KR102121111B1 - Composition for strengthening of muscle, preventing and treating Sarcopenia comprising Liquidambar styraciflua L. - Google Patents
Composition for strengthening of muscle, preventing and treating Sarcopenia comprising Liquidambar styraciflua L. Download PDFInfo
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- KR102121111B1 KR102121111B1 KR1020180079996A KR20180079996A KR102121111B1 KR 102121111 B1 KR102121111 B1 KR 102121111B1 KR 1020180079996 A KR1020180079996 A KR 1020180079996A KR 20180079996 A KR20180079996 A KR 20180079996A KR 102121111 B1 KR102121111 B1 KR 102121111B1
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Abstract
본 발명은 미국 풍나무(Liquidambar styraciflua L.) 열매 추출물을 포함하는 근력강화 또는 근감소증의 예방 및 치료용 조성물에 관한 것으로, 본 발명의 미국 풍나무 열매 추출물은 세포독성이 없고 항마이오스타틴의 활성에 효과가 뛰어나므로 근력강화 또는 근감소증의 예방 및 치료용 약학 조성물로 유용하게 이용할 수 있을 것이다.The present invention relates to a composition for the prevention and treatment of muscular strength or muscular dystrophy, including the American Plum tree ( Liquidambar styraciflua L. ) fruit extract, wherein the American Plum tree extract of the present invention has no cytotoxicity and activity of antimyostatin Because it has an excellent effect, it may be useful as a pharmaceutical composition for preventing or treating muscular strength or muscular dystrophy.
Description
본 발명은 미국 풍나무 열매 추출물을 포함하는 근력강화 또는 근감소증의 예방 및 치료용 조성물에 관한 것이다.The present invention relates to a composition for the prevention and treatment of muscular strength or muscular dystrophy, including the American Plum tree fruit extract.
20세기에 들어 인구의 수가 두 배로 증가한 사례는 두 차례나 있었지만, 21세기에 접어들면서 출산율 하락 및 평균 수명의 연장으로 인해 인구의 증가가 두 배로 증가하는 일은 한 번 있기도 어려운 실정이다. 2015년 유엔의 세계인구 전망 (World population prospects : the 2015 revision)에 의하면 2015년 9억 1000만 명이었던 60세 이상의 인구는 2030년 약 14억 명으로 증가할 것이며, 2050년에는 21억 명에 이를 것으로 추정하고 있다. 또한 80세 이상의 초고령 노년층은 2050년에 약 4억 3400만 명에 달할 것이며 이러한 증가는 향후 수십 년간 지속 될 것으로 전망하고 있다. 우리나라 또한 2000년에 65세 이상의 인구가 전체 인구의 7.2%에 달해 고령화 사회 (aging society)에 들어선 이후, 2018년에는 고령사회 (aged society)로 접어들고, 2026년에는 노인인구의 비율이 20.8%에 달해 초 고령사회 (post-aged society)에 진입한다는 것이 통계청의 전망이다. 또한 다른국가에 비해 우리나라는 고령사회 또는 초고령 사회까지 도달하는 기간이 매우 빠르게 접근하고 있는 것이 큰 문제점으로 지적되고 있다. 이러한 문제점은 최근 급격히 낮아지는 출산율이 원인으로 생각되어지며 이로 인해 노인인구의 수가 급격히 증가하는 현상이 나타나고 있다. In the twentieth century, there have been two cases of double population, but it is difficult for the population to double due to the drop in fertility rate and extension of life expectancy in the 21st century. According to the UN's World Population Prospects (the 2015 revision) in 2015, the population over the age of 60, who was 990 million in 2015, will increase to about 1.4 billion in 2030, reaching 2.1 billion in 2050. It is estimated. It is also projected that the elderly aged 80 and over will reach about 430 million in 2050, and this increase is expected to continue in the coming decades. Korea also entered the aging society in 2000, with a population of 65 years or older reaching 7.2% of the total population, and in 2018 it entered the aged society, and in 2026 the proportion of the elderly population was 20.8%. It is forecasted by the National Statistical Office that it will reach a post-aged society. In addition, compared to other countries, it is pointed out that it is a big problem in Korea that the period of reaching an elderly or ultra-aged society is approaching very quickly. These problems are thought to be caused by the rapidly falling fertility rate, and this has led to a rapid increase in the number of elderly people.
노화 (aging)란 생물의 신체기능이 시간이 흐름에 따라 퇴화하는 현상으로, 인간의 경우 80세가 되면 청각은 30%, 혈액박출양은 45%, 폐활량은 60%, 근육량은 50% 감소하는 것으로 알려져 있다. 노화에 따른 각종 생리활성은 모두 저하되지 않고 일부 효소 활성이나 호르몬 분비기능은 증가되기도 한다. 따라서 노화에 따른 생리적 변화는 대상성 기능증진 또는 제어기구의 결함이므로 단순한 생리활성의 저하가 아닌 적응능력의 저하라고 할 수 있다.Aging is a phenomenon in which the body function of a living body degrades over time. It is known that when humans turn 80, their hearing is reduced by 30%, blood output by 45%, lung capacity by 60%, and muscle mass by 50%. have. Various physiological activities due to aging do not decrease, and some enzyme activities or hormone secretion functions are also increased. Therefore, the physiological changes due to aging can be said to be a decrease in adaptive capacity, not a decrease in physiological activity, simply because of a target function enhancement or a defect of a control mechanism.
노화에 따른 대표적인 생리적 변화는 근육량 및 근력 감소이다. 근육량 감소는 40대 이후부터 발생하여 70대까지 10년에 약 8%의 감소가 일어나는 것으로 알려져 있으며, 이후에는 급격한 감소가 발생하여 10년에 최대 15%까지 발생하는 것으로 알려져 있다. 노인의 근감소증 (sarcopenia)는 직접적인 근력 감소를 유발하여 각종 신체 기능의 감소 및 장애로 인해 사망의 위험성을 증가시킬 뿐 아니라 신진대사의 감소 및 면역력 저하 등 고혈압, 당뇨, 관절염, 비만, 암 등과 같은 대사성 질환의 유병률을 높이는 원인이 되기도 한다.A typical physiological change according to aging is a decrease in muscle mass and muscle strength. It is known that the decrease in muscle mass occurs after the 40s and decreases by about 8% in 10 years until the 70s, and after that it is known that a rapid decrease occurs and occurs up to 15% in 10 years. Sarcopenia in the elderly causes direct muscle loss, which increases the risk of death due to a decrease in various body functions and impairments, as well as decreases in metabolism and decreases immunity such as hypertension, diabetes, arthritis, obesity, cancer, etc. It may also increase the prevalence of metabolic diseases.
이러한 근육량의 감소와 관련하여 골격근의 성장을 억제하는 마이오스타틴의 연구가 되고 있으며, 마이오스타틴의 기능만을 억제하기 위한 항체를 제조하였으나, 부작용이 나타났으며, 천연물을 이용한 항마이오스타틴 소재에 대한 연구는 진행되고 있으나 아직까지 세포 수준에서의 연구가 대부분이며 임상실험에 도달한 연구는 전무한 상황이다. In connection with this reduction in muscle mass, research has been conducted on myostatin to inhibit skeletal muscle growth. Antibodies have been prepared to inhibit only the function of myostatin, but side effects have been exhibited. Research has been conducted, but most of the studies at the cellular level have been conducted, and no studies have reached clinical trials.
본 발명의 목적은 미국 풍나무 열매 추출물을 포함하는 근력강화 또는 근감소증의 예방 및 치료용 약학 조성물을 제공하는 것이다. An object of the present invention is to provide a pharmaceutical composition for the prevention and treatment of muscular strength or muscular dystrophy, including the American Plum tree fruit extract.
본 발명의 다른 목적은 미국 풍나무 열매 추출물을 포함하는 근력강화 또는 근감소증의 예방 및 개선용 건강기능식품을 제공하는 것이다. Another object of the present invention is to provide a health functional food for the prevention and improvement of muscular strength or muscular dystrophy, including the American Plum tree fruit extract.
또한, 본 발명의 다른 목적은 건조된 미국 풍나무 열매에 알코올을 가하여 추출하는 단계; 상기 추출물을 감압 농축하여 용매를 제거하는 단계; 수득된 미국 풍나무 열매 추출물을 원심 분리하여 상등액을 회수하는 단계를 포함하는 근력강화 및 근감소증 예방 및 치료용 조성물의 제조 방법 을 제공하는 것이다. In addition, another object of the present invention is extracted by adding alcohol to the dried American wind-tree fruit; Concentrating the extract under reduced pressure to remove the solvent; It is to provide a method for preparing a composition for preventing and treating muscle strength and muscular dystrophy, comprising the step of recovering the supernatant by centrifuging the obtained American wind tree fruit extract.
또한, 본 발명의 다른 목적은 미국 풍나무 열매 추출물을 포함하는 사료 첨가제를 제공하는 것이다.In addition, another object of the present invention is to provide a feed additive comprising an American wind tree fruit extract.
본 발명자들은 근력강화 또는 노화에 의한 근감소증을 예방 및 치료하기 위한 천연물질을 개발하기 위하여 다양한 연구를 수행하던 중, 미국 풍나무 열매 추출물이 항마이오스타틴에 활성을 띄는 것을 확인하였으며, 상기 미국 풍나무 열매 추출물의 근력강화 또는 근감소증 치료제는 지금까지 전혀 알려지지 않았고, 본 발명자에 의하여 최초로 개발되는 점에서 그 의의가 매우 크다고 할 수 있다.The present inventors conducted a variety of studies to develop natural substances for preventing and treating muscular dystrophy due to muscle strengthening or aging, and confirmed that the American Plum tree fruit extract exhibits activity in antimyostatin, and the American style The treatment for muscle strengthening or muscular dystrophy of the tree fruit extract has not been known at all until now, and it can be said that its significance is very large in that it is first developed by the present inventors.
상기 과제를 해결하기 위하여 본 발명은 미국 풍나무 열매 추출물을 포함하는 근력강화 또는 근감소증의 예방 및 치료용 약학 조성물을 제공한다. In order to solve the above problems, the present invention provides a pharmaceutical composition for the prevention and treatment of muscular strength or muscular dystrophy, including the American Plum tree fruit extract.
본 발명의 일실시예에서, 상기 조성물은 항마이오스타틴 활성을 가지며, 근력 및 근밀도를 향상시키고, 근육량 증가 효과를 가지는 것을 특징으로 한다. In one embodiment of the present invention, the composition is characterized by having antimyostatin activity, improving muscle strength and muscle density, and having an effect of increasing muscle mass.
본 발명의 일실시예에서, 상기 근감소증은 근위축증, 근무력증, 근이영양증, 근경직증, 근긴장저하, 근력약화, 근육퇴행위축, 근위축성 측삭경화증 또는 중증 근무력증인 것일 수 있다.In one embodiment of the present invention, the myopathy may be muscular dystrophy, myasthenia gravis, muscular dystrophy, muscular spasticity, muscular dystonia, muscle weakness, muscular atrophy, amyotrophic lateral sclerosis or severe myasthenia gravis.
본 발명의 일실시예에 있어서, 상기 미국 풍나무 열매 추출물은 유기용매에 의한 추출물이고, 바람직하게는 물 또는 알코올 추출물이며, 보다 바람직하게는 에탄올 추출물이나, 이에 제한되는 것은 아니다. In one embodiment of the present invention, the American wind fruit extract is an organic solvent extract, preferably water or alcohol extract, more preferably an ethanol extract, but is not limited thereto.
다른 양태로서 본 발명은, 미국 풍나무 열매 추출물을 유효성분으로 포함하는 근감소증 예방 및 완화용 건강기능 식품을 제공한다. In another aspect, the present invention provides a health functional food for preventing and alleviating muscular dystrophy, which includes the American Plum tree fruit extract as an active ingredient.
또 다른 양태로서 본 발명은, 미국 풍나무 열매 추출물을 유효성분으로 포함하는 근력강화용 건강기능 식품을 제공한다. As another aspect, the present invention provides a health functional food for strengthening muscle strength, which includes an American wind tree fruit extract as an active ingredient.
다른 양태로서 본 발명은 건조된 미국 풍나무 열매에 열수를 가하여 추출하는 단계; 상기 추출물을 감압 농축하여 용매를 제거하는 단계; 수득된 미국 풍나무 열매 추출물을 원심 분리하여 상등액을 회수하는 단계를 포함하는 근감소증 예방 및 치료용 또는 근력 강화용 조성물의 제조 방법을 제공한다.In another aspect, the present invention extracts by adding hot water to the dried American wind-tree fruit; Concentrating the extract under reduced pressure to remove the solvent; It provides a method for preparing a composition for the prevention and treatment of muscular dystrophy or strengthening muscle strength, comprising the step of recovering the supernatant by centrifuging the obtained American wind tree fruit extract.
다른 양태로서 본 발명은 상기 제조 방법에 의해 제조된 미국 풍나무 열매 추출물을 포함하는 근감소증 예방 및 치료용 약학적 조성물 또는 근감소증 예방 및 완화용 식품을 제공한다.In another aspect, the present invention provides a pharmaceutical composition for preventing and treating muscular dystrophy or a food for preventing and alleviating muscular dystrophy, comprising the American wind tree fruit extract prepared by the above manufacturing method.
또 다른 양태로서 본 발명은 미국 풍나무 열매 추출물을 유효성분으로 포함하는 사료 첨가제를 제공한다.In another aspect, the present invention provides a feed additive comprising the American wind tree fruit extract as an active ingredient.
본 발명의 미국 풍나무 열매 추출물은 세포독성이 없고 항마이오스타틴의 활성에 효과가 뛰어나므로 결과적으로 근감소증과 같은 노인성 근질환에 대한 예방, 완화 및 치료용으로 사용될 수 있다.American wind fruit extract of the present invention is not cytotoxic and has an excellent effect on the activity of antimyostatin, and as a result, it can be used for prevention, alleviation, and treatment of senile myopathy such as muscular dystrophy.
도 1은 미국 풍나무 열매 추출물을 제조하는 과정을 나타낸 모식도이다.
도 2는 미국 풍나무 열매 추출물 처리 농도에 따른 세포독성 및 항산화 활성 결과를 나타낸 그래프이다:
A: 미국 풍나무 열매 열수 추출물(LSWE)의 농도 1000, 100, 10 ug/ml에 따른 세포 독성 결과,
B: 미국 풍나무 열매 열수 추출물(LSWE)의 농도 200, 100, 10, 1 ug/ml, AC(ascorbic acid) 50 ug/ml에 따른 항산화 결과.
도 3은 미국 풍나무 열매 추출물의 항마이오스타틴 활성, ActivinA와 GDF11 저해 활성 및 마이오스타틴 신호전달을 분석한 결과를 나타낸 그래프 및 필름 결과이다:
A: 미국 풍나무 열매 열수 추출물(LSWE)의 농도 10, 1, 0.1 ug/ml에 따른 항마이오스타틴 결과,
B: 미국 풍나무 열매 열수 추출물(LSWE)의 농도 10, 1.0, 0.1 ug/ml에 따른 ActivinA 저해 활성 결과,
C: 미국 풍나무 열매 열수 추출물(LSWE)의 농도 10, 1.0, 0.1 ug/ml에 따른 GDF11 저해 활성 결과,
D: Lane 1은 대조구(control, 처리 안함), Lane 2는 마이오스타틴만 처리, Lane 3은 양성 대조구(positive control)로서 마이오스타틴과 SB431542 (마이오스타틴이 결합하는 수용체의 인산화를 억제하는 small molecule)를 동시에 처리, Lane 4, 5는 마이오스타틴과 미국 풍나무 열매 열수 추출물(LSWE) 동시에 처리함.
도 4는 동물모델에서 미국 풍나무 열매 열수 추출물(LSWE) 처리 일수에 따른 근력 변화를 확인한 그래프이다:
A: 몸무게, B: 근력, C: 근밀도.
도 5는 미국 풍나무 열매 열수 추출물(LSWE)을 처리한 동물 모델에서 중성지방, 글루코즈 함량 및 근육피로도를 나타낸 그래프이다:
A: 트리글리세리드, B: 글루코즈, C: LDH 활성.
도 6은 미국 풍나무 열매 추출물(열수/에탄올)의 항마이오스타틴 활성을 나타낸 그래프이다:
A: 미국 풍나무 열매 열수 추출물(LSWE)의 농도 10, 1, 0.1 ug/ml에 따른 항마이오스타틴 결과,
B: 미국 풍나무 열매 에탄올 추출물(LSEE)의 농도 10, 1, 0.5, 0.1 ug/ml에 따른 항마이오스타틴 결과.1 is a schematic view showing a process of manufacturing a US wind tree fruit extract.
Figure 2 is a graph showing the results of cytotoxicity and antioxidant activity according to the treatment concentration of the American Plum fruit extract:
A: Cytotoxicity results according to the concentration of 1000, 100, 10 ug/ml of the American wind tree extract (LSWE),
B: Antioxidant results according to the concentration of 200, 100, 10, 1 ug/ml, and 50 ug/ml of AC (ascorbic acid) of American wind tree fruit extract (LSWE).
Figure 3 is a graph and film results showing the results of analyzing the anti-myostatin activity, ActivinA and GDF11 inhibitory activity and myostatin signaling of the American wind tree fruit extract:
A: Anti-myostatin results according to concentrations of 10, 1, and 0.1 ug/ml of American wind tree fruit extract (LSWE),
B: Results of ActivinA inhibitory activity according to concentrations of 10, 1.0, and 0.1 ug/ml of American wind tree fruit extract (LSWE),
C: GDF11 inhibitory activity results according to the concentration of 10, 1.0, 0.1 ug/ml of the American wind tree extract (LSWE),
D:
Figure 4 is a graph confirming the change in muscle strength according to the number of days treated with American wind tree fruit extract (LSWE) in animal models:
A: weight, B: muscle strength, C: muscle density.
5 is a graph showing triglyceride, glucose content, and muscle fatigue in an animal model treated with the American Plum tree hydrothermal extract (LSWE):
A: triglyceride, B: glucose, C: LDH activity.
6 is a graph showing the anti-myostatin activity of American wind tree fruit extract (hot water/ethanol):
A: Anti-myostatin results according to concentrations of 10, 1, and 0.1 ug/ml of American wind tree fruit extract (LSWE),
B: Antimyostatin results according to concentrations of 10, 1, 0.5, and 0.1 ug/ml of American ethanol extract (LSEE).
이하, 본 발명을 상세히 설명한다. Hereinafter, the present invention will be described in detail.
본 발명은 근력강화 또는 노화에 의한 근감소증을 예방 및 치료하기 위한 미국 풍나무 열매 추출물을 포함하는 근감소증의 예방 또는 치료용 약학 조성물에 관한 것이다. The present invention relates to a pharmaceutical composition for the prevention or treatment of muscular dystrophy, including the American Plum tree fruit extract for preventing and treating muscular dystrophy due to muscular strength or aging.
미국 풍나무(Liquidambar styraciflua L.)는 낙엽활엽교목으로 북아메리카가 원산지이다. 높이는 20m까지 자라는 큰나무이며 가을이면 노랑색과 오랜지색, 자주색 및 붉은색 등 다양한 색으로 단풍이 지는 이유로 우리나라에서는 주로 가로수, 경관수 또는 공원수로 이용되고 있는 식물이다. 또한 병충해에 강하며 성장이 빠른 속성수로서 화재나 수해 등으로 망가진 숲이나 자연녹지의 복구 조성에 적합한 나무이다. 영명은 Sweetgum이라 부르는데 이는 나무로부터 나오는 수지에서 유래되었다. 이러한 수지는 씹는껌을 만들거나 향수의 원료로 사용되기도 하며 아메리카 원주민들은 조미료용 향신료로 사용하기도 한다. 미국 풍나무 열매가 성숙하고 나서 종자가 날아가 버린 빈껍데기는 매우 단단하여 행인들이 많은 도로나 어린 학생들이 다니는 학교 주변에 떨어지면 위험할 수 있기 때문에 겨울철 문젯거리로 지적되고 있다. The American Plum tree ( Liquidambar styraciflua L. ) is a deciduous broad-leaved tree native to North America. It is a large tree that grows up to 20m in height. In autumn, it is a plant that is mainly used as street trees, landscape trees, or park trees in Korea because of the fall colors of yellow, orange, purple, and red. In addition, it is a tree suitable for the restoration of forests and natural green areas damaged by fire or water damage. Yeongmyeong is called Sweetgum, which is derived from the resin from the tree. These resins are used to make chewing gum or as a raw material for perfumes, and Native Americans use them as seasoning spices. It is pointed out as an issue in the winter, as it is very hard that the seeds of the American plum tree have grown and the seeds have been blown away.
본 발명에서 용어 "근력강화"는 근력 및 근밀도가 증가하는 것을 의미한다. In the present invention, the term "strengthening muscles" means increasing muscle strength and muscle density.
본 발명에서 용어“근감소증”은 근육의 부피 및 근력이 점진적으로 쇠퇴하는 질환을 의미한다.In the present invention, the term "muscular hypothyroidism" refers to a disease in which muscle volume and muscle strength gradually decline.
본 발명에서 상기 미국 풍나무 열매을 추출하는 사용되는 추출용매의 종류는 특별히 제한되지 않으며, 당해 기술 분야에서 공지된 임의의 용매를 사용할 수 있다. 상기 추출 용매의 비제한적인 예로는 물, 탄소수 1 내지 4의 알코올 또는 이들의 혼합 용매 등을 들 수 있으며, 이들은 단독으로 사용되거나 1종 이상 혼합하여 사용될 수 있다. 구체적으로 물 또는 에탄올이 사용될 수 있지만, 이에 제한되는 것은 아니며, 상기 에탄올은 1 내지 100%일 수 있지만, 이에 제한되는 것은 아니다. 본 발명에 있어서, 상기 추출물은 열수 추출물 또는 에탄올 추출물일 수 있으나, 이에 제한되는 않는다.In the present invention, the type of the extraction solvent used to extract the American wind fruit is not particularly limited, and any solvent known in the art may be used. Non-limiting examples of the extraction solvent include water, alcohols having 1 to 4 carbon atoms, or a mixed solvent thereof, and these may be used alone or in combination of one or more. Specifically, water or ethanol may be used, but is not limited thereto, and the ethanol may be 1 to 100%, but is not limited thereto. In the present invention, the extract may be a hot water extract or an ethanol extract, but is not limited thereto.
상기 추출물은 항마이오스타틴(anti Myostatin) 활성을 갖는 것이다.The extract is one having anti-myostatin activity.
즉, 본 발명은 상기 미국 풍나무 열매 추출물을 유효성분으로 포함하는 근감소증예방 및 치료용 조성물에 대한 것이며, 상기 조성물은 약학적 조성물, 식품 조성물을 포함한다. 근감소증(sarcopenia)은 골격 근육량의 감소로 인한 질환이며, 직접적으로 근력의 저하를 유발하고 그 결과 각종 신체기능의 감소 및 장애를 일으키며, 사망 위험성도 증가시키는 것으로 알려져 있다. 이는 노화와 연관되어 나타나는 점진적인 골격근 감소의 결과로 나타나는 질환이다(박성원, 2007, 노인의 근감소증, 대한내분비학회지 제22권 제1호). 특히, 본 발명의 미국 풍나무 열매 추출물은 상기 근육량 증가를 억제하는 인자인 마이오스타틴 활성을 특이적으로 저해하여 근감소증에 대한 치료 및 예방 효과를 가진다. That is, the present invention relates to a composition for preventing and treating muscular dystrophy, which includes the American wind tree fruit extract as an active ingredient, and the composition includes a pharmaceutical composition and a food composition. Sarcopenia is a disease caused by a decrease in skeletal muscle mass, and it is known to directly cause a decrease in muscle strength and, as a result, decrease and impair various physical functions, and increase the risk of death. This is a disease resulting from gradual skeletal muscle reduction associated with aging (Park Sung-won, 2007, muscular dystrophy in the elderly, Journal of the Korean Society of Endocrinology, Vol. 22, No. 1). In particular, the American Plum tree fruit extract of the present invention specifically inhibits myostatin activity, a factor that inhibits the increase in muscle mass, and thus has a therapeutic and prophylactic effect on muscular dystrophy.
아울러, 본 발명은, 상기 미국 풍나무 열매 추출물을 유효성분으로 포함하는 근력강화용 조성물에 대한 것이며, 상기 조성물은 건강식품 조성물 또는 식품 조성물을 포함한다. “근력 증가”는 골격근량의 증가 또는 근기능의 향상으로 인하여 전체적인 근력이 증가되는 현상을 말하는 것이며, 특정 질병의 환자군에 제한되는 효과를 말하는 것은 아니다. In addition, the present invention relates to a composition for strengthening muscle strength, comprising the American wind tree fruit extract as an active ingredient, and the composition includes a health food composition or a food composition. “Increased muscle strength” refers to a phenomenon in which the overall muscle strength is increased due to an increase in skeletal muscle mass or improvement of muscle function, and not an effect limited to a patient group of a specific disease.
본 발명의 용어, "마이오스타틴(Myostatin, MSTN)"은 근육성장을 조절하는 단백질로서 transforming growth factor-β TGF-β) 계열에 속하고 성장분화 인자 (growth and differentiation factor-8, GDF-8)이다. The term "myostatin (MSTN)", a term of the present invention, is a protein that regulates muscle growth, belongs to a transforming growth factor-β TGF-β family, and is a growth differentiation factor-8, GDF-8 )to be.
상기 마이오스타틴은 액티빈수용체 제2형과 직접 결합하며, 또한 Smad 신호전달 기작에도 영향을 주는 것으로 알려져 있다. 마이오스타틴의 활성을 억제할 경우, 근육 분화가 촉진되어 다양한 대사성 질환의 개선에도 중요한 역할을 할 수 있다는 점은 이미 공지된 사실이다. 본 발명에서는 상기 마이오스타틴 활성을 조절하여 근감소증과 같은 근육질환의 증상을 개선하고, 근력을 강화시킬 수 있는 미국 풍나무 열매 추출물을 포함한 약학적 조성물 및 식품 조성물을 제공한다.It is known that the myostatin directly binds the activin receptor type 2 and also affects the Smad signaling mechanism. It is already known that, when inhibiting the activity of myostatin, muscle differentiation is promoted and may play an important role in improving various metabolic diseases. The present invention provides a pharmaceutical composition and a food composition including an American wind tree fruit extract capable of improving the symptoms of muscle disease such as muscular dystrophy by regulating the myostatin activity and enhancing muscle strength.
본 발명의 조성물은 약제학적 조성물로 제조될 수 있다. 본 발명의 약제학적 조성물은 경구 또는 비경구 투여할 수 있으며, 바람직하게는 경구 투여 방식으로 적용된다. 본 발명의 약제학적 조성물의 적합한 투여량은 제제화 방법, 투여 방식, 환자의 연령, 체중, 성, 병적 상태, 음식, 투여 시간, 투여 경로, 배설 속도 및 반응 감응성과 같은 요인들에 의해 다양하게 처방될 수 있다. 본 발명의 약제학적 조성물의 일반적인 투여량은 성인 기준으로 0.001-100 ㎎/kg 범위 내이다.The composition of the present invention can be prepared as a pharmaceutical composition. The pharmaceutical composition of the present invention can be administered orally or parenterally, and is preferably applied by oral administration. Suitable dosages of the pharmaceutical compositions of the invention are variously prescribed by factors such as formulation method, mode of administration, patient's age, weight, sex, morbidity, food, time of administration, route of administration, rate of excretion, and response sensitivity. Can be. The general dosage of the pharmaceutical composition of the present invention is in the range of 0.001-100 mg/kg on an adult basis.
경구투여를 위한 고형제제에는 정제, 환제, 산제, 과립제, 캡슐제 등이 포함되며, 이러한 고형제제는 상기 미국 풍나무 열매 추출물에 적어도 하나 이상의 부형제 예를 들면, 전분, 칼슘카보네이트(calcium carbonate), 수크로스(sucrose) 또는 락토오스(lactose), 젤라틴 등을 섞어 조제된다. 또한 단순한 부형제 이외에 마그네슘 스티레이트, 탈크 같은 윤활제들도 사용된다. 경구를 위한 액상 제제로는 현탁제, 내용액제, 유제, 시럽제 등이 해당되는 데 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, 비수성 용제, 현탁제, 유제,동결건조 제제, 좌제가 포함된다. 비수성용제, 현탁제로는 프로필렌글리콜(propylene glycol), 폴리에틸렌 글리콜, 올리브오일과 같은 식물성 기름, 에틸올레이트와 같은 주사 가능한 에스테르 등이 사용될 수 있다. 좌제의 기제로는 위텝솔(witepsol), 마크로골, 트윈 61(tween 61), 카카오지, 라우린지, 글리세로제라틴 등이 사용될 수 있다.Solid preparations for oral administration include tablets, pills, powders, granules, capsules, etc. These solid preparations include at least one excipient such as starch, calcium carbonate, etc. It is prepared by mixing sucrose, lactose, or gelatin. Also, lubricants such as magnesium stearate and talc are used in addition to simple excipients. Liquid preparations for oral use may include various excipients, such as wetting agents, humectants, sweeteners, flavoring agents, preservatives, etc., in addition to water and liquid paraffin, which are simple diluents commonly used for suspending agents, liquid solutions, emulsions, syrups, etc. have. Formulations for parenteral administration include sterile aqueous solutions, non-aqueous solvents, suspensions, emulsions, freeze-dried preparations, and suppositories. Non-aqueous solvents and suspensions may include propylene glycol, polyethylene glycol, vegetable oils such as olive oil, and injectable esters such as ethyl oleate. As a base for suppositories, witepsol, macrogol, tween 61, cacao butter, laurin butter, and glycerogelatin may be used.
한편, 본 발명의 약학조성물은 약학적으로 유효한 양으로 투여한다. 본 발명의 용어 "약학적으로 유효한 양"은 의학적 치료에 적용 가능한 합리적인 수혜/위험 비율로 질환을 치료하기에 충분하며 부작용을 일으키지 않을 정도의 양을 의미하며, 유효용량 수준은 환자의 건강상태, 중증도, 약물의 활성, 약물에 대한 민감도, 투여 방법, 투여 시간, 투여 경로 및 배출 비율, 치료기간, 배합 또는 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 치료제와 순차적으로 또는 동시에 투여될 수 있으며, 단일 또는 다중 투여될 수있다. 상기한 요소들을 모두 고려하여, 부작용없이 최소한의 양으로 최대 효과를 얻을 수 있는 양을 투여하는 것이 중요하며, 이는 당업자에 의해 용이하게 결정될 수 있다.Meanwhile, the pharmaceutical composition of the present invention is administered in a pharmaceutically effective amount. The term "pharmaceutically effective amount" of the present invention means an amount sufficient to treat a disease at a reasonable benefit/risk ratio applicable to medical treatment and does not cause side effects, and an effective dose level is a patient's health condition, The severity, activity of the drug, sensitivity to the drug, method of administration, time of administration, route of administration and rate of excretion, duration of treatment, factors including the drug used in combination or co- and other factors well known in the medical field. The composition of the present invention may be administered as an individual therapeutic agent or in combination with other therapeutic agents, and may be administered sequentially or simultaneously with a conventional therapeutic agent, and may be administered single or multiple. Taking all of the above factors into consideration, it is important to administer an amount that can achieve the maximum effect in a minimal amount without side effects, which can be easily determined by those skilled in the art.
본 발명의 약학 조성물의 투여량은 사용목적, 질환의 중독도, 환자의 연령, 체중, 성별, 기왕력, 또는 유효성분으로 사용되는 물질의 종류 등을 고려하여 당업자가 결정할 수 있다. 예를 들어, 본 발명의 약학 조성물은 성인 1인당 약 0.1 ng 내지 약 100 mg/kg, 구체적으로 1 ng 내지 약 10 mg/kg로 투여할 수 있고, 본 발명의 조성물의 투여빈도는 특별히 이에 제한되지 않으나, 1일 1회 투여하거나 또는 용량을 분할하여 수회 투여할 수 있다. 그러나, 투여 경로, 질병의 중증도, 성별, 체중, 연령 등에 따라서 달라질 수 있으므로, 상기 투여량이 어떠한 방법으로도 본 발명의 범위를 한정하는 것은 아니다.The dosage of the pharmaceutical composition of the present invention can be determined by a person skilled in the art in consideration of the purpose of use, the degree of poisoning of the disease, the age, weight, sex, history of the patient, or the type of substance used as an active ingredient. For example, the pharmaceutical composition of the present invention may be administered at about 0.1 ng to about 100 mg/kg per adult, specifically 1 ng to about 10 mg/kg, and the frequency of administration of the composition of the present invention is particularly limited. However, it can be administered once a day or divided into doses and administered several times. However, since the administration route, disease severity, sex, weight, and age may vary, the dosage does not limit the scope of the present invention in any way.
또한 본 발명은 미국 풍나무 열매 추출물을 포함하는 근력증가 또는 근감소증의 예방 및 개선용 건강기능식품을 제공한다. In addition, the present invention provides a health functional food for preventing and improving muscular strength or muscular dystrophy, including the American Plum tree fruit extract.
본 발명의 식품 조성물은 기능성 식품(functional food), 영양 보조제(nutritional supplement), 건강식품(health food) 및 식품 첨가제(food additives) 등의 모든 형태의 식품에 대한 조성물을 포함한다. 상기 유형의 식품 조성물은 당업계에 공지된 통상적인 방법에 따라 다양한 형태로 제조할 수 있다. 예를 들면, 건강식품으로는 미국 풍나무 추출물이 함유된 껌, 비타민 복합체, 차, 주스 및 드링크 형태로 제조 할 수 있으며, 미국 풍나무 추출물을 유효성분으로 하는 식품 조성물을 과립화, 캡슐화 또는 분말화하여 섭취할 수 있다. 본 발명의 기능성 식품 조성물은 식품 제조 시에 통상적으로 첨가되는 성분을 포함할 수 있으며, 예를 들어, 단백질, 탄수화물, 지방, 영양소 및 조미제를 포함할 수 있다. 예컨대, 드링크제로 제조되는 경우에는 본 발명의 미국 풍나무 추출물 이외에 구연산, 액상과당, 설탕, 포도당, 초산, 사과산, 과즙, 대추 추출액, 감초 추출액 등을 추가로 포함 시킬 수 있다.The food composition of the present invention includes a composition for all types of foods, such as functional foods, nutritional supplements, health foods, and food additives. Food compositions of this type can be prepared in various forms according to conventional methods known in the art. For example, as a health food, it can be prepared in the form of gum, vitamin complex, tea, juice, and drink containing the American wind tree extract, and granulates, encapsulates, or powders the food composition using the American wind tree extract as an active ingredient. It can be ingested and consumed. The functional food composition of the present invention may include ingredients that are commonly added during food preparation, and may include, for example, proteins, carbohydrates, fats, nutrients, and flavoring agents. For example, when manufactured as a drink agent, citric acid, liquid fructose, sugar, glucose, acetic acid, malic acid, juice, jujube extract, licorice extract, etc. may be additionally included in addition to the American wind tree extract of the present invention.
상기 식품 조성물은 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 증점제, pH조절제, 안정화제, 방부제, 글리세린, 알코올, 탄산 음료에 사용되는 탄산화제 등을 함유할 수 있다. 그밖에 천연 과일쥬스 및 과일 쥬스 음료 및 야채 음료의 제조를 위한 추출물을 함유할 수 있다. 이러한 성분은 독립적으로 또는 조합하여 사용할 수 있다.The food composition includes various nutrients, vitamins, minerals (electrolytes), flavoring agents such as synthetic and natural flavoring agents, coloring agents and neutralizing agents (cheese, chocolate, etc.), pectic acid and salts thereof, alginic acid and salts thereof, and organic acids , A protective colloidal thickener, pH adjusting agent, stabilizer, preservative, glycerin, alcohol, carbonic acid used in carbonated beverages, and the like. In addition, it may contain extracts for the preparation of natural fruit juice and fruit juice beverages and vegetable beverages. These ingredients can be used independently or in combination.
또한, 본 발명은 미국 풍나무 열매 추출물을 유효성분으로 포함하는 사료 조성물을 제공한다. 상기 미국 풍나무 열매 추출물은 상기 약학 조성물이나 식품 조성물의 경우와 동일하게 준비될 수 있다.In addition, the present invention provides a feed composition comprising the American wind tree fruit extract as an active ingredient. The American wind tree fruit extract may be prepared in the same manner as in the case of the pharmaceutical composition or food composition.
본 발명의 미국 풍나무 열매 추출물은 골격근량의 증가 또는 근기능의 향상으로 인하여 전체적인 근력 증가 효과를 나타내므로 동물이나 가축의 성장 촉진제로서 사료 조성물에 포함될 수 있다.American wind fruit extract of the present invention can be included in the feed composition as a growth promoter for animals or livestock because it exhibits an overall increase in muscle strength due to an increase in skeletal muscle mass or improvement of muscle function.
구체적으로 본 발명에 따른 미국 풍나무 열매 추출물을 유효성분으로 포함하는 사료는 당업계에서 공지된 다양한 형태의 사료로 제조 가능하며, 바람직하게는 농후사료, 조사료 또는 특수사료가 포함될 수 있다.Specifically, the feed containing the American wind tree fruit extract according to the present invention as an active ingredient may be prepared as various types of feed known in the art, and preferably may include a thick feed, a forage or a special feed.
농후사료에는 밀, 귀리, 옥수수 등의 곡류를 포함하는 종자 열매류, 곡물을 정제하고 얻는 부산물로서 쌀겨, 밀 기울, 보릿겨 등을 포함하는 겨류, 콩, 유체, 깨, 아마인, 코코야자 등을 채유하고 얻는 부산물인 깻묵류와 고구마, 감자 등에서 녹말을 뺀 나머지인 녹말찌꺼기의 주성분인 잔존녹말질류 등의 찌꺼기류, 어분, 물고기찌꺼기, 어류에서 얻은 신선한 액상물(液狀物)을 농축시킨 것인 피시솔루블(fish soluble), 육분(肉粉), 혈분, 우모분, 탈지분유, 우유에서 치즈, 탈지유에서 카제인을 제조할 때의 잔액인 훼이(whey)를 건조한 건조훼이 등의 동물질사료, 효모, 클로렐라, 해조류 등이 있다.Thick feed includes seeds, fruits, grains such as wheat, oats, and corn, and by-products such as rice bran, wheat bran, barley bran, soybeans, fluid, sesame, flaxseed, cocoa, etc. Concentrated fresh liquids obtained from fish, fish meal, fish residues, fish residues, etc., which are the main components of starch residues, which are the remainders of starch residues obtained by subtracting starch from oil and sweet potatoes, potatoes, etc. Phosphor soluble (fish soluble), meat (肉粉), blood, milk powder, skim milk, cheese from milk, whey, the balance when manufacturing casein from skim milk, animal feed, such as dry whey, yeast , Chlorella, and seaweed.
조사료에는 야초, 목초, 풋베기 등의 생초(生草)사료, 사료용 순무, 사료용 비트, 순무의 일종인 루터베어거 등의 뿌리채소류, 생초, 풋베기작물, 곡실(穀實) 등을 사일로에 채워 놓고 젖산발효시킨 저장사료인 사일리지(silage), 야초, 목초를 베어 건조시킨 건초, 종축용(種畜用) 작물의 짚, 콩과 식물의 나뭇잎 등이 있다.Forage, silage of wild vegetables such as wild grasses, grasses, and greens, roots for feed, beet for feed, and root vegetables such as Luther Bearer, a kind of turnip, raw grass, green grass crops, and grain rooms There are silage, wild grass, hay that has been cut with grass, fermented lactic acid fermented feed, straw for breeding crops, and leaves of legumes.
특수사료에는 패각, 암염 등의 미네랄 사료, 요소나 그 유도체인 디우레이드이소부탄 등의 요소사료, 천연사료 원료만을 배합했을 때 부족하기 쉬운 성분을 보충하거나, 사료의 저장성을 높이기 위해서 배합사료에 미량으로 첨가하는 물질인 사료첨가물, 식이보조제 등이 있다.Special feeds include mineral feeds such as shellfish and rock salt, urea feeds such as urea or its derivatives such as diureid isobutane, and supplements with ingredients that are difficult to lack when blending only natural feed ingredients, or trace amounts in feeds to improve the storage of feed There are feed additives, dietary supplements, etc.
본 발명에 따른 사료 조성물은 다양한 사료 첨가제를 포함할 수 있다.The feed composition according to the present invention may include various feed additives.
본 발명에서 용어 "사료 첨가제" 란 영양소 보충 및 체중감소 예방, 사료 내 섬유소의 소화 이용성 증진, 유질개선, 번식장애 예방 및 수태율 향상, 하절기 고온 스트레스 예방 등 다양한 효과를 목적으로 사료에 첨가하는 물질을 말한다. 본 발명의 사료첨가제는 사료관리법상의 보조사료에 해당하며, 탄산수소나트륨(중조), 벤토나이트 (bentonite), 산화마그네슘, 복합광물질 등의 광물질제제, 아연, 구리, 코발트, 셀레늄 등의 미량 광물질인 미네랄제제, 케로틴, 비타민 E, 비타민 A, D, E, 니코틴산, 비타민 B 복합체 등의 비타민제, 메티오닌, 리이산 등의 보호아미노산제, 지방산 칼슘염 등의 보호지방산제, 생균제(유산균제), 효모배양물, 곰팡이 발효물 등의 생균, 효모제 등이 추가로 포함될 수 있다.In the present invention, the term "feed additive" refers to a substance that is added to the feed for various effects, such as supplementing nutrients and preventing weight loss, improving digestibility of fiber in feed, improving oil quality, preventing reproductive disorders and improving conception rates, and preventing high-temperature stress in the summer. Speak. The feed additive of the present invention corresponds to the supplementary feed under the feed management method, and mineral preparations such as sodium hydrogen carbonate (sodium bicarbonate), bentonite, magnesium oxide, and composite minerals, and minerals as trace minerals such as zinc, copper, cobalt, and selenium Formulations, keratin, vitamin E, vitamin A, D, E, nicotinic acid, vitamins such as vitamin B complex, protective amino acids such as methionine and lyic acid, protective fatty acids such as fatty acid calcium salt, probiotics (lactic acid bacteria), yeast culture Probiotics such as water and fungal fermentation products, yeasts, and the like may be additionally included.
본 발명에 따른 사료 조성물은 골격근량의 증가 또는 근기능의 향상으로 인하여 전체적인 근력 증가 효과 및 성장 촉진을 목적으로 하는 개체이면 특별히 한정되지 않고, 어떠한 것이든 적용 가능하다. 상기 개체는 동물, 예를 들어 비-영장류 (예를 들면, 소, 돼지, 말, 고양이, 개, 래트 및 마우스) 및 영장류 (예를 들면, 원숭이, 예를 들어 사이노몰구스 (cynomolgous) 원숭이 및 침팬지)를 비롯한 포유동물을 나타낸다. 또 다른 구체예에서, 상기 개체는 축산용 동물 (예를 들면, 말, 소, 돼지 등) 또는 애완용 동물 (예를 들면, 개 또는 고양이)이다. 또한, 어류, 예를 들어, 넙치, 가자미, 뱀장어, 민물장어, 바다장어, 우럭이다.The feed composition according to the present invention is not particularly limited as long as it is an object aimed at increasing the overall muscle strength and promoting growth due to an increase in skeletal muscle mass or improvement of muscle function, and any of them can be applied. Such individuals include animals, such as non-primates (e.g., cattle, pigs, horses, cats, dogs, rats and mice) and primates (e.g. monkeys, e.g. cynomolgous monkeys) and Chimpanzees). In another embodiment, the subject is a livestock animal (eg, horse, cow, pig, etc.) or a pet animal (eg, dog or cat). In addition, fish, for example, flounder, flounder, eel, freshwater eel, sea eel, and eel.
본 발명에 따른 사료 조성물의 복용량은 동물의 종(species), 크기(size), 무게(weight), 나이(age)와 같은 다수의 요인들에 좌우될 것이다. 원칙적으로, 전형적인 복용량은 동물/일 당 0.001 내지 10 g의 범위일 수 있다. 다만, 이에 한정되지 않는다.The dosage of the feed composition according to the invention will depend on a number of factors such as the animal's species, size, weight, and age. In principle, typical dosages can range from 0.001 to 10 g per animal/day. However, it is not limited to this.
이하, 실시예를 통하여 본 발명을 더욱 상세히 설명하고자 한다. 이들 실시예는 오로지 본 발명을 보다 구체적으로 설명하기 위한 것으로, 본 발명의 요지에 따라 본 발명의 범위가 이들 실시예에 의해 제한되지 않는다는 것은 당업계에서 통상의 지식을 가진 자에 있어서 자명할 것이다.Hereinafter, the present invention will be described in more detail through examples. These examples are only intended to illustrate the present invention more specifically, it will be apparent to those skilled in the art that the scope of the present invention is not limited by these examples according to the gist of the present invention. .
<실시예 1> 미국 풍나무 열매 추출물의 제조방법<Example 1> Preparation method of American wind fruit extract
미국산 풍나무 열매를 충분히 건조시킨 뒤 20 mg/ml의 농도로 열수 추출하였다. 열수 추출은 증류수를 이용하여 90℃에서 20분간 추출하였으며, 3회 반복 추축하였다. 추출된 시료는 회전 감압 농축기를 이용하여 대부분의 물을 제거하고 4000 rpm에서 20분간 원심분리하여 상등액만 회수하였다. 상등액은 원심회전 농축기를 이용하여 시료의 농도를 측정하였다. 3회 반복 추출한 결과 7.1%의 추출 수율을 확인할 수 있었다(도 1). After fully drying the American wind fruit, hot water was extracted at a concentration of 20 mg/ml. The hot water extraction was extracted at 90° C. for 20 minutes using distilled water, and repeated 3 times. The extracted sample was removed most of the water using a rotary vacuum concentrator and centrifuged at 4000 rpm for 20 minutes to recover only the supernatant. The concentration of the supernatant was measured using a centrifugal rotary concentrator. As a result of repeated extraction three times, an extraction yield of 7.1% was confirmed (FIG. 1).
<실시예 2> 미국 풍나무 열매 추출물의 세포 독성 및 항산화 활성 분석<Example 2> Analysis of cytotoxicity and antioxidant activity of American wind tree fruit extract
미국 풍나무 열매 추출물(L. stryracifluca hot water extracts, LSWE)의 세포 독성을 확인하기 위하여, 세포독성실험은 96 well plate에 well 당 Hek293 세포를 1×104 cell/100 ul (in DMEM with 10% FBS and 1% penicillin/streptomycin) 세포를 seeding 하여 5% CO2 배양기에서 배양하였다. 24시간 후 미국 풍나무 열매 열수 추출물(LSWE)을 농도별(0.5, 1, 10, 100 ug/ml)로 처리하여 5% CO2 배양기에서 12시간 동안 배양하였다. 이후 WST reagent (DaeilLab, Korea)를 10 ul 넣고 1시간 동안 반응 후 415 nm에서 흡광도를 측정하여 세포독성을 판단하였다. 추출물에 대한 처리 없이 세포만 처리한 것을 양성 대조군으로 하고, H2O2 처리군을 음성 대조군으로 하여, 아래의 식을 이용하여 세포독성에 대한 결과를 비교하였다.To confirm the cytotoxicity of American Prunus fruit extract ( L. stryracifluca hot water extracts, LSWE), For the cytotoxicity test, Hek293 cells per well were seeded in a 96 well plate and seeded with 1×10 4 cell/100 ul (in DMEM with 10% FBS and 1% penicillin/streptomycin) cells and cultured in a 5% CO 2 incubator. After 24 hours, the American Plum fruit hydrothermal extract (LSWE) was treated by concentration (0.5, 1, 10, 100 ug/ml) and cultured in a 5% CO 2 incubator for 12 hours. Subsequently, 10 ul of WST reagent (DaeilLab, Korea) was added, and after 1 hour of reaction, the absorbance was measured at 415 nm to determine cytotoxicity. Cells treated without extracts were treated as positive controls, and H 2 O 2 treated groups were used as negative controls, and the results for cytotoxicity were compared using the following formula.
그 결과, 미국 풍나무 열매 열수 추출물(LSWE)는 Hek293 세포에서 100 ug/ml의 농도에서 세포 독성을 나타내지 않았으며, 다른 농도에서도 5% 미만의 독성을 가지는 것을 확인하였다(도 2A).As a result, the American Plum tree hydrothermal extract (LSWE) did not show cytotoxicity at a concentration of 100 ug/ml in Hek293 cells, and was confirmed to have less than 5% toxicity at other concentrations (FIG. 2A).
또한, 미국 풍나무 열매 추출물의 항산화 활성을 확인하기 위하여, DPPH reagent 100 ul와 미국 풍나무 열매 열수 추출물(LSWE) 100 ul를 최종 농도 10, 1, 0.1 ug/ml이 되도록 처리하여 하여 상온, 암실에서 30분간 반응한 뒤 562 nm에서 흡광도를 측정하였다.In addition, in order to confirm the antioxidant activity of the American Plum tree fruit extract, 100 ul of DPPH reagent and 100 ul of the American Plum tree hot water extract (LSWE) are treated to a final concentration of 10, 1, 0.1 ug/ml, and then at room temperature and darkroom. After reacting for 30 minutes, the absorbance was measured at 562 nm.
대조군(Control lane)은 추출물을 처리하지 않은 lane이며 AC (10)은 양성대조군(positive control)로서 대표적인 항산화 물질인 비타민 C(ascorbic acid)를 10 ug/ml의 농도로 처리한 lane이다The control (control lane) is a lane that is not treated with the extract, and the AC (10) is a positive control, a lane treated with vitamin C (ascorbic acid), a typical antioxidant, at a concentration of 10 ug/ml.
그 결과, 미국 풍나무 열매 열수 추출물(LSWE)을 10 ug/ml 처리한 것은 비타민 C를 10 ug/ml의 농도로 처리한 것과 유사한 항산화 활성을 확인하였다(도 2B). As a result, the treatment with 10 ug/ml of the American wind tree fruit hydrothermal extract (LSWE) confirmed the antioxidant activity similar to that of the vitamin C treatment at a concentration of 10 ug/ml (FIG. 2B ).
<실시예 3> 미국 풍나무 열매 추출물의 항마이오스타틴 활성 분석<Example 3> Antimyostatin Activity Analysis of American Plum Fruit Extract
미국 풍나무 열매 추출물의 항마이오스타틴의 활성을 확인하기 위하여 발광 효소 분석(luciferase assay) 시스템을 통해 확인하였다. In order to confirm the activity of antimyostatin of American Plum tree fruit extract, it was confirmed through a luciferase assay system.
구체적으로, Hek293 세포는 DMEM 배지 (10% FBS, 1% penicillin/streptomycine, 1% geneticine)에서 96 well plate에 well 당 2.0×104 cell로 seeding 하여 5% CO2 배양기에서 배양하였다. 24시간 후, 배지는 FBS가 제거된 DMEM으로 교체하였고, 1 nM의 재조합 마이오스타틴 (R&D system, USA)과 미국 풍나무 열매 열수 추출물(LSWE)을 농도별로 처리하여 CO2 배양기에서 배양하였다. 24시간 뒤 배지를 제거하고 65 ul의 DMEM 배지와 65 ul의 reagent (Bright-Glo luciferase assay system, USA)를 처리하여 micro plate luminometer에서 발광을 측정하였다. 측정된 수치는 양성대조구(positive control)와 음성대조구(negative control)의 수치를 이용하여 항마이오스타틴 활성을 %로 나타내었다. 측정된 수치는 양성대조구(positive control, 마이오스타틴만 처리한 실험구, MSTN only)와 음성대조구(negative control, 마이오스타틴을 처리하지 않은 실험구, No MSTN)의 수치를 이용하여 아래와 같은 식을 이용하여 항마이오스타틴 활성을 %로 나타내었다. 마이오스타틴 저해활성 (%) = (1 nM 마이오스타틴만 처리한 실험구의 발광수치 - 미국 풍나무 열매 추출물 처리구의 발광수치) x 100 / (1 nM 마이오스타틴만 처리한 실험구의 발광수치 - 마이오스타틴을 처리하지 않은 실험구의 발광수치)Specifically, Hek293 cells were seeded with 2.0×10 4 cells per well in a 96 well plate in DMEM medium (10% FBS, 1% penicillin/streptomycine, 1% geneticine) and cultured in a 5% CO 2 incubator. After 24 hours, the medium was replaced with DMEM from which FBS was removed, and 1 nM of recombinant myostatin (R&D system, USA) and American Plum fruit hydrothermal extract (LSWE) were treated by concentration and cultured in a CO 2 incubator. After 24 hours, the medium was removed and treated with 65 ul of DMEM medium and 65 ul of reagent (Bright-Glo luciferase assay system, USA) to measure luminescence in a micro plate luminometer. The measured values were expressed in% of antimyostatin activity using the values of the positive control and the negative control. The measured values are as follows using the values of the positive control (test group treated with myostatin only, MSTN only) and the negative control (test group not treated with myostatin, no MSTN). The antimyostatin activity was expressed in% using. Myostatin Inhibitory Activity (%) = (Emission value of 1 nM myostatin-treated group-Luminous value of U.S. wind fruit extract treatment group) x 100 / (1 nM myostatin-treated group's luminescence value- Luminescence value of experimental group not treated with myostatin)
그 결과, 마이오스타틴에 대한 활성 저해 효과는 미국산 풍나무 추출물 처리 시, 농도 의존적으로 증가하는 것을 확인할 수 있었으며 y = 7.1808x + 24.467의 추세선 공식을 얻었다. 1 nM의 마이오스타틴에 대한 IC 50 value는 3.56 ug/ml인 것을 확인하였다(도 3A).As a result, it was confirmed that the activity inhibitory effect on myostatin increased in a concentration-dependent manner when the American wind extract was treated, and a trend line formula of y = 7.1808x + 24.467 was obtained. It was confirmed that the
<실시예 4> 미국 풍나무 열매 추출물의 ActivinA 및 GDF11 저해 활성 분석<Example 4> ActivinA and GDF11 inhibitory activity analysis of American wind fruit extract
미국 풍나무 열매 추출물의 ActivinA 및 GDF11 저해 활성을 확인하기 위하여 발광 효소 분석(luciferase assay) 시스템을 통해 확인하였다. In order to confirm the ActivinA and GDF11 inhibitory activity of the American Plum tree extract, it was confirmed through a luciferase assay system.
구체적으로, 미국 풍나무 열매 추출물에 대하여 마이오스타틴과 같은 superfamily에 속해있는 ActivinA와 GDF11의 저해활성을 측정하였다. Hek293 세포는 DMEM 배지 (10% FBS, 1% penicillin/streptomycine, 1% geneticine)에서 96 well plate에 well 당 2.0×104 cell로 seeding 하여 5% CO2 배양기에서 배양하였다. 24시간 후, 배지는 FBS가 제거된 DMEM으로 교체하였고, ActivinA 처리군은 ActivinA를 0.5 nM, GDF11 처리군은 GDF11를 1 nM를 각 well당 처리하고, 처리된 각 처리군에 미국 풍나무 열매 열수 추출물(LSWE)을 농도별로 처리하여 CO2 배양기에서 배양하였다. 24시간 뒤 배지를 제거하고 65 ul의 DMEM 배지와 65 ul의 reagent (Bright-Glo luciferase assay system, USA)를 처리하여 micro plate luminometer에서 발광을 측정하였다. 측정된 수치는 양성대조구(positive control)와 음성대조구(negative control)의 수치를 이용하여 항마이오스타틴 활성을 %로 나타내었다. 측정된 수치는 양성대조구(positive control, activinA 또는 GDF11만 처리한 실험구, activinA only 또는 GDF11 only)와 음성대조구(negative control, activinA 또는 GDF11를 처리하지 않은 실험구, No activinA 또는 No GDF11)의 수치를 이용하여 아래와 같은 식을 이용하여 항activinA 또는 항GDF11 활성을 %로 나타내었다. activinA 또는 GDF11 저해활성 (%) = (0.5 nM activinA 또는 1 nM GDF11만 처리한 실험구의 발광수치 - 미국 풍나무 열매 추출물 처리구의 발광수치) x 100 / (0.5 nM activinA 또는 1 nM GDF11만 처리한 실험구의 발광수치 - 0.5 nM activinA 또는 1 nM GDF11를 처리하지 않은 실험구의 발광수치)Specifically, the inhibitory activity of ActivinA and GDF11 belonging to a superfamily such as myostatin was measured with respect to the American fruit extract. Hek293 cells were seeded with 2.0×10 4 cells per well in a 96 well plate in DMEM medium (10% FBS, 1% penicillin/streptomycine, 1% geneticine) and cultured in a 5% CO 2 incubator. After 24 hours, the medium was replaced with DMEM with FBS removed, and the ActivinA-treated group treated ActivinA with 0.5 nM, the GDF11-treated group treated GDF11 with 1 nM per well, and each treated group was subjected to hot water of American wind fruit The extract (LSWE) was treated by concentration and cultured in a CO 2 incubator. After 24 hours, the medium was removed and treated with 65 ul of DMEM medium and 65 ul of reagent (Bright-Glo luciferase assay system, USA) to measure luminescence in a micro plate luminometer. The measured values were expressed in% of antimyostatin activity using the values of the positive control and the negative control. Measured values are those of the positive control (activinA or GDF11-only treatment, activinA only or GDF11 only) and negative control (negative control, activinA or GDF11-free treatment, No activinA or No GDF11). The anti-activinA or anti-GDF11 activity was expressed in% using the following formula. activinA or GDF11 inhibitory activity (%) = (luminescence value of the experimental group treated with 0.5 nM activinA or 1 nM GDF11 only-luminescence value of the American windberry extract treated group) x 100 / (0.5 nM activinA or 1 nM GDF11 only experiment Emission value of sphere-0.5 nM activinA or 1 nM GDF11-treated luminescence value)
그 결과, 0.5 nM ActivinA에 대한 미국 풍나무 열수 추출물의 신호전달억제는 미국 풍나무 열수 추출이 1000 ug/ml일 때 약 60% 억제되었으며, 100 ug/ml 일때는 20% 억제가 되었고, 10 ug/ml일 때 억제가 전혀 일어나지 않았다. 이러한 결과로부터 y=11.654ln(x)-25.091의 추세선 공식을 얻었고, 0.5 nM의 activinA에 대한 IC50 value가 628.52 ug/ml인 것을 확인하였다(도 3B).As a result, the signaling inhibition of the American wind tree hot water extract against 0.5 nM ActivinA was suppressed by about 60% when the American wind tree hot water extract was 1000 ug/ml, and 20% when it was 100 ug/ml, and 10 ug No inhibition occurred at /ml. From these results, a trend line formula of y=11.654ln(x)-25.091 was obtained, and it was confirmed that the IC50 value for activinA of 0.5 nM was 628.52 ug/ml (FIG. 3B).
또한, 1.0 nM GDF11에 대한 미국 풍나무 열수 추출물의 신호전달억제는 미국 풍나무 열수 추출물 10 ug/ml일 때 약 96% 억제 되었으며, 1.0 ug/ml일 때는 20% 억제가 되었다. 이러한 결과로부터 y = 8.7544x + 8.8995의 추세선 공식을 얻었고, 1 nM의 GDF11에 대한 IC50 value가 4.69 ug/ml인 것을 확인하였다. 이러한 결과를 종합할 때, 미국 풍나무 열수 추출물은 마이오스타틴에 대한 특이성이 IC50 값을 기준으로 했을 때, activinA보다 1.32 배, GDF11보다 176.54 배 더 높은 것으로 확인하였다(도 3C).In addition, the signaling inhibition of the American windwood hot water extract against 1.0 nM GDF11 was suppressed by 96% when the US windwood hot water extract was 10 ug/ml, and 20% when it was 1.0 ug/ml. From these results, a trend line formula of y = 8.7544x + 8.8995 was obtained, and it was confirmed that the IC50 value for GDF11 of 1 nM was 4.69 ug/ml. When synthesizing these results, it was confirmed that the U.S. wind tree hot water extract has a specificity for myostatin that is 1.32 times higher than activinA and 176.54 times higher than GDF11 (FIG. 3C).
<실시예 5> 미국 풍나무 열매 추출물의 마이오스타틴 신호 전달 분석<Example 5> Myostatin signal transduction analysis of American wind tree fruit extract
미국 풍나무 열매 열수 추출물(LSWE)이 마이오스타틴 신호전달 경로에 미치는 영향을 확인해 보기 위해 western blot을 통해 smad 2 전사인자의 인산화 정도를 확인하였다.The degree of phosphorylation of the smad 2 transcription factor was confirmed by western blot to confirm the effect of the American wind tree fruit extract (LSWE) on the myostatin signaling pathway.
구체적으로, smad 전사인자는 마이오스타틴이 속하는 TGF-β 수용체의 신호 유도의 리셉터로서, 세포의 성장과 분열에 중요한 역할을 수행한다. Western blot은 위해 HepG2 세포는 DMEM 배지 (10% FBS, 1% penicillin/streptomycine)에서 6 well plater에 well 당 2.0×105 cell로 seeding 하여 5% CO2 배양기에서 배양하였다. 24시간 후, 배지는 FBS가 제거된 DMEM으로 교체하였고, 4시간 뒤 10 nM의 재조합 마이오스타틴과 IC100(105 ug/ml)과 IC10(7 ug/ml) 농도의 미국 풍나무 열매 열수 추출물(LSWE)를 30분간 처리하였다. Specifically, the smad transcription factor is a receptor for signal induction of the TGF-β receptor to which myostatin belongs, and plays an important role in cell growth and division. For Western blot, HepG2 cells were seeded at 2.0×10 5 cells per well in a 6 well plater in DMEM medium (10% FBS, 1% penicillin/streptomycine) and cultured in a 5% CO 2 incubator. After 24 hours, the medium was replaced with DMEM from which FBS was removed, and after 4 hours, 10 nM of recombinant myostatin and IC100 (105 ug/ml) and IC10 (7 ug/ml) concentrations of American windberry fruit hot water extract ( LSWE) for 30 minutes.
세포는 PBS buffer로 2회 세척 후, RIPA buffer (20 mM tris-HCl, pH7.5, 150 mM NaCl, 1 mM Na2EDTA, 1 mM EGTA, 1% NP-40, 1% sodium deoxychloate, 2.5 mM sodium pyrophosphate, 1 mM β-glycerophosphate, 1 mM NA3VO4, 1 ug/ml leupeptin, cell signaling, USA)와 protease inhibitor cocktail, phosphatase inhibitor cocktail (Roche, USA)을 처리하여 세포를 얻었다.After washing the cells twice with PBS buffer, RIPA buffer (20 mM tris-HCl, pH 7.5, 150 mM NaCl, 1 mM Na2EDTA, 1 mM EGTA, 1% NP-40, 1% sodium deoxychloate, 2.5 mM sodium pyrophosphate , 1 mM β-glycerophosphate, 1 mM NA3VO4, 1 ug/ml leupeptin, cell signaling, USA), protease inhibitor cocktail, and phosphatase inhibitor cocktail (Roche, USA) to obtain cells.
세포는 sonicator를 이용하여 파쇄하였으며 4℃, 12,000 rpm에서 20분간 원심분리 하였다. 상등액은 BCA assay를 통해 단백질 정량을 하였고, 10% polyacrylamide gel에 전기영동하였다. 전기영동 후 PVDF membrane에 transfer 하였고 5% BSA 또는 5% skim milk를 이용하여 상온에서 2시간 동안 blocking 하였다. Membrane은 TBS-T buffer를 이용하여 상온에서 10분간 3회 washing 하였고 1차 항체 (Samd2, P-Smad2, Cell signaling, USA)를 상온에서 2시간 동안 반응하였다. 이후 TBS-T buffer을 이용하여 상온에서 10분간 3회 washing 하였고 2차 항체 (anti-Rabbit IgG (Cell signaling, USA))를 상온에서 2시간 동안 반응하였다. Membrane은 TBS-T buffer를 이용하여 상온에서 10분간 3회 washing 하였고 SuperSignal West Femto Maximum Sensitivity Substrate (Thermo Scientific, USA)를 이용하여 x-ray 필름에 감광하였다. Cells were crushed using a sonicator and centrifuged at 4°C and 12,000 rpm for 20 minutes. The supernatant was quantified by BCA assay and electrophoresed on 10% polyacrylamide gel. After electrophoresis, it was transferred to the PVDF membrane and blocked at room temperature for 2 hours using 5% BSA or 5% skim milk. Membrane was washed three times for 10 minutes at room temperature using TBS-T buffer, and the primary antibody (Samd2, P-Smad2, Cell signaling, USA) was reacted at room temperature for 2 hours. Thereafter, washing was performed three times for 10 minutes at room temperature using TBS-T buffer, and a secondary antibody (a nt i-Rabbit IgG (Cell signaling, USA)) was reacted at room temperature for 2 hours. Membrane was washed three times for 10 minutes at room temperature using TBS-T buffer, and was exposed to x-ray film using SuperSignal West Femto Maximum Sensitivity Substrate (Thermo Scientific, USA).
그 결과, Western blot을 통해서 미국 풍나무 열매 열수 추출물(LSWE)이 농도의존적으로 마이오스타틴 신호 전달을 방해함으로써 세포 안쪽으로 진행되는 신호 (Smad 전사인자의 인산화)를 저해하는 것을 확인하였다. 마이오스타틴 (10 nM), SB431542 (마이오스타틴이 결합하는 수용체의 인산화를 억제하는 small molecule) 및 미국 풍나무 열매 열수 추출물(LSWE)을 단독 또는 혼합하여 Smad2의 인산화를 확인하였다. 마이오스타틴, SB431542 및 미국 풍나무 열매 열수 추출물(LSWE) 모두를 세포에 처리하지 않은 경우에는 마이오스타틴의 신호가 수용체에 전달이 되지 않으므로 Smad2의 인산화가 전혀 일어나지 않았다. 마이오스타틴만 처리한 세포의 경우 마이오스타틴의 신호가 세포내로 전달되어 Smad2의 인산화가 일어났다. 마이오스타틴과 SB431542을 처리한 세포의 경우 SB431542가 마이오스타틴의 신호를 세포내로 전달하는 것을 막음으로써 Smad2의 인산화가 일어나지 않았다. 마이오스타틴과 미국 풍나무 열매 열수 추출물(LSWE) (IC100(105 ug/ml), IC10(7 ug/ml))을 처리한 세포의 경우 미국 풍나무 열매 열수 추출물(LSWE)이 마이오스타틴의 신호를 세포내로 전달하는 것을 막음으로써 Smad2의 인산화가 농도의존적으로 일어나지 않았다(도 3D). 그러므로 세포내에서 미국 풍나무 열수 추출물이 마이오스타틴의 신호전달을 억제하여 Smad2의 인산화를 방해하고 그 결과 핵 내로 신호 전달을 억제하는 것을 확인하였다.As a result, it was confirmed through Western blot that the American Plum fruit hydrothermal extract (LSWE) inhibited the myostatin signal transmission in a concentration-dependent manner, thereby inhibiting the signal that progresses inside the cell (phosphorylation of the Smad transcription factor). Myostatin (10 nM), SB431542 (a small molecule that inhibits the phosphorylation of the myostatin-binding receptor) and the American Plum fruit hydrothermal extract (LSWE) alone or mixed to confirm phosphorylation of Smad2. When neither myostatin, SB431542, nor American plum tree hydrothermal extract (LSWE) were treated with cells, phosphorylation of Smad2 did not occur at all because the myostatin signal was not transmitted to the receptor. In the case of cells treated with only myostatin, the signal of myostatin was transmitted into the cell, and phosphorylation of Smad2 occurred. In the case of cells treated with myostatin and SB431542, phosphorylation of Smad2 did not occur by preventing SB431542 from transmitting the signal of myostatin into the cell. For cells treated with Myostatin and American Plum Fruit Hot Water Extract (LSWE) (IC100 (105 ug/ml), IC10 (7 ug/ml)), the American Plum Fruit Hot Water Extract (LSWE) contains Phosphorylation of Smad2 did not occur in a concentration-dependent manner by preventing the signal from being transmitted into the cell (FIG. 3D). Therefore, it was confirmed that the American Plum tree hydrothermal extract inhibits myostatin signaling and thus inhibits Smad2 phosphorylation and, as a result, inhibits signal transmission into the nucleus.
<실시예 6> 동물모델에서 미국 풍나무 열매 추출물의 근육에 미치는 영향 분석<Example 6> Analysis of the effect on the muscle of the American wind tree fruit extract in animal models
In vivo 수준에서 미국 풍나무 열매 열수 추출물(LSWE)이 근육에 미치는 영향을 확인해보기 위해 ICR 마우스에 경구투여 하여 근력의 변화를 확인하였다.In order to confirm the effect of the American Plum tree hydrothermal extract (LSWE) on muscle at the in vivo level, changes in muscle strength were confirmed by oral administration to ICR mice.
구체적으로, 실험에 사용된 마우스는 4주령 된 수컷 ICR 마우스로서 14일 동안 1회/1일 경구투여 하였다. 주사량은 luciferase assay 실험을 통해 확인한 1 nM의 마이오스타틴에 대한 IC50 값에 15배를 1회 경구투여하였다. 0, 7, 14일에 체중과 근력테스트, 근지구력 테스트를 진행하였으며, 실험이 마친 후 앞다리와 뒷다리 근육의 무게와 부피를 측정함으로서 근밀도를 계산하였다.Specifically, the mice used in the experiment were 4 weeks old male ICR mice orally administered once/day for 14 days. The injection amount was orally administered 15 times once to the IC50 value for 1 nM myostatin confirmed through the luciferase assay experiment. On
또한, 혈액을 채취하여 혈액으로부터 분리된 혈청을 이용하여 중성지방, 글루코즈 및 LDH activity, 측정하였다. 중성지방, 글루코즈는 Lipidocare (SD biosense, Korea)장비를 이용하여 측정하였고, LDH activity, Biovision kit (Biovision, USA)을 이용하여 함량을 측정하였다. In addition, triglycerides, glucose and LDH activity were measured using serum separated from blood by collecting blood. Triglyceride and glucose were measured using Lipidocare (SD biosense, Korea) equipment, and LDH activity and Biovision kit (Biovision, USA) were used to measure the content.
그 결과, 미국 풍나무 열매 열수 추출물(LSWE)의 14일간 경구투여를 통해 마우스 체중은 대조군에 비해 유의적인 차이를 나타내지 않았다(도 4A). As a result, the mouse body weight was not significantly different from that of the control group through oral administration of the American wind tree fruit extract (LSWE) for 14 days (FIG. 4A ).
하지만 근력은 14일에 대조군에 비해 6.5% 유의적으로 증가하였다 (p<0.001)(도 4B). However, muscle strength was significantly increased by 6.5% compared to the control group on the 14th day (p<0.001) (FIG. 4B ).
14일의 경구투여 후 앞다리와 뒷다리의 질량과 부피결과를 바탕으로 계산한 근밀도는 뒷다리의 경우 대조군에 비해 11.4% 유의적으로 증가하였고(p<0.05), 앞다리는 대조군에 유의적인 차이를 나타내지 않았다(도 4C). After 14 days of oral administration, muscle density calculated on the basis of mass and volume results of the forelimbs and hind legs increased 11.4% significantly compared to the control group in the hind legs (p<0.05), and the forelimbs did not show a significant difference in the control group. Did (Figure 4C).
또한, 대조군에 비해 미국 풍나무 열매 열수 추출물(LSWE)을 처리한 동물 모델의 중성지방은 37% 유의적으로 감소하였고(p<0.01)(도 5A), 글루코즈 함량은 대조군에 비해 16.8% 유의적으로 감소하였다(p<0.05)(도 5B). 근육의 피로도에 대한 지표인 LDH activity는 대조군에 비해 23.6% 유의적으로 증가하였다(p<0.05)(도 5C).In addition, compared to the control group, triglyceride was significantly reduced (p<0.01) in the animal model treated with the American wind fruit extract (LSWE) (p<0.01) (FIG. 5A ), and the glucose content was 16.8% significant compared to the control group. Decreased to (p<0.05) (FIG. 5B). LDH activity, an index for muscle fatigue, was significantly increased by 23.6% compared to the control group (p<0.05) (FIG. 5C ).
<실시예 7> 추출용매에 따른 미국 풍나무 열매 추출물의 항마이오스타틴 활성 분석<Example 7> Analysis of antimyostatin activity of American windberry extract according to the extraction solvent
추출용매에 따른 미국 풍나무 열매 추출물의 항마이오스타틴의 활성을 확인하기 위하여 발광 효소 분석(luciferase assay) 시스템을 통해 확인하였다. In order to confirm the activity of antimyostatin of the American Plum tree extract according to the extraction solvent, it was confirmed through a luciferase assay system.
구체적으로, Hek293 세포는 DMEM 배지 (10% FBS, 1% penicillin/streptomycine, 1% geneticine)에서 96 well plate에 well 당 2.0×104 cell로 seeding 하여 5% CO2 배양기에서 배양하였다. 24시간 후, 배지는 FBS가 제거된 DMEM으로 교체하였고, 1 nM의 재조합 마이오스타틴 (R&D system, USA)과 미국 풍나무 열매 열수 추출물(LSWE)과 미국 풍나무 열매 에탄올 추출물(LSEE)을 농도별로 처리하여 CO2 배양기에서 배양하였다. 24시간 뒤 배지를 제거하고 65 ul의 DMEM 배지와 65 ul의 reagent (Bright-Glo luciferase assay system, USA)를 처리하여 micro plate luminometer에서 발광을 측정하였다. 측정된 수치는 양성대조구(positive control)와 음성대조구(negative control)의 수치를 이용하여 항마이오스타틴 활성을 %로 나타내었다. 측정된 수치는 양성대조구(positive control, 마이오스타틴만 처리한 실험구, MSTN only)와 음성대조구(negative control, 마이오스타틴을 처리하지 않은 실험구, No MSTN)의 수치를 이용하여 아래와 같은 식을 이용하여 항마이오스타틴 활성을 %로 나타내었다. 마이오스타틴 저해활성 (%) = (1 nM 마이오스타틴만 처리한 실험구의 발광수치 - 미국 풍나무 열매 추출물 처리구(열수/에탄올)의 발광수치) x 100 / (1 nM 마이오스타틴만 처리한 실험구의 발광수치 - 마이오스타틴을 처리하지 않은 실험구의 발광수치)Specifically, Hek293 cells were seeded with 2.0×10 4 cells per well in a 96 well plate in DMEM medium (10% FBS, 1% penicillin/streptomycine, 1% geneticine) and cultured in a 5% CO 2 incubator. After 24 hours, the medium was replaced with DMEM from which FBS was removed, and the concentration of 1 nM of recombinant myostatin (R&D system, USA), American Plum fruit hot water extract (LSWE), and American Plum fruit ethanol extract (LSEE) was concentrated. Treated separately and cultured in a CO 2 incubator. After 24 hours, the medium was removed and treated with 65 ul of DMEM medium and 65 ul of reagent (Bright-Glo luciferase assay system, USA) to measure luminescence in a micro plate luminometer. The measured values were expressed in% of antimyostatin activity using the values of the positive control and the negative control. The measured values are as follows using the values of the positive control (test group treated with myostatin only, MSTN only) and the negative control (test group not treated with myostatin, no MSTN). The antimyostatin activity was expressed in% using. Myostatin inhibitory activity (%) = (Emission value of experimental group treated with 1 nM myostatin only-Luminous value of American windberry extract treatment group (hot water/ethanol)) x 100 / (Only treated with 1 nM myostatin Luminescence value of experimental group-Luminescence value of experimental group without myostatin treatment)
그 결과, 마이오스타틴에 대한 활성 저해 효과는 미국산 풍나무 열매 열수 추출물(LSWE)은 1 nM의 마이오스타틴에 대한 IC 50 value는 3.56 ug/ml이였고(도 6A), 미국산 풍나무 열매 에탄올 추출물(LSWE)은 IC 50 value는 0.33 ug/ml인 것을 확인하였다(도 6B).As a result, the activity inhibitory effect on myostatin was that the American windwood fruit hydrothermal extract (LSWE) had an
본 발명이 속하는 기술 분야에서 통상의 지식을 가진 자는 본 발명이 본 발명의 본질적인 특성에서 벗어나지 않는 범위에서 변형된 형태로 구현될 수 있음을 이해할 수 있을 것이다. 그러므로 개시된 실시예들은 한정적인 관점이 아니라 설명적인 관점에서 고려되어야 한다. 본 발명의 범위는 전술한 설명이 아니라 특허청구범위에 나타나 있으며, 그와 동등한 범위 내에 있는 모든 차이점은 본 발명에 포함된 것으로 해석되어야 할 것이다.Those skilled in the art to which the present invention pertains will understand that the present invention may be implemented in a modified form without departing from the essential characteristics of the present invention. Therefore, the disclosed embodiments should be considered in terms of explanation, not limitation. The scope of the present invention is shown in the claims rather than the foregoing description, and all differences within the equivalent range should be interpreted as being included in the present invention.
Claims (17)
상기 조성물은 근력 및 근밀도를 향상시키는 것인, 약학 조성물.According to claim 1,
The composition is to improve muscle strength and muscle density, pharmaceutical composition.
상기 조성물은 근육량 증가 효과를 가지는 것인, 약학 조성물.According to claim 1,
The composition is to have an effect of increasing muscle mass, pharmaceutical composition.
상기 추출물은 열수 추출물 또는 에탄올 추출물인 것인, 약학 조성물.According to claim 1,
The extract is a hydrothermal extract or ethanol extract, pharmaceutical composition.
상기 근감소증은 근위축증, 근무력증, 근이영양증, 근경직증, 근육퇴행위축, 근위축성 측삭경화증 또는 중증 근무력증인 것인, 약학 조성물.According to claim 1,
The muscular dystrophy is muscular dystrophy, myasthenia gravis, muscular dystrophy, muscular spasm, muscular atrophy, amyotrophic lateral sclerosis or myasthenia gravis.
상기 추출물은 열수 추출물 또는 에탄올 추출물인 것인, 사료 첨가제.The method of claim 16,
The extract is a hot water extract or ethanol extract, feed additives.
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| US20150110862A1 (en) * | 2007-05-21 | 2015-04-23 | Board Of Supervisors Of Louisiana State University And Agricultural And Mechanical College | Sweet Gum Fruit Extract as a Therapeutic Agent |
| CN104644737A (en) | 2013-11-25 | 2015-05-27 | 青岛盛嘉信息科技有限公司 | Foot bath traditional Chinese medicinal composition for fatigue relieving, muscle and tendon relaxing and blood circulation stimulating |
| CN104740073A (en) * | 2013-12-26 | 2015-07-01 | 吴旭 | Drug for treating muscular atrophy |
| CN107184642A (en) | 2017-06-20 | 2017-09-22 | 合肥丰瑞隆生物科技有限公司 | Treat orthopedics plaster of lumbar muscle strain and preparation method thereof |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| US20150110862A1 (en) * | 2007-05-21 | 2015-04-23 | Board Of Supervisors Of Louisiana State University And Agricultural And Mechanical College | Sweet Gum Fruit Extract as a Therapeutic Agent |
| CN104644737A (en) | 2013-11-25 | 2015-05-27 | 青岛盛嘉信息科技有限公司 | Foot bath traditional Chinese medicinal composition for fatigue relieving, muscle and tendon relaxing and blood circulation stimulating |
| CN104740073A (en) * | 2013-12-26 | 2015-07-01 | 吴旭 | Drug for treating muscular atrophy |
| CN107184642A (en) | 2017-06-20 | 2017-09-22 | 合肥丰瑞隆生物科技有限公司 | Treat orthopedics plaster of lumbar muscle strain and preparation method thereof |
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