JP4604207B2 - Lactic acid bacteria having anti-aging action and uses thereof - Google Patents
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Description
本発明は、特定の乳酸菌を含有する老化抑制剤に関し、詳しくは、骨密度減少抑制能、皮膚潰瘍発生抑制能を有するラクトコッカス属乳酸菌を有効成分とする老化抑制剤および該乳酸菌を利用した薬剤（医薬品）に関する。
The present invention relates to an aging inhibitor containing a specific lactic acid bacterium, and more specifically, an aging inhibitor comprising a lactococcus lactic acid bacterium having an ability to suppress bone density reduction and skin ulcer generation as an active ingredient, and a drug using the lactic acid bacterium (Medicine)
高齢化社会の到来により、健康で長寿であることに対する関心が高まる中、老化反応を抑える物質の開発が望まれている。
これまでに抗老化剤、老化防止剤として、アスコルビン酸（特許文献１参照）やコラーゲン（特許文献２参照）などの物質を含有するものが報告されている。
一方、乳酸菌は、代表的なプロバイオティクス（宿主の健康維持に有益な働きをする微生物）として知られており、これまでにも様々な機能性が報告されているが、さらに新しい作用の発見も求められている。乳酸菌は医薬品としてだけでなく、発酵乳のような食品としても摂取が可能であり、疾病予防のために毎日摂取することにも、医薬品や先に挙げた物質を摂取するよりも抵抗は少ないと考えられる。従って、乳酸菌を利用した老化抑制、予防食品が望まれていた。
With the advent of an aging society, interest in health and longevity is increasing, and the development of substances that suppress the aging reaction is desired.
Until now, what contains substances, such as an ascorbic acid (refer patent document 1) and collagen (refer patent document 2), is reported as an anti-aging agent and an anti-aging agent.
Lactic acid bacteria, on the other hand, are known as typical probiotics (microorganisms that have a beneficial effect on maintaining the health of the host), and various functionalities have been reported so far. Is also sought. Lactic acid bacteria can be ingested not only as a medicinal product but also as a food such as fermented milk, and it is less resistant to ingesting daily for disease prevention than ingesting medicinal products and the substances listed above. Conceivable. Therefore, an antiaging and preventive food using lactic acid bacteria has been desired.
ところで、老化に関連する生理現象としては、記憶能の低下、免疫応答の低下、生体内酸化、骨密度の低下などがある。
これまでに報告されている乳酸菌についての知見としては、ある乳酸菌が老齢マウスの免疫応答を賦活化し、病原菌感染性を低下させたという報告（非特許文献１参照）や発酵乳投与マウスの寿命が延長されるとの報告（非特許文献２参照）がある。しかし、前者は老化を抑制するものではなく、後者は寿命が延びていても老化していないことには言及していない。
また、乳酸菌を用いた抗老化剤として、皮膚の老化防止として「皮膚外用剤」（特許文献３参照）、「皮膚老化防止用化粧料」（特許文献４参照）、「皮膚の免疫系のバランスを保つためのプロバイオティック乳酸菌」（特許文献５参照）などがある。前二者は、食品としての乳酸菌の効果に関するものではなく、第三の報告は、経口摂取によるものではあるが、老齢マウスを試験に使用していないため、老化に関連した潰瘍発生、他の病態に対する影響については検討されていない。
By the way, physiological phenomena related to aging include a decrease in memory ability, a decrease in immune response, in-vivo oxidation, and a decrease in bone density.
As for the knowledge about lactic acid bacteria reported so far, there is a report that a certain lactic acid bacterium has activated the immune response of an aged mouse and reduced infectivity of pathogenic bacteria (see Non-patent Document 1), and the life of mice administered with fermented milk. There is a report that it will be extended (see Non-Patent Document 2). However, the former does not suppress aging, and the latter does not mention that it is not aging even if its life is extended.
In addition, as an anti-aging agent using lactic acid bacteria, “skin external preparation” (see Patent Document 3), “skin anti-aging cosmetic” (see Patent Document 4), “skin immune system balance” Probiotic lactic acid bacteria for maintaining the resistance "(see Patent Document 5). The former two did not relate to the effects of lactic acid bacteria as food, and the third report was due to oral intake, but because aging mice were not used for testing, ulcers related to aging, other The effect on the disease state has not been studied.
老化に伴う生理現象の解析には、老化促進モデルマウス（Senescence-Accelerated Mouse 、ＳＡＭ）を用いた研究が有効である。ＳＡＭは１９９１年時で、Ｐ系群８系統、Ｒ系群３系統が維持されている。１例を挙げれば、Ｐ／１系は老化アミロイド症、Ｐ／６系は老年性骨粗鬆症、Ｐ／８系は学習・記憶障害を発症する。ＳＡＭ研究会では、前記の病態の他にマウスの行動や外観（皮膚）の老化の程度を表す老化スコアを設定している。ＳＡＭを用いた老化関連病態に及ぼす乳酸菌投与の報告はこれまでにない。 Research using a senescence-accelerated mouse (SAM) is effective in analyzing physiological phenomena associated with aging. SAM was in 1991, and 8 lines of P system group and 3 lines of R system group were maintained. For example, the P / 1 system develops senile amyloidosis, the P / 6 system develops senile osteoporosis, and the P / 8 system develops learning / memory disorders. In addition to the above pathological conditions, the SAM Study Group has set an aging score that represents the degree of aging of the behavior and appearance (skin) of mice. There have been no reports of lactic acid bacteria administration on aging-related pathologies using SAM.
骨粗鬆症には、原発性と持続性の二つのタイプがあり、原発性はさらに閉経後骨粗鬆症と老年性骨粗鬆症に分けられる。骨代謝には、骨形成と骨吸収があり、正常であれば、両者のバランスがとれている。閉経後骨粗鬆症は、骨吸収が骨形成よりも異常に亢進しているために見られるもので、骨吸収抑制剤（ビスホスホネート製剤など）の投与が有効である。
骨粗鬆症に対する乳酸菌の効果については、乳酸菌を用いて発酵させた発酵乳（特許文献６参照）やプロピオン酸または乳酸菌体培養物（特許文献７参照）で骨密度の増加や減少抑制に効果があったと報告されている。しかし、これらの報告では、卵巣摘出手術を施したラットあるいは無処置のラットが試験に用いられており、これまでに老化に伴う骨密度の減少に対する乳酸菌の効果を調べた報告はない。老齢時では、骨吸収、骨形成がともに低下した状態であり、閉経後骨粗鬆症モデルラットでは老年性骨粗鬆症の病態と一致しない。
There are two types of osteoporosis, primary and persistent, and primary is further divided into postmenopausal osteoporosis and senile osteoporosis. Bone metabolism includes bone formation and bone resorption, and if normal, both are balanced. Postmenopausal osteoporosis is observed because bone resorption is abnormally enhanced than bone formation, and administration of a bone resorption inhibitor (such as a bisphosphonate preparation) is effective.
Regarding the effect of lactic acid bacteria on osteoporosis, fermented milk fermented with lactic acid bacteria (see Patent Document 6), propionic acid or lactic acid bacterial cell culture (see Patent Document 7) was effective in suppressing increase or decrease in bone density. It has been reported. However, in these reports, rats that have undergone ovariectomy or untreated rats have been used in the study, and so far there has been no report examining the effect of lactic acid bacteria on the decrease in bone density associated with aging. In old age, both bone resorption and bone formation are in a reduced state, and postmenopausal osteoporosis model rats do not agree with the pathological condition of senile osteoporosis.
活性酸素は、生体内で過酸化脂質を生成し、疾病、細胞老化の原因となると考えられている。乳酸菌の抗酸化作用については、「抗酸化剤」（特許文献８参照）などの報告があるが、老化に関連した病態としての骨密度減少、皮膚の潰瘍発生に対する抗酸化作用を有する乳酸菌摂取の効果に関する報告はない。 Active oxygen is thought to produce lipid peroxides in vivo and cause disease and cellular aging. As for the antioxidant action of lactic acid bacteria, there are reports such as "Antioxidant" (see Patent Document 8). There is no report about the effect.
乳酸菌は２０属に分かれているが、機能性研究が進んでいるのは、ラクトバチルス属、エンテロコッカス属、ストレプトコッカス属、ラクトコッカス属である。しかし、エンテロコッカス、ストレプトコッカス属乳酸菌については、そのグループに属する菌株がすべて安全であるとは限らず、病原性を有する菌株も存在するため、使用する菌株を慎重に選ぶ必要がある。
ラクトバチルス属乳酸菌は、乳酸菌のなかでも安全性が高いグループであることが知られているが、一般に牛乳中での生育が悪いものが多く、発酵乳の製造の際、十分に生育させるには乳由来の乳酸菌と混合したり、タンパク分解物などを添加しなければならない。ラクトコッカス属乳酸菌は、ラクトバチルス属乳酸菌と並んで安全性が高く、かつ、牛乳中での生育がよく、乳製品の製造に適した乳酸菌グループである。また、通性嫌気性細菌のため、取り扱いも容易である。従って、ラクトコッカス属乳酸菌の中から、新規な、付加価値の高い乳製品製造開発に向け、老化抑制効果を有する乳酸菌株が求められていた。
Lactic acid bacteria are divided into 20 genera, but functional studies are progressing in the genera Lactobacillus, Enterococcus, Streptococcus, and Lactococcus. However, for Enterococcus and Streptococcus lactic acid bacteria, all the strains belonging to the group are not necessarily safe, and there are strains having pathogenicity, so it is necessary to carefully select the strain to be used.
Lactobacillus lactic acid bacteria are known to be a highly safe group of lactic acid bacteria, but in general, many of them do not grow well in milk. It must be mixed with milk-derived lactic acid bacteria and added with proteolytic products. Lactococcus lactic acid bacteria are a group of lactic acid bacteria that are safer than Lactobacillus lactic acid bacteria, have good growth in milk, and are suitable for the production of dairy products. In addition, it is easy to handle because of facultative anaerobic bacteria. Accordingly, among the Lactococcus lactic acid bacteria, a lactic acid strain having an antiaging effect has been demanded for the development of a new and high-value-added dairy product.
「プロバイオティクス」とは、もともと「宿主の腸内フローラのバランスを改善することにより宿主動物に有益に働く微生物添加物」（非特許文献３参照）と定義されており、乳酸菌がプロバイオティクスとしての機能を十分に発揮するためには、腸管まで生きたまま到達することが望ましいとされてきた。
しかし、最近ではプロバイオティクスは「宿主の健康維持に有益な働きをする微生物」（非特許文献４参照）として広い意味で用いられることが多く、死菌体でもプロバイオティクスに含めることができるという考えもみられる（非特許文献５参照）。すなわち、機能性によっては死菌体でも生菌と同じ作用を有する場合がある。例えば、免疫賦活作用、コレステロール低下作用、抗腫瘍効果などである。死菌体は生菌に比べて取り扱いが容易であり、製剤としての利用が可能であり、または食品に添加してもよい。従って、生菌だけでなく、死菌体でも抗老化作用を有する乳酸菌が求められていた。
“Probiotic” was originally defined as “microbe additive that works beneficially for host animals by improving the balance of intestinal flora of the host” (see Non-Patent Document 3). It has been considered desirable to reach the intestinal tract in order to fully exert its functions.
Recently, however, probiotics are often used in a broad sense as “microorganisms that have a beneficial effect on maintaining the health of the host” (see Non-Patent Document 4), and even dead cells can be included in probiotics. (See Non-Patent Document 5). That is, depending on the functionality, dead cells may have the same action as live cells. For example, immunostimulatory action, cholesterol lowering action, antitumor effect and the like. Dead cells are easier to handle than live cells, can be used as a preparation, or may be added to food. Accordingly, there has been a demand for lactic acid bacteria that have an anti-aging effect not only on live bacteria but also on dead cells.
本発明は、安全性に問題がなく、経口的に摂取可能である乳酸菌の中から特定の菌株を選抜し、該菌株含有する骨密度減少抑制剤、皮膚潰瘍発生抑制剤、老化抑制剤、該菌株を用いた食品・製剤を提供することを目的とする。
本発明者らは、研究の過程で老化と密接な関わりがある抗酸化能を有する乳酸菌を見出し、本発明に到達した。
The present invention selects a specific strain from lactic acid bacteria that have no safety problems and can be taken orally, and contains a bone density reduction inhibitor, a skin ulcer generation inhibitor, an aging inhibitor, The object is to provide foods and preparations using strains.
In the course of research, the present inventors have found a lactic acid bacterium having an antioxidant ability that is closely related to aging, and reached the present invention.
請求項１記載の本発明は、乳酸菌ラクトコッカス・ラクティス・サブスピーシーズ クレモリス（Lactococcus lactis subsp. cremoris） Ｈ−６１株（ＮＩＴＥ Ｐ−９２）を有効成分として含有することを特徴とする老化抑制剤である。
請求項２記載の本発明は、ラクトコッカス・ラクティス・サブスピーシーズ クレモリス（Lactococcus lactis subsp. cremoris） Ｈ−６１株（ＮＩＴＥ Ｐ−９２）が生菌である請求項１記載の老化抑制剤である。
請求項３記載の本発明は、ラクトコッカス・ラクティス・サブスピーシーズ クレモリス（Lactococcus lactis subsp. cremoris） Ｈ−６１株（ＮＩＴＥ Ｐ−９２）が死菌体である請求項１記載の老化抑制剤である。
The present invention according to claim 1 is an aging inhibitor comprising a lactic acid bacterium Lactococcus lactis subsp. Cremoris H-61 strain (NITE P- 92) as an active ingredient. is there.
The present invention according to
The present invention according to claim 3 is the aging inhibitor according to claim 1, wherein the Lactococcus lactis subsp. Cremoris H-61 strain (NITE P- 92) is a dead cell. .
請求項４記載の本発明は、老化抑制が骨密度減少抑制であることに由来する請求項１〜３のいずれかに記載の老化抑制剤である。
請求項５記載の本発明は、老化抑制が皮膚潰瘍発生抑制であることに由来する請求項１〜３のいずれかに記載の老化抑制剤である。
請求項６記載の本発明は、乳酸菌ラクトコッカス・ラクティス・サブスピーシーズ クレモリス（Lactococcus lactis subsp. cremoris） Ｈ−６１株（ＮＩＴＥ Ｐ−９２）を有効成分として含有する老化抑制剤を含むことを特徴とする薬剤である。
The present invention according to claim 4 is the aging inhibitor according to any one of claims 1 to 3, which is derived from the fact that aging suppression is suppression of bone density reduction.
The present invention according to claim 5 is the aging inhibitor according to any one of claims 1 to 3, which is derived from the fact that the suppression of aging is skin ulcer generation suppression.
The present invention according to claim 6 includes an aging inhibitor containing a lactic acid bacterium Lactococcus lactis subsp. Cremoris H-61 strain (NITE P- 92) as an active ingredient. It is a drug to do.
本発明により、乳酸菌の中でもラクトバチルス属と並んで安全性が高く、しかも乳製品製造に適しているラクトコッカス属乳酸菌であるＨ−６１株を利用した老化抑制剤および該乳酸菌を利用した食品や薬剤が提供される。この乳酸菌の機能性は生菌のみならず死菌体でも見られることから、食材に添加したり、またはサプリメント等としても利用できる。
したがって、本発明により、付加価値の高い新規な乳製品の開発に向けた、かつ高齢者向けプロバイオティック食品の開発が期待できる。また、死菌体を食材に添加して、その機能性を利用できる。
According to the present invention, among lactic acid bacteria, the aging inhibitor using the H-61 strain, which is a Lactococcus lactic acid bacterium that is highly safe and suitable for producing dairy products, along with the Lactobacillus genus, and foods using the lactic acid bacteria, Drugs are provided. Since the functionality of this lactic acid bacterium can be seen not only in living bacteria but also in dead cells, it can be added to foods or used as supplements.
Therefore, the present invention can be expected to develop a new dairy product with high added value and to develop a probiotic food for elderly people. Moreover, the dead microbial cell can be added to a foodstuff and the functionality can be utilized.
以下、本発明を詳細に説明する。
本発明者らは、前記した目的を達成すべく検討を重ねた結果、各種の乳酸菌の中から、ラクトコッカス・ラクティス・サブスピーシーズ クレモリス（Lactococcus lactis subsp．cremoris）Ｈ−６１株が、経口投与により抗酸化作用を有することを見出した。この知見に基づいて、該乳酸菌Ｈ−６１株を、老齢期に骨粗鬆症を発症する老化促進モデルマウスに対して経口投与したところ、非投与群に比べて骨密度の減少が有意に抑制されることが明らかとなった。さらに、このＨ−６１株は、老化の程度を表す老化スコアについて、非投与に比べてスコアを低下させることも判明した。Ｈ−６１株は、独立行政法人製品評価技術基盤機構 特許微生物寄託センターに寄託されており、その受託番号はＮＩＴＥ Ｐ−９２（独立行政法人農業生物資源研究所の農業生物資源ジーンバンクに寄託されているＭＡＦＦ Ｎｏ．４００００７と同一株である。）である。
本発明者らは、他属の乳酸菌は勿論のこと、ラクトコッカス属に属する乳酸菌の中でもＨ−６１株以外に有用な菌株を未だ見出していない。
Hereinafter, the present invention will be described in detail.
As a result of repeated studies to achieve the above-described object, the present inventors have found that Lactococcus lactis subsp. Cremoris H-61 strain is orally administered from various lactic acid bacteria. It was found to have an antioxidant effect. Based on this finding, when the lactic acid bacteria H-61 strain was orally administered to an aging-promoting model mouse that develops osteoporosis in the aging period, a decrease in bone density is significantly suppressed compared to the non-administered group. Became clear. Furthermore, this H-61 strain was also found to decrease the score with respect to the aging score representing the degree of aging compared to non-administration. The H-61 strain has been deposited with the Patent Microorganisms Depositary Center for Product Evaluation Technology, NITE P- 92 (deposited with the Agricultural Bioresource Genebank of the National Institute of Agrobiological Sciences). It is the same strain as MAFF No. 400007.).
The present inventors have not found any useful strains other than H-61 strain among lactic acid bacteria belonging to the genus Lactococcus as well as lactic acid bacteria of other genera.
このラクトコッカス属乳酸菌Ｈ−６１株としては、乳酸菌の培養の常法に従い、任意の条件で培養した後、遠心分離等の手段によって集菌したものを１−２回、好ましくは２回、生理食塩水や滅菌水などで洗浄したものをそのまま用いることができる。また、本菌株の製剤化の形態にも特に制限はなく、凍結乾燥粉末、噴霧乾燥粉末、液体への懸濁など、使用目的に合った方法を採用できる。 The Lactococcus lactic acid bacteria H-61 strain is obtained by culturing under arbitrary conditions according to a conventional method for culturing lactic acid bacteria, and then collecting cells collected by means such as centrifugation 1-2 times, preferably twice. What was washed with saline solution or sterilized water can be used as it is. Moreover, there is no restriction | limiting in particular also in the form of formulation of this strain, The method suitable for the intended purpose, such as freeze-dried powder, spray-dried powder, and suspension in a liquid, is employable.
本発明による老化抑制には、本菌株を含む製剤などを経口投与することが望ましい。その場合の投与量については、今回、マウス（体重４０ｇ）あたり、菌体重量で１．０〜２．５ｍｇ／日投与で効果が認められたことから、ヒトに対しては体重１ｋｇあたり、菌体重量２５．０〜６２．５ｍｇ／日で十分な効果が期待できるが、多量に摂取しても安全性の面では問題はない。
したがって、１日あたり２５．０ｍｇ／ｋｇ以上、通常は２５．０〜１３０ｍｇ／ｋｇ、好ましくは２５．０〜６５．０ｍｇ／ｋｇ程度の投与が適当である。
上記の菌体量を含む剤を１日１回、または数回に分けて摂取する。本菌株は、牛乳中でもよく生育するため、本菌株を用いて製造した発酵乳の形態で摂取することもできる。
In order to suppress aging according to the present invention, it is desirable to orally administer a preparation containing this strain. Regarding the dose in that case, since the effect was observed at 1.0 to 2.5 mg / day administration in terms of bacterial cell weight per mouse (40 g body weight) this time, A body weight of 25.0 to 62.5 mg / day can be expected to have a sufficient effect, but even if consumed in large amounts, there is no problem in terms of safety.
Therefore, administration of 25.0 mg / kg or more per day, usually 25.0 to 130 mg / kg, preferably about 25.0 to 65.0 mg / kg is appropriate.
The above-mentioned agent containing the amount of cells is taken once a day or divided into several times. Since this strain grows well in milk, it can be ingested in the form of fermented milk produced using this strain.
以下において、本発明を実施例により詳しく説明するが、本発明はこれら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 thereto.
（実施例１）
ＢＡＬＢ／ｃマウス（8ヶ月齢、平均体重30ｇ）は、搬入後、2ヶ月間、市販の飼料（ＭＭ−３、船橋農場製、千葉）と水で飼育した。
ラクトコッカス・ラクティス・サブスピーシーズ クレモリス Ｈ−６１株（ＮＩＴＥ Ｐ−９２）およびラクトバチルス・アシドフィルス ＪＣＭ１１３２株（理化学研究所）は、予め常法に従って一昼夜培養した。
次に、上記の各乳酸菌株を０．８５％食塩水で２回洗浄し、２００μｌ当たり１０９ｃｆｕになるように１０％脱脂乳（雪印スキムミルク、雪印乳業製）に懸濁した。
Example 1
BALB / c mice (8 months old, average body weight 30 g) were reared with commercial feed (MM-3, Funabashi Farm, Chiba) and water for 2 months after delivery.
Lactococcus lactis subspecies Cremoris H-61 strain (NITE P- 92) and Lactobacillus acidophilus JCM1132 strain (RIKEN) were cultured in advance overnight according to a conventional method.
Next, each lactic acid strain was washed twice with 0.85% saline and suspended in 10% nonfat milk (Snow Brand Skimmed Milk, Snow Brand Milk Products Co., Ltd.) so as to be 10 9 cfu per 200 μl.
このようにして得られるＨ−６１株およびＪＣＭ１１３２株の生菌体の１０％脱脂乳懸濁液２００μｌを、ＢＡＬＢ／ｃマウス（１群あたり３匹）に１日１回、７日間強制的に連続して経口投与した。なお、対照群には、１０％脱脂乳のみを同様に経口投与した。
各乳酸菌体の脱脂乳懸濁液の投与開始前、および投与終了後に、マウスより血清を採取し、チオバルビツール酸法（内藤・山中、日本老年医学雑誌、15：187-191、1975）により血中の過酸化脂質量を測定した。
その結果、Ｈ−６１株生菌体投与群では、対照群に比べ、血中過酸化脂質量が77.3％まで減少したのに対し、ＪＣＭ１１３２投与群ではそのような効果は認められなかった。
このことから、Ｈ−６１株には、抗酸化機能があることが明らかとなった。
200 μl of a 10% skim milk suspension of the viable cells of H-61 and JCM1132 strains obtained in this way was forcibly applied once to BALB / c mice (3 mice per group) for 7 days. Orally administered continuously. In the control group, only 10% nonfat milk was orally administered in the same manner.
Serum was collected from mice before and after the administration of skim milk suspension of each lactic acid bacterium, and thiobarbituric acid method (Naito / Yamanaka, Japan Geriatrics Journal, 15: 187-191, 1975) The amount of lipid peroxide in the blood was measured.
As a result, in the H-61 strain live cell administration group, the blood lipid peroxide level decreased to 77.3% compared to the control group, whereas in the JCM1132 administration group, such an effect was not observed.
This revealed that the H-61 strain has an antioxidant function.
（実施例２）
老化促進マウス（６ヶ月齢、老年性骨粗鬆症系、平均体重４０ｇ）は、搬入後、３ヶ月間、市販の飼料（ＭＭ−３、船橋農場製、千葉）と水で飼育した。
ラクトコッカス・ラクティス・サブスピーシーズ クレモリス Ｈ−６１株（ＮＩＴＥ Ｐ−９２）は、予め常法に従って一昼夜培養した。
次に、上記の乳酸菌株を蒸留水で２回洗浄し、１００℃で５０分間熱処理を行った後、凍結乾燥を行った。得られた乾燥菌体を０．０５％濃度で市販の飼料（ＭＭ−３）に混合し、この飼料を５−６ヶ月間、老化促進マウス（１群あたり５−７匹）に与えた。一方、対照群には、菌体非含有飼料を与えた。
Ｈ−６１株投与２ヵ月後に老化の程度を表す老化スコア（細川・梅澤、老化促進モデルマウスを用いた機能評価、pp.294-297、食品機能研究法、篠原・鈴木・上野川編、光琳、2000）にて老化度を判定した。投与終了後、骨密度をＤＸＡ装置（Dual Energy X-ray Absorptiometry、アロカ社製、ＤＣＳ−６００）にて測定した。
(Example 2)
Aging-promoting mice (6 months old, senile osteoporosis system, average body weight 40 g) were bred with commercial feed (MM-3, Funabashi Farm, Chiba) and water for 3 months after delivery.
Lactococcus lactis subspecies Cremolis strain H-61 (NITE P- 92) was cultured in advance overnight according to a conventional method.
Next, the lactic acid strain was washed twice with distilled water, heat-treated at 100 ° C. for 50 minutes, and then lyophilized. The obtained dried cells were mixed with a commercial feed (MM-3) at a concentration of 0.05%, and this feed was given to aging-promoted mice (5-7 mice per group) for 5-6 months. On the other hand, the control group was fed with a fungus-free feed.
Aging score indicating degree of aging 2 months after H-61 strain administration (Hosokawa / Umezawa, functional evaluation using aging promoting model mice, pp.294-297, Food Function Research Method, Shinohara / Suzuki / Uenogawa Hen, Mitsuaki) , 2000). After the administration was completed, the bone density was measured with a DXA device (Dual Energy X-ray Absorptiometry, manufactured by Aroka, DCS-600).
マウス皮膚外観について、上記の方法により老化スコアを算出した。老化スコアの算出は、脱毛、潰瘍、および目の腫れの各項目について行った。その結果、潰瘍発生や体の一部が脱毛状態のマウス、目の周りの皮膚が変化しているマウスが対照群では７匹中６匹で見られたのに対し、Ｈ−６１株投与群では脱毛、潰瘍を発生したマウスが一匹も認められず、目の周りの皮膚が変化しているマウスが７匹中１匹のみであった（表１）。 For mouse skin appearance, the aging score was calculated by the above method. The aging score was calculated for each item of hair loss, ulcer, and eye swelling. As a result, mice with ulcers and a part of the body with hair loss and mice with skin changes around the eyes were seen in 6 out of 7 mice in the control group, whereas in the H-61 strain administration group However, no mouse with hair loss or ulcer was found, and only 1 out of 7 mice had changed skin around the eyes (Table 1).
また、マウス右大腿骨骨密度を測定した。測定は、村山・藤巻（2000）の方法（骨評価関連検査、組織培養工学、26（13）：31-34、ニューサイエンス社）により実施した。その結果、対照群に比べてＨ−６１株投与群で有意に（ｐ＜0.001）高かった（図1）。一方、対照群においては、５ヶ月齢の老化促進マウスの骨密度は４０．２〜４０．５ｍｇ／ｃｍ２であり、１４ヶ月齢では対照群は３８．５ｍｇ／ｃｍ２であったのに対し、Ｈ−６１株投与群では４４．４ｍｇ／ｃｍ２であった（図1）ことから、Ｈ−６１株は加齢に伴う骨密度の減少を抑制することができることが明らかとなった。 The mouse right femur bone density was also measured. The measurement was carried out by the method of Murayama and Fujimaki (2000) (Bone evaluation-related examination, tissue culture engineering, 26 (13): 31-34, New Science). As a result, the H-61 strain administration group was significantly (p <0.001) higher than the control group (FIG. 1). On the other hand, in the control group, the bone density of the aging-promoted mice at 5 months of age was 40.2 to 40.5 mg / cm 2 , whereas at 14 months of age, the control group was 38.5 mg / cm 2 In the H-61 strain administration group, it was 44.4 mg / cm 2 (FIG. 1), and it became clear that the H-61 strain can suppress a decrease in bone density associated with aging.
（比較例１）
実施例２において、Ｈ−６１株の代わりにラクトコッカス・ラクティス・サブスピーシーズ ラクチス Ｇ５０株（ＦＥＲＭ Ｐ−18415）を用いた他は、同様にして飼料に混合し、１ヶ月齢の老化促進マウス（１群あたり８匹）に１１ヶ月間投与した。
その結果、皮膚の老化度は、対照群と比べて差が認められなかった。また、大腿骨骨密度についても、Ｇ５０株投与群と対照群で有意な差は認められなかった。
(Comparative Example 1)
In Example 2, except that Lactococcus lactis sub-species Lactis G50 strain (FERM P-18415) was used instead of H-61 strain, the mixture was mixed with the feed in the same manner, and a one-month-old aging-promoting mouse ( 8 animals per group) for 11 months.
As a result, the skin aging degree was not different from the control group. Further, regarding the femur bone density, no significant difference was observed between the G50 strain administration group and the control group.
本発明により、安全性が高く、しかも乳製品の製造に適しているラクトコッカス属乳酸菌であるＨ−６１株を利用した老化抑制剤および該乳酸菌を利用した食品や薬剤が提供される。
したがって、本発明により、付加価値の高い開発高齢者向けプロバイオティック食品の発が期待できる。
INDUSTRIAL APPLICABILITY According to the present invention, an aging inhibitor using the H-61 strain, which is a Lactococcus lactic acid bacterium that is highly safe and suitable for the production of dairy products, and a food and a drug using the lactic acid bacterium are provided.
Therefore, according to the present invention, the development of probiotic foods for developed elderly people with high added value can be expected.
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| JP2015182954A (en) * | 2014-03-20 | 2015-10-22 | 株式会社Ｌｉｋｅ Ｔｏｄｏ Ｊａｐａｎ製薬 | anti-glycation agent |
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