, arteriosclerosis, dyslipidemia, diabetes, diabetic complications, etc.). It can be preferably used for prevention and / or treatment. Further, for the purpose of alleviating the onset and symptoms of these diseases, it can be preferably used in applications for people who develop these diseases or who have a high risk of developing them.
本発明の組成物は、1回又は複数回(好ましくは2〜3回)に分けて摂取することができる。また、摂取対象としてはヒトが好ましいが、ヒト以外の非ヒト哺乳動物であってもよい。 The composition of the present invention can be ingested once or in a plurality of times (preferably 2 to 3 times). In addition, although humans are preferable as the ingestion target, non-human mammals other than humans may be used.
また、本発明の組成物に含まれる米糠酵素処理物は優れたNrf2の発現促進作用を有することから、抗酸化作用、より具体的には血管内皮における抗酸化作用などの作用を発揮することができ、本発明の組成物はこのような作用を目的とした用途に好ましく用いることができる。例えば、本発明の組成物は、抗酸化用、より具体的には血管内皮の抗酸化用などの用途に用いることができる。 Further, since the rice bran enzyme-treated product contained in the composition of the present invention has an excellent Nrf2 expression promoting action, it can exert an antioxidant action, more specifically, an antioxidant action on the vascular endothelium. The composition of the present invention can be preferably used for the purpose of such an action. For example, the composition of the present invention can be used for antioxidants, more specifically for antioxidants of vascular endothelium.
さらに、本発明の組成物に含まれる米糠酵素処理物はSirt1の発現促進作用を有することから、抗細胞老化作用、抗動脈硬化作用などの作用を発揮することができ、本発明の組成物はこのような作用を目的とした用途に好ましく用いることができる。例えば、本発明の組成物は、抗老化用、抗動脈硬化用などの用途に用いることができる。 Furthermore, since the rice bran enzyme-treated product contained in the composition of the present invention has an action of promoting the expression of Sirtu1, it is possible to exert actions such as anti-cell aging action and anti-arteriosclerosis action, and the composition of the present invention can exert an action. It can be preferably used for applications aimed at such an action. For example, the composition of the present invention can be used for anti-aging, anti-arteriosclerosis and the like.
本発明の組成物の形態としては特に限定されないが、経口組成物として利用する場合には、例えば、ハードカプセル、ソフトカプセル、サプリメント、チュアブル錠、飲料、粉末飲料、顆粒、フィルムなどの形態とすることができる。また、飲食品として使用する場合には、例えば、茶系飲料、スポーツ飲料、美容飲料、果汁飲料、炭酸飲料、アルコール飲料、清涼飲料、ゼリー飲料、水や湯、炭酸水等で希釈する濃縮タイプの飲料等の飲料、水や湯等に溶解又は懸濁させて飲用する粉末や顆粒、タブレット等の乾燥固形物、タブレット菓子、ゼリー類、スナック類、焼き菓子、揚げ菓子、ケーキ類、チョコレート、ガム、飴、グミなどの菓子類、スープ類、めん類、米飯類、シリアル等などの食品形態にすることもできる。このうち通常の生活において利用する場合には、サプリメントタイプ、チュアブル錠、ワンショットドリンクタイプなどの形態が好ましく、運動効果を高める目的で摂取する場合には、スポーツ飲料などの飲料の形態が最も好ましい。さらに、これらの経口組成物は容器に充填された容器詰食品として消費者に提供することができる。容器は密封できるものであれば特に限定されない。 The form of the composition of the present invention is not particularly limited, but when it is used as an oral composition, it may be in the form of, for example, a hard capsule, a soft capsule, a supplement, a chewable tablet, a beverage, a powdered beverage, granules, or a film. it can. When used as a food or drink, for example, a concentrated type that is diluted with tea-based beverages, sports beverages, beauty beverages, fruit juice beverages, carbonated beverages, alcoholic beverages, soft drinks, jelly beverages, water, hot water, carbonated water, etc. Beverages such as beverages, powders and granules to be drunk by dissolving or suspending in water or hot water, dried solids such as tablets, tablet confectionery, jellies, snacks, baked confectionery, fried confectionery, cakes, chocolate, It can also be in the form of foods such as sweets such as gum, candy and gummy, soups, noodles, rice and cereals. Of these, supplement types, chewable tablets, one-shot drink types, etc. are preferable when used in normal life, and beverage forms such as sports drinks are most preferable when ingested for the purpose of enhancing exercise effects. .. In addition, these oral compositions can be provided to consumers as packaged foods filled in containers. The container is not particularly limited as long as it can be sealed.
錠剤、顆粒剤、カプセル剤等の経口用固形製剤、内服液剤、シロップ剤等の経口用液体製剤などの場合は、乾燥物換算で経口組成物全量に対して、本発明の組成物を0.01 〜95質量%程度、好ましくは5〜90質量%程度、最も好ましくは10〜80質量%程度配合すればよい。上記以外の経口組成物の場合は、本発明の組成物を0.001〜50質量%程度、好ましくは0.005〜30質量%程度、最も好ましくは0.01〜10質量%程度配合すればよい。 In the case of oral solid preparations such as tablets, granules and capsules, and oral liquid preparations such as oral liquids and syrups, the composition of the present invention is 0. It may be blended in an amount of about 01 to 95% by mass, preferably about 5 to 90% by mass, and most preferably about 10 to 80% by mass. In the case of an oral composition other than the above, the composition of the present invention may be blended in an amount of about 0.001 to 50% by mass, preferably about 0.005 to 30% by mass, and most preferably about 0.01 to 10% by mass. Good.
以下、実施例を挙げて本発明をさらに詳細に説明するが、本発明は下記の例に限定されるものではない。 Hereinafter, the present invention will be described in more detail with reference to examples, but the present invention is not limited to the following examples.
製造例:米糠酵素処理物の調製
本製造例では、米糠としてハイブレフ(サンブラン社製)を、酵素としてサーモリシンを3%含有している酵素製剤を用いた。なお、ハイブレフは、米糠を圧搾することにより脱脂を行った圧搾脱脂米糠である。水に米糠を30g/Lとなるように混合し、これにサーモリシンを0.0045g/Lとなるように加えた。そして、当該混合物を55℃で15時間撹拌した。その後、80℃で5分間撹拌し、酵素失活させた。次いで、得た処理液に珪藻土を用いてろ過した後に濃縮し、さらに濃縮液を121℃15分間殺菌した。このようにして得た殺菌済みの濾液を凍結乾燥し、米糠酵素処理物を得た。
Production example: Preparation of rice bran enzyme-treated product In this production example, an enzyme preparation containing Hybref (manufactured by Saint-Blanc) as rice bran and 3% thermolysin as an enzyme was used. The high bref is a squeezed degreased rice bran that has been degreased by squeezing the rice bran. Rice bran was mixed with water to a concentration of 30 g / L, and thermolysin was added to the mixture to a concentration of 0.0045 g / L. Then, the mixture was stirred at 55 ° C. for 15 hours. Then, the mixture was stirred at 80 ° C. for 5 minutes to inactivate the enzyme. Then, the obtained treatment liquid was filtered using diatomaceous earth and then concentrated, and the concentrated liquid was further sterilized at 121 ° C. for 15 minutes. The sterilized filtrate thus obtained was freeze-dried to obtain a rice bran enzyme-treated product.
試験例:Nrf2、及びSirt1の遺伝子発現への影響の検討
サンプルとして、上記製造例で調製した米糠酵素処理物を用いた。また、H2O2及びレスベラトロール、並びにDMSOを対照として使用した。12ウェルプレートを用い、2%FBS培地800μL中で、ヒト臍帯静脈内皮細胞(HUVECs、三光純薬社製)を培養し、各種サンプルを下記表1に記載の最終濃度の5倍となるように溶解した2%FBS培地を200μL添加し、6時間及び24時間培養した。次いで、Total RNAをTotal RNA Mini Kitを用いて抽出した。1本鎖のcDNA(sscDNA)は0.35μgのTotal RNAよりPrimeScript RT reagent Kitを使用して合成した。なお、Total RNAの回収量が不足している場合には、回収量に応じてsscDNAの希釈率を変更した上でmRNAの定量分析に供した。Nrf2及びSirt1のmRNAの定量分析は、リアルタイムPCRシステム(Applied Biosystems社製)を使用して実施した。また、Premix Ex Taq(タカラバイオ社製)、Assay−on−Demand、及びGene Expression Products(Hs00232352_m1 for NFE2L2(Nrf2)、Hs01009005_m1 for Sirt1、及びHs02387368_g1 for RPS18)を定量的リアルタイムPCR分析に使用した。定量データはそれぞれ、Ribosomal protein S18(RPS18)の発現レベルでΔΔCt methodで補正した。結果を下記表1に示す。
Test Example: The rice bran enzyme-treated product prepared in the above production example was used as a sample for examining the effects of Nrf2 and Sirtu1 on gene expression. H 2 O 2 and resveratrol, as well as DMSO were used as controls. Human umbilical vein endothelial cells (HUVECs, manufactured by Sanko Junyaku Co., Ltd.) were cultured in 800 μL of 2% FBS medium using a 12-well plate, and various samples were adjusted to 5 times the final concentration shown in Table 1 below. 200 μL of dissolved 2% FBS medium was added and cultured for 6 hours and 24 hours. The Total RNA was then extracted using the Total RNA Mini Kit. Single-strand cDNA (ssDNA) was synthesized from 0.35 μg of Total RNA using the PrimeScript RT reagent Kit. When the amount of total RNA recovered was insufficient, the dilution rate of ssDNA was changed according to the amount of recovery, and then the mRNA was subjected to quantitative analysis. Quantitative analysis of Nrf2 and Sirtuin mRNAs was performed using a real-time PCR system (Applied Biosystems). In addition, Premix Ex Taq (manufactured by Takara Bio Inc.), Assay-on-Demand, and Gene Expression Products (Hs00232352_m1 for NFE2L2 (Nrf2), Hs0109005_m1 for Sirt1) Quantitatively, Hs0109005_m1 for Quantitative data were corrected by ΔΔCt method at the expression level of Ribosomal protein S18 (RPS18), respectively. The results are shown in Table 1 below.
表1から、米糠酵素処理物は、優れたNrf2発現促進作用及びSirt1発現促進作用を有することが分かった。これらの結果から、米糠酵素処理物は、Nrf2及びSirt1の発現を促進することによって、優れた血管内皮機能改善作用、抗酸化作用、抗動脈硬化作用などを奏することが考察される。 From Table 1, it was found that the rice bran enzyme-treated product had an excellent Nrf2 expression promoting action and a Sirt1 expression promoting action. From these results, it is considered that the rice bran enzyme-treated product exerts an excellent vascular endothelial function improving action, an antioxidant action, an anti-arteriosclerosis action, and the like by promoting the expression of Nrf2 and Sirtu1.
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