JP5808772B2 - Method for activating mitochondria in hepatocytes - Google Patents

Method for activating mitochondria in hepatocytes Download PDF

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JP5808772B2
JP5808772B2 JP2013101375A JP2013101375A JP5808772B2 JP 5808772 B2 JP5808772 B2 JP 5808772B2 JP 2013101375 A JP2013101375 A JP 2013101375A JP 2013101375 A JP2013101375 A JP 2013101375A JP 5808772 B2 JP5808772 B2 JP 5808772B2
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純子 千堂
純子 千堂
征次 阿部
征次 阿部
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Description

本発明は、肝細胞の活動を活性化させる作用を有する肝細胞活性化剤に関する。   The present invention relates to a hepatocyte activator having an action of activating hepatocyte activity.

近年、肝臓病患者が多くなり、各種肝臓疾患への対策が求められている。特に生活の西洋化や運動不足、飲酒量の増加等に伴って、脂肪肝患者及びその予備軍が増加している。肝臓への脂肪蓄積を改善する方法としては、食餌療法、運動療法、薬物療法などが試行されているが、これらの方法は、コントロールや継続的な実施が困難であるために、必ずしも満足のいく治療効果が得られないのが実状である。そのため、様々な肝臓疾患の予防剤、改善剤、治療剤が開発されている。   In recent years, the number of patients with liver disease has increased, and countermeasures against various liver diseases have been demanded. Especially with the westernization of life, lack of exercise, and increased alcohol consumption, fatty liver patients and their reserves are increasing. Dietary therapy, exercise therapy, drug therapy, etc. have been tried as methods for improving fat accumulation in the liver, but these methods are not always satisfactory because they are difficult to control and continuously perform. The reality is that no therapeutic effect can be obtained. Therefore, preventive agents, ameliorating agents, and therapeutic agents for various liver diseases have been developed.

例えば、特許文献1には、少なくとも98%の高純度のエイコサペンタエン酸、その塩及びそのエステルから選ばれる少なくとも一種類からなる不飽和脂肪酸類を含む非アルコール性脂肪性肝臓疾患の治療薬が開示されている。また、特許文献2には、セイヨウニンジンボクエキスを含有する糖尿病性脂肪肝の予防、改善または治療用組成物が開示されている。また、特許文献3には、オンコスタチンM受容体アゴニストを有効成分として含有する肝臓疾患治療又は予防薬が開示されている。   For example, Patent Document 1 discloses a therapeutic agent for non-alcoholic fatty liver disease containing at least one type of unsaturated fatty acid selected from eicosapentaenoic acid having a high purity of at least 98%, a salt thereof and an ester thereof. Has been. Patent Document 2 discloses a composition for preventing, improving, or treating diabetic fatty liver containing carrot extract. Patent Document 3 discloses a therapeutic or prophylactic agent for liver diseases containing an oncostatin M receptor agonist as an active ingredient.

国際公開第2009/028457号パンフレットInternational Publication No. 2009/028457 Pamphlet 特開2012−201593号公報JP 2012-201593 A 特開2004−26768号公報JP 2004-26768 A

特許文献1〜3等で開示された肝臓疾患の予防剤、改善剤、治療剤は、特定の肝臓疾患に対しては有効なものである。一方で、肝臓疾患は、近年の生活様式の変化をはじめとする様々な要因が相互に重なり合い、肝臓における肝細胞の活性低下に起因して引き起こされることが多く、そのためその治療方法は一様ではない。
また、肝臓疾患の予防剤、改善剤、治療剤としては、生体に対する安全性が高く、飲食品の成分として使用できるものが好ましい。
The preventive agent, ameliorating agent, and therapeutic agent for liver diseases disclosed in Patent Literatures 1 to 3 and the like are effective for specific liver diseases. On the other hand, liver diseases are often caused by various factors, including changes in lifestyles in recent years, that are caused by decreased activity of hepatocytes in the liver. Absent.
In addition, as a preventive agent, ameliorating agent, and therapeutic agent for liver diseases, those that are highly safe for living bodies and that can be used as ingredients in foods and drinks are preferable.

かかる状況下、本発明は、生体に対する安全性が高く、肝機能自体を活性化させる作用を有する、新規の肝細胞活性化剤を提供することを目的とする。また、本発明の他の目的は、当該肝細胞活性化剤を含有し、日常的に摂取のしやすい医薬及び機能性食品を提供することである。   Under such circumstances, an object of the present invention is to provide a novel hepatocyte activator that is highly safe for living bodies and has an action of activating liver function itself. Another object of the present invention is to provide a medicine and a functional food that contain the hepatocyte activator and are easily taken on a daily basis.

本発明者は、上記課題を解決すべく鋭意研究を重ねた結果、ショウガ由来の成分である、ショーガオール類に肝細胞自体を活性化させる作用があることを見出し、本発明に至った。   As a result of intensive studies to solve the above-mentioned problems, the present inventor has found that shogaols, which are ginger-derived components, have an action of activating hepatocytes themselves, leading to the present invention.

すなわち、本発明は、以下の発明に係るものである。
<1> 6−ショウガオールを有効成分として含有する肝細胞内のミトコンドリアの活性化剤。
<2> 前記<1>に記載の活性化剤を含有することを特徴とする固形製剤。
<3> 前記<1>に記載の活性化剤を含有することを特徴とする液状製剤。
<4> 前記<1>に記載の活性化剤を含有する脂肪肝の予防剤、改善剤、又は治療剤。
<5> 肝細胞を含む培養液に、6−ショウガオールを投与し、肝細胞内のミトコンドリアを活性化させる肝細胞内のミトコンドリアの活性化方法。
That is, the present invention relates to the following inventions.
<1> A mitochondrial activator in hepatocytes containing 6-shogaol as an active ingredient.
<2> A solid preparation characterized by containing an active activators of <1>.
<3> liquid formulation characterized by containing an active activators of <1>.
<4> The preventive agent for fatty liver containing the active activators according to <1>, improving agents, or therapeutic agents.
<5> in culture medium containing liver cells, administered 6-shogaol, method for activating mitochondria in hepatocytes to activate the mitochondria in hepatocytes.

本発明によれば、肝細胞に対して優れた活性作用を有する肝細胞活性化剤が提供される。また、本発明の肝細胞活性化剤はショーガオール類というショウガ由来の成分を有効成分とするため、当該肝細胞活性化剤を含有する医薬及び機能性食品は、日常的に摂取しやすい。   ADVANTAGE OF THE INVENTION According to this invention, the hepatocyte activator which has the outstanding active effect | action with respect to a hepatocyte is provided. In addition, since the hepatocyte activator of the present invention contains a ginger-derived component called shogaol as an active ingredient, the medicine and functional food containing the hepatocyte activator are easily taken on a daily basis.

高精度表面プラズモン共鳴装置の模式図である。It is a schematic diagram of a high precision surface plasmon resonance apparatus. 高精度表面プラズモン共鳴(HP−SPR)試験方法の概念図である。It is a conceptual diagram of a high precision surface plasmon resonance (HP-SPR) test method. 6−ショーガオールよるHP−SPR角度変化の評価結果である。It is an evaluation result of HP-SPR angle change by 6-shogaol.

以下、本発明について例示物等を示して詳細に説明するが、本発明は以下の例示物等に限定されるものではなく、本発明の要旨を逸脱しない範囲において任意に変更して実施できる。   Hereinafter, the present invention will be described in detail with reference to examples and the like, but the present invention is not limited to the following examples and the like, and can be arbitrarily modified and implemented without departing from the gist of the present invention.

(肝細胞活性化剤)
本発明の肝細胞内のミトコンドリアの活性化剤は、ショウガオール類を有効成分として含有することを特徴とする。なお、本明細書において、「肝細胞内のミトコンドリアの活性化剤」を、「肝細胞活性化剤」と記載する場合がある。
(Hepatocyte activating agent)
The activator for mitochondria in hepatocytes of the present invention is characterized by containing gingerol as an active ingredient. In the present specification, “an activator of mitochondria in hepatocytes” is sometimes referred to as “hepatocyte activator”.

本発明において、「肝細胞活性化剤」とは、肝細胞内のミトコンドリアが活性化する作用を有することを意味する。肝細胞内のミトコンドリアの活性化は、高精度表面プラズモン共鳴試験方法(以下、「HP−SPR試験方法」と記載する。)にて評価することができる。HP−SPR試験方法は国際公開第2007/069692号パンフレットで開示された「細胞内のミトコンドリアの分極モニタリング」に記載された方法で行うことができる。具体的な評価方法は後述の実施例にて説明する。   In the present invention, the “hepatocyte activator” means having an action of activating mitochondria in hepatocytes. Activation of mitochondria in hepatocytes can be evaluated by a high-precision surface plasmon resonance test method (hereinafter referred to as “HP-SPR test method”). The HP-SPR test method can be carried out by the method described in “Monitoring of intracellular mitochondrial polarization” disclosed in WO 2007/069692. A specific evaluation method will be described in Examples described later.

本発明の肝細胞活性化剤は、肝細胞自体を活性化する作用を有するため、特定の肝臓疾患に限定されず、脂肪肝、肝炎、肝硬変など様々な肝臓疾患に対して有効あると予測される。
特に肝細胞内のミトコンドリアが活性化することにより、肝臓の代謝を活性化し、脂肪を燃焼する効果があるので、本発明の肝細胞活性化剤は、脂肪肝の予防、改善、治療に効果的であると予測される。そのため、本発明の肝細胞活性化剤は、脂肪肝の予防剤、改善剤、治療剤の用途で使用できる。なお、脂肪肝はアルコール性脂肪肝、非アルコール性脂肪肝のどちらも対象になる。
Since the hepatocyte activator of the present invention has an action of activating hepatocytes themselves, it is not limited to specific liver diseases, and is expected to be effective for various liver diseases such as fatty liver, hepatitis, and cirrhosis. The
In particular, the activation of mitochondria in hepatocytes activates liver metabolism and burns fat, so the hepatocyte activator of the present invention is effective in preventing, improving and treating fatty liver. It is predicted that. Therefore, the hepatocyte activator of the present invention can be used as a preventive agent, ameliorating agent, or therapeutic agent for fatty liver. As for fatty liver, both alcoholic fatty liver and non-alcoholic fatty liver are targeted.

以下、本発明の肝細胞活性化剤の構成成分について、より詳細に説明する。
本発明の肝細胞活性化剤の有効成分であるショウガオール類は、下記式(1)で表される化合物である。
Hereinafter, the components of the hepatocyte activator of the present invention will be described in more detail.
Shogaols, which are active ingredients of the hepatocyte activator of the present invention, are compounds represented by the following formula (1).

本発明の肝細胞活性化剤において、ショウガオール類の中でも、式(1)で表される化合物においてn=4に相当する6−ショウガオールを有効成分とすることが好ましい。   In the hepatocyte activator of the present invention, among the shogaols, 6-shogaol corresponding to n = 4 in the compound represented by the formula (1) is preferably used as an active ingredient.

本発明の肝細胞活性化剤は、肝臓疾患治療に適用する場合、経口で投与することができる。また、非経口で直接肝臓に投与してもよい。
投与量は、通常成人一人当たり1日につきジンゲロール類換算で0.1〜1000mg程度である。1〜3回に分けて経口あるいは非経口投与される。なお、本発明における摂取量は、対象者の年齢、性別、体重、病状などの個別差により一定ではないため、上記範囲にのみ限定されるものではなく、本発明の所望の効果が得られるように、個別具体的に投与量を適宜設定すればよい。
The hepatocyte activator of the present invention can be administered orally when applied to the treatment of liver diseases. It may also be administered parenterally and directly into the liver.
The dose is usually about 0.1 to 1000 mg in terms of gingerols per day per adult. Orally or parenterally divided into 1 to 3 times. In addition, since the intake in the present invention is not constant due to individual differences such as the age, sex, weight, and medical condition of the subject, it is not limited to the above range, and the desired effect of the present invention can be obtained. In addition, the dose may be appropriately set individually and specifically.

(肝細胞活性化剤の形態)
本発明の肝細胞活性化剤は、その有効量を薬学的に許容される担体とともに配合し、固形製剤又は液状製剤として経口又は非経口的に投与することができる。剤形は通常の経口投与または非経口投与に使用されるものならどのような剤形でもよい。
経口投与または非経口投与に利用される剤形としては、具体的には、固形製剤として、粉末剤、顆粒剤、錠剤、カプセル剤、トローチ等が挙げられる。また、液状製剤として内用液剤、外用液剤、懸濁剤、乳剤、シロップ剤、注射液、輸液等が例示され、これら剤形やその他の剤形が目的に応じて適宜選択される。
(Form of hepatocyte activator)
The hepatocyte activator of the present invention can be compounded in an effective amount with a pharmaceutically acceptable carrier, and can be administered orally or parenterally as a solid preparation or a liquid preparation. The dosage form may be any dosage form used for normal oral administration or parenteral administration.
Specific examples of dosage forms used for oral administration or parenteral administration include powders, granules, tablets, capsules, troches and the like as solid preparations. Examples of liquid preparations include internal solutions, external solutions, suspensions, emulsions, syrups, injection solutions, infusions, and the like, and these dosage forms and other dosage forms are appropriately selected according to the purpose.

固形製剤において、主剤である本発明の肝細胞活性化剤に、賦形剤、結合剤、崩壊剤、潤沢剤、矯味剤、安定化剤などの補助剤を用いてもよい。主剤と補助剤の比率は目的に応じて適宜選択される。
固形製剤における賦形剤の好適な例としては、例えば乳糖、D−マンニトール、デンプンなどが挙げられる。結合剤の好適な例としては、例えば、結晶セルロース、白糖、D−マンニトール、デキストリン、ヒドロキシプロピルセルロース等が挙げられる。崩壊剤の好適な例としては、例えば、デンプン、カルボキシメチルセルロース、カルボキシメチルセルロースカルシウム等が挙げられる。また、必要に応じて防腐剤、抗酸化剤、着色剤、甘味剤などの製剤添加物を用いてもよい。
In solid preparations, adjuvants such as excipients, binders, disintegrants, lubricants, corrigents and stabilizers may be used for the hepatocyte activator of the present invention which is the main agent. The ratio of the main agent and the auxiliary agent is appropriately selected according to the purpose.
Preferable examples of the excipient in the solid preparation include lactose, D-mannitol, starch and the like. Preferable examples of the binder include crystalline cellulose, sucrose, D-mannitol, dextrin, hydroxypropyl cellulose and the like. Preferable examples of the disintegrant include starch, carboxymethyl cellulose, carboxymethyl cellulose calcium and the like. Moreover, you may use formulation additives, such as antiseptic | preservative, antioxidant, a coloring agent, and a sweetener, as needed.

また、液状製剤として用いる場合、溶媒としては有効成分であるショウガオール類の分散性を有し、生体安全性があるものが選択される。溶媒の好適な例としては、例えば、注射用水、エタノール、プロピレングリコールなどが挙げられる。   Moreover, when using as a liquid formulation, what has the dispersibility of the gingerol which is an active ingredient, and a biological safety is selected as a solvent. Preferable examples of the solvent include water for injection, ethanol, propylene glycol and the like.

また、液状製剤は、主剤である本発明の肝細胞活性化剤と共に、溶解補助剤、懸濁化剤、等張化剤、緩衝剤、抗酸化剤等の補助成分を含んでいてもよい。
溶解補助剤の好適な例としては、エタノール、ポリエチレングリコール、プロピレングリコール、安息香酸ベンジル、炭酸ナトリウム、クエン酸ナトリウムなどが挙げられる。懸濁化剤の好適な例としては、ラウリル硫酸ナトリウム、ラウリルアミノプロピオン酸、レシチン、塩化ベンザルコニウム、塩化ベンゼトニウム、モノステアリン酸グリセリン、ポリビニルアルコール、ポリビニルピロリドン、カヒドロキシメチルセルロース等が挙げられる。緩衝剤の好適な例としては、リン酸塩、酢酸塩、炭酸塩等の緩衝液が挙げられる。抗酸化剤の好適な例としては、亜硫酸塩、アスコルビン酸塩などが挙げられる。
The liquid preparation may contain auxiliary components such as a solubilizing agent, a suspending agent, an isotonic agent, a buffering agent and an antioxidant together with the hepatocyte activator of the present invention which is the main agent.
Preferable examples of the solubilizer include ethanol, polyethylene glycol, propylene glycol, benzyl benzoate, sodium carbonate, sodium citrate and the like. Preferable examples of the suspending agent include sodium lauryl sulfate, laurylaminopropionic acid, lecithin, benzalkonium chloride, benzethonium chloride, glyceryl monostearate, polyvinyl alcohol, polyvinyl pyrrolidone, cahydroxymethyl cellulose and the like. Preferable examples of the buffer include buffers such as phosphates, acetates and carbonates. Preferable examples of the antioxidant include sulfite and ascorbate.

上記固形製剤や液状製剤の製法は、一般的な医薬品の製法を適用することができる。   The manufacturing method of the said solid formulation and liquid formulation can apply the manufacturing method of a general pharmaceutical.

(機能性食品)
一方、日常的に飲食することで、本発明の肝細胞活性化剤を摂取したい場合には、該食品、飲料に含有させて機能性食品としてもよい。
ここでいう「機能性食品」とは、一般食品に加えて、健康食品、栄養補助食品、栄養機能食品、栄養保険食品等、健康の維持の目的で摂取する食品および/又は飲料を意味している。なお、機能性食品として製品化する場合には、食品に用いられる様々な添加剤、具体的には、着色料、保存料、増粘安定剤、酸化防止剤漂白剤、防菌防黴剤、酸味料、調味料、乳化剤、強化剤、製造用剤、香料等を添加していてもよい。
(Functional food)
On the other hand, when it is desired to ingest the hepatocyte activator of the present invention by eating and drinking on a daily basis, it may be contained in the food or beverage to obtain a functional food.
The term “functional food” as used herein means foods and / or beverages ingested for the purpose of maintaining health, such as health foods, nutritional supplements, functional nutritional foods, nutrition insurance foods, in addition to general foods. Yes. In addition, when commercializing as a functional food, various additives used in food, specifically, coloring agents, preservatives, thickening stabilizers, antioxidant bleaching agents, antibacterial and antifungal agents, A sour agent, a seasoning, an emulsifier, a reinforcing agent, a manufacturing agent, a fragrance and the like may be added.

本発明の機能性食品の対象となる、食品、飲料は特に限定されるものではないが、特にショウガの風味が加えられることが好適な食品、飲料が好ましい。例えば、食品として、ソーセージ、ハム、魚介加工品、ゼリー、キャンディー、チューインガムなどの食品類が挙げられる。また、飲料としては、各種の茶類、清涼飲料水、酒類、栄養ドリンクなどが挙げられる。この中でも、茶、ゼリーであることが特に好ましい。
本発明の肝細胞活性化剤は、このような食品、飲料に添加することにより、簡易に経口摂取することができる。
The foods and beverages that are the targets of the functional food of the present invention are not particularly limited, but foods and beverages to which ginger flavor is preferably added are particularly preferable. Examples of food include foods such as sausage, ham, processed seafood, jelly, candy, and chewing gum. Examples of the beverage include various teas, soft drinks, alcoholic beverages, and energy drinks. Among these, tea and jelly are particularly preferable.
The hepatocyte activator of the present invention can be easily taken orally by adding to such foods and beverages.

なお、本発明の肝細胞活性化剤におけるショーガオール類を多量に含む点で、特開2011−32248号公報で開示した方法により、ショーガオール類を富化させた加熱発酵ショウガを機能性食品に使用することが好適である。前記加熱発酵ショウガは、食品、飲料に添加することにより、簡易に経口摂取することができる。また配合量を調節することにより肝細胞活性化効果だけではなく薬味としても使用することができる。   In addition, the heat fermented ginger enriched with shogaols by the method disclosed in Japanese Patent Application Laid-Open No. 2011-32248 is used as a functional food in that it contains a large amount of shogaols in the hepatocyte activator of the present invention. It is preferred to use. The heat-fermented ginger can be easily taken orally by adding it to foods and beverages. Moreover, it can be used not only as a hepatocyte activation effect but also as a spice by adjusting the blending amount.

本発明の肝細胞活性化剤は、ヒトのみならず、動物に対しても同様な効果を有する。そのため、動物用の医薬品として用いることもできし、ペットフードに添加することもできる。   The hepatocyte activator of the present invention has the same effect not only on humans but also on animals. Therefore, it can be used as a pharmaceutical product for animals and can be added to pet food.

以下、実施例により本発明を更に詳細に説明するが、本発明は、その要旨を変更しない限り以下の実施例に限定されるものではない。   EXAMPLES Hereinafter, although an Example demonstrates this invention further in detail, this invention is not limited to a following example, unless the summary is changed.

(細胞培養)
供試細胞にはヒト肝臓がん細胞である Hep G2を用いた。この細胞をペニシリン(50 units/mL)とストレプトマイシン(50μL/mL)の混合溶液1%(v/v)、並びにウシ胎仔血清(FBS) 10%(v/v)を含むダルベッコ改変イーグル培地(DMEM)にて37℃、CO2 5%の条件下で培養した。
(Cell culture)
Hep G2 which is a human liver cancer cell was used as a test cell. Dulbecco's modified Eagle medium (DMEM) containing 1% (v / v) of a mixed solution of penicillin (50 units / mL) and streptomycin (50 μL / mL) and fetal bovine serum (FBS) 10% (v / v) ) At 37 ° C. and 5% CO 2 .

(HP−SPR試験)
SPRシグナルの測定は測定対象物である細胞の上部に蛍光顕微鏡、下部にSPRセンサーを有するカスタムメイドの高精度表面プラズモン共鳴装置で行った。図1に模式図を示す。SPRセンサーはkretschmann配置の光学系を用い、プリズムにBK7(屈折率1.51)、光源として半導体レーザー(波長670nm、出力3mW、ビーム径1mm)、検出器にはシリコンフォトダイオード検出器を用いた。測定は大気下で行った。
(HP-SPR test)
The SPR signal was measured with a custom-made high-precision surface plasmon resonance apparatus having a fluorescence microscope on the upper part of the measurement target cell and an SPR sensor on the lower part. A schematic diagram is shown in FIG. The SPR sensor uses an optical system of kretschmann arrangement, BK7 (refractive index 1.51) as a prism, a semiconductor laser (wavelength 670 nm, output 3 mW, beam diameter 1 mm) as a light source, and a silicon photodiode detector as a detector. . The measurement was performed in the atmosphere.

「実施例」
細胞を一晩CO2インキュベータ内(37℃、CO2 5%)で基板上に接着した後、HP−SPR装置のプリズム上にセットし、6−ショーガオール(6-Shogaol,Sigma)の濃度が0、1nM、10nM及び100nM(DMSOの最終濃度0.01%)の各培養液を供与した。
各成分が細胞に作用する時間帯であるサンプル投入後45分から55分間のおける安定した直線的なシグナル部分を5分間モニター、さらにサンプル成分が細胞に代謝され作用し始める時間帯である薬剤投入後55分以降で、安定した直線的なシグナル部分を5分間モニターし、各細胞におけるコントロールの変化率を差し引き、HP−SPR角度変化率として求めた。結果を図3に示す。各バーは、測定二回の平均値を、エラーバーは二回のそれぞれの値を示す。
"Example"
The cells were allowed to adhere to the substrate overnight in a CO 2 incubator (37 ° C., CO 2 5%), and then set on the prism of the HP-SPR device. The concentration of 6-Shogaol (Sigma) was Each culture broth at 0, 1 nM, 10 nM and 100 nM (final DMSO concentration 0.01%) was donated.
A stable linear signal portion from 45 minutes to 55 minutes after the sample input, which is a time zone in which each component acts on the cell, is monitored for 5 minutes, and further after the drug injection, which is a time zone in which the sample component begins to be metabolized to the cell After 55 minutes, the stable linear signal portion was monitored for 5 minutes, and the rate of change of HP-SPR angle was determined by subtracting the rate of change of control in each cell. The results are shown in FIG. Each bar represents an average value of two measurements, and an error bar represents each value of two measurements.

(結果と考察)
まず、試験の方法で45分待機してから測定に入る場合(Primary effect)と55分待機してから測定に入る場合(Secondary effect)を検討しているが、これは成分が肝臓で代謝され、変換されてから効果を示している場合も多いことから、このような二つの時間帯に設定した。こういう事象は、肝臓の代謝においては良く認められる。
図3に見られるように、サンプルの各種濃度により、HP−SPRの角度変化が認められた。HP−SPR試験法では、経時的なシグナルの変化は、上昇の場合はミトコンドリアの脱分極、下降の場合は分極を表わすことが判明している。
(Results and discussion)
First of all, we are examining the case of entering the measurement after waiting for 45 minutes in the test method (Primary effect) and the case of entering the measurement after waiting for 55 minutes (Secondary effect). This is because the components are metabolized in the liver. Since there are many cases where the effect has been shown since the conversion, it was set to such two time zones. These events are common in liver metabolism.
As can be seen in FIG. 3, changes in the angle of HP-SPR were observed depending on various concentrations of the sample. In the HP-SPR test method, it has been found that the change in signal over time represents mitochondrial depolarization when rising and polarization when falling.

図3に示すように、6−ショーガオールにおいて顕著に肝細胞が活性化していることがわかる。100nMにおいて非常に強い活性を示すことが判明した。また、代謝前の直接的な作用とともに、代謝後でも活性があること、さらに、その効果が高くなることも認められた。以上から、6−ショーガオールは、肝細胞を活性化することが判明し、肝臓の代謝を活性化し、脂肪を燃焼する効果があることが示唆された。   As shown in FIG. 3, it can be seen that the hepatocytes are remarkably activated in 6-shogaol. It was found to show very strong activity at 100 nM. In addition to the direct action before metabolism, it was confirmed that the activity was also present after metabolism and that the effect was enhanced. From the above, it was found that 6-shogaol activates hepatocytes, suggesting that it has the effect of activating liver metabolism and burning fat.

本発明の肝細胞活性化剤は、肝機能自体を活性化させる作用を有し、様々な肝臓疾患の予防、改善、治療に有用である。また、生体に対する安全性が高いため、日常的に摂取することもできる。   The hepatocyte activator of the present invention has an effect of activating liver function itself, and is useful for prevention, improvement and treatment of various liver diseases. Moreover, since it is highly safe for living bodies, it can be taken on a daily basis.

Claims (1)

肝細胞を含む培養液に、培養液中の濃度が1〜100nMになるように6−ショウガオールを投与し、肝細胞内のミトコンドリアを活性化させることを特徴とする肝細胞内のミトコンドリアの活性化方法。 6-shogaol is administered to a culture solution containing hepatocytes so that the concentration in the culture solution is 1 to 100 nM, and the mitochondria in the hepatocytes are activated. Method.
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