KR20200104834A - Composition for Preventing or Treating Muscular disease containing Artemisia dracunculus L. extract - Google Patents
Composition for Preventing or Treating Muscular disease containing Artemisia dracunculus L. extract Download PDFInfo
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- KR20200104834A KR20200104834A KR1020200080598A KR20200080598A KR20200104834A KR 20200104834 A KR20200104834 A KR 20200104834A KR 1020200080598 A KR1020200080598 A KR 1020200080598A KR 20200080598 A KR20200080598 A KR 20200080598A KR 20200104834 A KR20200104834 A KR 20200104834A
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Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/28—Asteraceae or Compositae (Aster or Sunflower family), e.g. chamomile, feverfew, yarrow or echinacea
- A61K36/282—Artemisia, e.g. wormwood or sagebrush
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
- A23L33/105—Plant extracts, their artificial duplicates or their derivatives
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2200/00—Function of food ingredients
- A23V2200/30—Foods, ingredients or supplements having a functional effect on health
- A23V2200/316—Foods, ingredients or supplements having a functional effect on health having an effect on regeneration or building of ligaments or muscles
Abstract
Description
본 발명은 타라곤(영문: Tarragon, Little Dragon, Mugwort, Estragon, 학명: Artemisia dracunculus L.) 추출물을 함유하는 근감소증, 근위축증, 근이영양증, 근육퇴화 등을 포함하는 근육질환 예방 또는 치료용 조성물에 관한 것이다.The present invention relates to a composition for preventing or treating muscle diseases including sarcopenia, muscular atrophy, muscular dystrophy, muscle degeneration, etc., containing extracts of tarragon (English: Tarragon, Little Dragon, Mugwort, Estragon, scientific name: Artemisia dracunculus L.) .
근육(Muscle)은 인체에서 40% 정도를 담당하며 인체의 기능적 능력을 유지하고 대사성 질환을 예방하기 위해서는 적정 근육량의 확보가 필수적으로 요구된다. 크게 평활근(smooth muscle), 심장근(cardiac muscle), 골격근(skeletal muscle)으로 나누어지고, 골격근은 우리 몸 전체에서 상당한 부분을 차지하면서 골격의 움직임을 촉진한다. Muscle (Muscle) is responsible for about 40% in the human body, and in order to maintain the functional ability of the human body and prevent metabolic diseases, it is essential to secure adequate muscle mass. It is largely divided into smooth muscle, cardiac muscle, and skeletal muscle, and skeletal muscle occupies a significant part of the entire body and promotes the movement of the skeleton.
근육질환은 골격근의 약화로 인해 점차 보행 및 이동기능의 장애가 오고 일상생활 동작(activities of daily living, ADL)이 어려워지면서 독립적인 생활이 불가능해지는 경과를 거친다. 더불어 심폐기능 장애를 초래하고 다른 합병증들을 병발하므로 각각의 근육질환의 특성을 정확히 이해하고 접근을 하는 것이 중요하다.Muscle diseases gradually go through a course of impairment of walking and mobility due to weakening of skeletal muscles, and as activities of daily living (ADL) become difficult and independent life becomes impossible. In addition, it causes cardiopulmonary dysfunction and causes other complications, so it is important to accurately understand and approach the characteristics of each muscle disease.
근감소증(sarcopenia)은 골격근의 수축을 유도하는 운동신경이 퇴행하여 골격근의 수축이 진행되지 않거나 골격근 내에서 근육의 수축에 관여하는 단백질의 발현이 감소 혹은 변형되어 정상적인 골격근의 수축이 진행되지 않으며, 장기적으로는 상기 운동신경 또는 골격근이 섬유성 조직으로 변형되는 것으로 알려져 있다. 또한 노화, 호르몬 이상, 영양 부족, 신체 활동 부족, 염증 및 퇴행성 질환 등 다양한 원인에 의해 발생하는 것으로 알려져 있다.In sarcopenia, the motor nerve that induces the contraction of the skeletal muscle is degenerated and the contraction of the skeletal muscle does not proceed, or the expression of the protein involved in the contraction of the muscle in the skeletal muscle is decreased or altered, so that the normal skeletal muscle contraction does not proceed. In the long term, it is known that the motor nerve or skeletal muscle is transformed into a fibrous tissue. It is also known to be caused by various causes, such as aging, hormonal abnormalities, poor nutrition, lack of physical activity, inflammation and degenerative diseases.
근감소증에는 운동, 단백질 및 칼로리 보충이 도움이 된다고 알려져 있으나, 근감소증 환자의 대부분을 차지하는 노인들에서는 크게 도움이 되지 않아 근감소증 치료제가 절실히 요구되고 있다. 다만, 현재 근감소증에 사용되는 치료제들은 근육감소 개선 및 근육량 증진에 직접적인 효과를 나타내는 약물은 아직까지는 임상시험 수준의 단계이며, 현재 최종적으로 FDA 승인을 받은 약제는 없는 상황이다.It is known that exercise, protein, and calorie supplementation are helpful for sarcopenia, but it is not very helpful in the elderly, who make up the majority of sarcopenia patients, and thus a treatment for sarcopenia is urgently required. However, drugs that are currently used for sarcopenia have a direct effect on improving muscle loss and improving muscle mass, and are in the stage of clinical trials so far, and there are currently no drugs that have been finally approved by the FDA.
염증성 근육병은 근육과 주변 조직에 염증이 발생하고 상기 염증이 근육조직을 파괴하여 근육이 약화되어 힘이 빠지고 근육통이 발생하며, 장기적으로는 근육량이 줄어 근육 위축이 나타날 수 있는 것으로 알려져 있다. 근육에 염증이 생기기 때문에 근육염이라고 부르기도 하며 크게 다발성 근육염과 피부근육염으로 분류된다. 몸의 면역체계에 이상이 발생하여 발생하는 자가면역성 질환으로 바이러스나 일부 약물(페니실라민, 알파 인터페론, 시메티딘, 페니토인, B형 간염백신 등)에 의해서 발생 될 수 있다고 알려져 있다.Inflammatory myopathy is known that inflammation occurs in muscles and surrounding tissues, and the inflammation destroys muscle tissues, weakening the muscles, resulting in loss of strength and muscle pain, and in the long term, muscle atrophy may occur due to reduced muscle mass. Because muscles are inflamed, they are sometimes called myositis and are largely classified into polymyositis and dermatomyositis. It is known that it is an autoimmune disease caused by abnormalities in the body's immune system and can be caused by viruses or some drugs (penicillamine, alpha interferon, cimetidine, phenytoin, hepatitis B vaccine, etc.).
다발성 근육염이나 피부근육염을 치료하기 위한 약물로는 스테로이드가 주로 사용되며, 70 ~ 80%의 환자에서 호전되는 반응을 보인다. 고농도 경구 요법으로 사용되거나 주사제로 사용되며, 근력이 현저하게 호전될 수 있으나 부작용(체중 증가, 골다공증, 당뇨 악화, 속쓰림, 소화불량, 위궤양 악화 등)이 발생하여 이를 줄이기 위해 다른 면역억제제(이뮤란 등)를 병용한다. 또한, 다양한 면역억제제에 대해 치료 효과가 떨어지거나 부작용으로 사용할 수 없을 때는 정맥 면역글로불린이 사용되기도 한다. 한편, 최근 들어 새롭게 개발된 면역억제제 등도 다발성 근육염에 일부 효과가 있음이 알려져 있으나, 부작용이 없는 치료제 개발이 꾸준히 요구되고 있다.Steroids are mainly used as drugs for the treatment of polymyositis or dermatomyositis, and the response is improved in 70 to 80% of patients. It is used as a high-concentration oral therapy or as an injection, and muscle strength can be remarkably improved, but side effects (weight gain, osteoporosis, worsening diabetes, heartburn, indigestion, worsening stomach ulcers, etc.) occur, and other immunosuppressants (imuraan Etc.) are used together. In addition, intravenous immunoglobulins are sometimes used when the therapeutic effect of various immunosuppressants is poor or cannot be used due to side effects. On the other hand, recently developed immunosuppressants, etc., are known to have some effects on multiple myositis, but the development of therapeutic agents without side effects is constantly required.
또한, 근위축증(muscular atrophy)은 사지의 근육이 위축되는 질환으로 MuRF-1과 Atrogin-1의 발현이 증가하여 근육의 미오신 헤비체인(Myosin heavy chain)을 분해시킴으로써 근육의 크기가 줄어드는 근육위축증이 발생하게 되는 것으로 알려져 있다.In addition, muscular atrophy is a disease in which the muscles of the limbs are atrophy, and the expression of MuRF-1 and Atrogin-1 is increased to break down the myosin heavy chain of the muscles, resulting in muscle atrophy, which decreases the size of the muscles. It is known to be done.
한편, 관련선행기술로 한국등록특허 1,921,085호는 글루카곤 유사 펩타이드-1(GLP-1), GLP-1 유래 펩타이드, 또는 GLP-1 분해 억제제를 포함하는 근감소증 또는 근위축증 치료용 약학 조성물에 관한 것으로, 체중증가, 골격근 중량 증가, 근육 단백질을 생성하는 유전자의 발현 증가, 근육 단백질을 파괴하는 유전자의 발현 억제, 및 이들의 조합으로 구성된 군으로부터 선택되는 효과를 나타내는 조성물에 대해 개시하고 있다.On the other hand, as a related prior art, Korean Patent No. 1,921,085 relates to a pharmaceutical composition for the treatment of sarcopenia or muscular atrophy, including glucagon-like peptide-1 (GLP-1), a GLP-1 derived peptide, or a GLP-1 degradation inhibitor, Disclosed is a composition exhibiting an effect selected from the group consisting of weight gain, skeletal muscle weight increase, increased expression of a gene that generates muscle protein, suppression of expression of a gene that destroys muscle protein, and combinations thereof.
또한, 한국등록특허 1,809,156호는 퓨코스테롤을 포함하는 근육질환 예방, 개선 또는 치료용 또는 근 기능 개선용 조성물에 관한 것으로, 퓨코스테롤, 모자반, 모자반 분쇄물, 모자반 추출물, 톳, 톳 분쇄물 또는 톳 추출물은 근단백질 합성에 관여하는 주요 유전자 p-mTOR의 단백질 발현 증가, 근단백질 분해에 관여하는 MuRF-1과 Atrogin-1의 mRNA 발현 억제, 근육 분화에 관여하는 MyoD와 Myogenin의 mRNA 발현을 증가시킴에 따라, 근 기능을 탁월하게 증강하는 효과가 있고 천연물이므로 부작용 없이 안전하게 사용될 수 있음을 개시하고 있다.In addition, Korean Patent No. 1,809,156 relates to a composition for preventing, improving or treating muscle diseases or improving muscle function, including fucosterol, fucosterol, maternal and maternal crushed material, maternal and maternal extract, maternal and maternal crushed product Alternatively, the extract of Fudo chinensis increases the protein expression of p-mTOR, a major gene involved in muscle protein synthesis, suppresses the mRNA expression of MuRF-1 and Atrogin-1, which are involved in muscle protein degradation, and the mRNA expression of MyoD and Myogenin, which are involved in muscle differentiation. As it increases, it has the effect of remarkably enhancing muscle function and is a natural product, so it is disclosed that it can be safely used without side effects.
그러나 상기 문헌들은 근육 단백질의 생성 및 분해하는 유전자에 대해서만 개시되어 있을 뿐이며 타라곤 추출물의 항산화 및 항염증 효과, 근육 단백질을 생성하는 MyoD 및 Myogenin 유전자의 발현량 증가 및 근육 단백질을 파괴하는 Atrogin-1 및 MuRF-1 유전자의 발현량 감소 효능에 대해서는 개시되어 있지 않다.However, the above documents only disclose genes that produce and degrade muscle proteins, and the antioxidant and anti-inflammatory effects of tarragon extract, increase the expression levels of MyoD and Myogenin genes that produce muscle proteins, and Atrogin-1 that destroys muscle proteins. The efficacy of reducing the expression level of the MuRF-1 gene is not disclosed.
이에 본 발명의 발명자는 근감소 개선효과를 갖는 천연물을 개발하기 위해 노력한 결과, 타라곤(영문: Tarragon, Little Dragon, Mugwort, Estragon, 학명: Artemisia dracunculus L.) 추출물이 항산화 및 항염증 효능이 있으며, 근육 단백질을 생성하는 MyoD 및 Myogenin 유전자의 발현량을 증가시키고, 근육 단백질을 파괴하는 Atrogin-1 및 MuRF-1 유전자의 발현량을 감소시킬 수 있다는 점을 새로이 규명하고, 상기 타라곤 추출물을 근육질환 치료에 사용될 수 있음을 밝힘으로써, 본 발명을 완성하였다.Accordingly, the inventors of the present invention endeavored to develop a natural product having an effect of improving muscle reduction, and as a result, the extract of tarragon (English: Tarragon, Little Dragon, Mugwort, Estragon, scientific name: Artemisia dracunculus L.) has antioxidant and anti-inflammatory effects. It was newly identified that it can increase the expression levels of MyoD and Myogenin genes that produce muscle proteins, and decrease the expression levels of Atrogin-1 and MuRF-1 genes that destroy muscle proteins, and use the tarragon extract to treat muscle diseases. By revealing that it can be used in, the present invention was completed.
본 발명은 타라곤(영문: Tarragon, Little Dragon, Mugwort, Estragon, 학명: Artemisia dracunculus L.) 추출물을 유효성분으로 함유하는 근육질환 예방 또는 치료용 약학적 조성물, 및 건강식품을 제공하기 위한 것이다.The present invention is to provide a pharmaceutical composition for preventing or treating muscle diseases, and a health food containing an extract of tarragon (English: Tarragon, Little Dragon, Mugwort, Estragon, scientific name: Artemisia dracunculus L.) as an active ingredient.
본 발명은 타라곤(영문: Tarragon, Little Dragon, Mugwort, Estragon, 학명: Artemisia dracunculus L.) 추출물을 유효성분으로 함유하는 근육질환 예방 및 치료용 약학적 조성물을 제공한다.The present invention provides a pharmaceutical composition for preventing and treating muscle diseases containing an extract of tarragon (English: Tarragon, Little Dragon, Mugwort, Estragon, scientific name: Artemisia dracunculus L.) as an active ingredient.
또한, 본 발명은 타라곤 추출물을 유효성분으로 함유하는 근육질환 예방 또는 개선용 건강식품을 제공한다.In addition, the present invention provides a health food for preventing or improving muscle diseases containing tarragon extract as an active ingredient.
본 발명에 따른 타라곤(영문: Tarragon, Little Dragon, Mugwort, Estragon, 학명: Artemisia dracunculus L.) 추출물은 항산화 및 항염증 효능뿐만 아니라, 근육 단백질을 생성하는 유전자 발현량의 증가, 근육 단백질을 파괴하는 유전자 발현량을 감소시키므로 다양한 근육질환 치료에 유용하게 사용될 수 있다.Tarragon (English: Tarragon, Little Dragon, Mugwort, Estragon, scientific name: Artemisia dracunculus L.) extract according to the present invention not only has antioxidant and anti-inflammatory effects, but also increases the amount of gene expression that produces muscle proteins, destroys muscle proteins. Since it reduces the amount of gene expression, it can be usefully used in the treatment of various muscle diseases.
도 1은 용매에 따른 타라곤 추출물 제조공정의 모식도이다.
도 2는 타라곤 추출물의 세포 독성을 확인한 도이다.
도 3은 타라곤 추출물의 ROS 생성량 측정 결과를 나타낸 도이다.
도 4는 타라곤 에탄올 추출물의 IL-1β 생성량 측정 결과를 나타낸 도이다.
도 5는 타라곤 추출물의 IL-6 생성량 측정 결과를 나타낸 도이다.
도 6은 C2C12 세포에 대한 타라곤 추출물의 세포 독성을 확인한 도이다.
도 7은 타라곤 열수 추출물의 MyoD 유전자 발현량 측정 결과를 나타낸 도이다.
도 8은 타라곤 추출물의 Myogenin 유전자 발현량 측정 결과를 나타낸 도이다.
도 9는 타라곤 에탄올 추출물의 Atrogin-1 유전자 발현량 측정 결과를 나타낸 도이다.
도 10은 타라곤 에탄올 추출물의 MuRF-1 유전자 발현량 측정 결과를 나타낸 도이다.
도 11은 타라곤 열수 추출물의 근관 넓이 변화를 광학현미경으로 촬영한 사진을 나타낸 도이다.
도 12는 타라곤 열수 추출물의 근관 넓이 변화 측정 결과를 나타낸 도이다.1 is a schematic diagram of a manufacturing process of tarragon extract according to the solvent.
2 is a diagram confirming the cytotoxicity of tarragon extract.
3 is a diagram showing the measurement result of ROS production of tarragon extract.
Figure 4 is a diagram showing the result of measuring the amount of IL-1β production of ethanol extract of tarragon.
Figure 5 is a diagram showing the measurement result of IL-6 production of tarragon extract.
6 is a diagram confirming the cytotoxicity of tarragon extract against C2C12 cells.
7 is a diagram showing the result of measuring the MyoD gene expression level of the hot water extract of tarragon.
8 is a diagram showing the result of measuring the expression level of Myogenin gene of a tarragon extract.
9 is a diagram showing the result of measuring the Atrogin-1 gene expression level of ethanol extract of tarragon.
10 is a diagram showing the measurement result of MuRF-1 gene expression level of ethanol extract of tarragon.
11 is a view showing a picture taken with an optical microscope of the change in the area of the root canal of the hot water extract of tarragon.
12 is a diagram showing the measurement result of the change in the area of the root canal of the hot water extract of tarragon.
이하 본 발명을 보다 상세히 설명한다.Hereinafter, the present invention will be described in more detail.
본 발명의 타라곤(영문: Tarragon, Little Dragon, Mugwort, Estragon, 학명: Artemisia dracunculus L.)추출물을 유효성분으로 함유하는 근육질환 예방 또는 치료용 약학적 조성물을 제공한다.It provides a pharmaceutical composition for preventing or treating muscle diseases containing the extract of tarragon (English: Tarragon, Little Dragon, Mugwort, Estragon, scientific name: Artemisia dracunculus L.) of the present invention as an active ingredient.
상기 타라곤 추출물은 하기의 단계들을 포함하는 제조방법에 의해 제조되는 것이 바람직하나 이에 한정되지 않는다:The tarragon extract is preferably prepared by a manufacturing method comprising the following steps, but is not limited thereto:
1) 타라곤에 추출용매를 가하여 추출하는 단계;1) extracting by adding an extraction solvent to tarragon;
2) 단계 1)의 추출물을 여과하는 단계; 및2) filtering the extract of step 1); And
3) 단계 2)의 여과한 추출물을 감압농축한 후 건조하는 단계.3) drying the filtered extract of step 2) after concentration under reduced pressure.
상기 방법에 있어서, 단계 1)의 상기 추출용매는 물, C1 내지 C2의 저급알코올 또는 이들의 혼합물을 용매로 하여 추출한 것을 특징으로 하는 것이 바람직하나, 이에 한정되지 않는다.In the above method, the extraction solvent in step 1) is preferably extracted using water, C 1 to C 2 lower alcohol or a mixture thereof as a solvent, but is not limited thereto.
상기 방법에 있어서, 단계 1)의 저급알코올은 에탄올 또는 메탄올인 것이 바람직하나 이에 한정하지 않는다.In the above method, the lower alcohol of step 1) is preferably ethanol or methanol, but is not limited thereto.
상기 방법에 있어서, 단계 3)의 감압농축은 진공감압농축기 또는 진공회전증발기를 이용하는 것이 바람직하나, 이에 한정하지 않는다. 또한, 건조는 감압건조, 진공건조, 비등건조, 분무 건조 또는 동결건조하는 것이 바람직하나 이에 한정하지 않는다.In the above method, the vacuum concentration in step 3) is preferably a vacuum vacuum concentrator or a vacuum rotary evaporator, but is not limited thereto. In addition, drying is preferably vacuum drying, vacuum drying, boiling drying, spray drying, or freeze drying, but is not limited thereto.
상기 타라곤 추출물은 항산화 및 항염증 효능이 있으며, 근육 단백질을 생성하는 유전자 발현량의 증가, 근육 단백질을 파괴하는 유전자 발현량을 감소시키는 효과를 통해 근육질환 예방 또는 치료 효과를 갖는 것이 바람직하나 이로 한정되지 않는다.The tarragon extract has antioxidant and anti-inflammatory effects, and preferably has an effect of preventing or treating muscle diseases through the effect of increasing the amount of gene expression that generates muscle protein and reducing the amount of gene expression that destroys muscle protein. It doesn't work.
상기 근육질환으로는 근감소증(sarcopenia), 근위축증(muscular atrophy), 근무력증(myasthenia), 근이영양증(muscular dystrophy), 근육긴장증(myotonia), 근긴장 저하(hypotonia), 근력 약화(muscular weakness), 근육퇴행위축(muscular dystrophy), 근위축성 측삭경화증(amyotrophic lateral sclerosis) 및 염증성 근육병(inflammatory myopathy)으로 이루어진 군에서 선택되는 하나 이상의 질환인 것이 바람직하다.The muscle diseases include sarcopenia, muscular atrophy, myasthenia, muscular dystrophy, myotonia, hypotonia, muscular weakness, and muscular weakness. (muscular dystrophy), amyotrophic lateral sclerosis (amyotrophic lateral sclerosis) and inflammatory myopathy (inflammatory myopathy) is preferably at least one disease selected from the group consisting of.
본 발명의 구체적인 실시예에서, 본 발명자들은 타라곤 열수 또는 에탄올 추출물을 제조하였다(도 1 참조).In a specific embodiment of the present invention, the present inventors prepared tarragon hot water or ethanol extract (see Fig. 1).
또한, 타라곤 추출물의 세포 독성을 확인하기 위해, 상기 추출물을 RAW 264.7 세포에 처리하여 450 ㎚ 에서 흡광도를 측정한 결과, 타라곤 추출물은 세포 독성이 나타나지 않음을 확인하였다(도 2, 표 5 및 표 6 참조).In addition, in order to confirm the cytotoxicity of the tarragon extract, the extract was treated with RAW 264.7 cells and the absorbance was measured at 450 nm. As a result, it was confirmed that the tarragon extract did not show cytotoxicity (Fig. 2, Table 5, and Table 6). Reference).
또한, 타라곤 추출물의 항산화 효과를 확인하기 위해, 상기 추출물을 RAW 264.7 세포에 처리하여 유세포 분석기로 형광강도의 세기에 따른 변화를 측정한 결과, 타라곤 추출물은 추출물은 ROS(Reactive oxygen species) 생성량을 감소시키므로, 항산화 효과가 있음을 확인하였다(도 3, 표 7 참조).In addition, in order to confirm the antioxidant effect of the tarragon extract, the extract was treated with RAW 264.7 cells and the change according to the intensity of fluorescence intensity was measured with a flow cytometer. As a result, the extract of the tarragon extract reduced the amount of ROS (Reactive oxygen species) produced. Therefore, it was confirmed that there is an antioxidant effect (see Fig. 3 and Table 7).
또한, 타라곤 추출물의 항염증 효과를 확인하기 위해, 상기 추출물을 RAW 264.7 세포에 처리하여 Luminex로 측정한 결과, 타라곤 추출물은 IL-1β 및 IL-6 생성량을 감소시키므로, 항염증 효과가 있음을 확인하였다(도 4, 도 5, 표 8 및 표 9 참조).In addition, in order to confirm the anti-inflammatory effect of the tarragon extract, the extract was treated with RAW 264.7 cells and measured with Luminex. As a result, the tarragon extract reduced the production of IL-1β and IL-6, and thus it was confirmed that it has an anti-inflammatory effect. (See Fig. 4, Fig. 5, Table 8 and Table 9).
또한, 타라곤 추출물의 근육질환 치료 효과를 확인하기 위해, 상기 추출물을 C2C12 세포에 처리하여 450 ㎚ 에서 흡광도를 측정한 결과, 타라곤 추출물은 근육세포에 독성이 나타나지 않음을 확인하였다(도6, 표 10 및 표 11 참조).In addition, in order to confirm the therapeutic effect of the tarragon extract on muscle diseases, the extract was treated with C2C12 cells and the absorbance was measured at 450 nm. As a result, it was confirmed that the tarragon extract did not show toxicity to muscle cells (Fig. 6, Table 10). And Table 11).
또한, 타라곤 추출물의 근육질환 치료 효과를 확인하기 위해, 상기 추출물을 C2C12 세포에 처리하여 근육 단백질 합성 또는 분해에 관여하는 유전자 발현 효과를 확인한 결과, 타라곤 추출물은 근육 합성에 관여하는 MyoD 유전자 및 Myogenin 유전자 발현을 증가시키고, 근육 분해에 관여하는 Atrogin-1 유전자 및 MuRF-1 유전자 발현을 감소시키므로, 근육질환 치료 효과가 있음을 확인하였다(도 7, 도 8, 도 9, 도 10, 표 13, 표 14, 표 15 및 표 16 참조).In addition, in order to confirm the therapeutic effect of tarragon extract on muscle diseases, as a result of confirming the effect of expression of genes involved in muscle protein synthesis or decomposition by processing the extract on C2C12 cells, the tarragon extract was found to be MyoD gene and Myogenin gene involved in muscle synthesis. It was confirmed that the expression was increased and the Atrogin-1 gene and MuRF-1 gene expression involved in muscle decomposition were reduced, so that there was an effect of treating muscle diseases (FIGS. 7, 8, 9, 10, Table 13, Table 14, Table 15 and Table 16).
또한, 타라곤 추출물의 근육질환 치료 효과를 확인하기 위해, 상기 추출물을 C2C12 세포에 처리하여 근관 넓이를 측정한 결과, 타라곤 추출물은 근관 넓이를 증가시키므로, 근육질환 치료 효과가 있음을 확인하였다(도 11, 도 12 및 표 17 참조).In addition, in order to confirm the effect of treating muscle diseases of the tarragon extract, as a result of measuring the root canal area by treating the extract to C2C12 cells, it was confirmed that the tarragon extract increased the area of the root canal, thus having an effect of treating muscle diseases (Fig. 11 , See Fig. 12 and Table 17).
따라서, 본 발명의 타라곤 (영문: Tarragon, Little Dragon, Mugwort, Estragon, 학명: Artemisia dracunculus L.) 추출물은 항산화 또는 항염증 효과를 나타내고, 근육 단백질 합성에 관여하는 유전자 발현 증가 및 분해에 관여하는 유전자 발현 감소 효과를 나타내며, 근관 넓이를 증가시키는 효과를 나타냄으로써, 상기 타라곤 추출물은 근육질환 예방 또는 치료용 약학적 조성물에 유용하게 사용될 수 있다.Therefore, the extract of tarragon (English: Tarragon, Little Dragon, Mugwort, Estragon, scientific name: Artemisia dracunculus L.) of the present invention exhibits an antioxidant or anti-inflammatory effect, and genes involved in increasing and degrading gene expression involved in muscle protein synthesis By showing the effect of reducing expression and increasing the width of the root canal, the tarragon extract may be usefully used in a pharmaceutical composition for preventing or treating muscle diseases.
본 발명의 타라곤 추출물을 함유하는 조성물은 상기 성분에 추가로 동일 또는 유사한 기능을 나타내는 유효성분을 1종 이상 함유할 수 있다.The composition containing the tarragon extract of the present invention may contain one or more active ingredients exhibiting the same or similar functions in addition to the above ingredients.
본 발명의 조성물은 약제학적으로 허용 가능한 첨가제를 더 포함할 수 있으며, 이때 약제학적으로 허용 가능한 첨가제로는 전분, 젤라틴화 전분, 미결정셀룰로오스, 유당, 포비돈, 콜로이달실리콘디옥사이드, 인산수소칼슘, 락토스, 만니톨, 엿, 아라비아고무, 전호화전분, 옥수수전분, 분말셀룰로오스, 히드록시프로필셀룰로오스, 오파드라이, 전분글리콜산나트륨, 카르나우바 납, 합성규산알루미늄, 스테아린산, 스테아린산마그네슘, 스테아린산알루미늄, 스테아린산칼슘, 백당, 덱스트로스, 소르비톨 및 탈크 등이 사용될 수 있다. 본 발명에 따른 약제학적으로 허용 가능한 첨가제는 상기 조성물에 대해 0.1 ~ 90 중량부 포함되는 것이 바람직하나 이에 한정되는 것은 아니다.The composition of the present invention may further include a pharmaceutically acceptable additive, wherein the pharmaceutically acceptable additives include starch, gelatinized starch, microcrystalline cellulose, lactose, povidone, colloidal silicon dioxide, calcium hydrogen phosphate, lactose , Mannitol, syrup, arabic rubber, pregelatinized starch, corn starch, powdered cellulose, hydroxypropyl cellulose, opadry, sodium starch glycolate, lead carnauba, synthetic aluminum silicate, stearic acid, magnesium stearate, aluminum stearate, calcium stearate , Sucrose, dextrose, sorbitol, talc, and the like can be used. The pharmaceutically acceptable additive according to the present invention is preferably contained in an amount of 0.1 to 90 parts by weight based on the composition, but is not limited thereto.
즉, 본 발명의 조성물은 실제 임상 투여 시에 경구 및 비경구의 여러 가지 제형으로 투여될 수 있는데, 제제화 할 경우에는 보통 사용하는 충진제, 증량제, 결합제, 습윤제, 붕해제, 계면활성제 등의 희석제 또는 부형제를 사용하여 조제될 수 있다. 경구투여를 위한 고형제제에는 정제, 환제, 산제, 과립제, 캡슐제 등이 포함되며, 이러한 고형 제제는 타라곤 추출물에 적어도 하나 이상의 부형제 예를 들면, 전분, 칼슘카보네이트(Calcium carbonate), 수크로스(Sucrose), 락토오스(Lactose) 또는 젤라틴 등을 섞어 조제될 수 있다. 또한, 단순한 부형제 이외에 마그네슘 스티레이트 탈크 같은 윤활제들도 사용될 수 있다. 경구를 위한 액상 제제로는 현탁제, 내용액제, 유제 및 시럽제 등이 해당되는데 흔히 사용되는 단순희석제인 물, 리퀴드 파라핀 이외에 여러 가지 부형제, 예를 들면 습윤제, 감미제, 방향제, 보존제 등이 포함될 수 있다. 비경구 투여를 위한 제제에는 멸균된 수용액, 비수성용제, 현탁제, 유제, 동결건조제제, 좌제가 포함될 수 있다. 비수성용제, 현탁용제로는 프로필렌글리콜(Propylene glycol), 폴리에틸렌 글리콜, 올리브 오일과 같은 식물성 기름, 에틸올레이트와 같은 주사 가능한 에스테르 등이 사용될 수 있다. 좌제의 기제로는 위텝솔(witepsol), 마크로골, 트윈(tween) 61, 카카오지, 라우린지, 글리세로제라틴 등이 사용될 수 있다.That is, the composition of the present invention can be administered in various oral and parenteral dosage forms at the time of actual clinical administration.When formulated, diluents or excipients such as fillers, extenders, binders, wetting agents, disintegrants, surfactants, etc. It can be prepared using. Solid preparations for oral administration include tablets, pills, powders, granules, capsules, and the like, and these solid preparations include at least one excipient, such as starch, calcium carbonate, and sucrose, in the tarragon extract. ), lactose, or gelatin. In addition, in addition to simple excipients, lubricants such as magnesium stearate and talc may also be used. Liquid preparations for oral use include suspensions, liquid solutions, emulsions, and syrups. In addition to water and liquid paraffin, which are commonly used simple diluents, various excipients such as wetting agents, sweetening agents, fragrances, and preservatives may be included. . Formulations for parenteral administration may include sterilized aqueous solutions, non-aqueous solutions, suspensions, emulsions, lyophilized formulations, and suppositories. As the non-aqueous solvent and the suspension solvent, propylene glycol, polyethylene glycol, vegetable oil such as olive oil, and injectable ester such as ethyl oleate may be used. As a base for suppositories, witepsol, macrogol, tween 61, cacao butter, laurin, glycerogelatin, and the like may be used.
본 발명의 조성물은 목적하는 방법에 따라 경구 투여하거나 비경구 투여할 수 있으며, 비경구 투여시 피부 외용 또는 복강내주사, 직장내주사, 피하주사, 정맥주사, 근육내 주사 또는 흉부내 주사 주입방식을 선택하는 것이 바람직하다. 투여량은 환자의 체중, 연령, 성별, 건강상태, 식이, 투여시간, 투여방법, 배설률 및 질환의 중증도 등에 따라 그 범위가 다양하다.The composition of the present invention may be administered orally or parenterally according to a desired method, and when administered parenterally, external use of the skin or intraperitoneal injection, rectal injection, subcutaneous injection, intravenous injection, intramuscular injection or intrathoracic injection injection method It is preferable to choose. The dosage ranges vary depending on the patient's weight, age, sex, health status, diet, administration time, administration method, excretion rate, and disease severity.
본 발명에 따른 조성물은 약제학적으로 유효한 양으로 투여한다. 본 발명에 있어서, "약제학적으로 유효한 양"은 의학적 치료에 적용 가능한 합리적인 수혜/위험 비율로 질환을 치료하기에 충분한 양을 의미하며, 유효용량 수준은 환자의 질환의 종류, 중증도, 약물의 활성, 약물에 대한 민감도, 투여 시간, 투여 경로 및 배출 비율, 치료기간, 동시 사용되는 약물을 포함한 요소 및 기타 의학 분야에 잘 알려진 요소에 따라 결정될 수 있다. 본 발명의 조성물은 개별 치료제로 투여하거나 다른 치료제와 병용하여 투여될 수 있고 종래의 치료제와는 순차적 또는 동시에 투여될 수 있으며, 단일 또는 다중 투여될 수 있다. 상기한 요소들을 모두 고려하여 부작용없이 최소한의 양으로 최대 효과를 얻을 수 있는 양을 투여하는 것이 중요하며, 이는 당업자에 의해 용이하게 결정될 수 있다.The composition according to the present invention is administered in a pharmaceutically effective amount. In the present invention, "pharmaceutically effective amount" means an amount sufficient to treat a disease at a reasonable benefit/risk ratio applicable to medical treatment, and the effective dose level is the type of disease, severity, and drug activity of the patient. , Sensitivity to drugs, time of administration, route of administration and rate of excretion, duration of treatment, factors including drugs used concurrently, and other factors well known in the medical field. The composition of the present invention may be administered as an individual therapeutic agent or administered in combination with other therapeutic agents, may be administered sequentially or simultaneously with a conventional therapeutic agent, and may be administered single or multiple. It is important to administer an amount capable of obtaining the maximum effect in a minimum amount without side effects in consideration of all the above factors, and this can be easily determined by a person skilled in the art.
구체적으로, 본 발명에 따른 조성물의 유효량은 환자의 나이, 성별, 체중에 따라 달라질 수 있으며, 일반적으로는 체중 1 kg 당 0.1 mg 내지 100 mg, 바람직하게는 0.5 mg 내지 10 mg을 매일 또는 격일 투여하거나 1일 1 내지 3회로 나누어 투여할 수 있다. 그러나 투여 경로, 비만의 중증도, 성별, 체중, 연령 등에 따라서 증감될 수 있으므로 상기 투여량이 어떠한 방법으로도 본 발명의 범위를 한정하는 것은 아니다.Specifically, the effective amount of the composition according to the present invention may vary depending on the age, sex, and body weight of the patient, and in general, 0.1 mg to 100 mg, preferably 0.5 mg to 10 mg per 1 kg of body weight is administered daily or every other day. Alternatively, it can be administered in 1 to 3 times a day. However, since it may increase or decrease according to the route of administration, the severity of obesity, sex, weight, age, etc., the dosage amount does not limit the scope of the present invention in any way.
또한, 본 발명의 타라곤 추출물을 유효성분으로 함유하는 근육질환 예방 또는 개선용 건강식품을 제공한다.In addition, it provides a health food for preventing or improving muscle diseases containing the tarragon extract of the present invention as an active ingredient.
상기 타라곤 추출물은 추출물은 근육질환 예방 또는 개선 활성을 가지는 것이 바람직하나 한정하지 않는다.The tarragon extract preferably has an activity for preventing or improving muscle disease, but is not limited thereto.
본 발명의 타라곤 추출물은 유의적으로 근육질환 예방 또는 치료 효과를 나타내므로, 상기 타라곤 추출물은 근육질환 예방 또는 개선용 건강식품 조성물로 유용하게 사용될 수 있다.Since the tarragon extract of the present invention has a significant effect of preventing or treating muscle diseases, the tarragon extract may be usefully used as a health food composition for preventing or improving muscle diseases.
상기 식품의 종류에는 특별한 제한은 없다. 상기 물질을 첨가할 수 있는 식품의 예로는 과자류, 빵류, 면류 등과 같은 각종 식품류, 물, 청량음료, 과실음료 등의 드링크류, 껌, 차, 비타민 복합제, 조미료류, 건강기능 식품류 등이 있으며, 통상적인 의미에서의 건강기능식품을 모두 포함한다.There is no particular limitation on the type of food. Examples of foods to which the above substances can be added include various foods such as confectionery, bread, and noodles, drinks such as water, soft drinks, fruit drinks, gum, tea, vitamin complexes, seasonings, health functional foods, etc. It includes all health functional foods in the usual sense.
본 발명의 타라곤 추출물은 식품에 그대로 첨가하거나 다른 식품 또는 식품 성분과 함께 사용될 수 있고, 통상적인 방법에 따라 적절하게 사용될 수 있다. 유효 성분의 혼합량은 그의 사용 목적(예방 또는 개선용)에 따라 적합하게 결정될 수 있다. 일반적으로, 건강식품 중의 상기 화합물의 양은 전체 식품 중량의 0.01 내지 15 중량%, 바람직하게는 0.1 내지 5 중량%로 가할 수 있으며 건강음료 조성물에는 100 을 기준으로 0.01 내지 5.0 g, 바람직하게는 0.01 내지 1.0 g의 비율로 첨가할 수 있다. 그러나 건강 조절을 목적으로 하는 장기간의 섭취의 경우에는 상기 양은 상기 범위 이하일 수 있으며, 안전성 면에서 아무런 문제가 없기 때문에 유효성분은 상기 범위 이상의 양으로도 사용될 수 있다.The tarragon extract of the present invention may be added to food as it is or may be used together with other foods or food ingredients, and may be appropriately used according to a conventional method. The mixing amount of the active ingredient may be appropriately determined depending on the purpose of use (for prevention or improvement). In general, the amount of the compound in the health food can be added in an amount of 0.01 to 15% by weight, preferably 0.1 to 5% by weight of the total food weight, and in the health beverage composition, 0.01 to 5.0 g, preferably 0.01 to It can be added in a proportion of 1.0 g. However, in the case of long-term intake for the purpose of health control, the amount may be less than the above range, and since there is no problem in terms of safety, the active ingredient may be used in an amount above the above range.
본 발명의 건강 기능성 음료 조성물은 지시된 비율로 필수 성분으로서 상기 화합물을 함유하는 외에는 다른 성분에는 특별한 제한이 없으며 통상의 음료와 같이 여러가지 향미제 또는 천연 탄수화물 등을 추가 성분으로서 함유할 수 있다. 상술한 천연 탄수화물의 예는 모노사카라이드, 예를 들어, 포도당, 과당 등; 디사카라이드, 예를 들어, 말토스, 수크로즈 등 및 폴리사카라이드, 예를 들어, 덱스트린, 사이클로덱스트린 등과 같은 통상적인 당, 및 자일리톨, 소르비톨, 에리스리톨 등의 당알코올이다. 상술한 것 이외의 향미제로서 천연 향미제(타우마킨, 스테비아 추출물 등), 및 합성 향미제(사카린, 아스파르탄 등)를 유리하게 사용할 수 있다. 상기 천연 탄수화물의 비율은 본 발명의 조성물 100 당 일반적으로 약 0.1 내지 2.0 g, 바람직하게는 약 0.1 내지 1.0 g이다.The health functional beverage composition of the present invention is not particularly limited in other ingredients, except for containing the compound as an essential ingredient in the indicated ratio, and may contain various flavoring agents or natural carbohydrates as an additional ingredient, such as a conventional beverage. Examples of the above-described natural carbohydrates include monosaccharides such as glucose, fructose, and the like; Disaccharides such as maltose, sucrose, and the like, and polysaccharides such as dextrin, cyclodextrin, and the like, and sugar alcohols such as xylitol, sorbitol, and erythritol. As flavoring agents other than those described above, natural flavoring agents (taumachin, stevia extract, etc.), and synthetic flavoring agents (saccharin, aspartan, etc.) can be advantageously used. The proportion of the natural carbohydrate is generally about 0.1 to 2.0 g, preferably about 0.1 to 1.0 g per 100 of the composition of the present invention.
본 발명의 건강기능식품은 식품의 제조공정 중에 상술한 본 발명의 추출물을 첨가하는 공정을 가함으로써 또는 식품의 제조 후에 상술한 본 발명의 추출물을 첨가하는 공정을 가함으로써 용이하게 얻을 수 있다. 이때 필요에 따라 맛과 냄새 교정제를 첨가하여도 좋다.The health functional food of the present invention can be easily obtained by adding the extract of the present invention described above during the manufacturing process of the food or by adding the extract of the present invention described above after the preparation of the food. At this time, taste and odor correction agents may be added as necessary.
상기 외에 본 발명의 타라곤 추출물은 여러 가지 영양제, 비타민, 광물(전해질), 합성 풍미제 및 천연 풍미제 등의 풍미제, 착색제 및 중진제(치즈, 초콜릿 등), 펙트산 및 그의 염, 알긴산 및 그의 염, 유기산, 보호성 콜로이드 중점제, pH 조절제, 안정화제, 방부제, 글리세린, 알코올, 탄산음료에 사용되는 탄산화제 등을 함유할 수 있다. 그밖에 본 발명의 타라곤 추출물은 천연 과일 주스 및 과일 주스 음료 및 야채 음료의 제조를 위한 과육을 함유할 수 있다. 이러한 성분은 독립적으로 또는 조합하여 사용할 수 있다. 이러한 첨가제의 비율은 그렇게 중요하진 않지만 본 발명의 타라곤 추출물 100 중량부 당 약 20 중량부의 범위에서 선택되는 것이 일반적이다.In addition to the above, the tarragon extract of the present invention includes various nutrients, vitamins, minerals (electrolytes), flavoring agents such as synthetic flavoring agents and natural flavoring agents, coloring agents and heavy weight agents (cheese, chocolate, etc.), pectic acid and salts thereof, alginic acid, and It may contain salts, organic acids, protective colloidal heavy agents, pH adjusters, stabilizers, preservatives, glycerin, alcohols, carbonates used in carbonated beverages, and the like. In addition, the tarragon extract of the present invention may contain flesh for the manufacture of natural fruit juices and fruit juice beverages and vegetable beverages. These components may be used independently or in combination. The proportion of these additives is not so important, but is generally selected in the range of about 20 parts by weight per 100 parts by weight of the tarragon extract of the present invention.
이하, 본 발명을 실시예 및 실험예에 의해서 상세히 설명한다.Hereinafter, the present invention will be described in detail by examples and experimental examples.
단, 하기의 실시예 및 실험예는 본 발명을 구체적으로 예시하는 것이며, 본 발명의 내용이 실시예 및 실험예에 의해 한정되는 것은 아니다.However, the following examples and experimental examples specifically illustrate the present invention, and the contents of the present invention are not limited by the examples and experimental examples.
<실시예 1> 타라곤 추출물의 제조<Example 1> Preparation of tarragon extract
<1-1> 타라곤 에탄올 추출물의 제조<1-1> Preparation of ethanol extract of tarragon
타라곤(영문: Tarragon, Little Dragon, Mugwort, Estragon, 학명: Artemisia dracunculus L.) 시료의 16배 양의 70% 에탄올을 사용하여 45 내지 75℃에서 8 내지 14시간 추출하였고, 감압여과하여(Whatman filter paper #2) 농축하였으며 이 후 -20℃에서 보관하였다.Tarragon (English: Tarragon, Little Dragon, Mugwort, Estragon, scientific name: Artemisia dracunculus L.) was extracted for 8 to 14 hours at 45 to 75 °C using 16 times the amount of 70% ethanol, and filtered under reduced pressure (Whatman filter paper #2) was concentrated and then stored at -20°C.
또한, 추출온도 및 추출시간에 따른 추출수율은 하기 [표 1] 및 [표 2]에 나타내었다.In addition, the extraction yield according to the extraction temperature and extraction time is shown in the following [Table 1] and [Table 2].
한편, 하기 실험예는 타라곤을 70% 에탄올을 사용하여 75℃에서 12시간 추출한 타라곤 에탄올 추출물을 이용하여 실험을 수행한 것이다.On the other hand, in the following experimental example, an experiment was performed using an ethanol extract of tarragon extracted at 75° C. for 12 hours using 70% ethanol.
<1-2> 타라곤 열수 추출물의 제조<1-2> Preparation of hot water extract of tarragon
타라곤 시료의 16배 양의 증류수를 사용하여 65 내지 95℃에서 8 내지 14시간 추출하였고, 상온으로 냉각한 후, 여과 및 농축하여 타라곤 열수 추출물을 제조하였다.Extraction was performed for 8 to 14 hours at 65 to 95°C using 16 times the amount of distilled water of the tarragon sample, cooled to room temperature, filtered and concentrated to prepare a tarragon hot water extract.
또한, 추출온도 및 추출시간에 따른 추출수율은 하기 [표 3] 및 [표 4]에 나타내었다.In addition, the extraction yield according to the extraction temperature and extraction time is shown in the following [Table 3] and [Table 4].
한편, 하기 실험예는 타라곤을 증류수를 사용하여 95℃에서 12시간 추출한 타라곤 열수 추출물을 이용하여 실험을 수행한 것이다.Meanwhile, in the following experimental example, an experiment was performed using a hot water extract of tarragon extracted at 95° C. for 12 hours using distilled water.
<실험예 1> 세포 독성 확인<Experimental Example 1> Confirmation of cytotoxicity
<1-1> RAW 264.7 세포 계대배양<1-1> RAW 264.7 cell subculture
동결된 RAW 264.7 세포를 50 ㎖ 튜브에 옮기고 PBS 9 ㎖을 넣어 세포를 부유시킨 뒤 1,200 rpm에서 5분간 원심분리 하여 상층액을 제거하였다. 세포는 10% FBS(fetal bovine serum)와 1% penicillin/streptomycin으로 조성된 DMEM(Dulbecco's modified Eagle's medium) 배지 1 ㎖을 넣어 부유시켜 세포 배양기(37℃, 5% CO2)에서 배양하였다. 계대배양 횟수는 5회 이상으로 하였고, 시료들을 처리하기 전에 24시간을 적응시켰다.The frozen RAW 264.7 cells were transferred to a 50 ml tube, 9 ml of PBS was added to suspend the cells, and then centrifuged at 1,200 rpm for 5 minutes to remove the supernatant. Cells were suspended in 1 ml of DMEM (Dulbecco's modified Eagle's medium) medium composed of 10% FBS (fetal bovine serum) and 1% penicillin/streptomycin, and cultured in a cell incubator (37° C., 5% CO 2 ). The number of subcultures was 5 or more, and 24 hours were acclimated before processing the samples.
<1-2> 세포 독성 측정<1-2> cytotoxicity measurement
타라곤 추출물의 세포 독성을 측정하기 위해 상기 실험예 <1-1>에서 배양한 RAW 264.7 세포를 이용하였다. RAW 264.7 세포를 96 well plate에 1.5×105 cells/well로 분주하여 세포 배양기(37℃, 5% CO2)에서 24시간 동안 배양하였다. 배양 후 새로운 배양액으로 교체하고 타라곤 추출물을 25, 50 및 100 ㎍/㎖의 농도로 처리한 후, 다시 24시간 동안 세포 배양기에서 배양하였다. 배양 후 10 ㎕의 WST solution을 첨가하여 세포 배양기(37℃, 5% CO2)에서 30분간 반응시켰다. 반응 후 450 ㎚에서 흡광도를 측정하여 타라곤 추출물 처리를 하지 않은 대조군에 대한 세포 생존율을 백분율로 표시하였다.In order to measure the cytotoxicity of the tarragon extract, RAW 264.7 cells cultured in Experimental Example <1-1> were used. RAW 264.7 cells were dispensed into a 96 well plate at 1.5×10 5 cells/well and cultured in a cell incubator (37° C., 5% CO 2 ) for 24 hours. After culturing, it was replaced with a new culture solution, and the tarragon extract was treated at concentrations of 25, 50 and 100 µg/ml, and then cultured in a cell incubator for 24 hours. After incubation, 10 µl of WST solution was added and reacted for 30 minutes in a cell incubator (37° C., 5% CO 2 ). After the reaction, the absorbance was measured at 450 nm, and the cell viability of the control group not treated with the tarragon extract was expressed as a percentage.
그 결과, [도 2], [표 5] 및 [표 6]에 나타낸 바와 같이, RAW 264.7 세포를 통해 세포 독성을 측정한 결과는 대조군을 100.0±1.0%로 나타냈을 때, 타라곤 추출물 모든 처리 농도에서 대조군 대비 90% 이상의 생존율이 나타나 안전한 것을 확인하였다(도 2).As a result, as shown in [Fig. 2], [Table 5] and [Table 6], the result of measuring cytotoxicity through RAW 264.7 cells was 100.0±1.0% of the control group, and all treatment concentrations of tarragon extract It was confirmed that the survival rate of 90% or more appeared compared to the control group in (Fig. 2).
하기 실험은 세포 독성이 확인되지 않은 농도 중 50 ㎍/㎖ 농도를 선택하여 진행하였다.The following experiment was carried out by selecting a concentration of 50 μg/ml among the concentrations in which cytotoxicity was not confirmed.
<실험예 2> 항산화 효과 확인<Experimental Example 2> Confirmation of antioxidant effect
타라곤 추출물의 항산화 효과를 확인하기 위해서 상기 실험예 <1-1>에서 제조한 RAW 264.7 세포를 이용하여 ROS(Reactive oxygen species) 생성량을 측정하였다.In order to confirm the antioxidant effect of the tarragon extract, the production amount of ROS (Reactive oxygen species) was measured using RAW 264.7 cells prepared in Experimental Example <1-1>.
RAW 264.7 세포를 12 well plate에 2×105 cells/well로 분주하여 세포 배양기(37℃, 5% CO2)에서 24시간 동안 배양하였다. 배양 후 새로운 배양액으로 교체하였으며, 타라곤 추출물 50 ㎍/㎖의 농도에 LPS를 1 ㎍/㎖의 농도로 처리한 후, 다시 24시간 동안 세포 배양기에서 배양하였다. 배양 후 4℃, 1,200 rpm에서 5분간 원심분리하여 모은 세포를 PBS로 2회 세척하고 DCFH-DA(2',7'-dichlorodihydrofluorescein diacetate)를 20 μM이 되도록 첨가하여 15분 동안 세포 배양기에서 염색시켰다. 염색 후 다시 4℃, 1,200 rpm에서 5분간 원심분리 한 다음 상청액을 제거하고 다시 PBS 400 ㎕를 부유시켜 유세포 분석기를 이용하여 형광강도의 세기에 따른 변화를 측정하여 LPS만을 처리한 대조군에 대한 ROS 생성량을 백분율로 나타내었다.RAW 264.7 cells were dispensed into a 12 well plate at 2×10 5 cells/well and cultured in a cell incubator (37° C., 5% CO 2 ) for 24 hours. After cultivation, it was replaced with a new culture solution, and LPS was treated at a concentration of 50 μg/ml of tarragon extract at a concentration of 1 μg/ml, and then cultured in a cell incubator for 24 hours. After incubation, the collected cells were washed twice with PBS by centrifugation for 5 minutes at 4°C and 1,200 rpm, and DCFH-DA (2',7'-dichlorodihydrofluorescein diacetate) was added to 20 μM, followed by staining in a cell incubator for 15 minutes. . After staining, centrifuge again at 4°C and 1,200 rpm for 5 minutes, remove the supernatant, and then suspend 400 µl of PBS again, and measure the change according to the intensity of fluorescence intensity using a flow cytometer. Expressed as a percentage.
그 결과, [도 3] 및 [표 7]에 나타낸 바와 같이, LPS만을 처리한 대조군의 ROS 생성량을 100.0±1.0%로 나타냈을 때, 타라곤 추출물은 ROS 생성을 유의적으로 감소시키는 것을 확인하였다(도 3).As a result, as shown in [Fig. 3] and [Table 7], when the ROS production amount of the control group treated with LPS alone was 100.0±1.0%, it was confirmed that the tarragon extract significantly reduced ROS production ( Fig. 3).
NameName
NameName
에탄올
추출물Tarragon
ethanol
extract
±4.325.9
±4.3
±1.0100.0
±1.0
열수
추출물Tarragon
Hydrothermal
extract
±4.419.0
±4.4
±1.0100.0
±1.0
<실험예 3> 항염증 효과 확인<Experimental Example 3> Confirmation of anti-inflammatory effect
타라곤 추출물의 항염증 효과를 확인하기 위해서 상기 실험예 <1-1>에서 제조한 RAW 264.7 세포를 이용하여 Cytokine 생성량을 측정하였다.In order to confirm the anti-inflammatory effect of the tarragon extract, the amount of cytokine produced was measured using RAW 264.7 cells prepared in Experimental Example <1-1>.
RAW 264.7 세포를 12 well plate에 2×105 cells/well로 분주하여 세포 배양기(37℃, 5% CO2)에서 24시간 동안 배양하였다. 배양 후 새로운 배양액으로 교체하고 타라곤 추출물 50 ㎍/㎖의 농도에 LPS를 1 ㎍/㎖의 농도로 처리한 후, 다시 24시간 동안 세포 배양기에서 배양하였다. 배양 후 1,200 rpm에서 5분간 원심분리하여 상층액을 획득하여 Milliplex map mouse cytokine/chemokine magnetic bead panel-immunology multiplex assay kit의 구성된 물품을 이용하여 다음과 같이 측정하였다. 96 well plate에 상층액 25 ㎕씩 분주하고 assay buffer 및 matrix buffer, antibody-immobilized beads를 각 25 ㎕씩 가하여 혼합한 후 2시간 동안 실온에서 반응시키고 washing 완충 용액을 이용하여 2회 세척하였다. 세척 후 25 ㎕의 detection antibody을 가하여 1시간 동안 실온에서 암소 반응시키고 추가로 25 ㎕의 Streptavidin-Phycoerythrin을 가하여 30분 동안 실온에서 반응시킨 후 washing 완충 용액을 이용하여 2회 세척하였다. 세척 후 PBS를 150 ㎕ 넣고 5분간 shaking한 후 Luminex를 이용하여 측정하였다.RAW 264.7 cells were dispensed into a 12 well plate at 2×10 5 cells/well and cultured in a cell incubator (37° C., 5% CO 2 ) for 24 hours. After cultivation, it was replaced with a new culture solution, treated with a concentration of 50 µg/ml of tarragon extract and 1 µg/ml of LPS, and cultured in a cell incubator for 24 hours. After incubation, the supernatant was obtained by centrifugation at 1,200 rpm for 5 minutes, and measured as follows using an article composed of a Milliplex map mouse cytokine/chemokine magnetic bead panel-immunology multiplex assay kit. 25 µl of the supernatant was dispensed into a 96 well plate, 25 µl of each of the assay buffer, matrix buffer, and antibody-immobilized beads were added and mixed, followed by reaction at room temperature for 2 hours and washed twice using a washing buffer solution. After washing, 25 µl of detection antibody was added to react in the dark for 1 hour at room temperature, and 25 µl of Streptavidin-Phycoerythrin was added to react at room temperature for 30 minutes, followed by washing twice with a washing buffer solution. After washing, 150 µl of PBS was added, shaken for 5 minutes, and measured using Luminex.
그 결과, [도 4] 및 [표 8]에 나타낸 바와 같이, LPS만을 처리한 대조군의 IL-1β 생성량이 123.3±3.3 pg/㎖로 나타났을 때, 본 발명의 타라곤 에탄올 추출물은 상기 IL-1β 생성을 유의적으로 감소시키는 것을 확인하였다(도 4).As a result, as shown in [Fig. 4] and [Table 8], when the IL-1β production amount of the control group treated with only LPS was 123.3±3.3 pg/ml, the ethanol extract of tarragon of the present invention was the IL-1β It was confirmed that the production was significantly reduced (Fig. 4).
또한, [도 5] 및 [표 9]에 나타낸 바와 같이, LPS만을 처리한 대조군의 IL-6 생성량이 각각 151839.8±2593.1 pg/㎖, 145561.7±18836.0 pg/㎖로 나타났을 때, 본 발명의 타라곤 추출물은 각각 111151.5±13370.4, 100273.6±12658.0로 나타나 IL-6 생성을 현저히 감소시키는 것을 확인하였다(도 5).In addition, as shown in [Fig. 5] and [Table 9], when the IL-6 production amount of the control group treated with LPS alone was 151839.8±2593.1 pg/ml and 145561.7±18836.0 pg/ml, respectively, the tarragon of the present invention The extracts were 111151.5±13370.4 and 100273.6±12658.0, respectively, and it was confirmed that IL-6 production significantly decreased (FIG. 5).
NameName
NameName
에탄올
추출물Tarragon
ethanol
extract
±27.3116.8
±27.3
±2593.1151839.8
±2593.1
±13370.4111151.5
±13370.4
열수
추출물Tarragon
Hydrothermal
extract
±12.7118.3
±12.7
±18836.0145561.7
±18836.0
±12658.0100273.6
±12658.0
따라서 본 발명의 타라곤 추출물은 염증성 Cytokine인 IL-1β 및 IL-6 생성을 감소시키므로, 유의적인 항염증 효과를 나타냄을 확인하였다.Therefore, it was confirmed that the tarragon extract of the present invention reduces the production of IL-1β and IL-6, which are inflammatory cytokines, and thus exhibits a significant anti-inflammatory effect.
<실험예 4> 타라곤 추출물의 근육질환 치료 효과 확인<Experimental Example 4> Confirmation of the effect of tarragon extract on treating muscle diseases
<4-1> 시약<4-1> reagent
시약은 Dulbecco's Modified Eagle's Medium (DMEM; Gibco BRL, U.S.A.), fetal bovine serum (FBS; Gibco BRL, U.S.A.), trypsin-EDTA (Thermofisher, U.S.A.), trypan blue (Sigma Co., U.S.A), EZ-Cytox (Daeilab, Korea), dulbecco's phosphate buffered saline (Welgene, Korea), RIPA buffer (Thermo Co., U.S.A.), sample loading buffer (BIO-RAD Co., Japan), 30% Acrylamide/Bis Solution 29:1(3.3%C) (BIO-RAD Co., Japan), Skim Milk (BD Co., France), Pierce BCA Proein Assay Kit (Thermo Co., U.S.A.), TEMED (BIO-RAD Co., Japan), phosphorylation-AKT (p-AKT), AKT, phosphorylation-mTOR (p-mTOR), mTOR antibody (Danvers., U.S.A), Protease inhibitor cocktail, phosphatase inhibitor cocktail (Sigma Co., U.S.A), Total RNA prep kit (Intronbio, Korea), AccuPower CycleScript RT PreMix (Bioneer, Korea), SYBR Green (Qiagen, Germany) 등을 사용하였다. Reagents include Dulbecco's Modified Eagle's Medium (DMEM; Gibco BRL, USA), fetal bovine serum (FBS; Gibco BRL, USA), trypsin-EDTA (Thermofisher, USA), trypan blue (Sigma Co., USA), EZ-Cytox ( Daeilab, Korea), dulbecco's phosphate buffered saline (Welgene, Korea), RIPA buffer (Thermo Co., USA), sample loading buffer (BIO-RAD Co., Japan), 30% Acrylamide/Bis Solution 29:1(3.3%) C) (BIO-RAD Co., Japan), Skim Milk (BD Co., France), Pierce BCA Proein Assay Kit (Thermo Co., USA), TEMED (BIO-RAD Co., Japan), phosphorylation-AKT ( p-AKT), AKT, phosphorylation-mTOR (p-mTOR), mTOR antibody (Danvers., USA), Protease inhibitor cocktail, phosphatase inhibitor cocktail (Sigma Co., USA), Total RNA prep kit (Intronbio, Korea), AccuPower CycleScript RT PreMix (Bioneer, Korea), SYBR Green (Qiagen, Germany), etc. were used.
<4-2> 기기<4-2> Device
기기는 centrifuge (Sigma Co., U.S.A.), deep-freezer (Sanyo Co., Japan), vortex mixer (Vision scientific Co., Korea), plate shaker (Lab-Line Co., U.S.A.), ELISA reader (Molecular Devices Co., U.S.A.), optical microscope (Carl ZEISS Co., Germany), Light Microscope (Carl Zeiss, Co., Germany), Mini-Protean tetra Cell (BIO-RAD Co., Japan), Nanodrop (Thermo fisher, U.S.A.), Alpha Cycler 1 PCRmax (PCRmax, U.K.) real time PCR (Qiagen, Germany) 등을 사용하였다.Instruments include centrifuge (Sigma Co., USA), deep-freezer (Sanyo Co., Japan), vortex mixer (Vision scientific Co., Korea), plate shaker (Lab-Line Co., USA), ELISA reader (Molecular Devices) Co., USA), optical microscope (Carl ZEISS Co., Germany), Light Microscope (Carl Zeiss, Co., Germany), Mini-Protean tetra Cell (BIO-RAD Co., Japan), Nanodrop (Thermo fisher, USA) ),
<4-3> C2C12 세포 계대배양<4-3> C2C12 cell subculture
C2C12 세포를 American Type Culture Collection (ATCC, U.S.A.)에서 구매하였으며, 10% FBS가 첨가된 DMEM 배지를 사용하여 세포 배양기(37℃, 5% CO2)에서 배양하였다.C2C12 cells were purchased from the American Type Culture Collection (ATCC, USA), and cultured in a cell incubator (37° C., 5% CO 2 ) using DMEM medium added with 10% FBS.
<4-4> 세포 독성 측정<4-4> Cytotoxicity measurement
타라곤 추출물의 근육세포에 대한 세포 독성을 측정하기 위해서 상기 실험예 <4-3>에서 배양한 C2C12 세포를 이용하였다. C2C12 세포를 96 well plate에 1×104 cells/well 씩 분주하여 24시간 동안 배양하였다. 새로운 배양액으로 교체하고 타라곤 추출물을 25, 50 및 100 ㎍/㎖의 농도로 처리하여 다시 48시간 동안 배양하였다. 배양 후 10 ㎕의 EZ-Cytox 용액을 첨가하여 세포 배양기에서 30분간 반응시켰다. 반응 후 450 ㎚에서 흡광도의 변화를 측정하여 타라곤 추출물 처리를 하지 않은 대조군에 대한 세포 생존율을 백분율로 표시하였다.In order to measure the cytotoxicity of the tarragon extract to muscle cells, C2C12 cells cultured in Experimental Example <4-3> were used. C2C12 cells were aliquoted into 96 well plates at 1×10 4 cells/well and cultured for 24 hours. It was replaced with a new culture solution, and the tarragon extract was treated at concentrations of 25, 50 and 100 µg/ml, and cultured for another 48 hours. After incubation, 10 µl of EZ-Cytox solution was added and reacted for 30 minutes in a cell incubator. After the reaction, the change in absorbance at 450 nm was measured, and the cell viability for the control group not treated with the tarragon extract was expressed as a percentage.
그 결과, [도 6], [표 10] 및 [표 11]에 나타낸 바와 같이, C2C12 cell을 통해 세포 독성을 측정한 결과는 대조군을 100.00±2.25%로 나타냈을 때, 타라곤 추출물 모든 처리 농도에서 대조군 대비 90% 이상의 생존율이 나타나 안전한 것을 확인하였다(도 6).As a result, as shown in [Fig. 6], [Table 10] and [Table 11], the result of measuring cytotoxicity through C2C12 cells was 100.00±2.25% as the control group, at all treatment concentrations of tarragon extract It was confirmed that a survival rate of 90% or more appeared compared to the control group (Fig. 6).
하기 실험은 세포 독성이 확인되지 않은 농도 중 50 ㎍/㎖ 농도를 선택하여 진행하였다.The following experiment was carried out by selecting a concentration of 50 μg/ml among the concentrations in which cytotoxicity was not confirmed.
<4-5> 근육 단백질 합성 또는 분해에 관여하는 유전자 발현 효과 확인<4-5> Confirmation of the effect of gene expression involved in muscle protein synthesis or degradation
타라곤 추출물의 근육 단백질 합성 또는 분해에 관여하는 유전자 발현 효과를 확인하기 위해 상기 실험예 <4-3>에서 제조한 C2C12 세포를 이용하였다.C2C12 cells prepared in Experimental Example <4-3> were used to confirm the effect of expression of genes involved in the synthesis or degradation of muscle proteins of the tarragon extract.
C2C12 세포를 6 well plate에 6×105 cells/well씩 분주하여 24시간 동안 배양하였다. 24시간 후에 세포 분화를 시키기 위해 분화배지로 교체하였고, 6일 동안 이틀에 한 번씩 배지 교환해줬다. 6일 후 50 ㎍/㎖ + TNF-α를 처리하여 다시 48시간 동안 반응하였다. Cell lysis buffer를 1 ㎖씩 넣어 혼합 후 chloroform을 200 ㎕씩 첨가하여 다시 혼합하였다. 이를 13,000 rpm에서 10분간 원심분리 후 400 ㎕의 상층액을 회수하여 binding buffer를 400 ㎕씩 넣어 혼합하여 column에 주입하고 원심분리 하였다. column에 washing buffer A를 700 ㎕씩 넣어 원심분리 하고 washing buffer B를 700 ㎕씩 넣어 원심분리 후 elution buffer 50 ㎕을 넣고 원심분리 하여 RNA를 추출하였다.C2C12 cells were aliquoted into 6 well plates by 6×10 5 cells/well and cultured for 24 hours. After 24 hours, the medium was replaced with a differentiation medium for cell differentiation, and the medium was exchanged every two days for 6 days. After 6 days, 50 ㎍ / ㎖ + TNF-α was treated and reacted for 48 hours again. 1 ml of cell lysis buffer was added and mixed, then 200 μl of chloroform was added and mixed again. After centrifugation at 13,000 rpm for 10 minutes, 400 µl of the supernatant was collected, 400 µl of binding buffer was added, mixed, injected into a column, and centrifuged. 700 µl of washing buffer A was added to the column for centrifugation, and 700 µl of washing buffer B was added to each column, followed by centrifugation, 50 µl of elution buffer was added, and RNA was extracted by centrifugation.
역전사 (reverse transcription) 반응은 RT premix (reverse transcriptase, reaction buffer, dNTPs, dT20 primer, stabilizer)에 total RNA를 1 ㎍ 첨가하고 DEPC(diethyl pyrocarbonate)처리된 증류수를 최종 부피가 20 ㎕가 되도록 하여 첨가하였다. 이 혼합액을 섞은 후 2,000 rpm에서 5초간 원심 침강하고 45℃ heating block에서 60분 동안 반응시켜 first-strand cDNA를 합성하였다. 이를 다시 95℃에서 5분 동안 반응시켜 M-MLV RT를 불활성화시킨 후 합성이 완료된 cDNA를 PCR에 사용하였다.For the reverse transcription reaction, 1 μg of total RNA was added to the RT premix (reverse transcriptase, reaction buffer, dNTPs, dT20 primer, stabilizer), and diethyl pyrocarbonate (DEPC)-treated distilled water was added to a final volume of 20 μl. . After mixing the mixture, centrifugal sedimentation at 2,000 rpm for 5 seconds and reacting for 60 minutes in a 45°C heating block to synthesize first-strand cDNA. This was reacted again at 95° C. for 5 minutes to inactivate M-MLV RT, and then the synthesized cDNA was used for PCR.
합성이 완료된 cDNA를 증폭시키기 위하여 real-time PCR을 진행하였으며, real-time 전용 tube에 cDNA 1 ㎕, 각 primer 2 ㎕, SYBR Green 10 ㎕, DEPC-DW 5 ㎕씩 넣어 다음과 같이 진행하였다. 94℃에서 5분 동안 반응한 다음 94℃에서 15초, 각 primer의 annealing 온도에서 30초, 72℃에서 30초를 진행하였고 94℃에서 1분 동안 반응시킨 후 55℃에서 1분 동안 반응시켰다. 마지막으로 primer의 annealing에서 94℃까지 0.5℃씩 상승시켜 94℃에 이를 때까지의 형광 접합 물질인 SYBR Green이 발생하는 마지막 과정을 수행하였다. 사용된 primer의 sequence와 annealing 온도는 [표 12]와 같다.In order to amplify the synthesized cDNA, real-time PCR was performed, and 1 µl of cDNA, 2 µl of each primer, 10 µl of SYBR Green, 5 µl of DEPC-DW were added to a real-time dedicated tube. The reaction was performed at 94°C for 5 minutes, followed by 15 seconds at 94°C, 30 seconds at the annealing temperature of each primer, 30 seconds at 72°C, and reacted at 94°C for 1 minute and then at 55°C for 1 minute. Finally, the final process of generating SYBR Green, a fluorescent conjugation material, was performed by increasing the primer annealing by 0.5℃ to 94℃ by 0.5℃. The sequence and annealing temperature of the primer used are shown in [Table 12].
F : forward, R : reverse F: forward, R: reverse
(bp)Size
(bp)
Temp. (℃)Annealing
Temp. (℃)
그 결과, [도 7] 및 [표 13]에 나타낸 바와 같이, TNF-α만 처리한 대조군의 MyoD 유전자 발현량을 1.00±0.00%로 나타냈을 때, 본 발명의 타라곤 열수 추출물은 MyoD 유전자 발현을 유의하게 증가시키는 것을 확인하였다(도 7).As a result, as shown in [Fig. 7] and [Table 13], when the MyoD gene expression level of the control group treated with only TNF-α was 1.00±0.00%, the tarragon hot water extract of the present invention showed MyoD gene expression. It was confirmed that it significantly increased (Fig. 7).
또한, [도 8] 및 [표 14]에 나타낸 바와 같이, TNF-α만 처리한 대조군의 Myogenin 유전자 발현량을 1.00±0.00%로 나타냈을 때, 본 발명의 타라곤 추출물은 Myogenin 유전자 발현을 현저히 증가시키는 것을 확인하였다(도 8).In addition, as shown in [Fig. 8] and [Table 14], when the Myogenin gene expression level of the control group treated with only TNF-α was 1.00±0.00%, the tarragon extract of the present invention significantly increased Myogenin gene expression. It was confirmed to be made (Fig. 8).
NameName
NameName
에탄올
추출물Tarragon
ethanol
extract
±1.00.90
±1.0
±0.001.00
±0.00
열수
추출물Tarragon
Hydrothermal
extract
±1.00.90
±1.0
±0.001.00
±0.00
또한, [도 9] 및 [표 15]에 나타낸 바와 같이, TNF-α만 처리한 대조군의 Atrogin-1 유전자 발현량을 1.00±0.00%로 나타냈을 때, 본 발명의 타라곤 에탄올 추출물은 Atrogin-1 유전자 발현을 유의하게 감소시키는 것을 확인하였다(도 9).In addition, as shown in [Fig. 9] and [Table 15], when the Atrogin-1 gene expression level of the control group treated with only TNF-α was 1.00±0.00%, the ethanol extract of tarragon of the present invention was Atrogin-1 It was confirmed that the gene expression was significantly reduced (FIG. 9).
또한, [도 10] 및 [표 16]에 나타낸 바와 같이 TNF-α만 처리한 대조군의 MuRF-1 유전자 발현량을 1.00±0.00%로 나타냈을 때, 본 발명의 타라곤 에탄올 추출물은 MuRF-1 유전자 발현을 유의하게 감소시키는 것을 확인하였다(도 10).In addition, as shown in [Fig. 10] and [Table 16], when the expression level of MuRF-1 gene of the control group treated with only TNF-α is 1.00±0.00%, the ethanol extract of tarragon of the present invention is MuRF-1 gene It was confirmed that the expression was significantly reduced (FIG. 10).
따라서 본 발명의 타라곤 추출물은 근육 합성에 관여하는 MyoD유전자 및 Myogenin유전자 발현을 증가시키고 근육 분해에 관여하는 Atrogin-1유전자 및 MuRF-1유전자 발현을 감소시키므로, 타라곤 추출물을 근감소증 치료에 사용할 수 있음을 확인하였다.Therefore, the tarragon extract of the present invention increases the expression of the MyoD gene and the Myogenin gene involved in muscle synthesis and reduces the expression of the Atrogin-1 gene and MuRF-1 gene involved in muscle degradation, so the tarragon extract can be used for the treatment of sarcopenia. Was confirmed.
<4-6> 근관 넓이 측정<4-6> Measurement of root canal width
타라곤 추출물의 근관 넓이 증가 효과를 확인하기 위해 상기 실험예 <4-3>에서 제조한 C2C12 세포를 이용하였다.C2C12 cells prepared in Experimental Example <4-3> were used to confirm the effect of increasing the root canal area of the tarragon extract.
C2C12 세포를 6 well plate에 6×105 cells/well씩 분주하여 24시간 동안 배양하였다. 24시간 후에 세포 분화를 시키기 위해 분화 배지로 교체하였고, 6일 동안 이틀에 한 번씩 배지 교환해줬다. 6일 후 50 ㎍/㎖ + TNF-α를 처리하여 다시 48시간 동안 반응하였다. 48시간 반응 후에 디지털카메라가 장착된 광학현미경으로 세포 근관 넓이를 확인하였다.C2C12 cells were aliquoted into 6 well plates by 6×10 5 cells/well and cultured for 24 hours. After 24 hours, the culture medium was replaced with a differentiation medium for cell differentiation, and the medium was changed every two days for 6 days. After 6 days, 50 ㎍ / ㎖ + TNF-α was treated and reacted for 48 hours again. After 48 hours reaction, the cell root canal width was confirmed with an optical microscope equipped with a digital camera.
그 결과, [도 11] 및 [도 12] 및 [표 17]에 나타낸 바와 같이 TNF-α만 처리한 대조군의 경우, 근관 넓이가 13.8±1.38 cm였으며, 타라곤 열수 추출물 처리군에서는 22.20±2.47 cm인 것으로 나타나 넓이가 유의하게 증가하는 것을 확인하였다.(도 11 및 도 12).As a result, as shown in [Figs. 11], [Fig. 12] and [Table 17], in the case of the control group treated with only TNF-α, the root canal area was 13.8±1.38 cm, and in the group treated with tarragon hot water extract, 22.20±2.47 cm It was confirmed that the area was significantly increased (Figs. 11 and 12).
Claims (5)
근감소증(sarcopenia), 근위축증(muscular atrophy), 근무력증(myasthenia), 근이영양증(muscular dystrophy), 근육긴장증(myotonia), 근긴장 저하(hypotonia), 근력 약화(muscular weakness), 근육퇴행위축(muscular dystrophy), 근위축성 측삭경화증(amyotrophic lateral sclerosis) 및 염증성 근육병(inflammatory myopathy)으로 이루어진 군에서 선택되는 근육질환 예방 또는 치료용 약학적 조성물.
Contains an extract of tarragon (English: Tarragon, Little Dragon, Mugwort, Estragon, scientific name: Artemisia dracunculus L.) as an active ingredient, wherein the extract is C 1 to C 2 lower alcohol or water and C 1 to C 2 lower alcohol It is extracted with a mixed solvent of,
Sarcopenia, muscle atrophy, myasthenia, muscle dystrophy, myotonia, hypotonia, muscle weakness, muscle dystrophy, A pharmaceutical composition for preventing or treating muscle diseases selected from the group consisting of amyotrophic lateral sclerosis and inflammatory myopathy.
The pharmaceutical composition for preventing or treating muscle diseases according to claim 1, wherein the composition exhibits an antioxidant or anti-inflammatory effect.
The pharmaceutical composition for preventing or treating muscle diseases according to claim 1, wherein the composition increases the expression of MyoD or Myogenin.
The pharmaceutical composition for preventing or treating muscle diseases according to claim 1, wherein the composition reduces the expression of Atrogin-1 or MuRF-1.
근감소증(sarcopenia), 근위축증(muscular atrophy), 근무력증(myasthenia), 근이영양증(muscular dystrophy), 근육긴장증(myotonia), 근긴장 저하(hypotonia), 근력 약화(muscular weakness), 근육퇴행위축(muscular dystrophy), 근위축성 측삭경화증(amyotrophic lateral sclerosis) 및 염증성 근육병(inflammatory myopathy)으로 이루어진 군에서 선택되는 근육질환 예방 또는 개선용 건강식품.
Contains an extract of tarragon (English: Tarragon, Little Dragon, Mugwort, Estragon, scientific name: Artemisia dracunculus L.) as an active ingredient, wherein the extract is C 1 to C 2 lower alcohol or water and C 1 to C 2 lower alcohol It is extracted with a mixed solvent of,
Sarcopenia, muscle atrophy, myasthenia, muscle dystrophy, myotonia, hypotonia, muscle weakness, muscle dystrophy, Healthy food for preventing or improving muscle diseases selected from the group consisting of amyotrophic lateral sclerosis and inflammatory myopathy.
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KR101809156B1 (en) | 2015-05-26 | 2017-12-14 | (주)앗코스텍 | Composition for prevention, improvement or treatment of muscular disorder or improvement of muscular functions comprising fucosterol |
KR101921085B1 (en) | 2018-05-21 | 2018-11-22 | 이뮤노포지 주식회사 | Pharmaceutical composition for treating muscle atrophy comprising glucagon like-peptide-1, GLP-1 derived peptide, or GLP-1 degradation inhibitor |
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KR101809156B1 (en) | 2015-05-26 | 2017-12-14 | (주)앗코스텍 | Composition for prevention, improvement or treatment of muscular disorder or improvement of muscular functions comprising fucosterol |
KR101921085B1 (en) | 2018-05-21 | 2018-11-22 | 이뮤노포지 주식회사 | Pharmaceutical composition for treating muscle atrophy comprising glucagon like-peptide-1, GLP-1 derived peptide, or GLP-1 degradation inhibitor |
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