JP2019180345A - Vitamin A metabolism promoter - Google Patents
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本発明は、肝臓中のビタミンAの代謝を亢進するビタミンA代謝促進剤に関する。 The present invention relates to a vitamin A metabolism promoter that enhances the metabolism of vitamin A in the liver.
欧米化や運動不足による肥満は、脂質異常症、高血圧、2型糖尿病の原因となるのみならず、肥満は 非アルコール性脂肪肝(NAFLD)の原因で日本人の10〜30%が罹患していると推定されており、非アルコール性脂肪性肝炎(NASH)を経て、肝癌へと変遷することが知られている。生活習慣病は、糖尿病、脂質異常症、高血圧、高尿酸血症など、生活習慣が発症原因に深く関与していると考えられている疾患の総称であるが、このような疾患と肥満が複合した状態は、がん、脳血管疾患、心臓病の3大死因のリスクを上げるといわれているため、早急な対策が求められている。 Obesity due to westernization and lack of exercise not only causes dyslipidemia, hypertension, and type 2 diabetes, but obesity affects non-alcoholic fatty liver (NAFLD) and affects 10-30% of Japanese people. It has been estimated that it is transformed into liver cancer via non-alcoholic steatohepatitis (NASH). Lifestyle-related diseases are a general term for diseases in which lifestyle-related diseases are thought to be deeply involved in the cause of onset, such as diabetes, dyslipidemia, hypertension, and hyperuricemia. Since it is said that the risk of three major causes of death, cancer, cerebrovascular disease and heart disease, is urgently required.
中でも、肝機能障害に関しては、代謝機能、解毒作用、エネルギーの貯蔵、胆汁の生成等、様々な機能に障害を引き起こす要因となるため、これまでも多方面から検討がなされ、解決手段が提案されている。 In particular, liver dysfunction is a factor that causes damage to various functions such as metabolic function, detoxification, energy storage, bile production, etc., and so far has been studied from various aspects and proposed solutions. ing.
例えば、特開2009−221193号公報には、米由来ペプチドの新たな用途として、酒粕を、セルラーゼ及びβアミラーゼで処理した後、プロテアーゼNアマノG、及びスミチームAPで処理する工程を含む方法により得られるペプチド混合物、又は酒粕を、セルラーゼ及びβアミラーゼで処理した後、サモアーゼで処理する工程を含む方法により得られるペプチド混合物からなる肝機能障害抑制剤が開示されている(特許文献1)。 For example, Japanese Patent Application Laid-Open No. 2009-221193 provides a new use of a rice-derived peptide by a method comprising a step of treating sake lees with cellulase and β-amylase and then treating with protease N Amano G and Sumiteam AP. A liver dysfunction inhibitor comprising a peptide mixture obtained by a method comprising treating a peptide mixture or sake lees obtained with cellulase and β-amylase and then treating with samoylase is disclosed (Patent Document 1).
脂質代謝異常は、ビタミンA欠乏によって引き起こされることが知られている。そのため、肝臓中のビタミンA代謝を改善できれば、ビタミンA代謝異常を原因とする種々の疾病も改善されることが期待される。 It is known that abnormal lipid metabolism is caused by vitamin A deficiency. Therefore, if vitamin A metabolism in the liver can be improved, various diseases caused by abnormal vitamin A metabolism are expected to be improved.
従って本発明の目的は、肝臓中のビタミンA代謝を改善させるビタミンA代謝促進剤を提供することにある。 Accordingly, an object of the present invention is to provide a vitamin A metabolism promoter that improves vitamin A metabolism in the liver.
本発明者らは上記課題を解決するため鋭意検討を行った結果、アルファ化した玄米を摂取することでビタミンA代謝が亢進し脂質代謝異常を改善することを見出し、本発明を完成するに至った。 As a result of intensive studies to solve the above problems, the present inventors have found that ingestion of pregelatinized brown rice increases vitamin A metabolism and improves lipid metabolism abnormalities, and has completed the present invention. It was.
本発明はかかる知見に基づきなされたものであり、アルファ化した玄米を有効成分として含有することを特徴とする、ビタミンA代謝促進剤を提供するものである。 The present invention has been made based on such findings, and provides a vitamin A metabolism promoter characterized by containing pregelatinized brown rice as an active ingredient.
本発明によれば、ビタミンA代謝促進剤を摂取することにより、肝臓中のビタミンA代謝が亢進するため、ビタミンA代謝の低下に起因する種々の疾病(視覚作用、皮膚炎、成長不良、脂質代謝異常など)の予防、改善、治療等に適用することができる。 According to the present invention, since vitamin A metabolism in the liver is increased by ingesting a vitamin A metabolism promoter, various diseases (visual effects, dermatitis, poor growth, lipids) caused by a decrease in vitamin A metabolism are caused. It can be applied to prevention, improvement, treatment, etc. of metabolic abnormalities).
以下、本発明に係る実施形態について詳細に説明する。本実施形態において、「玄米」とは、外側を覆っているもみ殻を取り除いた状態の米であって、糠(果皮、種皮、糊粉層)、胚乳(白米)及び胚芽からなるものをいう。米の品種や種類は特に限定されず、うるち米、もち米、発芽玄米、胚芽米、分搗き米、黒米、赤米及びこれらから2種以上をブレンドしたブレンド米などが使用できる。 Hereinafter, embodiments according to the present invention will be described in detail. In the present embodiment, “brown rice” is rice in a state in which the rice husk covering the outside is removed, and is made of rice bran (fruit skin, seed coat, glue layer), endosperm (white rice), and germ. . The varieties and types of rice are not particularly limited, and glutinous rice, glutinous rice, germinated brown rice, germinated rice, split rice, black rice, red rice, and blended rice obtained by blending two or more of these can be used.
本実施形態において、玄米はアルファ化した玄米を使用する。アルファ化の方法は特に限定されることはなく、通常の玄米の炊飯で用いられているものが利用でき、直火加熱、蒸気加熱などが例示される。加熱処理条件は、玄米を均一に炊飯状態(アルファ化状態)とする条件であればよく、90〜135℃(好ましくは98〜125℃)で10〜60分(好ましくは20〜50分)が好適であるが、この範囲に限定はされない。 In this embodiment, the brown rice used is pregelatinized brown rice. There are no particular limitations on the method of pregelatinization, and those used in ordinary brown rice cooking can be used, and examples include direct fire heating and steam heating. Heat processing conditions should just be the conditions which make brown rice into a rice cooking state (alpha-ized state) uniformly, and are 10 to 60 minutes (preferably 20 to 50 minutes) at 90-135 degreeC (preferably 98-125 degreeC). Although preferred, this range is not limited.
本実施形態において、玄米は玄米の形状を維持したそのものでもよいが、玄米を粗く粉砕したもの、細かく粉砕したものなどの粉砕物でもよく、また、玄米と粉砕物の混合物、各種粉砕物の混合物でもよい。 In the present embodiment, the brown rice may be the same as maintaining the shape of the brown rice, but may be a pulverized product such as a coarsely pulverized or finely pulverized brown rice, a mixture of brown rice and pulverized material, and a mixture of various pulverized products. But you can.
本実施形態に係るビタミンA代謝促進剤は、公知の製剤化方法、特に経口摂取に適した製剤化技術を使用して製剤化することができる。製剤としては、錠剤被覆錠剤、カプセル剤、顆粒剤、細粒剤、散剤、乳剤、シロップ剤等を挙げることができる。 The vitamin A metabolism promoter according to the present embodiment can be formulated using a known formulation method, particularly a formulation technique suitable for oral intake. Examples of the preparation include tablet-coated tablets, capsules, granules, fine granules, powders, emulsions, syrups and the like.
本実施形態のビタミンA代謝促進剤は、本発明の目的を損なわない限り、種々の食品原料又は添加物を配合することができる。好ましい食品原料又は添加物としては、例えば、ビタミンAの前駆体であるβカロテン、ビタミンAの吸収を促進する油、白米(白米にも多少の効果があり、玄米単体よりも食べやすくなるため)等を挙げることができる。 The vitamin A metabolism promoter of this embodiment can be blended with various food ingredients or additives as long as the object of the present invention is not impaired. Preferred food ingredients or additives include, for example, beta-carotene, which is a precursor of vitamin A, oil that promotes absorption of vitamin A, white rice (because white rice has some effects and is easier to eat than brown rice alone) Etc.
1.材料と方法
6週齢の雄性Zucker fattyラット、野生型である雄性Zucker LeanラットをAIN93Gで4日間予備飼育した後、Lean群、対照群、WR(白米)、BR(玄米)の4つの実験群に分け、10週間飼育した(表1)。飼料組成はLean群、対照群にはAIN93Gを、WRまたはBRはAIN93Gを基本組成として、炭水化物源であるコーンスターチとアルファ化コーンスターチをすべてアルファ化白米粉末または、アルファ化玄米粉末に置き換えたもの(53重量%)を調整した。アルファ化白米およびアルファ化玄米ともに、アルファー食品(株)より供給されたものを使用し、それらをジェット粉砕機((株)セイシン工業)にて、粒度150μm以下(100メッシュパス)に粉砕した粉末を飼料に用いた。なお、Zucker fatty ratはNAFLDを発症する肥満モデル動物であり、AIN-93Gは米国国立栄養研究所(American Institute of Nutrition)から1993年に発表されたマウス・ラット用の栄養研究のための標準精製飼料組成である。
1. Materials and methods
6 weeks old male Zucker fatty rats, wild type male Zucker Lean rats were pre-bred for 4 days with AIN93G, then divided into 4 experimental groups: Lean group, control group, WR (white rice), BR (brown rice), They were raised for 10 weeks (Table 1). Feed composition is Lean group, control group is AIN93G, WR or BR is AIN93G as basic composition. % By weight) was adjusted. Powders obtained by using alpha food products supplied from Alpha Foods Co., Ltd. and pulverizing them to a particle size of 150 μm or less (100 mesh pass) using a jet crusher (Seishin Industry Co., Ltd.). Was used for feed. Zucker fatty rat is an obese model animal that develops NAFLD, and AIN-93G is a standard refinement for nutritional research for mice and rats published in 1993 by the American Institute of Nutrition. Feed composition.
ビタミンA代謝産物のレチニィルパルミテートは、HPLC(島津製作所社製、形式 CTO-10ASVP)で測定した。HPLC条件については、カラム:Wakosil II 5C18AR;4.6mm×250mm、Mightysil RP-18GP II 150-4.6、流速0.8ml/min、溶媒はエタノール:水=95:5、検出は蛍光 励起波長(325nm)吸収波長(470nm)で行った。肝臓αSMA、LRAT、ビタミンA代謝酵素であるRaldh1、レチノイン酸受容体β(RARβ)、β酸化関連因子の核内受容体であるPPARα、ミトコンドリアのβ酸化律速酵素であるCPT1aとインスリン応答因子であるMTPの遺伝子発現量については、リアルタイムPCR(Applied Biotechnology社製、形式StepOne)にて分析した。 Retinyl palmitate of vitamin A metabolite was measured by HPLC (manufactured by Shimadzu Corporation, type CTO-10ASVP). For HPLC conditions, column: Wakosil II 5C18AR; 4.6 mm x 250 mm, Mightysil RP-18GP II 150-4.6, flow rate 0.8 ml / min, solvent ethanol: water = 95: 5, detection is fluorescence excitation wavelength (325 nm) absorption Performed at a wavelength (470 nm). Liver αSMA, LRAT, vitamin A metabolizing enzyme Raldh1, retinoic acid receptor β (RARβ), β-oxidation-related factor nuclear receptor PPARα, mitochondrial β-oxidation rate-limiting enzyme CPT1a and insulin response factor The gene expression level of MTP was analyzed by real-time PCR (Applied Biotechnology, format StepOne).
2.結果
図1は、アルファ化玄米を摂取したラットにおける肝臓αSMA遺伝子発現量を測定した結果を示す図である。BRの肝臓αSMA遺伝子発現は、対照群と比較して、有意に減少した(p<0.05)。
2. Results FIG. 1 is a diagram showing the results of measuring the expression level of liver αSMA gene in rats fed with pregelatinized brown rice. BR liver αSMA gene expression was significantly reduced compared to the control group (p <0.05).
図2は、アルファ化玄米を摂取したラットにおける肝臓レチニィルパルミテート濃度(a)及びLRAT(b)を測定した結果を示す図であり、図3は、Raldh1遺伝子発現量(a)及びRARβ遺伝子発現量(b)を測定した結果を示す図である。 FIG. 2 is a graph showing the results of measurement of liver retinyl palmitate concentration (a) and LRAT (b) in rats fed pregelatinized brown rice. FIG. 3 shows Raldh1 gene expression level (a) and RARβ gene. It is a figure which shows the result of having measured the expression level (b).
図2、図3に示すように、肝臓レチニィルパルミテート濃度とRaldh1、RARβ遺伝子発現は、対照群と比較して有意に増加した(p< 0.05)。また、図1〜3の結果より、アルファ化玄米の摂取によりビタミンAの代謝が亢進していることが判明した。 As shown in FIGS. 2 and 3, liver retinyl palmitate concentration, Raldh1, and RARβ gene expression were significantly increased compared to the control group (p <0.05). Moreover, it turned out that the metabolism of vitamin A is accelerated | stimulated by the intake of pregelatinized brown rice from the result of FIGS.
図4は、β酸化および脂肪症に対するCPT1およびMTP効果を説明するための図である。ビタミンA活性本体であるレチノイン酸の受容体であるRARβ2のアゴニストがPPARαを活性化させ、脂肪酸β酸化が活性化することでNAFLDを軽減するという報告がある。レチノイン酸量と相関があるRARβ遺伝子発現量が玄米摂取により対照群と比較して有意に上昇している(図2b)。つまり、アルファ化玄米摂取によってビタミンA代謝、特にレチノイン酸量によって発現が制御されているRARβが上昇し、PPARα、CPT1aなどのβ酸化関連遺伝子発現量が上昇し、脂肪肝改善に関与している可能性が示唆された(図4a、b)。また、玄米摂取によりMTPの遺伝子発現量の上昇し、中性脂肪(TG)を超低密度リポタンパク質(VLDL)として血液中に放出することが促進され、NAFLDが改善していると考えられる(図4c)。 FIG. 4 is a diagram for explaining the effects of CPT1 and MTP on β-oxidation and steatosis. There is a report that an agonist of RARβ2, which is a receptor for retinoic acid, which is a vitamin A active body, activates PPARα and activates fatty acid β oxidation to reduce NAFLD. The RARβ gene expression level correlated with the amount of retinoic acid is significantly increased by brown rice intake compared to the control group (FIG. 2b). In other words, pre-gelatinized brown rice intake increases RARβ, whose expression is controlled by vitamin A metabolism, especially retinoic acid level, and increases the expression levels of β-oxidation-related genes such as PPARα and CPT1a, and is involved in fatty liver improvement The possibility was suggested (Fig. 4a, b). In addition, brown rice intake increases MTP gene expression and promotes the release of neutral fat (TG) into the blood as very low density lipoprotein (VLDL), which is thought to improve NAFLD ( FIG. 4c).
以上の結果から、アルファ化玄米を有効成分として含有するビタミンA代謝改善剤が肝臓におけるビタミンA貯蔵を改善し、それにより肥満を伴う肝臓脂質代謝を改善できることが判明した。 From the above results, it was found that a vitamin A metabolism improving agent containing pregelatinized brown rice as an active ingredient can improve vitamin A storage in the liver and thereby improve liver lipid metabolism accompanying obesity.
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JPS56148237A (en) * | 1980-04-15 | 1981-11-17 | Yoshihide Hagiwara | Food or beverage made of lactic fermentation product from unpolished rice |
JPH0622724A (en) * | 1992-07-08 | 1994-02-01 | Kumamoto Pref Gov | Preparation of nutrient food |
JPH10229836A (en) * | 1997-02-19 | 1998-09-02 | Akio Kohama | Manufacture of powder food material, and mixer and ball mill therefor |
JP2001172192A (en) * | 1999-12-21 | 2001-06-26 | Yasuhiko Fujisaki | Therapeutic diet |
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JP2009201383A (en) * | 2008-02-26 | 2009-09-10 | Konan Shokuryo Kk | Functional food |
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JPS56148237A (en) * | 1980-04-15 | 1981-11-17 | Yoshihide Hagiwara | Food or beverage made of lactic fermentation product from unpolished rice |
JPH0622724A (en) * | 1992-07-08 | 1994-02-01 | Kumamoto Pref Gov | Preparation of nutrient food |
JPH10229836A (en) * | 1997-02-19 | 1998-09-02 | Akio Kohama | Manufacture of powder food material, and mixer and ball mill therefor |
JP2001172192A (en) * | 1999-12-21 | 2001-06-26 | Yasuhiko Fujisaki | Therapeutic diet |
JP2004161656A (en) * | 2002-11-12 | 2004-06-10 | Kanegafuchi Chem Ind Co Ltd | Peroxisome proliferator-activated receptor ligand agent |
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日本食品保蔵科学会誌, vol. 42, no. 1, JPN6022008125, 2016, pages 3 - 8, ISSN: 0004720995 * |
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