JP6961257B2 - Compositions for the treatment, prevention and / or alleviation of heavy metal-induced cytotoxicity - Google Patents

Compositions for the treatment, prevention and / or alleviation of heavy metal-induced cytotoxicity Download PDF

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JP6961257B2
JP6961257B2 JP2020019628A JP2020019628A JP6961257B2 JP 6961257 B2 JP6961257 B2 JP 6961257B2 JP 2020019628 A JP2020019628 A JP 2020019628A JP 2020019628 A JP2020019628 A JP 2020019628A JP 6961257 B2 JP6961257 B2 JP 6961257B2
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厚司 武田
洋平 西原
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株式会社にしはらグループ
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Description

本発明は、パクチー抽出物を有効成分として含有することを特徴とする、重金属誘発性細胞傷害の治療、予防及び/又は緩和用組成物に関する。 The present invention relates to a composition for treating, preventing and / or alleviating heavy metal-induced cytotoxicity, which comprises containing coriander extract as an active ingredient.

<パクチー>
最近、料理や食品に用いる香辛料は、その香りや味ばかりでなく、健康面への有用性が注目されている。パクチー(別名:コリアンダー、香菜、学名:Coriandrum sativum)は、各地で古くから食用とされてきた。パクチーは、食欲増進の効果があるといわれているほか、消化不良、鼓腸の改善等への効果が知られている(非特許文献1)。
近年、パクチーは、胃癌上皮細胞におけるピロリ菌感染による活性酸素種の産生を抑制する効果を有することが報告された(非特許文献1)。すなわち、パクチーには、胃において、活性酸素種の産生抑制を介して、ピロリ菌誘発性細胞傷害を抑制する効果を有する可能性があると考えられている。
しかし、当該効果は、胃等の消化管に限られている。また、パクチーについて、ピロリ菌以外の原因により引き起こされる細胞傷害に対する細胞傷害抑制作用の有無は、明らかになっていない。
<Coriander>
Recently, spices used in cooking and foods are attracting attention not only for their aroma and taste, but also for their usefulness in terms of health. Pakuchi (also known as coriander, coriander, scientific name: Coriandrum sativum) has long been edible in many places. Coriander is said to have an appetite-promoting effect, and is also known to have an effect on indigestion, flatulence, and the like (Non-Patent Document 1).
In recent years, it has been reported that coriander has an effect of suppressing the production of reactive oxygen species due to Helicobacter pylori infection in gastric cancer epithelial cells (Non-Patent Document 1). That is, it is considered that coriander may have an effect of suppressing Helicobacter pylori-induced cytotoxicity in the stomach through suppression of production of reactive oxygen species.
However, the effect is limited to the digestive tract such as the stomach. In addition, it has not been clarified whether or not coriander has a cytotoxic inhibitory effect on cytotoxicity caused by causes other than Helicobacter pylori.

<重金属誘発性細胞傷害>
細胞傷害の一つに重金属誘発性細胞傷害がある。過剰量の重金属は、人体に悪影響を及ぼすことが知られている。重金属誘発性細胞傷害は、過剰摂取等により体内に蓄積した重金属がもたらす細胞傷害である。細胞傷害とは、物質の作用等により、細胞が、機能障害や増殖阻害を引き起こされ、あるいは細胞死に至ることをいう。
これまでに、重金属誘発性細胞死の抑制や体内の重金属濃度の低減といった、パクチーによる重金属誘発性細胞傷害の抑制効果を直接証明する報告はされていなかった。
<Heavy metal-induced cytotoxicity>
One of the cytotoxicity is heavy metal-induced cytotoxicity. Excessive amounts of heavy metals are known to have an adverse effect on the human body. Heavy metal-induced cytotoxicity is cytotoxicity caused by heavy metals accumulated in the body due to overdose or the like. Cytotoxicity means that a cell causes dysfunction, inhibition of proliferation, or cell death due to the action of a substance or the like.
So far, there have been no reports directly demonstrating the inhibitory effect of heavy metal-induced cell damage by pacty, such as suppression of heavy metal-induced cell death and reduction of heavy metal concentration in the body.

J Ethnopharmacol 2012; 141: 403-410.J Ethnopharmacol 2012; 141: 403-410.

本発明は、重金属誘発性細胞傷害を抑制することができる、重金属誘発性細胞傷害の治療、予防及び/又は緩和用組成物を提供することを目的とする。 An object of the present invention is to provide a composition for treating, preventing and / or alleviating heavy metal-induced cytotoxicity, which can suppress heavy metal-induced cytotoxicity.

本発明者らは、上記課題を解決するために鋭意検討を重ねた結果、パクチー抽出物が、重金属誘発性細胞傷害を抑制できることを見出し、本発明を完成するに至った。 As a result of diligent studies to solve the above problems, the present inventors have found that coriander extract can suppress heavy metal-induced cell damage, and have completed the present invention.

すなわち、本発明は、以下の通りである。
1.パクチー抽出物を有効成分として含有する、重金属誘発性細胞傷害の治療、予防及び/又は緩和用組成物。
2.前記重金属誘発性細胞傷害が、脳、肝臓及び/又は腎臓における重金属誘発性細胞傷害である、前項1に記載の組成物。
3.前記重金属が、亜鉛、ヒ素、鉄、又はカドミウムである、前項1又は2に記載の組成物。
4.前記重金属誘発性細胞傷害が、脳における亜鉛誘発性細胞傷害である、前項1〜3のいずれか一項に記載の組成物。
5.前記重金属誘発性細胞傷害が、肝臓における鉄誘発性細胞傷害である、前項1〜3のいずれか一項に記載の組成物。
6.前記重金属誘発性細胞傷害が、腎臓におけるヒ素、鉄、亜鉛又はカドミウム誘発性細胞傷害である、前項1〜3のいずれか一項に記載の組成物。
7.前記組成物が、重金属誘発性細胞傷害の緩和及び/又は予防用食品である、前項1〜6のいずれか一項に記載の組成物。
8.前記組成物が、重金属誘発性細胞傷害の治療及び/又は予防用治療剤である、前項1〜6のいずれか一項に記載の組成物。
That is, the present invention is as follows.
1. 1. A composition for treating, preventing and / or alleviating heavy metal-induced cytotoxicity containing coriander extract as an active ingredient.
2. The composition according to item 1 above, wherein the heavy metal-induced cytotoxicity is a heavy metal-induced cytotoxicity in the brain, liver and / or kidney.
3. 3. The composition according to item 1 or 2 above, wherein the heavy metal is zinc, arsenic, iron, or cadmium.
4. The composition according to any one of items 1 to 3 above, wherein the heavy metal-induced cytotoxicity is zinc-induced cytotoxicity in the brain.
5. The composition according to any one of items 1 to 3 above, wherein the heavy metal-induced cytotoxicity is iron-induced cytotoxicity in the liver.
6. The composition according to any one of items 1 to 3 above, wherein the heavy metal-induced cytotoxicity is arsenic, iron, zinc or cadmium-induced cytotoxicity in the kidney.
7. The composition according to any one of the preceding items 1 to 6, wherein the composition is a food for alleviating and / or preventing heavy metal-induced cytotoxicity.
8. The composition according to any one of the preceding items 1 to 6, wherein the composition is a therapeutic agent for treating and / or preventing heavy metal-induced cytotoxicity.

本発明によれば、重金属誘発性細胞死の抑制及び腎臓の重金属濃度を低減することを可能とする、重金属誘発性細胞傷害の治療、予防及び/又は緩和用組成物を提供することができる。 According to the present invention, it is possible to provide a composition for treating, preventing and / or alleviating heavy metal-induced cell injury, which can suppress heavy metal-induced cell death and reduce the concentration of heavy metal in the kidney.

ヒ素誘発性細胞死の抑制の評価の結果を示す。縦軸は、ヒ素及びパクチー抽出液(パクチーエキス)を添加しなかったウエルを100%として算出した細胞生存率を示す。「Asなし」は、ヒ素を添加しなかったウエルの結果を示し、「Asあり」は、ヒ素を添加したウエルの結果を示す。横軸の「0」は、パクチー抽出液を添加しなかったウエルの結果を示し、「パクチー」は、パクチー抽出液を添加したウエルの結果を示す。図中の「*」、「**」、「***」は、有意差があることを示す(*:p<0.05、**:p<0.01、***:p<0.001)。A.ヒ素4μM+パクチー抽出液0.05%の群を示す。B.ヒ素8μM+パクチー抽出液0.05%の群の結果を示す。C.ヒ素16 μM+パクチー抽出液0.05%の群の結果を示す。D.ヒ素8 μM+パクチー抽出液0.1%の群の結果を示す。E.ヒ素16 μM+パクチー抽出液0.1%の群の結果を示す。The results of the evaluation of the suppression of arsenic-induced cell death are shown. The vertical axis shows the cell viability calculated with 100% of the wells to which arsenic and coriander extract (coriander extract) were not added. “Without As” indicates the result of the well without arsenic added, and “with As” indicates the result of the well with arsenic added. “0” on the horizontal axis indicates the result of the well to which the coriander extract was not added, and “Pakuchi” indicates the result of the well to which the coriander extract was added. “*”, “**”, and “***” in the figure indicate that there is a significant difference (*: p <0.05, **: p <0.01, ***: p < 0.001). A. The group of arsenic 4 μM + cilantro extract 0.05% is shown. B. The results of the group of 8 μM arsenic + 0.05% coriander extract are shown. C. The results of the group of 16 μM arsenic + 0.05% coriander extract are shown. D. The results of the group of 8 μM arsenic + 0.1% coriander extract are shown. E. The results of the group of 16 μM arsenic + 0.1% coriander extract are shown. マウス腎臓におけるヒ素濃度低減の評価の結果を示す。縦軸は、検出されたヒ素の量(ng/腎臓1g)を示す。横軸の「パクチーなし」は、パクチー抽出液を含まない水を飲水として与えた群の結果を示し、「パクチー0.25%」は、パクチー抽出液を0.25%含む水を飲水として与えた群の結果を示す。図中の「***」は、有意差があることを示す(p<0.001)。The results of the evaluation of the reduction of arsenic concentration in the mouse kidney are shown. The vertical axis shows the amount of arsenic detected (ng / kidney 1 g). “No coriander” on the horizontal axis shows the result of the group in which water without coriander extract was given as drinking water, and “Pakuchi 0.25%” was given with water containing 0.25% coriander extract as drinking water. The results of the group are shown. “***” in the figure indicates that there is a significant difference (p <0.001). マウス肝臓及び腎臓における鉄濃度低減の評価の結果を示す。縦軸は、検出された鉄の量(μg/臓器1g)を示す。「パクチーなし」はパクチー抽出液を含まない水を飲水として与えた群の結果を示し、「パクチー0.25%」は、パクチー抽出液を0.25%含む水を飲水として与えた群の結果を示す。「肝臓」は肝臓における結果を、「腎臓」は腎臓における結果を示す。図中の「*」は、有意差があることを示す(p<0.05)。網掛け部分は、マウスの各臓器に通常含まれる鉄の量の目安を示す。The results of the evaluation of iron concentration reduction in mouse liver and kidney are shown. The vertical axis shows the amount of iron detected (μg / organ 1 g). "No coriander" shows the result of the group that gave water without coriander extract as drinking water, and "Pakuchi 0.25%" shows the result of the group that gave water containing 0.25% of coriander extract as drinking water. Is shown. "Liver" indicates the result in the liver, and "kidney" indicates the result in the kidney. “*” In the figure indicates that there is a significant difference (p <0.05). The shaded area indicates the amount of iron normally contained in each organ of the mouse. マウス腎臓及び脳における亜鉛濃度低減の評価の結果を示す。縦軸は、検出された亜鉛の量(μg/臓器1g)を示す。「パクチーなし」はパクチー抽出液を含まない水を飲水として与えた群の結果を示し、「パクチー0.25%」は、パクチー抽出液を0.25%含む水を飲水として与えた群の結果を示す。「腎臓」は腎臓における結果を、「脳」は脳における結果を示す。網掛け部分は、マウスの各臓器に通常含まれる亜鉛の量の目安を示す。The results of the evaluation of zinc concentration reduction in mouse kidney and brain are shown. The vertical axis shows the amount of zinc detected (μg / organ 1 g). "No coriander" shows the result of the group that gave water without coriander extract as drinking water, and "Pakuchi 0.25%" shows the result of the group that gave water containing 0.25% of coriander extract as drinking water. Is shown. "Kidney" indicates the result in the kidney, and "brain" indicates the result in the brain. The shaded area indicates the amount of zinc normally contained in each organ of the mouse. マウス腎臓におけるカドミウム濃度低減の評価の結果を示す。縦軸は、検出されたカドミウムの量(μg/腎臓1g)を示す。「パクチーなし」はパクチー抽出液を含まない水を飲水として与えた群の結果を示し、「パクチー0.25%」は、パクチー抽出液を0.25%含む水を飲水として与えた群の結果を示す。網掛け部分は、マウスの腎臓に通常含まれるカドミウムの量の目安を示す。The results of the evaluation of the reduction of cadmium concentration in the mouse kidney are shown. The vertical axis shows the amount of cadmium detected (μg / kidney 1 g). "No coriander" shows the result of the group that gave water without coriander extract as drinking water, and "Pakuchi 0.25%" shows the result of the group that gave water containing 0.25% of coriander extract as drinking water. Is shown. The shaded area provides an indication of the amount of cadmium normally contained in the kidneys of mice.

<有効成分>
本発明の組成物は、パクチー抽出物を有効成分として含有する。なお、本明細書において、パクチーは学名Coriandrum sativumとする植物を指す。本発明に用いられるパクチーの品種は、Common、 Santos 、Cilantro、Calypso、Leisure、Chechnya、Moroccan、Green Aroma、Confetti、Marino等を例示することができるが、特に限定されない。
本発明においてパクチーは、好ましくは、葉、茎及び根を含む。
<Active ingredient>
The composition of the present invention contains coriander extract as an active ingredient. In this specification, coriander refers to a plant having the scientific name Coriandrum sativum. The varieties of coriander used in the present invention can be exemplified by Common, Santos, Cilantro, Calypso, Leisure, Chechnya, Moroccan, Green Aroma, Confetti, Marino and the like, but are not particularly limited.
In the present invention, coriander preferably includes leaves, stems and roots.

<パクチー抽出物>
「パクチー抽出物」とは、パクチー由来の抽出物を意味し、その他の微量成分等が含まれていてもよい。
「抽出物」の形態には、抽出液、搾汁若しくはそれら混合物の形態、並びに、該抽出液、搾汁若しくはそれら混合物を濃縮、希釈及び/又は乾燥した、濃縮物、希釈物又は乾燥物の形態が含まれる。
「抽出液」は、パクチーを抽出媒体により抽出することにより調製することができる。抽出に用いるパクチーの形状は、原型のまま、あるいは適当な寸法又は形状にカットした状態、あるいは後述の乾燥物、破砕物、又は搾汁の形状であることができる。抽出媒体としては水、有機溶媒等の溶媒等が挙げられる。より詳しくは、水のほか、エタノール等のアルコール、アセトン等の親水性有機溶媒、ヘキサン等の疎水性有機溶媒、あるいはそれらの混合溶媒を用いることができる。溶媒抽出により抽出液を製造する場合には、有効成分を適量の溶媒(例えば、生のパクチーに対して重量基準で0.5〜20倍量)中に浸漬し、適宜撹拌又は静置して溶媒中に溶媒可溶性成分を溶出させる。抽出時間は、特に限定されないが、5分間〜120分間、例えば、15分間〜90分間とすることができる。抽出温度は、特に限定されないが、0℃〜125℃、例えば60℃〜125℃とすることができる。抽出後、溶媒可溶性成分を含む溶媒画分と、不溶性画分を含む固体画分とを、自体公知の固液分離手段、例えば、濾過により分離し、抽出液として溶媒画分を取得する。
「搾汁」は、パクチーを破砕・圧搾して、液体画分と固体画分とを分離し、液体画分を取得することにより調製することができる。液体画分と固体画分との分離は、濾過、遠心分離等の通常の固液分離手段により行うことができる。
「乾燥物」は、前記抽出液又は搾汁あるいはそれら混合物を乾燥することにより製造することができる。乾燥は、前記抽出液又は搾汁あるいはそれら混合物を通常の乾燥手段、例えば、スプレー法を用いて乾燥することにより実施することができる。濃縮又は乾燥に際して、前記搾汁、前記抽出液、前記濃縮物又は前記乾燥物と、賦形剤等の他の成分とを組み合わせて濃縮又は乾燥を行ってもよい。
「濃縮物」は、前記抽出液又は搾汁あるいはそれら混合物を濃縮することにより製造することができる。濃縮の方法としては、例えば、減圧濃縮、膜濃縮が採用できる。
<Coriander extract>
The “coriander extract” means an extract derived from coriander, and may contain other trace components and the like.
The form of "extract" includes the forms of extracts, juices or mixtures thereof, and concentrates, dilutions or dried products obtained by concentrating, diluting and / or drying the extracts, juices or mixtures thereof. Morphology is included.
The "extract" can be prepared by extracting coriander with an extraction medium. The shape of coriander used for extraction can be the original shape, cut into appropriate dimensions or shapes, or the shape of dried, crushed or squeezed juice, which will be described later. Examples of the extraction medium include water, a solvent such as an organic solvent, and the like. More specifically, in addition to water, an alcohol such as ethanol, a hydrophilic organic solvent such as acetone, a hydrophobic organic solvent such as hexane, or a mixed solvent thereof can be used. When the extract is produced by solvent extraction, the active ingredient is immersed in an appropriate amount of solvent (for example, 0.5 to 20 times the amount of raw pakuchi by weight), and the mixture is appropriately stirred or allowed to stand. The solvent-soluble component is eluted in the solvent. The extraction time is not particularly limited, but may be 5 minutes to 120 minutes, for example, 15 minutes to 90 minutes. The extraction temperature is not particularly limited, but can be 0 ° C. to 125 ° C., for example, 60 ° C. to 125 ° C. After extraction, the solvent fraction containing the solvent-soluble component and the solid fraction containing the insoluble fraction are separated by a solid-liquid separation means known per se, for example, filtration, and the solvent fraction is obtained as an extract.
"Juice" can be prepared by crushing and squeezing coriander, separating the liquid fraction and the solid fraction, and obtaining the liquid fraction. The liquid fraction and the solid fraction can be separated by ordinary solid-liquid separation means such as filtration and centrifugation.
The "dried product" can be produced by drying the extract or juice or a mixture thereof. Drying can be carried out by drying the extract or juice or a mixture thereof using ordinary drying means, for example, a spray method. At the time of concentration or drying, the juice, the extract, the concentrate or the dried product may be combined with other components such as excipients to concentrate or dry.
The "concentrate" can be produced by concentrating the extract or juice or a mixture thereof. As a method of concentration, for example, vacuum concentration and membrane concentration can be adopted.

本発明の組成物の一例である食品(特に、サプリメント)に含まれているパクチー抽出物の製造例は、以下の通りである。
生のパクチーに水を加え、約90℃に昇温し、30分〜数時間撹絆抽出を行う。抽出後濾過し、得られた濾過液を減圧濃縮した後、約90℃に昇温し、数分〜1時間加熱殺菌を行い、ペースト状のパクチー濃縮液を得る。
この濃縮液に水を加え、昇温しながら撹絆して均質にし、約90℃で数分〜1時間加熱殺菌を行い、液状のパクチー抽出液を得る。
上記で得られた液状のパクチー抽出液をスプレー法で乾燥することにより、パクチー抽出物を乾燥物として得る。
Examples of production of coriander extract contained in foods (particularly supplements) which are examples of the compositions of the present invention are as follows.
Water is added to raw coriander, the temperature is raised to about 90 ° C., and stirring bond extraction is performed for 30 minutes to several hours. After extraction, the mixture is filtered, and the obtained filtrate is concentrated under reduced pressure, then heated to about 90 ° C. and sterilized by heating for several minutes to 1 hour to obtain a paste-like Pakuchi concentrate.
Water is added to this concentrated solution, and the mixture is stirred and homogenized while raising the temperature, and sterilized by heating at about 90 ° C. for several minutes to 1 hour to obtain a liquid coriander extract.
The liquid coriander extract obtained above is dried by a spray method to obtain a coriander extract as a dried product.

本発明の組成物に含まれる有効成分の含有量は特に限定されないが、単回投与による投与量にして、例えば、食品1gあたり、以下の範囲よりそれぞれ選択される量(乾燥重量に基づく)を含めることができる。
パクチー抽出物:0.0004〜0.97 g/g食品、好ましくは0.024〜0.24 g/g食品。
なお、生重量に換算すると、パクチー含有量は、0.01〜20g/g食品、好ましくは0.5〜5 g/g食品である。
The content of the active ingredient contained in the composition of the present invention is not particularly limited, but the dose selected from the following ranges per 1 g of food (based on dry weight) can be used as a single dose. Can be included.
Coriander extract: 0.0004 to 0.97 g / g food, preferably 0.024 to 0.24 g / g food.
When converted to raw weight, the coriander content is 0.01 to 20 g / g food, preferably 0.5 to 5 g / g food.

<本発明の組成物の効能・効果>
本発明の組成物は、重金属誘発性の細胞傷害、重金属中毒、ヒ素中毒、鉄中毒、亜鉛中毒、カドミウム中毒の疾患の予防、緩和又は治療のために用いることができる。本発明の組成物は、重金属由来の細胞傷害、重金属中毒、ヒ素中毒、鉄中毒、亜鉛中毒、カドミウム中毒の患者や、体内、臓器、腎臓、肝臓、脳、血液、細胞における重金属濃度が高い傾向にある対象者だけでなく、健常な対象者に対しても有効である。
<Efficacy / Effect of Composition of the Present Invention>
The compositions of the present invention can be used for the prevention, alleviation or treatment of diseases of heavy metal-induced cytotoxicity, heavy metal poisoning, arsenic poisoning, iron poisoning, zinc poisoning and cadmium poisoning. The composition of the present invention tends to have a high concentration of heavy metals in patients with heavy metal-derived cytotoxicity, heavy metal poisoning, arsenic poisoning, iron poisoning, zinc poisoning, cadmium poisoning, and in the body, organs, kidneys, liver, brain, blood, and cells. It is effective not only for the subjects in the above but also for healthy subjects.

本発明の組成物は、慢性又は急性の重金属の蓄積による、細胞傷害を抑制することが可能である。さらに、本発明の組成物は、重金属を低減することができる。「重金属を低減する」とは、体内、臓器、腎臓、肝臓、脳、血液、細胞における慢性的又は急性的な重金属の蓄積を抑制する以上の効果を意味し、重金属が蓄積する以前の水準以下の水準にまで低減させることを意味する。 The compositions of the present invention are capable of suppressing cytotoxicity due to chronic or acute accumulation of heavy metals. Furthermore, the compositions of the present invention can reduce heavy metals. "Reducing heavy metals" means more than suppressing the accumulation of chronic or acute heavy metals in the body, organs, kidneys, liver, brain, blood and cells, and is below the level before the accumulation of heavy metals. It means to reduce to the level of.

本発明において、「重金属」とは、比重が4g/cm以上の金属をいう。具体的な重金属としては、比重が4g/cm以上の金属であれば、特に限定されないが、例えば、ヒ素、鉄、亜鉛、カドミウム、鉛、銅、水銀、ニッケル等が挙げられる。 In the present invention, the "heavy metal" refers to a metal having a specific gravity of 4 g / cm 3 or more. Specific heavy metals are not particularly limited as long as they have a specific gravity of 4 g / cm 3 or more, and examples thereof include arsenic, iron, zinc, cadmium, lead, copper, mercury, and nickel.

<本発明の組成物の摂取対象>
本発明の組成物の対象は、典型的にはヒトであるが、ヒトには限定されず他の非ヒト動物、例えばヒト以外の哺乳類(イヌ、ネコ、ウマ、ブタ、ウシ等)であってもよい。
また、必要量以上の重金属(特に、亜鉛、ヒ素、鉄、カドミウム等)が体内(特に、脳、肝臓、腎臓等)に蓄積している患者も対象とする。
<Ingestion target of the composition of the present invention>
The subject of the composition of the present invention is typically human, but is not limited to humans and is other non-human animals such as non-human mammals (dogs, cats, horses, pigs, cows, etc.). May be good.
It also targets patients who have accumulated more heavy metals (particularly zinc, arsenic, iron, cadmium, etc.) than necessary in their bodies (particularly, brain, liver, kidneys, etc.).

<本発明の組成物の形態>
本発明の組成物は、食品の形態で用いることができる。ここで、食品の形態には、特に限定されないが、例えば、サプリメント、米飯類、麺類、パン類、穀類、野菜、食肉、各種加工食品、菓子類、牛乳、清涼飲料水、アルコール飲料、ゼリー、ガム、タブレット(錠剤)、栄養補助食品、食品添加物等が含まれる。なお、食品には、機能性食品、健康食品、健康志向食品等も含まれる。
<Form of the composition of the present invention>
The composition of the present invention can be used in the form of food. Here, the form of the food is not particularly limited, but for example, supplements, rice, noodles, breads, grains, vegetables, meat, various processed foods, confectionery, milk, soft drinks, alcoholic beverages, jellies, etc. Includes gums, tablets, dietary supplements, food additives, etc. The food includes functional foods, health foods, health-oriented foods and the like.

<本発明の組成物の他の成分>
本発明の組成物は、全体が上記有効成分のみからなるものであってもよいし、上記有効成分と他の成分とを含むものであってもよい。「他の成分」は、食品において許容される成分である限り特に限定されず、例えば、目的の食品を構成する諸成分、油性成分、賦形剤、崩壊剤、結合剤、滑沢剤、コーティング剤、着色剤、発色剤、矯味剤、着香剤、酸化防止剤、防腐剤、呈味剤、酸味剤、甘味剤、強化剤、ビタミン剤、膨張剤、増粘剤、界面活性剤等を挙げることができ、本発明の組成物の形態に応じて、適当なものを選択し、適宜組み合わせて用いることができる。
<Other components of the composition of the present invention>
The composition of the present invention may be composed entirely of the above active ingredients, or may contain the above active ingredients and other ingredients. The "other ingredients" are not particularly limited as long as they are acceptable ingredients in foods, and for example, various ingredients constituting the target food, oily ingredients, excipients, disintegrants, binders, lubricants, coatings. Agents, colorants, color formers, flavoring agents, flavoring agents, antioxidants, preservatives, flavoring agents, acidulants, sweeteners, enhancers, vitamins, swelling agents, thickeners, surfactants, etc. It can be mentioned, and an appropriate one can be selected and used in an appropriate combination according to the form of the composition of the present invention.

以下に具体例を挙げて本発明を詳細に説明するが、本発明はこれらの実施例に限定されない。 The present invention will be described in detail below with reference to specific examples, but the present invention is not limited to these examples.

(パクチー抽出液の抽出方法)
生のパクチー(葉、茎及び根を含む)5kgに水を50L加え、90℃に昇温し、1時間撹絆抽出を行った。抽出後濾過し、得られた濾過液を減圧濃縮した後、90℃に昇温し、30分間加熱殺菌を行い、ペースト状のパクチー濃縮液349.5g{固形分(乾燥重量)242.5g}を得た。
この濃縮液100 gに水を100 g加え、昇温しながら撹絆して均質にし、90℃で30分間加熱殺菌を行い、液状のパクチー抽出液200g(固形分69.4 g)を得た。
(Extraction method of coriander extract)
50 L of water was added to 5 kg of raw coriander (including leaves, stems and roots), the temperature was raised to 90 ° C., and stirring bond extraction was performed for 1 hour. After extraction, the filtrate is filtered, and the obtained filtrate is concentrated under reduced pressure, heated to 90 ° C., sterilized by heating for 30 minutes, and paste-like coriander concentrate 349.5 g {solid content (dry weight) 242.5 g}. Got
100 g of water was added to 100 g of this concentrated solution, and the mixture was stirred and homogenized while raising the temperature, and sterilized by heating at 90 ° C. for 30 minutes to obtain 200 g of a liquid coriander extract (solid content 69.4 g). ..

(ヒ素誘発性細胞死の抑制の評価)
96ウエルプレートにPC12細胞(ラット副腎皮質由来の褐色細胞腫の培養細胞株、2x 10細胞/ウエル、一群8ウエル)を添加し、24時間培養後、培養液にヒ素溶液1 μL(溶媒:9 μM NaOHを含む無血清培地)、パクチー抽出液(溶媒:水)及び/又は各種溶媒のみをそれぞれ10 μL添加した(最終液量111 μL)。最終濃度で、ヒ素4μM+パクチー抽出液0.05%、ヒ素8μM+パクチー抽出液0.05%の群、ヒ素16 μM+パクチー抽出液0.05%の群、ヒ素8 μM+パクチー抽出液0.1%の群、及びヒ素16 μM+パクチー抽出液0.1%の群を準備した。また、各群において、ヒ素及びパクチー抽出液を添加しなかったウエル、パクチー抽出液のみを添加したウエル、ヒ素のみを添加したウエル、ヒ素及びパクチー抽出液を添加したウエルを準備して、それらの結果を比較した。なお、ヒ素及び/又はパクチー抽出液を添加しない場合には、それぞれ代わりに各溶媒を添加した。
さらに、24時間培養後に培養液量の10%に相当するAlamar blue液を添加し、1時間後に蛍光強度(励起波長、540−570nm;測定波長、580−610 nm)を測定した。ヒ素及びパクチー抽出液を添加しなかったウエルを100%として、蛍光強度から、細胞生存率を求めた。
(Evaluation of suppression of arsenic-induced cell death)
96-well plates in PC12 cells (cell lines of pheochromocytoma rat adrenal cortex, 2x 10 4 cells / well, group 8 well) were added, after 24 hours of culture, arsenic solution 1 [mu] L culture solution (solvent: (Serum-free medium containing 9 μM NaOH), Pakuchi extract (solvent: water) and / or only 10 μL of each of various solvents were added (final solution volume 111 μL). At the final concentration, arsenic 4 μM + arsenic extract 0.05%, arsenic 8 μM + arsenic extract 0.05%, arsenic 16 μM + arsenic extract 0.05%, arsenic 8 μM + arsenic extract 0.1% A group and a group of 16 μM arsenic + 0.1% arsenic extract were prepared. Further, in each group, wells to which arsenic and cilantro extract were not added, wells to which only cilantro extract was added, wells to which only arsenic was added, and wells to which arsenic and cilantro extract were added were prepared. The results were compared. When arsenic and / or coriander extract was not added, each solvent was added instead.
Further, after culturing for 24 hours, an Aramar blue solution corresponding to 10% of the amount of the culture solution was added, and after 1 hour, the fluorescence intensity (excitation wavelength, 540-570 nm; measurement wavelength, 580-610 nm) was measured. The cell viability was determined from the fluorescence intensity, with the well to which arsenic and coriander extract were not added as 100%.

結果を図1に示す。
図1から明らかなように、全ての群で、パクチー抽出液の添加により、ヒ素を添加した場合の細胞生存率が上昇した。特に、ヒ素16μM+パクチー抽出液0.1%の群では、ヒ素を添加したウエルにおいて、パクチー抽出液を添加した細胞群は、パクチー抽出液を添加しなかった細胞群と比較して、細胞生存率が約2倍であった。このことから、パクチー抽出液が、ヒ素により誘発される細胞死を抑制することが確認でき、パクチーによる重金属誘発性細胞傷害に対する抑制効果を確認できた。
The results are shown in Figure 1.
As is clear from FIG. 1, in all groups, the addition of coriander extract increased the cell viability when arsenic was added. In particular, in the group of 16 μM arsenic + 0.1% coriander extract, in the wells to which arsenic was added, the cell group to which the coriander extract was added had a cell viability rate as compared with the cell group to which the coriander extract was not added. Was about twice as much. From this, it was confirmed that the coriander extract suppresses arsenic-induced cell death, and the inhibitory effect on heavy metal-induced cytotoxicity caused by coriander was confirmed.

(マウス腎臓におけるヒ素濃度低減の評価)
パクチー抽出液0.25%を含む水又はパクチー抽出液を含まない水を飲水としてddYマウス(4週齢、オス、一群3匹)に与えて8週間飼育した。その後、各マウスから腎臓0.5〜0.7gを摘出し、2%硝酸で溶解させ、ヒ素の濃度をICP発光分光分析計(アジレントテクノロジー(株)ICP Expert II 700−ES)で測定した。BLANKとして、2%硝酸を使用した。
(Evaluation of reduction of arsenic concentration in mouse kidney)
Water containing 0.25% of coriander extract or water without coriander extract was given to ddY mice (4 weeks old, male, 3 animals in a group) as drinking water and bred for 8 weeks. Then, 0.5 to 0.7 g of kidney was removed from each mouse, dissolved in 2% nitric acid, and the concentration of arsenic was measured by an ICP emission spectrophotometer (ICP Expert II 700-ES, Agilent Technologies, Ltd.). 2% nitric acid was used as BLANK.

結果を図2に示す。
図2から明らかなように、パクチー抽出液を与えなかった群では、平均で腎臓1gあたり約81 ngのヒ素が検出されたのに対し、パクチー抽出液を与えた群では、ヒ素が検出されなかった(平均で腎臓1 gあたり0g以下であった)。すなわち、パクチー抽出液を与えたことにより、腎臓中のヒ素濃度を100%低減した。このことから、パクチー抽出液が、腎臓中のヒ素濃度を低減させることが確認でき、腎臓中の重金属の蓄積を抑制できることが確認できた。
The results are shown in FIG.
As is clear from FIG. 2, in the group not given coriander extract, about 81 ng of arsenic was detected per 1 g of kidney on average, whereas in the group given coriander extract, arsenic was not detected. (On average, it was less than 0 g per 1 g of kidney). That is, the arsenic concentration in the kidney was reduced by 100% by giving the coriander extract. From this, it was confirmed that the coriander extract reduced the arsenic concentration in the kidney and could suppress the accumulation of heavy metals in the kidney.

(マウス肝臓及び腎臓における鉄濃度低減の評価)
パクチー抽出液0.25%を含む水又はパクチー抽出液を含まない水を飲水としてddYマウス(4週齢、オス、一群3匹)に与えて8週間飼育した。その後、マウスから肝臓及び腎臓を摘出し、2%硝酸で溶解させ、鉄の濃度をICP発光分光分析計(アジレントテクノロジー(株)ICP Expert II 700−ES)で測定した。
(Evaluation of iron concentration reduction in mouse liver and kidney)
Water containing 0.25% of coriander extract or water without coriander extract was given to ddY mice (4 weeks old, male, 3 animals in a group) as drinking water and bred for 8 weeks. Then, the liver and kidney were removed from the mouse, dissolved in 2% nitric acid, and the iron concentration was measured by an ICP emission spectrophotometer (ICP Expert II 700-ES, Agilent Technologies, Inc.).

結果を図3に示す。
肝臓において、パクチー抽出液を与えなかった群では、平均で肝臓1gあたり約150μgの鉄が検出されたのに対し、パクチー抽出液を与えた群では、平均で肝臓1gあたり約128μgの鉄が検出された(図3)。すなわち、パクチー抽出液を与えたことにより、肝臓中の鉄濃度を約15%低減した。
また、腎臓において、パクチー抽出液を与えなかった群では、平均で腎臓1gあたり約60μgの鉄が検出されたのに対し、パクチー抽出液を与えた群では、平均で腎臓1gあたり約40μgの鉄が検出された(図3)。すなわち、パクチー抽出液を与えたことにより、腎臓中の鉄濃度を約33%低減した。
このことから、パクチー抽出液が、肝臓及び腎臓において鉄の蓄積を軽減し、腎臓及び腎臓における鉄濃度を低下させることが明らかになった。
The results are shown in FIG.
In the liver, about 150 μg of iron was detected per 1 g of liver on average in the group not given coriander extract, whereas about 128 μg of iron was detected per 1 g of liver on average in the group given coriander extract. (Fig. 3). That is, the iron concentration in the liver was reduced by about 15% by giving the coriander extract.
In the kidney, about 60 μg of iron was detected per 1 g of kidney on average in the group not given Pakuchi extract, whereas about 40 μg of iron was detected per 1 g of kidney in the group given Pakuchi extract. Was detected (Fig. 3). That is, the iron concentration in the kidney was reduced by about 33% by giving the coriander extract.
From this, it was clarified that the coriander extract reduces the accumulation of iron in the liver and the kidney and lowers the iron concentration in the kidney and the kidney.

(マウス腎臓及び脳における亜鉛濃度低減の評価)
パクチー抽出液0.25%を含む水又はパクチー抽出液を含まない水を飲水としてddYマウス(4週齢、オス、一群3匹)に与えて8週間飼育した。その後、マウスから腎臓及び脳を摘出し、2%硝酸で溶解させ、亜鉛の濃度をICP発光分光分析計(アジレントテクノロジー(株)ICP Expert II 700−ES)で測定した。
(Evaluation of reduced zinc concentration in mouse kidney and brain)
Water containing 0.25% of coriander extract or water without coriander extract was given to ddY mice (4 weeks old, male, 3 animals in a group) as drinking water and bred for 8 weeks. Then, the kidney and brain were removed from the mouse, dissolved in 2% nitrate, and the zinc concentration was measured with an ICP emission spectrophotometer (ICP Expert II 700-ES, Agilent Technologies, Inc.).

結果を図4に示す。
腎臓において、パクチー抽出液を与えなかった群では、平均で腎臓1gあたり約42μgの亜鉛が検出されたのに対し、パクチー抽出液を与えた群では、平均で腎臓1gあたり約29μgの亜鉛が検出された(図4)。すなわち、パクチー抽出液を与えたことにより、腎臓中の亜鉛濃度を約31%低減した。
また、脳において、パクチー抽出液を与えなかった群では、平均で脳1gあたり約57μgの亜鉛が検出されたのに対し、パクチー抽出液を与えた群では、平均で脳1gあたり約53μgの亜鉛が検出された(図4)。すなわち、パクチー抽出液を与えたことにより、脳中の亜鉛濃度を約7%低減した。
このことから、パクチー抽出液が、腎臓及び脳において亜鉛の蓄積を軽減し、腎臓及び脳における亜鉛濃度を低下させることが明らかになった。
The results are shown in FIG.
In the kidneys, an average of about 42 μg of zinc was detected per gram of kidney in the group not given coriander extract, whereas an average of about 29 μg of zinc was detected per gram of kidney in the group given coriander extract. (Fig. 4). That is, the zinc concentration in the kidney was reduced by about 31% by giving the coriander extract.
In the brain, about 57 μg of zinc was detected per 1 g of brain on average in the group not given coriander extract, whereas about 53 μg of zinc per 1 g of brain was detected in the group given coriander extract. Was detected (Fig. 4). That is, the zinc concentration in the brain was reduced by about 7% by giving the coriander extract.
From this, it was clarified that the coriander extract reduces the accumulation of zinc in the kidney and the brain and lowers the zinc concentration in the kidney and the brain.

(マウス腎臓におけるカドミウム濃度低減の評価)
パクチー抽出液0.25%を含む水又はパクチー抽出液を含まない水を飲水としてddYマウス(4週齢、オス、一群3匹)に与えて8週間飼育した。その後、マウスから腎臓を摘出し、2%硝酸で溶解させ、カドミウムの濃度をICP発光分光分析計(アジレントテクノロジー(株)ICP Expert II 700−ES)で測定した。
(Evaluation of reduction in cadmium concentration in mouse kidney)
Water containing 0.25% of coriander extract or water without coriander extract was given to ddY mice (4 weeks old, male, 3 animals in a group) as drinking water and bred for 8 weeks. Then, the kidney was removed from the mouse, dissolved in 2% nitrate, and the concentration of cadmium was measured by an ICP emission spectrophotometer (ICP Expert II 700-ES, Agilent Technologies, Inc.).

結果を図5に示す。
腎臓において、パクチー抽出液を与えなかった群では、平均で腎臓1gあたり約10ngのカドミウムが検出されたのに対し、パクチー抽出液を与えた群では、平均で腎臓1gあたり約6ngのカドミウムが検出された(図5)。すなわち、パクチー抽出液を与えたことにより、腎臓中のカドミウム濃度を約40%低減した。このことから、パクチー抽出液が、腎臓においてカドミウムの蓄積を軽減し、腎臓におけるカドミウム濃度を低下させることが明らかになった。
The results are shown in FIG.
In the kidneys, an average of about 10 ng of cadmium per gram of kidney was detected in the group not given coriander extract, whereas an average of about 6 ng of cadmium was detected per gram of kidney in the group given coriander extract. (Fig. 5). That is, the cadmium concentration in the kidney was reduced by about 40% by giving the coriander extract. From this, it was clarified that the coriander extract reduces the accumulation of cadmium in the kidney and lowers the cadmium concentration in the kidney.

(総論)
以上の結果より、パクチー抽出液は、重金属であるヒ素による細胞死を抑制し、腎臓中のヒ素、鉄、亜鉛及びカドミウムの濃度、肝臓中の鉄濃度、並びに脳中の亜鉛濃度を、それぞれ低減する作用を有することが確認された。
よって、パクチーが、重金属誘発性細胞傷害を抑制する効果を有することが明らかになった。
(General)
Based on the above results, Pacty extract suppresses cell death due to heavy metal arsenic, and reduces the concentrations of arsenic, iron, zinc and cadmium in the kidney, iron concentration in the liver, and zinc concentration in the brain, respectively. It was confirmed that it has the effect of
Therefore, it was clarified that coriander has an effect of suppressing heavy metal-induced cytotoxicity.

重金属誘発性細胞傷害を抑制する組成物を提供することができる。 A composition that suppresses heavy metal-induced cytotoxicity can be provided.

Claims (4)

パクチー抽出物を有効成分として含有する、腎臓におけるヒ素蓄積低減剤。
An arsenic accumulation reducing agent in the kidney containing coriander extract as an active ingredient.
パクチー抽出物を有効成分として含有する、健常者の腎臓におけるヒ素蓄積低減剤。
An arsenic accumulation reducing agent in the kidneys of healthy subjects containing coriander extract as an active ingredient.
前記パクチー抽出物は、葉、茎及び根の抽出物である、請求項1に記載のヒ素蓄積低減剤。
The arsenic accumulation reducing agent according to claim 1, wherein the coriander extract is an extract of leaves, stems and roots.
前記パクチー抽出物は、葉、茎及び根の抽出物である、請求項2に記載のヒ素蓄積低減剤 The arsenic accumulation reducing agent according to claim 2, wherein the coriander extract is an extract of leaves, stems and roots .
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