JP6960217B2 - Ghrelin signal enhancer and food composition for ghrelin signal enhancer - Google Patents
Ghrelin signal enhancer and food composition for ghrelin signal enhancer Download PDFInfo
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- JP6960217B2 JP6960217B2 JP2016202425A JP2016202425A JP6960217B2 JP 6960217 B2 JP6960217 B2 JP 6960217B2 JP 2016202425 A JP2016202425 A JP 2016202425A JP 2016202425 A JP2016202425 A JP 2016202425A JP 6960217 B2 JP6960217 B2 JP 6960217B2
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- ghrelin
- ginseng
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Description
本発明は、グレリンシグナルを増強するグレリンシグナル増強剤およびグレリンシグナル増強用食品組成物に関する。 The present invention relates to a ghrelin signal enhancer that enhances ghrelin signal and a food composition for enhancing ghrelin signal.
高齢者の体重減少や筋力あるいは精神的な活動が低下した状態など、加齢による一定以上の機能の低下は、ストレスや感染、ケガや基礎疾患などの環境因子に対して脆弱性が高まった状態であると考えられる。このような高齢者の状態は、健康と要介護の境界状態として、一般に「フレイル」と定義される。このような状態を放置すると、さまざまな疾病の発症、認知機能の低下、転倒や骨折および社会的孤立など健康障害の連鎖で介護が必要な状態に陥るリスクが高い。そのため、いわゆるフレイルの段階で改善に向けて取り組むことが重要である。 A certain level of functional decline due to aging, such as weight loss and decreased muscle strength or mental activity in the elderly, is a condition in which the elderly are more vulnerable to environmental factors such as stress, infection, injury and underlying illness. Is considered to be. Such a condition of the elderly is generally defined as "frail" as a boundary condition between health and long-term care. If left unchecked, there is a high risk of needing long-term care due to a chain of health problems such as the onset of various illnesses, cognitive decline, falls and fractures and social isolation. Therefore, it is important to work toward improvement at the so-called frail stage.
一方で、高齢者のフレイルへの移行は、低栄養と密接に関わっており、加齢に伴う様々な要因からの摂食量の低下が、慢性的な栄養不足の状態を作り出し、筋力や骨密度、体重、免疫力、運動能力や社会的活動の低下を間接的に引き起こす事が知られている。このため、フレイルの対策としての摂食改善は、有効な戦略の一つである。摂食行動は、脳の視床下部を中心として、大脳皮質から脊髄までの神経ネットワークによって管理されており、主にホルモンや神経ペプチドによって、その方向性が制御されている。その中で、グレリンは、末梢では唯一の摂食亢進ホルモンである。 On the other hand, the transition to frailty in the elderly is closely related to undernutrition, and the decrease in food intake due to various factors associated with aging creates a chronic undernourishment state, and muscle strength and bone density. , Weight, immunity, athletic performance and social activity are known to indirectly cause malnutrition. Therefore, improving eating as a measure against frailty is one of the effective strategies. Feeding behavior is controlled by a neural network from the cerebral cortex to the spinal cord, centered on the hypothalamus of the brain, and its direction is controlled mainly by hormones and neuropeptides. Among them, ghrelin is the only peripheral hyperphagia hormone.
グレリンは、強力な摂食促進作用を持つペプチドホルモンであり、胃や視床下部に存在するグレリン分泌細胞と、その受容体を持つ細胞群によって、摂食意欲や行動、消化酵素や胃酸の分泌など、摂食行動に向けた様々な段階が統合的に制御されている。またグレリンは、典型的なGタンパク質共役受容体であるグレリン受容体の活性化を介して下垂体からの成長ホルモン（GH）分泌を促進する作用も報告されており、摂食促進だけではなく、高齢者の運動能力を担保するための筋肉の維持にも重要であると考えられている。 Ghrelin is a peptide hormone that has a strong feeding-promoting effect. , Various stages towards feeding behavior are controlled in an integrated manner. Ghrelin has also been reported to promote growth hormone (GH) secretion from the pituitary gland through activation of the ghrelin receptor, which is a typical G protein-coupled receptor. It is also considered to be important for maintaining muscles to ensure the athletic performance of the elderly.
また、グレリンは、摂食促進やGH分泌促進作用以外にも多彩な生理作用を有しており、カヘキシア（悪液質）を呈する心不全および慢性閉塞性肺疾患（COPD）、メタボリックシンドローム、認知症、機能性胃腸症、神経性食思不振症、胃全摘手術並びに癌などに対する改善効果が報告されている。 In addition to promoting feeding and GH secretion, ghrelin has various physiological effects such as heart failure with cachexia (cachexia), chronic obstructive pulmonary disease (COPD), metabolic syndrome, and dementia. , Functional gastroenteropathy, neuropathic cachexia, total gastrectomy, and improvement effects on cancer have been reported.
一方で、高齢者の食欲不振やカヘキシアをきたしたCOPDや癌患者などでは、血中グレリン濃度が高いにもかかわらずグレリン反応性が低下するなど、グレリンの分泌が食欲の促進や筋肉量の上昇に結びつかない、グレリン抵抗性を発現していることが知られている。 On the other hand, in COPD and cancer patients with anorexia and cachexia in the elderly, ghrelin secretion promotes appetite and increases muscle mass, such as decreased ghrelin responsiveness despite high blood ghrelin concentration. It is known that it expresses ghrelin resistance that does not lead to ghrelin.
グレリン抵抗性に着目した改善剤として、たとえば特許文献1には、ソウジュツを含有する六君子湯を有効成分とする悪液質改善剤が記載されている。 As an improving agent focusing on ghrelin resistance, for example, Patent Document 1 describes a cachexia improving agent containing Rikkunshito containing Soujutsu as an active ingredient.
本発明は、グレリンシグナルを増強させることで、グレリン抵抗性を改善することができる新規の手段を提供することを目的とする。 An object of the present invention is to provide a novel means capable of improving ghrelin resistance by enhancing the ghrelin signal.
グレリン受容体（GHSR受容体）は、活性化すると細胞内のカルシウムイオン濃度を上昇させることがわかっている。そこで、本発明者らは、ヒトグレリン受容体を安定的に発現している細胞を用いて細胞内のカルシウムイオンの上昇を調べることにより、種々の物質によるグレリンシグナルに対する効果を調べた。その結果、人参のエキスがグレリン存在下でグレリンシグナルを増強することを見出した。また、本発明者らは、人参由来のパナキサジオール、プロトパナキサジオール、パナキサトリオールおよびプロトパナキサトリオールもまた、グレリン存在下でグレリンシグナルを増強することを見出した。 Ghrelin receptor (GHSR receptor) is known to increase intracellular calcium ion concentration when activated. Therefore, the present inventors investigated the effects of various substances on ghrelin signals by examining the increase in intracellular calcium ions using cells stably expressing the human ghrelin receptor. As a result, it was found that the ginseng extract enhances the ghrelin signal in the presence of ghrelin. We have also found that ginseng-derived panaxadiol, protopanaxadiol, panaxatriol and protopanaxatriol also enhance the ghrelin signal in the presence of ghrelin.
本発明は、人参を有効成分として含有する、グレリンシグナル増強剤を提供する。 The present invention provides a ghrelin signal enhancer containing ginseng as an active ingredient.
また本発明は、上記グレリンシグナル増強剤において、人参が、人参から抽出したエキスとして含有されるグレリンシグナル増強剤を提供する。 The present invention also provides a ghrelin signal enhancer in which ginseng is contained as an extract extracted from ginseng in the above ghrelin signal enhancer.
また本発明は、ダンマラン系トリテルペンまたはその配糖体を有効成分として含有する、グレリンシグナル増強剤を提供する。 The present invention also provides a ghrelin signal enhancer containing dammarane-based triterpenes or glycosides thereof as an active ingredient.
また本発明は、上記グレリンシグナル増強剤において、ダンマラン系トリテルペンまたはその配糖体が、パナキサジオール、プロトパナキサジオール、パナキサトリオールおよびプロトパナキサトリオールからなる群より選択される少なくとも1つまたはその配糖体を含む、グレリンシグナル増強剤を提供する。 Further, in the above-mentioned ghrelin signal enhancer, at least one dammarane-based triterpene or a glycoside thereof is selected from the group consisting of panaxadiol, protopanaxadiol, panaxatriol and protopanaxatriol. Provided is a ghrelin signal enhancer containing the glycoside.
また本発明は、人参を有効成分として含有する、グレリンシグナル増強用食品組成物を提供する。 The present invention also provides a food composition for enhancing ghrelin signal, which contains ginseng as an active ingredient.
本発明であれば、グレリンシグナルを増強させ、グレリン抵抗性を改善することができる。 According to the present invention, the ghrelin signal can be enhanced and the ghrelin resistance can be improved.
本発明は、グレリンシグナル増強剤を提供する。本明細書において、「グレリンシグナル」とは、グレリンによって引き起こされる細胞応答をいう。グレリンによって引き起こされる細胞応答には、グレリン受容体の活性化およびグレリン受容体の下流のシグナル伝達の活性化などが含まれ、たとえばグレリン受容体（GHSR）の下流のシグナル伝達の活性化、およびグレリンの刺激によって増強される各種ホルモンの細胞からの産生などが含まれる。「グレリンシグナルを増強する」とは、グレリンによる細胞応答を増強させ、増加させ、または上昇させること、すなわちグレリン受容体を介したシグナル伝達を増強させ、増加させ、または上昇させることをいう。 The present invention provides a ghrelin signal enhancer. As used herein, the term "ghrelin signal" refers to a cellular response evoked by ghrelin. Cellular responses evoked by ghrelin include activation of ghrelin receptors and activation of signal transduction downstream of ghrelin receptors, such as activation of signal transduction downstream of ghrelin receptor (GHSR), and ghrelin. It includes the production of various hormones from cells that are enhanced by the stimulation of. By "enhancing the ghrelin signal" is meant enhancing, increasing, or increasing the cellular response by ghrelin, that is, enhancing, increasing, or increasing signal transduction via the ghrelin receptor.
本発明のグレリンシグナル増強剤は、グレリン単独で刺激するよりも、グレリンシグナルを増強し、グレリンに対する細胞応答を高めることができる。そのため、本発明のグレリンシグナル増強剤は、グレリン抵抗性を改善することができる。本明細書において「グレリン抵抗性」とは、グレリンに対する反応性が低下している状態をいう。 The ghrelin signal enhancer of the present invention can enhance the ghrelin signal and enhance the cellular response to ghrelin, as compared with stimulating ghrelin alone. Therefore, the ghrelin signal enhancer of the present invention can improve ghrelin resistance. As used herein, the term "ghrelin resistance" refers to a state in which the reactivity to ghrelin is reduced.
本発明のグレリンシグナル増強剤は、人参を有効成分として含有する。本発明に使用する人参は、薬用人参であり、たとえば高麗人参（朝鮮人参）、御種人参、竹節人参および田七人参などが含まれる。 The ghrelin signal enhancer of the present invention contains ginseng as an active ingredient. The ginseng used in the present invention is ginseng, and includes, for example, ginseng (Korean ginseng), ginseng, Panax japonicus, and Panax notoginseng.
本発明に使用する人参は、たとえば人参末および人参から抽出したエキス（人参エキス）などであってもよい。人参末は、従来公知の方法により得ることができ、たとえば人参を粉砕し乾燥することにより得ることができる。人参エキスは、従来公知の抽出方法を使用して人参から得ることができ、たとえば人参を水等の溶媒に加えて加熱抽出し、ろ過後に乾燥することによって得ることができる。 The ginseng used in the present invention may be, for example, ginseng powder and an extract extracted from ginseng (ginseng extract). The carrot powder can be obtained by a conventionally known method, for example, by crushing and drying the carrot. The ginseng extract can be obtained from ginseng using a conventionally known extraction method. For example, ginseng can be obtained by adding ginseng to a solvent such as water, heat-extracting it, filtering it, and then drying it.
本発明はまた、ダンマラン系トリテルペンまたはその配糖体を有効成分として含有する、グレリンシグナル増強剤を提供する。ダンマラン系トリテルペンは、2，3-オキシドスクアレンがchair-chair-chair-boatの構造をとって環化してなる、ダンマラン型のトリテルペン群である。本発明のグレリンシグナル増強剤は、1つまたは複数のダンマラン系トリテルペンまたはその配糖体を含有することができる。本発明に使用するダンマラン系トリテルペンまたはその配糖体は、人参由来のダンマラン系トリテルペンまたはその配糖体であってもよい。 The present invention also provides a ghrelin signal enhancer containing dammarane triterpenes or glycosides thereof as an active ingredient. Dammarane-based triterpenes are a group of dammarane-type triterpenes in which 2,3-oxide squalene is cyclized in a chair-chair-chair-boat structure. The ghrelin signal enhancer of the present invention can contain one or more dammarane-based triterpenes or glycosides thereof. The dammarane-based triterpenes or glycosides thereof used in the present invention may be ginseng-derived dammarane-based triterpenes or glycosides thereof.
本発明に使用するダンマラン系トリテルペンまたはその配糖体は、パナキサジオール、プロトパナキサジオール、パナキサトリオールおよびプロトパナキサトリオールからなる群より選択される少なくとも1つまたはその配糖体であることができる。パナキサジオール、プロトパナキサジオール、パナキサトリオールおよびプロトパナキサトリオールは、ダンマラン系トリテルペンであり、人参に含まれるサポニン（配糖体）から糖が外れたアグリコン体の一種である。 The dammarane triterpene or its glycoside used in the present invention is at least one selected from the group consisting of panaxadiol, protopanaxadiol, panaxatriol and protopanaxatriol, or a glycoside thereof. Can be done. Panaxadiol, protopanaxadiol, panaxatriol and protopanaxatriol are dammarane-based triterpenes and are a type of aglycone in which sugar is removed from saponin (glycoside) contained in ginseng.
本明細書において「配糖体」とは、糖基（グリコン）がグリコシド結合によりアグリコンに結合した化合物をいう。パナキサジオール、プロトパナキサジオール、パナキサトリオールおよびプロトパナキサトリオールは、天然の人参において、たとえばギンセノシド（Ginsenoside）などの配糖体の形で存在する。本発明に使用するパナキサジオール、プロトパナキサジオール、パナキサトリオールおよびプロトパナキサトリオールの配糖体は、特に限定されないが、天然の人参において存在する形態でもよく、たとえばギンセノシドRb1などが含まれる。 As used herein, the term "glycoside" refers to a compound in which a sugar group (glycone) is bound to aglycone by a glycosidic bond. Panaxadiol, protopanaxadiol, panaxatriol and protopanaxatriol are present in natural ginseng in the form of glycosides, such as ginsenoside. The glycosides of panaxadiol, protopanaxadiol, panaxatriol and protopanaxatriol used in the present invention are not particularly limited, but may be in the form existing in natural ginseng, and include, for example, ginsenoside Rb1. ..
本発明のグレリンシグナル増強剤は、任意の形態の製剤であることができる。本発明のグレリンシグナル増強剤は、経口投与製剤として、たとえば糖衣錠、バッカル錠、コーティング錠およびチュアブル錠等の錠剤；トローチ剤；丸剤；散剤；硬カプセル剤および軟カプセル剤を含むカプセル剤；顆粒剤；ならびに懸濁剤、乳剤、シロップ剤およびエリキシル剤等の液剤などであることができる。 The ghrelin signal enhancer of the present invention can be a preparation in any form. The grelin signal enhancer of the present invention can be used as an orally administered preparation, for example, tablets such as sugar-coated tablets, buccal tablets, coated tablets and chewable tablets; troches; pills; powders; capsules containing hard capsules and soft capsules; granules. Agents; as well as liquids such as suspending agents, emulsions, syrups and elixyl agents.
また、本発明のグレリンシグナル増強剤は、静脈注射、皮下注射、腹腔内注射、筋肉内注射、経皮投与、経鼻投与、経肺投与、経腸投与、口腔内投与および経粘膜投与などの非経口投与製剤であることができる。本発明のグレリンシグナル増強剤は、たとえば、注射剤、経皮吸収テープ、エアゾール剤および坐剤などであることができる。 The grelin signal enhancer of the present invention includes intravenous injection, subcutaneous injection, intraperitoneal injection, intramuscular injection, transdermal administration, nasal administration, pulmonary administration, enteral administration, oral administration and transmucosal administration. It can be a parenteral administration formulation. The ghrelin signal enhancer of the present invention can be, for example, an injection, a transdermal tape, an aerosol and a suppository.
また、本発明のグレリンシグナル増強剤は、食用に適した形態であることができ、たとえば固形状、液状、顆粒状、粒状、粉末状、カプセル状、クリーム状およびペースト状などであってもよい。 In addition, the ghrelin signal enhancer of the present invention may be in an edible form, for example, in solid form, liquid form, granular form, granular form, powder form, capsule form, cream form and paste form. ..
本発明のグレリンシグナル増強剤は、医薬品、医薬部外品および食品に通常用いられる任意の成分をさらに含むことができる。たとえば、本発明のグレリンシグナル増強剤は、薬学的に許容される基剤、担体、賦形剤、結合剤、崩壊剤、滑沢剤および着色剤などをさらに含んでもよい。 The ghrelin signal enhancer of the present invention can further contain any ingredient commonly used in pharmaceuticals, quasi-drugs and foods. For example, the ghrelin signal enhancer of the present invention may further include pharmaceutically acceptable bases, carriers, excipients, binders, disintegrants, lubricants and colorants.
本発明のグレリンシグナル増強剤に使用する担体および賦形剤の例には、乳糖、ブドウ糖、白糖、マンニトール、デキストリン、馬鈴薯デンプン、トウモロコシデンプン、炭酸カルシウム、リン酸カルシウム、硫酸カルシウムおよび結晶セルロースなどを含む。 Examples of carriers and excipients used in the grelin signal enhancer of the present invention include lactose, glucose, sucrose, mannitol, dextrin, potato starch, corn starch, calcium carbonate, calcium phosphate, calcium sulfate and crystalline cellulose.
結合剤の例には、デンプン、ゼラチン、シロップ、トラガントゴム、ポリビニルアルコール、ポリビニルエーテル、ポリビニルピロリドン、ヒドロキシプロピルセルロース、メチルセルロース、エチルセルロースおよびカルボキシメチルセルロースなどを含む。 Examples of binders include starch, gelatin, syrup, tragant rubber, polyvinyl alcohol, polyvinyl ether, polyvinylpyrrolidone, hydroxypropyl cellulose, methyl cellulose, ethyl cellulose, carboxymethyl cellulose and the like.
崩壊剤の例には、デンプン、寒天、ゼラチン末、結晶セルロース、炭酸カルシウム、炭酸水素ナトリウム、アルギン酸ナトリウム、カルボキシメチルセルロースナトリウムおよびカルボキシメチルセルロースカルシウムなどを含む。 Examples of disintegrants include starch, agar, gelatin powder, crystalline cellulose, calcium carbonate, sodium hydrogen carbonate, sodium alginate, sodium carboxymethyl cellulose, calcium carboxymethyl cellulose and the like.
滑沢剤の例には、ステアリン酸マグネシウム、水素添加植物油、タルクおよびマクロゴールなどを含む。着色剤は、医薬品、医薬部外品および食品に添加することが許容されている任意の着色剤を使用することができる。 Examples of lubricants include magnesium stearate, hydrogenated vegetable oils, talc and macrogol. As the colorant, any colorant that is allowed to be added to pharmaceutical products, quasi-drugs and foods can be used.
また、本発明のグレリンシグナル増強剤は、必要に応じて、白糖、ゼラチン、精製セラック、ゼラチン、グリセリン、ソルビトール、エチルセルロース、ヒドロキシプロピルセルロース、ヒドロキシプロピルメチルセルロース、ポリビニルピロリドン、フタル酸セルロースアセテート、ヒドロキシプロピルメチルセルロースフタレート、メチルメタクリレートおよびメタアクリル酸重合体などで一層以上の層で被膜してもよい。 The grelin signal enhancer of the present invention is, if necessary, sucrose, gelatin, purified cellac, gelatin, glycerin, sorbitol, ethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, polyvinyl pyrrolidone, phthalate cellulose acetate, hydroxypropyl methyl cellulose. It may be coated with one or more layers such as phthalate, methyl methacrylate and methacrylic acid polymer.
また、本発明のグレリンシグナル増強剤は、必要に応じて、pH調節剤、緩衝剤、安定化剤、保存剤、防腐剤、希釈剤、コーティング剤、甘味剤、香料および可溶化剤などを添加してもよい。 Further, the ghrelin signal enhancer of the present invention is added with a pH regulator, a buffer, a stabilizer, a preservative, a preservative, a diluent, a coating agent, a sweetener, a fragrance, a solubilizer and the like, if necessary. You may.
本発明のグレリンシグナル増強剤における人参またはダンマラン系トリテルペンの含有量は、グレリンシグナル増強効果を発揮することができる量であればよく、適用する対象、目的および投与方法（摂取方法）に応じて適宜設定することができる。 The content of ginseng or dammarane-based triterpene in the ghrelin signal enhancer of the present invention may be an amount capable of exerting the ghrelin signal enhancer effect, and is appropriately determined according to the subject to be applied, the purpose and the administration method (ingestion method). Can be set.
本発明はまた、人参を有効成分として含有する、グレリンシグナル増強用食品組成物を提供する。本発明の食品組成物は、上述したグレリンシグナル増強剤と同様に構成することができる。 The present invention also provides a food composition for enhancing ghrelin signal, which contains ginseng as an active ingredient. The food composition of the present invention can be constructed in the same manner as the above-mentioned ghrelin signal enhancer.
本明細書において「食品組成物」には、一般的な飲食品だけでなく、病者用食品、健康食品、機能性食品、特定保健用食品、栄養補助食品およびサプリメントなどが含まれる。一般的な飲食品には、たとえば各種飲料、各種食品、加工食品、液状食品（スープ等）、調味料、栄養ドリンクおよび菓子類などが含まれる。本明細書において「加工食品」とは、天然の食材（動物および植物など）に対し加工および／または調理を施したものをいい、たとえば肉加工品、野菜加工品、果実加工品、冷凍食品、レトルト食品、缶詰食品、瓶詰食品およびインスタント食品などが含まれる。本発明の食品組成物は、グレリンシグナルを増強する旨の表示を付した食品であってもよい。また、本発明の食品組成物は、袋および容器等に封入された形態で提供されてもよい。本発明において使用する袋および容器は、食品に通常使用される任意の袋および容器であることができる。 In the present specification, the "food composition" includes not only general foods and drinks but also foods for the sick, health foods, functional foods, foods for specified health uses, dietary supplements and supplements. Common foods and drinks include, for example, various beverages, various foods, processed foods, liquid foods (soups and the like), seasonings, energy drinks and confectionery. As used herein, the term "processed food" refers to natural foodstuffs (animals, plants, etc.) that have been processed and / or cooked, such as processed meat products, processed vegetable products, processed fruit products, and frozen foods. Includes retort foods, canned foods, bottled foods and instant foods. The food composition of the present invention may be a food product labeled to enhance the ghrelin signal. Further, the food composition of the present invention may be provided in a form enclosed in a bag, a container or the like. The bag and container used in the present invention can be any bag and container normally used for food.
以下に実施例を示し、本発明の実施の形態についてさらに詳しく説明するが、本発明は以下の実施例に限定されるものではない。 Examples are shown below, and embodiments of the present invention will be described in more detail, but the present invention is not limited to the following examples.
（実施例1：人参エキスの調製方法）
オタネニンジンの根を乾燥させた人参生薬の刻み（クラシエ製薬）1.5kgを量り、15kgの温水を入れ、20分間かけて100℃に昇温し、100℃で60分間加熱還流抽出した後、100メッシュの篩いでろ過した。ろ液を減圧下で6倍濃縮した後、噴霧乾燥し、噴霧乾燥エキス210gを得た。
(Example 1: Preparation method of ginseng extract)
Weigh 1.5 kg of chopped ginseng herbal medicine (Classier Pharmaceuticals) with dried ginseng roots, add 15 kg of warm water, heat to 100 ° C over 20 minutes, heat at 100 ° C for 60 minutes, reflux extract, and then 100 mesh. It was filtered with a sieve. The filtrate was concentrated 6-fold under reduced pressure and then spray-dried to obtain 210 g of a spray-dried extract.
（試験例1：カルシウム流量アッセイ）
グレリン受容体（GHSR受容体）は、活性化されると細胞内のカルシウムイオン濃度を上昇させる。人参エキスおよび種々の化合物によるグレリンシグナルの増強作用を観察するために、以下のようにカルシウム流量アッセイを行った。
(Test Example 1: Calcium flow assay)
The ghrelin receptor (GHSR receptor) increases the intracellular calcium ion concentration when activated. In order to observe the enhancing effect of ginseng extract and various compounds on the ghrelin signal, a calcium flow assay was performed as follows.
グレリン受容体を発現していないCHO-K1細胞に、ヒトグレリン受容体(GHSR1a)を安定的に発現させた細胞株（Genscript Co. No.M00189）を得た。この細胞を、10% FBS＋F12 medium 20μL中に15,000cell/wellとなるように382wellに播種し、18時間、37℃、5%CO2条件で培養した。 A cell line (Genscript Co. No. M00189) was obtained in which the human ghrelin receptor (GHSR1a) was stably expressed in CHO-K1 cells that did not express the ghrelin receptor. The cells were seeded in 382 wells at 15,000 cells / well in 20 μL of 10% FBS + F12 medium and cultured for 18 hours at 37 ° C. under 5% CO 2 conditions.
次に、20μLのFLIPR Ca4染色液（Molecular device）をウェルに添加し、37℃で60分間インキュベートし、続いて室温にて15分間インキュベートした。 Next, 20 μL of FLIPR Ca4 stain (Molecular device) was added to the wells and incubated at 37 ° C. for 60 minutes, followed by room temperature for 15 minutes.
アゴニストコントロールとして、ヒト活性型グレリン（Genscript）の2.5nM溶液を調製した。実施例1の人参エキスは、5μg/mL、30μg/mLおよび100μg/mLの試料溶液として調製した。また、人参の含有成分であるパナキサジオール、プロトパナキサジオール、パナキサトリオールおよびプロトパナキサトリオールの試料溶液を調製した。パナキサジオール（クラシエ製薬）、プロトパナキサジオール（Abcam）、パナキサトリオール（クラシエ製薬）およびプロトパナキサトリオール（Abcam）は、0.1％、0.3％または0.6％のジメチルスルホキシド（DMSO）、メタノール（MeOH）またはPBSに、10μM、30μMまたは60μMとなるように溶解した。 As an agonist control, a 2.5 nM solution of human active ghrelin (Genscript) was prepared. The ginseng extract of Example 1 was prepared as a sample solution of 5 μg / mL, 30 μg / mL and 100 μg / mL. In addition, sample solutions of ginseng-containing components panaxadiol, protopanaxadiol, panaxatriol and protopanaxatriol were prepared. Panaxadiol (Classier Pharmaceuticals), Protopanaxadiol (Abcam), Panaxatriol (Classier Pharmaceuticals) and Protopanaxatriol (Abcam) are 0.1%, 0.3% or 0.6% dimethyl sulfoxide (DMSO), methanol ( It was dissolved in MeOH) or PBS to a concentration of 10 μM, 30 μM or 60 μM.
試料溶液およびグレリン、試料溶液のみ、またはグレリンのみ（10μL）をウェルに添加し、蛍光シグナルを120秒間モニターした。 Sample solution and ghrelin, sample solution alone, or ghrelin alone (10 μL) were added to the wells and the fluorescence signal was monitored for 120 seconds.
最初の20秒の平均値をベースラインとし、最大の蛍光強度(21s〜120s)からベースラインの平均値を差し引くことによって、相対蛍光強度(ΔRFU)を算出した。グレリンシグナル活性（%Stimulation）は、グレリンおよび試料を添加しなかったときの相対蛍光強度に対するサンプルの相対蛍光強度の割合（％）として算出した。 The relative fluorescence intensity (ΔRFU) was calculated by subtracting the baseline average value from the maximum fluorescence intensity (21s to 120s) with the average value for the first 20 seconds as the baseline. The ghrelin signal activity (% Stimulation) was calculated as the ratio (%) of the relative fluorescence intensity of the sample to the relative fluorescence intensity when ghrelin and the sample were not added.
（人参エキス）
人参エキスを5μg/mL、30μg/mLまたは100μg/mL添加し、グレリン存在下でのグレリンシグナルの増強効果を調べた。図1は、人参エキスによるグレリンシグナル増強作用を示すグラフである。図1に示すように、人参エキスは、グレリン存在下で、用量依存的にグレリンシグナルを増強させた。
(Ginseng extract)
Ginseng extract was added at 5 μg / mL, 30 μg / mL or 100 μg / mL, and the effect of enhancing the ghrelin signal in the presence of ghrelin was examined. FIG. 1 is a graph showing the ghrelin signal enhancing effect of ginseng extract. As shown in FIG. 1, ginseng extract enhanced the ghrelin signal in a dose-dependent manner in the presence of ghrelin.
（パナキサジオール）
パナキサジオールを10μM、30μMまたは60μM添加し、グレリン存在下でのグレリンシグナルの増強効果を調べた。図2は、パナキサジオールによるグレリンシグナル増強作用を示すグラフである。図2に示すように、パナキサジオールは、グレリン存在下で、用量依存的にグレリンシグナルを増強させた。
(Panaxadiol)
10 μM, 30 μM or 60 μM of panaxadiol was added, and the effect of enhancing the ghrelin signal in the presence of ghrelin was investigated. FIG. 2 is a graph showing the ghrelin signal enhancing effect of panaxadiol. As shown in FIG. 2, panaxadiol enhanced the ghrelin signal in a dose-dependent manner in the presence of ghrelin.
（プロトパナキサトリオール）
プロトパナキサトリオールを60μM添加し、グレリン存在下でのグレリンシグナルの増強効果を調べた。図3は、プロトパナキサトリオールによるグレリンシグナル増強作用を示すグラフである。図3に示すように、プロトパナキサトリオールは、グレリン存在下でグレリンシグナルを増強させた。
(Protopanax triol)
60 μM of protopanaxatriol was added, and the effect of enhancing ghrelin signal in the presence of ghrelin was investigated. FIG. 3 is a graph showing the ghrelin signal enhancing effect of protopanaxatriol. As shown in FIG. 3, protopanaxatriol enhanced the ghrelin signal in the presence of ghrelin.
（パナキサトリオール）
パナキサトリオールを60μM添加し、グレリン存在下でのグレリンシグナルの増強効果を調べた。図4は、パナキサトリオールによるグレリンシグナル増強作用を示すグラフである。図4に示すように、パナキサトリオールは、グレリン存在下でグレリンシグナルを増強させた。
(Panaxatriol)
60 μM of panaxatriol was added, and the effect of enhancing ghrelin signal in the presence of ghrelin was investigated. FIG. 4 is a graph showing the ghrelin signal enhancing effect of panaxatriol. As shown in FIG. 4, panaxatriol enhanced the ghrelin signal in the presence of ghrelin.
（プロトパナキサジオール）
プロトパナキサジオールを60μM添加し、グレリン存在下でのグレリンシグナルの増強効果を調べた。図5は、プロトパナキサジオールによるグレリンシグナル増強作用を示すグラフである。図5に示すように、プロトパナキサジオールは、グレリン存在下でグレリンシグナルを増強させた。
したがって、図2〜図5に示すように、人参由来のダンマラン系トリテルペンにグレリンシグナル増強作用があることが示唆された。
(Protopanaxadiol)
60 μM of protopanaxadiol was added, and the effect of enhancing ghrelin signal in the presence of ghrelin was investigated. FIG. 5 is a graph showing the ghrelin signal enhancing effect of protopanaxadiol. As shown in FIG. 5, protopanaxadiol enhanced the ghrelin signal in the presence of ghrelin.
Therefore, as shown in FIGS. 2 to 5, it was suggested that ginseng-derived dammarane triterpenes have a ghrelin signal-enhancing effect.
本発明は、グレリンシグナルを増強させ、グレリン抵抗性を改善するための医薬、医薬部外品および食品として好適に利用可能である。 INDUSTRIAL APPLICABILITY The present invention can be suitably used as pharmaceuticals, quasi-drugs and foods for enhancing ghrelin signal and improving ghrelin resistance.
Claims (4)
A food composition containing ginseng as an active ingredient for enhancing calcium influx via a ghrelin signal in the presence of ghrelin (excluding those containing ghrelin).
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