KR20230124846A - Composition for preventing, treating or improving obesity or fatty liver comprising extract of Celosia cristata flower as an active ingredient - Google Patents
Composition for preventing, treating or improving obesity or fatty liver comprising extract of Celosia cristata flower as an active ingredient Download PDFInfo
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- KR20230124846A KR20230124846A KR1020230019436A KR20230019436A KR20230124846A KR 20230124846 A KR20230124846 A KR 20230124846A KR 1020230019436 A KR1020230019436 A KR 1020230019436A KR 20230019436 A KR20230019436 A KR 20230019436A KR 20230124846 A KR20230124846 A KR 20230124846A
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- 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
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
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- A—HUMAN NECESSITIES
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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
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Abstract
본 발명은 맨드라미(Celosia cristata) 꽃 추출물을 유효성분으로 포함하는 비만 예방, 치료 또는 개선용 조성물에 관한 것으로, 맨드라미 꽃 추출물이 지방 세포에서 지방 생성 억제, 중성지방 합성 억제 및 중성지방 분해 촉진; 지방세포 분화 및 에너지대사 관련 전사인자의 발현 억제; 간 조직 내 지방공포(lipid vacuole)의 수 및 지방세포 크기 감소; 및 혈중 간기능 지표물질 및 혈중지질농도 지표물질 조절 효과를 나타내는 것을 확인함으로써, 비만 또는 지방간 예방, 치료 또는 개선용 조성물로서 유용하게 활용될 수 있다.The present invention is cockscomb ( Celosia cristata ) relates to a composition for preventing, treating or improving obesity comprising a flower extract as an active ingredient, wherein the cockscomb flower extract inhibits lipogenesis in fat cells, inhibits neutral fat synthesis and promotes neutral fat decomposition; inhibition of expression of transcription factors related to adipocyte differentiation and energy metabolism; reduction in the number of lipid vacuoles and size of adipocytes in liver tissue; And it can be usefully used as a composition for preventing, treating or improving obesity or fatty liver by confirming that the blood liver function indicator and blood lipid concentration indicator exhibit a regulatory effect.
Description
본 발명은 맨드라미(Celosia cristata) 꽃 추출물을 유효성분으로 포함하는 비만 또는 지방간 예방, 치료 또는 개선용 조성물에 관한 것이다.The present invention is cockscomb ( Celosia cristata ) relates to a composition for preventing, treating or improving obesity or fatty liver comprising a flower extract as an active ingredient.
비만은 최근 생활수준의 향상으로 위생환경이 개선되고 식생활이 서구화하여 평균 수명이 연장되면서, 질병의 양상 또한 선진국형으로 급격히 변화되고 있는 양상 중에 가장 대표적인 질환이다. 따라서, 성인병이 오늘날 가장 큰 의학적 과제로 등장하게 되었으며 이러한 성인병의 주요한 원인이 되고 있는 비만도 급격하게 증가되고 있는 상황이다. Obesity is the most representative disease among the aspects of the disease that is rapidly changing to the type of advanced countries as the sanitary environment is improved due to the recent improvement in living standards and the average life span is extended due to westernization of dietary life. Therefore, adult diseases have emerged as the biggest medical challenge today, and obesity, which is a major cause of these adult diseases, is also rapidly increasing.
비만은 소모하는 열량에 비해 과다한 열량을 섭취함으로써 여분의 열량이 체내에 지방의 형태로 축적되는 현상을 말한다. 남자는 체지방이 체중의 25％, 여자는 체중의 30％ 이상일 때 비만으로 보며, 임상적으로는 BMI(Body Mass Index: 체질량지수)가 25.0 내지 30.0이면 과체중으로 정의하고, 30.0 이상인 경우를 비만으로 정의한다. 비만은 유전적 영향, 서구화되는 식생활에 의한 환경적인 영향, 스트레스에 의한 심리적인 영향 등 다양한 원인에 의해 유발되는 것으로 알려져 있으나, 아직 그 정확한 원인이나 기작에 관해서는 명확히 정립된 바가 없는 상황이다. Obesity refers to a phenomenon in which excess calories are stored in the body in the form of fat due to intake of excessive calories compared to calories consumed. Men are considered obese when body fat is more than 25% of their body weight, and women are considered obese when their body fat is more than 30% of their body weight. define. Obesity is known to be caused by various causes, such as genetic influences, environmental influences due to westernized dietary habits, and psychological effects due to stress, but the exact cause or mechanism has not yet been clearly established.
비만 치료제는 일반적으로 3가지의 범주 즉 식욕 억제제, 체내 에너지대사 촉진제 및 소화 흡수 억제제로 구분된다. 식욕을 억제하는 약리 기전을 이용하는 대표적인 비만 치료제로서는 리덕틸(Reductil™, 애보트사, 미국)을 들 수 있고, 체내 에너지를 촉진하는 약리 기전을 이용하는 대표적인 비만 치료제로서는 엑소리제(Exorise™,아코 파마사, 프랑스)를 들 수 있으며, 지방의 소화 흡수를 억제하는 약리기전을 이용하는 대표적인 비만 치료제로서는 제니칼(Xenical™, 로슈제약회사, 스위스)을 들 수 있다.Anti-obesity drugs are generally divided into three categories: appetite suppressants, energy metabolism promoters and digestion and absorption inhibitors. A typical obesity treatment using a pharmacological mechanism to suppress appetite is Reductil™ (Abbott, USA), and a representative obesity treatment using a pharmacological mechanism to promote energy in the body is Exorise™ (Ako Pharma, Inc.) France), and a representative anti-obesity drug using a pharmacological mechanism that inhibits digestion and absorption of fat is Xenical™ (Roche Pharmaceuticals, Switzerland).
비만이 발생하여 그 상태가 지속되면 고혈압, 혈중 콜레스테롤 상승, 신장 질환, 뇌졸증, 동맥경화증, 지방간, 관절염, 암, 수면무호흡증, 당뇨병 등 여러 질환의 원인으로도 작용할 수 있기 때문에, 전 세계적으로 비만 치료에 많은 관심이 모아지고 있는 실정이다.If obesity occurs and persists, it can also act as a cause of various diseases such as high blood pressure, elevated blood cholesterol, kidney disease, stroke, arteriosclerosis, fatty liver, arthritis, cancer, sleep apnea, diabetes, etc. is currently receiving a lot of attention.
한편, 맨드라미(Celosia cristata L.)는 쌍떡잎식물 중심자목 비름과(Amaranthaceae)에 속하는 1년생 한해살이풀이며 관상용으로 재배되어 왔으나, 한방에서는 맨드라미 꽃을 "계관화"라 하여 전통 약제로 사용되어 왔다. 줄기와 잎은 치질, 이질, 토혈, 코피, 혈붕, 두드러기 등을 치료하고, 종자는 양혈과 지혈의 효능, 혈변, 이질, 간장병, 눈병 등을 치료하는 효능이 알려져 있다. 특히, 꽃은 양혈과 지혈의 효능, 치루로 인한 하혈, 이질, 토혈, 객혈, 혈림 등을 치료하는 효능이 알려져 있다.On the other hand, cockscomb ( Celosia cristata L.) is an annual herb belonging to the dicotyledonous plant Amaranthaceae and has been cultivated for ornamental purposes. Stems and leaves are known to treat hemorrhoids, dysentery, hematemesis, nosebleeds, hemorrhoids, hives, etc., and seeds are known to have hemorrhagic and hemostasis effects, bloody stools, dysentery, liver diseases, and eye diseases. In particular, the flower is known for its efficacy in excreting blood and hemostasis, and in treating hemorrhage, dysentery, hematemesis, hemoptysis, hemorrhoids, etc. caused by perianal fistula.
맨드라미의 유효성분으로는 베타시아닌(beta-cyanin), 켐페리트린(kaempferitrin), 아마란틴(amaranthin), 피니톨(pinitol) 등이 알려져 있으며, 많은 양의 질산칼륨과 이미 알려진 5개의 플라보노이드(flavonoid)와 새로운 이소플라본(isoflavone)인 크리스타테인(cristatein; 5-hydroxy-6-hydroxy-methyl-7, 2'-demethoxyisoflavone)과 식물계에 널리 존재하는 페놀류(phenolic)가 함유되어 다양한 약리적, 생물학적인 활성과 항산화 작용을 하는 것으로 알려져 있다.Beta-cyanin, kaempferitrin, amaranthin, and pinitol are known as active ingredients of cockscomb, and a large amount of potassium nitrate and five known flavonoids ( flavonoid), cristatein (5-hydroxy-6-hydroxy-methyl-7, 2'-demethoxyisoflavone), a new isoflavone, and phenolic, which are widely present in plants, have various pharmacological and biological effects. It is known to have activity and antioxidant activity.
본 발명의 목적은 맨드라미(Celosia cristata) 꽃 추출물을 유효성분으로 포함하는 비만 또는 지방간 예방, 치료 또는 개선용 조성물을 제공하는 것이다.An object of the present invention is cockscomb ( Celosia cristata ) To provide a composition for preventing, treating or improving obesity or fatty liver comprising a flower extract as an active ingredient.
상기 목적을 달성하기 위해, 본 발명은 맨드라미(Celosia cristata) 꽃 추출물을 유효성분으로 포함하는 비만 예방 또는 치료용 약학 조성물을 제공한다.In order to achieve the above object, the present invention is cockscomb ( Celosia cristata ) It provides a pharmaceutical composition for preventing or treating obesity comprising a flower extract as an active ingredient.
또한, 본 발명은 맨드라미(Celosia cristata) 꽃 추출물을 유효성분으로 포함하는 비만 예방 또는 개선용 건강기능식품 조성물을 제공한다.In addition, the present invention is cockscomb ( Celosia cristata ) It provides a health functional food composition for preventing or improving obesity containing a flower extract as an active ingredient.
또한, 본 발명은 맨드라미(Celosia cristata) 꽃 추출물을 유효성분으로 포함하는 지방간 예방 또는 치료용 약학 조성물을 제공한다.In addition, the present invention is cockscomb ( Celosia cristata ) It provides a pharmaceutical composition for preventing or treating fatty liver comprising a flower extract as an active ingredient.
또한, 본 발명은 맨드라미(Celosia cristata) 꽃 추출물을 유효성분으로 포함하는 지방간 예방 또는 개선용 건강기능식품 조성물을 제공한다.In addition, the present invention is cockscomb ( Celosia cristata ) It provides a health functional food composition for preventing or improving fatty liver containing a flower extract as an active ingredient.
본 발명에 따르면, 맨드라미(Celosia cristata) 꽃 추출물이 지방 세포에서 지방 생성 억제, 중성지방 합성 억제 및 중성지방 분해 촉진; 지방세포 분화 및 에너지대사 관련 전사인자의 발현 억제; 간 조직 내 지방공포(lipid vacuole)의 수 및 지방세포 크기 감소; 및 혈중 간기능 지표물질 및 혈중지질농도 지표물질 조절 효과를 나타내는 것을 확인함으로써, 비만 또는 지방간 예방, 치료 또는 개선용 조성물로서 유용하게 활용될 수 있다.According to the present invention, cockscomb ( Celosia cristata ) flower extract inhibits adipogenesis, inhibits triglyceride synthesis and promotes triglyceride decomposition in adipocytes; inhibition of expression of transcription factors related to adipocyte differentiation and energy metabolism; reduction in the number of lipid vacuoles and size of adipocytes in liver tissue; And it can be usefully used as a composition for preventing, treating or improving obesity or fatty liver by confirming that the liver function indicators and blood lipid concentration indicators have a regulatory effect.
도 1은 맨드라미 꽃 추출물의 마우스 지방전구세포인 3T3-L1 세포에서 농도별 지방생성 억제 효과를 분석한 결과이다.
도 2는 맨드라미 꽃 추출물의 마우스 지방전구세포인 3T3-L1 세포에서 농도별 지방생성 억제 효과를 백분율로 나타낸 도면이다.
도 3은 맨드라미 꽃 추출물의 마우스 지방전구세포인 3T3-L1 세포에서 농도별 중성지방인 트리글리세라이드 생성 억제 효과를 분석한 결과이다.
도 4는 맨드라미 꽃 추출물의 마우스 지방전구세포인 3T3-L1 세포에서 농도별 지방세포 분화 관련 전사인자(PPARγ, C/EBPα, FABP4)와 에너지대사 관련 전사인자(Adipoq)의 유전자 발현 억제 효과를 분석한 결과이다.
도 5는 맨드라미 꽃 추출물의 마우스 지방전구세포인 3T3-L1 세포에서 세포독성을 분석한 결과이다.
도 6은 맨드라미 꽃 추출물의 지방세포의 중성지방 분해효과를 분석한 결과이다.
도 7은 고지방식 비만 마우스 동물모델에서 맨드라미 꽃 추출물의 체중 감소 효과를 분석한 결과이다.
도 8은 고지방식 비만 마우스 동물모델에서 맨드라미 꽃 추출물의 체지방량 감소 효과를 분석한 결과이다.
도 9는 고지방식 비만 마우스 동물모델에서 맨드라미 꽃 추출물의 대사능 개선 효과를 분석한 결과이다.
도 10은 고지방식 비만 마우스 동물모델에서 맨드라미 꽃 추출물의 지방간 및 지방조직 크기 감소 효과를 분석한 결과이다.
도 11은 고지방식 비만 마우스 동물모델에서 맨드라미 꽃 추출물의 혈중 간기능지표 및 지질 농도 개선 효과를 분석한 결과이다.
도 12는 고지방식 비만 마우스 동물모델에서 맨드라미 꽃 추출물의 당 대사 기능 개선 효과를 분석한 결과이다.
도 13은 고지방식 비만 마우스 동물모델에서 맨드라미 꽃 추출물의 지방세포 분화 관련 전사인자의 발현억제 효과를 분석한 결과이다.
도 14는 고지방식 비만 마우스 동물모델에서 맨드라미 꽃 추출물의 체중 감소 효과를 분석한 결과이다.
도 15는 고지방식 비만 마우스 동물모델에서 맨드라미 꽃 추출물의 지방세포 분화 관련 전사인자의 발현억제 효과를 분석한 결과이다.1 is a result of analyzing the adipogenesis inhibitory effect of cockscomb flower extract by concentration in 3T3-L1 cells, which are mouse preadipocytes.
Figure 2 is a view showing the adipogenesis inhibitory effect by concentration in 3T3-L1 cells, which are mouse preadipocytes, of cockscomb flower extract as a percentage.
3 is a result of analyzing the inhibitory effect of triglyceride production, which is a neutral fat, by concentration in 3T3-L1 cells, which are mouse preadipocytes, of cockscomb flower extract.
Figure 4 analyzes the gene expression inhibitory effect of adipocyte differentiation-related transcription factors (PPARγ, C/EBPα, FABP4) and energy metabolism-related transcription factors (Adipoq) by concentration in 3T3-L1 cells, which are mouse precursor cells of cockscomb flower extract. is a result
5 is a result of analyzing the cytotoxicity of cockscomb flower extract in 3T3-L1 cells, which are mouse preadipocytes.
Figure 6 is the result of analyzing the triglyceride decomposition effect of the adipocytes of cockscomb flower extract.
Figure 7 is a result of analyzing the weight loss effect of cockscomb flower extract in a high-fat diet obese mouse animal model.
8 is a result of analyzing the body fat reduction effect of cockscomb flower extract in a high-fat diet obese mouse animal model.
9 is a result of analyzing the metabolic function improvement effect of cockscomb flower extract in a high-fat diet obese mouse animal model.
10 is a result of analyzing the effect of reducing the size of fatty liver and adipose tissue of cockscomb flower extract in a high-fat diet obese mouse animal model.
11 is a result of analyzing the effect of improving blood liver function indicators and lipid concentrations of cockscomb flower extract in a high-fat diet obese mouse animal model.
12 is a result of analyzing the sugar metabolism function improvement effect of cockscomb flower extract in a high-fat diet obese mouse animal model.
13 is a result of analyzing the expression inhibitory effect of transcription factors related to adipocyte differentiation of cockscomb flower extract in a high-fat diet obese mouse animal model.
14 is a result of analyzing the weight loss effect of cockscomb flower extract in a high-fat diet obese mouse animal model.
15 is a result of analyzing the expression inhibitory effect of transcription factors related to adipocyte differentiation of cockscomb flower extract in a high-fat diet obese mouse animal model.
이하, 본 발명을 보다 상세하게 설명한다. Hereinafter, the present invention will be described in more detail.
본 발명은 맨드라미(Celosia cristata) 꽃 추출물을 유효성분으로 포함하는 비만 예방 또는 치료용 약학 조성물을 제공한다.The present invention is cockscomb ( Celosia cristata ) It provides a pharmaceutical composition for preventing or treating obesity comprising a flower extract as an active ingredient.
상기 추출물은 물, (C1~C4) 알코올 또는 이의 혼합 용매로 추출한 것일 수 있고, 바람직하게는 30% 에탄올로 추출한 것일 수 있다.The extract may be extracted with water, (C1-C4) alcohol, or a mixed solvent thereof, preferably with 30% ethanol.
또한, 상기 추출물은 지방세포에서 지방 생성 억제, 중성지방 합성 억제 또는 중성지방 분해 촉진 효과를 나타낼 수 있다.In addition, the extract may exhibit effects of inhibiting adipogenesis, inhibiting triglyceride synthesis, or promoting triglyceride decomposition in adipocytes.
또한, 상기 추출물은 산소 소비량, 이산화탄소 소비량, 호흡교환율(Respiratory exchange ratio) 또는 에너지 소비량(Energy expenditure)을 증가시킬 수 있다.In addition, the extract may increase oxygen consumption, carbon dioxide consumption, respiratory exchange ratio or energy expenditure.
또한, 상기 추출물은 혈중 총 콜레스테롤(total cholesterol) 또는 저밀도지질단백질(low-density lipoprotein; LDL)을 감소시키고, 고밀도지질단백질(high-density lipoprotein; HDL)을 증가시킬 수 있다.In addition, the extract can reduce blood total cholesterol (total cholesterol) or low-density lipoprotein (LDL) and increase high-density lipoprotein (HDL).
또한, 상기 추출물은 PPARγ(Peroxisome proliferator-activated receptor γ), C/EBPα(CCAAT/enhancer binding protein α), FABP4(Fatty acid binding protein 4), FASN(Fatty acid synthase) 및 아디포넥틴(Adiponectin; Adipoq)으로 이루어진 군에서 선택된 하나 이상의 발현을 억제할 수 있으나, 이에 한정되는 것은 아니다.In addition, the extract is PPARγ (Peroxisome proliferator-activated receptor γ), C / EBPα (CCAAT / enhancer binding protein α), FABP4 (Fatty acid binding protein 4), FASN (Fatty acid synthase) and adiponectin (Adipoq) It is possible to inhibit the expression of one or more selected from the group consisting of, but is not limited thereto.
본 발명의 한 구체예에서, 상기 약학 조성물은 통상적인 방법에 따라 주사제, 과립제, 산제, 정제, 환제,캡슐제, 좌제, 겔, 현탁제, 유제, 점적제 또는 액제로 이루어진 군에서 선택된 어느 하나의 제형을 사용할 수 있다. In one embodiment of the present invention, the pharmaceutical composition is any one selected from the group consisting of injections, granules, powders, tablets, pills, capsules, suppositories, gels, suspensions, emulsions, drops or liquids according to conventional methods. formulations can be used.
본 발명의 다른 구체예에서, 약학 조성물은 약학 조성물의 제조에 통상적으로 사용하는 적절한 담체, 부형제, 붕해제, 감미제, 피복제, 팽창제, 윤활제, 활택제, 향미제, 항산화제, 완충액, 정균제, 희석제, 분산제, 계면활성제, 결합제 및 윤활제로 이루어진 군에서 선택되는 하나 이상의 첨가제를 추가로 포함할 수 있다.In another embodiment of the present invention, the pharmaceutical composition is a suitable carrier, excipient, disintegrant, sweetener, coating agent, swelling agent, lubricant, lubricant, flavoring agent, antioxidant, buffer, bacteriostatic agent, One or more additives selected from the group consisting of diluents, dispersants, surfactants, binders and lubricants may be further included.
구체적으로 담체, 부형제 및 희석제는 락토즈, 덱스트로즈, 수크로스, 솔비톨, 만니톨, 자일리톨, 에리스리톨, 말티톨, 전분, 아카시아 고무, 알지네이트, 젤라틴, 칼슘 포스페이트, 칼슘 실리케이트, 셀룰로즈, 메틸 셀룰로즈, 미정질 셀룰로스, 폴리비닐 피롤리돈, 물, 메틸히드록시벤조에이트, 프로필히드록시벤조에이트, 탈크, 마그네슘 스테아레이트 및 광물유를 사용할 수 있으며, 경구투여를 위한 고형제제에는 정제, 환제, 산제, 과립제, 캡슐제 등이 포함되며, 이러한 고형제제는 상기 조성물에 적어도 하나 이상의 부형제, 예를 들면, 전분, 칼슘카보네이트, 수크로스 또는 락토오스, 젤라틴 등을 섞어 조제할 수 있다. 또한 단순한 부형제 이외에 마그네슘 스티레이트, 탈크 같은 윤활제들도 사용할 수 있다. 경구를 위한 액상제제로는 현탁제, 내용액제, 유제, 시럽제 등이 있으며 흔히 사용되는 단순 희석제인 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, 좌제 등이 포함된다. 비수성용제, 현탁제로는 프로필렌글리콜, 폴리에틸렌 글리콜, 올리브오일과 같은 식물성 기름, 에틸올레이트와 같은 주사 가능한 에스테르 등이 사용될 수 있다. 좌제의 기재로는 위텝솔(witepsol), 마크로골, 트윈(tween)61, 카카오지, 라우린지, 글리세로제라틴 등이 사용될 수 있다.Specifically, carriers, excipients and diluents are lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, gum acacia, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methyl cellulose, microcrystalline Cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate, and mineral oil may be used, and solid dosage forms for oral administration include tablets, pills, powders, granules, and capsules. These solid preparations may be prepared by mixing at least one or more excipients, for example, starch, calcium carbonate, sucrose or lactose, gelatin, etc., with the composition. In addition to simple excipients, lubricants such as magnesium stearate and talc may also be used. Liquid preparations for oral administration include suspensions, solutions for oral use, emulsions, syrups, and the like, and various excipients such as wetting agents, sweeteners, aromatics, and preservatives may be included in addition to commonly used simple diluents such as water and liquid paraffin. Preparations for parenteral administration include sterilized aqueous solutions, non-aqueous solvents, suspensions, emulsions, freeze-dried preparations, suppositories, and the like. Propylene glycol, polyethylene glycol, vegetable oils such as olive oil, and injectable esters such as ethyl oleate may be used as non-aqueous solvents and suspensions. As a base material of the suppository, witepsol, macrogol, tween 61, cacao butter, laurin paper, glycerogeratin, and the like may be used.
본 발명의 일실시예에 따르면, 상기 약학 조성물은 정맥내, 동맥내, 복강내, 근육내, 동맥내, 복강내, 흉골내, 경피, 비측내, 흡입, 국소, 직장, 경구, 안구내 또는 피내 경로를 통해 통상적인 방식으로 대상체로 투여할 수 있다.According to one embodiment of the present invention, the pharmaceutical composition is intravenous, intraarterial, intraperitoneal, intramuscular, intraarterial, intraperitoneal, intrasternal, transdermal, intranasal, inhalational, topical, rectal, oral, intraocular or It can be administered to a subject in a conventional manner via the intradermal route.
본 발명에 따른 유효성분의 투여량은 대상체의 상태 및 체중, 질환의 종류 및 정도, 약물 형태, 투여경로 및 기간에 따라 달라질 수 있으며 당업자에 의해 적절하게 선택될 수 있다. 본 발명의 일실시예에 따르면 이에 제한되는 것은 아니지만 1일 투여량이 0.01mg/kg ~ 200mg/kg, 구체적으로는 0.1mg/kg ~ 200mg/kg, 보다 구체적으로는 0.1mg/kg ~ 100mg/kg 일 수 있다. 투여는 하루에 한번 투여할 수도 있고 수회로 나누어 투여할 수도 있으며, 이에 의해 본 발명의 범위가 제한되는 것은 아니다.The dosage of the active ingredient according to the present invention may vary depending on the condition and weight of the subject, the type and severity of the disease, the type of drug, the route and duration of administration, and may be appropriately selected by those skilled in the art. According to one embodiment of the present invention, although not limited thereto, the daily dosage is 0.01 mg/kg to 200 mg/kg, specifically 0.1 mg/kg to 200 mg/kg, and more specifically 0.1 mg/kg to 100 mg/kg. can be Administration may be administered once a day or divided into several times, and the scope of the present invention is not limited thereby.
또한, 본 발명은 맨드라미(Celosia cristata) 꽃 추출물을 유효성분으로 포함하는 비만 예방 또는 개선용 건강기능식품 조성물을 제공한다.In addition, the present invention is cockscomb ( Celosia cristata ) It provides a health functional food composition for preventing or improving obesity containing a flower extract as an active ingredient.
본 발명은 통상적으로 이용되는 식품으로써 일반적으로 사용될 수 있다.The present invention can be generally used as a commonly used food.
본 발명의 식품 조성물은 건강기능식품으로서 사용될 수 있다. 상기 "건강기능 식품"이라 함은 건강기능 식품에 관한 법률에 따른 인체에 유용한 기능성을 가진 원료나 성분을 사용하여 제조 및 가공한 식품을 의미하며, "기능성"이라 함은 인체의 구조 및 기능에 대하여 영양소를 조절하거나 생리학적 작용 등과 같은 보건용도에 유용한 효과를 얻을 목적으로 섭취하는 것을 의미한다.The food composition of the present invention can be used as a health functional food. The term "health functional food" refers to food manufactured and processed using raw materials or ingredients having useful functionalities for the human body in accordance with the Health Functional Food Act, and "functional" refers to food that is not related to the structure and function of the human body. It refers to intake for the purpose of obtaining useful effects for health purposes such as regulating nutrients or physiological functions.
상기 건강기능식품 조성물은 통상의 식품 첨가물을 포함할 수 있으며, 상기 "식품 첨가물"로서의 적합 여부는 다른 규정이 없는 한, 식품의약품안전처에 승인된 식품 첨가물 공전의 총칙 및 일반시험법 등에 따라 해당 품목에 관한 규격 및 기준에 의하여 판정한다.The health functional food composition may include conventional food additives, and the suitability as the "food additive" is determined in accordance with the General Rules and General Test Methods of Food Additives approved by the Ministry of Food and Drug Safety, unless otherwise specified. It is judged according to the specifications and standards for the item.
상기 "식품 첨가물 공전"에 수재된 품목으로는 예를 들어, 케톤류, 글리신, 구연산칼륨, 니코틴산, 계피산 등의 화학적 합성물, 감색소, 감초추출물, 결정셀룰로오스, 고량색소, 구아검 등의 천연첨가물, L-글루타민산나트륨 제제, 면류첨가알칼리제, 보존료제제, 타르색소제제 등의 혼합제제류들을 들 수 있다.Items listed in the "Food Additive Code" include, for example, chemical compounds such as ketones, glycine, potassium citrate, nicotinic acid, and cinnamic acid, natural additives such as dark pigment, licorice extract, crystalline cellulose, goyang pigment, guar gum, and mixed preparations such as sodium L-glutamate preparations, noodle-added alkali preparations, preservative preparations, and tar color preparations.
본 발명의 식품 조성물은 정제, 캡슐, 분말, 과립, 액상, 환 등의 형태로 제조 및 가공할 수 있다. 예를 들어, 캡슐 형태의 건강기능 식품 중 경질 캡슐제는 통상의 경질 캡슐에본 발명에 따른 조성물을 부형제 등의 첨가제와 혼합 및 충진하여 제조할 수 있으며, 연질 캡슐제는 본 발명에 따른 조성물을 부형제 등의 첨가제와 혼합하고 젤라틴 등 캡슐기제에 충진하여 제조할 수 있다. 상기 연질 캡슐제는 필요에 따라 글리세린 또는 소르비톨 등의 가소제, 착색제, 보존제 등을 함유할 수 있다.The food composition of the present invention can be prepared and processed in the form of tablets, capsules, powders, granules, liquids, pills and the like. For example, among health functional foods in capsule form, hard capsules can be prepared by mixing and filling a composition according to the present invention with additives such as excipients in a conventional hard capsule, and soft capsules contain the composition according to the present invention. It can be prepared by mixing with additives such as excipients and filling in a capsule base such as gelatin. The soft capsule may contain a plasticizer such as glycerin or sorbitol, a coloring agent, a preservative, and the like, if necessary.
상기 부형제, 결합제, 붕해제, 활택제, 교미제, 착향제 등에 대한 용어 정의는 당업계에 공지된 문헌에 기재된 것으로 그 기능 등이 동일 내지 유사한 것들을 포함한다. 상기 식품의 종류에는 특별한 제한이 없으며, 통상적인 의미에서의 건강기능식품을 모두 포함한다.Definitions of terms for the excipients, binders, disintegrants, lubricants, corrigents, flavoring agents, etc. are described in literature known in the art, and include those having the same or similar functions. There is no particular limitation on the type of food, and it includes all health functional foods in the usual sense.
본 발명에서 용어 “예방”이란 본 발명에 따른 조성물의 투여로 질환의 억제 또는 지연시키는 모든 행위를 말한다. 본 발명에서 용어 “치료”는 본 발명에 따른 조성물의 투여로 질환의 증세가 호전되거나 이롭게 변경하는 모든 행위를 말한다. 본 발명에서 "개선"이란 본 발명의 조성물을 개체에 투여하거나 섭취시켜 질환의 나쁜 상태를 좋게 하는 모든 행위를 의미한다.In the present invention, the term "prevention" refers to all activities that inhibit or delay a disease by administering the composition according to the present invention. In the present invention, the term "treatment" refers to all activities that improve or beneficially change the symptoms of a disease by administering the composition according to the present invention. In the present invention, "improvement" means any action that improves the bad condition of a disease by administering or ingesting the composition of the present invention to a subject.
또한, 본 발명은 맨드라미(Celosia cristata) 꽃 추출물을 유효성분으로 포함하는 지방간 예방 또는 치료용 약학 조성물을 제공한다.In addition, the present invention is cockscomb ( Celosia cristata ) It provides a pharmaceutical composition for preventing or treating fatty liver comprising a flower extract as an active ingredient.
상기 추출물은 간 조직 내 지방공포(lipid vacuole)의 수 또는 지방세포 크기를 감소시킬 수 있다.The extract can reduce the number of lipid vacuoles or the size of adipocytes in liver tissue.
또한, 상기 추출물은 혈중 AST(Aspartate aminotransferase) 또는 ALT(Alanine aminotransferase)를 감소시킬 수 있다.In addition, the extract may reduce blood AST (Aspartate aminotransferase) or ALT (Alanine aminotransferase).
또한, 본 발명은 맨드라미(Celosia cristata) 꽃 추출물을 유효성분으로 포함하는 지방간 예방 또는 개선용 건강기능식품 조성물을 제공한다.In addition, the present invention is cockscomb ( Celosia cristata ) It provides a health functional food composition for preventing or improving fatty liver containing a flower extract as an active ingredient.
이하, 본 발명의 이해를 돕기 위하여 실시예를 들어 상세하게 설명하기로 한다. 다만 하기의 실시예는 본 발명의 내용을 예시하는 것일 뿐 본 발명의 범위가 하기 실시예에 한정되는 것은 아니다. 본 발명의 실시예는 당업계에서 평균적인 지식을 가진 자에게 본 발명을 보다 완전하게 설명하기 위해 제공되는 것이다.Hereinafter, examples will be described in detail to aid understanding of the present invention. However, the following examples are merely illustrative of the contents of the present invention, but the scope of the present invention is not limited to the following examples. The embodiments of the present invention are provided to more completely explain the present invention to those skilled in the art.
[실험예 1] 맨드라미 꽃 추출물 제조[Experimental Example 1] Preparation of cockscomb flower extract
건조 맨드라미(Celosia cristata) 꽃에 30% 주정(에탄올)을 10배수 첨가하여 70℃에서 8시간 동안 1차 추출을 진행하고 여과하였다. 1차 추출 후 남은 잔여물에 30% 주정을 다시 10배수 첨가하여 70℃에서 6시간 동안 2차 추출을 진행하고 여과한 후 감압 및 농축하여 맨드라미 꽃 추출물을 제조하였다.Dry cockscomb ( Celosia cristata ) 30% alcohol (ethanol) was added 10 times to the flowers, and the primary extraction was performed at 70 ° C. for 8 hours, followed by filtration. A cockscomb flower extract was prepared by adding 10 times more 30% alcohol to the residue remaining after the first extraction, performing a second extraction at 70° C. for 6 hours, filtering, and concentrating under reduced pressure.
[실험예 2] 세포 배양[Experimental Example 2] Cell culture
세포 배양 실험에 사용된 마우스 지방전구세포인 3T3-L1 세포는 American Type Culture Collection(ATCC, USA)에서 구입하여, 10% bovine serum(Gibco, USA) 및 항생제 1% Antibiotic-Antimycotic(이하 AA라 함, Gibco)을 첨가한 DMEM(Dulbecco’s Modified Eagle Medium, Welgene, Korea) 배지를 사용하여 5% CO2 및 37℃ 조건의 세포배양기에서 배양하였다. 3T3-L1 cells, which are mouse preadipocytes used in cell culture experiments, were purchased from American Type Culture Collection (ATCC, USA) and supplemented with 10% bovine serum (Gibco, USA) and 1% Antibiotic-Antimycotic (hereinafter referred to as AA). , Gibco) using DMEM (Dulbecco's Modified Eagle Medium, Welgene, Korea) medium supplemented with 5% CO 2 and cultured in a cell culture medium at 37°C.
[실시예 1] 맨드라미 꽃 추출물의 지방생성 억제 효과 확인[Example 1] Confirmation of adipogenesis inhibitory effect of cockscomb flower extract
1-1. 3T3-L1 지방전구세포의 지방세포로의 분화 유도1-1. Induction of differentiation of 3T3-L1 preadipocytes into adipocytes
상기 실험예 2에서 배양한 3T3-L1 세포에 3가지 혼합물질(MDI: 3-Isobutyl-1-methylxanthine(IBMX) 0.5mM, Dexamethasone(Dexa) 1μM 및 인슐린 10㎍/mL)과 10% fetal bovine serum(FBS, Gibco) 및 1% AA를 포함한 DMEM을 처리하는 동시에 실험예 1에서 제조한 맨드라미 꽃 30% 주정 추출물을 멸균증류수에 용해시켜 농도별로(10, 20, 30, 40 및 50㎍/mL) 처리하였으며, 대조군으로는 같은 양의 생리식염수를 처리하여 분화를 유도하였고, 분화 유도 72시간 후 인슐린 10㎍/mL가 함유된 10% FBS DMEM 배양액으로 교체하였다. 그 후 5일 동안 세포배양 후에 분화 정도를 분석하였다. 3 mixtures (MDI: 3-Isobutyl-1-methylxanthine (IBMX) 0.5 mM, Dexamethasone (Dexa) 1 μM, and insulin 10 μg/mL) and 10% fetal bovine serum were added to the 3T3-L1 cells cultured in Experimental Example 2 above. (FBS, Gibco) and DMEM containing 1% AA, while dissolving the 30% alcohol extract of cockscomb flowers prepared in Experimental Example 1 in sterile distilled water by concentration (10, 20, 30, 40 and 50 μg/mL) As a control, differentiation was induced by treatment with the same amount of physiological saline, and 72 hours after induction of differentiation, the culture medium was replaced with 10% FBS DMEM containing 10 μg/mL of insulin. After culturing the cells for 5 days, the degree of differentiation was analyzed.
1-2. 맨드라미 꽃 추출물에 의한 지방세포의 지방생성 억제효과 확인1-2. Confirmation of adipogenesis inhibitory effect of cockscomb flower extract in adipocytes
맨드라미 꽃 추출물이 지방세포의 지방생성에 미치는 영향을 알아보기 위해, 오일레드 O(Oil Red O) 지방분석법을 이용하여 확인하였다. 구체적으로, 상기 지방세포로 분화된 3T3-L1 세포의 배지를 제거하고 PBS(phosphate-buffered saline)로 세척한 다음 4% 파라포름알데하이드(paraformaldehyde) 용액을 30분간 처리하여 세포를 상온에서 고정시켰다. 이후 PBS로 1회 세척 후 70% 이소프로필알코올(isopropyl alcohol)을 5분간 처리한 다음 상온에서 완전건조시켰다. 이후 오일레드 O 용액을 1시간 처리하는 염색방법으로 세포내 지방축적 정도를 조사하였다. 지방세포로 분화를 유도하지 않은 3T3-L1 세포를 음성대조군(Mock), 지방세포로 분화를 유도하고 추출물을 처리하지 않은 지방세포를 양성대조군(Control)으로 사용하였다. 각각 염색된 세포를 증류수로 2회 세척한 후 광학현미경을 사용하여 관찰하였다. 이후 이소프로필알코올 용액으로 세척 처리한 다음 ELISA reader를 통해 450nm에서 흡광도를 측정하여 시료 처리군의 흡광도 값을 시료 무처리군(Control)의 흡광도 값으로 나누어 세포의 지방 함량을 백분율로 나타내었다.In order to examine the effect of cockscomb flower extract on adipogenesis of adipocytes, it was confirmed using Oil Red O fat analysis method. Specifically, the medium of the 3T3-L1 cells differentiated into adipocytes was removed, washed with PBS (phosphate-buffered saline), and then treated with a 4% paraformaldehyde solution for 30 minutes to fix the cells at room temperature. Thereafter, after washing once with PBS, 70% isopropyl alcohol was treated for 5 minutes, and then completely dried at room temperature. Thereafter, the degree of intracellular fat accumulation was examined by a staining method in which Oil Red O solution was treated for 1 hour. 3T3-L1 cells not induced to differentiate into adipocytes were used as a negative control (Mock), and adipocytes induced to differentiate into adipocytes and not treated with the extract were used as a positive control (Control). After washing each stained cell twice with distilled water, it was observed using an optical microscope. After washing with an isopropyl alcohol solution, the absorbance was measured at 450 nm using an ELISA reader, and the absorbance value of the sample treated group was divided by the absorbance value of the sample untreated group (Control), and the fat content of the cells was expressed as a percentage.
그 결과, 도 1 및 도 2에 나타난 바와 같이, 맨드라미 꽃 추출물은 농도 의존적으로 지방세포의 지방생성 억제 효과를 나타내는 것을 확인하였다.As a result, as shown in FIGS. 1 and 2 , it was confirmed that the cockscomb flower extract exhibited an effect of inhibiting adipogenesis of adipocytes in a concentration-dependent manner.
[[ 실시예Example 2] 맨드라미 꽃 추출물에 의한 지방세포의 2] Fat cells by cockscomb flower extract 트리글리세라이드triglyceride 생성 억제효과 확인 Confirmation of production inhibition effect
맨드라미 꽃 추출물이 지방세포의 중성지방에 미치는 영향을 알아보기 위해, 맨드라미 꽃 추출물을 3T3-L1 세포에 처리하고 지방세포 분화를 유도한 후 트리글리세라이드 생성을 TG 분석법을 통하여 확인하였다.In order to examine the effect of cockscomb flower extract on triglyceride in adipocytes, 3T3-L1 cells were treated with cockscomb flower extract and differentiation of adipocytes was induced, and triglyceride production was confirmed by TG assay.
구체적으로, 상기 실험예 1-1에 기재된 방법과 동일한 방법으로 상기 실험예 1에서 제조한 맨드라미 꽃 추출물을 농도별로(0, 10, 30 및 50μg/ml) 상기 실험예 2에서 배양한 3T3-L1 세포에 처리하고 지방세포 분화를 유도하였다. 그 다음, 지방세포 분화 유도를 위한 3가지 혼합물질(MDI: 3-Isobutyl-1-methylxanthine(IBMX) 0.5mM, Dexamethasone(Dexa) 1μM 및 인슐린 10㎍/mL)을 포함한 새로운 10% FBS 혈청배지로 교체하여 지방생성자극을 72시간 유지하고, 혈청과 인슐린 10㎍/mL를 포함한 새로운 배지로 5일 동안 지방축적을 유도하였다. 이후 배지를 제거하고 차가운 PBS로 세포를 세척한 후, NP-40 용액으로 세포를 용해하여 트리글리세라이드 키트(Cayman, USA)를 통해 590nm로 흡광도를 측정하였다.Specifically, 3T3-L1 cultured in Experimental Example 2 with the cockscomb flower extract prepared in Experimental Example 1 in the same manner as in Experimental Example 1-1 by concentration (0, 10, 30 and 50 μg/ml) Cells were treated and adipocyte differentiation was induced. Then, a new 10% FBS serum medium containing three mixtures (MDI: 3-Isobutyl-1-methylxanthine (IBMX) 0.5mM, Dexamethasone (Dexa) 1μM, and insulin 10μg/mL) for inducing adipocyte differentiation Adipogenesis stimulation was maintained for 72 hours by replacement, and fat accumulation was induced for 5 days with a new medium containing 10 μg/mL of serum and insulin. After removing the medium and washing the cells with cold PBS, the cells were lysed with NP-40 solution and the absorbance was measured at 590 nm using a triglyceride kit (Cayman, USA).
그 결과, 도 3에 나타난 바와 같이, 맨드라미 꽃 추출물은 농도 의존적으로 지방세포 내의 중성지방 합성 억제 효과를 나타내는 것을 확인하였다.As a result, as shown in FIG. 3, it was confirmed that the cockscomb flower extract exhibited an inhibitory effect on neutral fat synthesis in adipocytes in a concentration-dependent manner.
[[ 실시예Example 3] 맨드라미 꽃 추출물에 의한 지방세포 분화 관련 전사인자 및 에너지대사 관련 전사인자의 발현억제 효과 확인 3] Confirmation of expression inhibition effect of transcription factors related to adipocyte differentiation and energy metabolism by cockscomb flower extract
맨드라미 꽃 추출물이 지방세포 분화 관련 전사인자 및 에너지대사 관련 전사인자의 발현에 미치는 영향을 알아보기 위하여, Real time quantitative PCR을 실시하였다. 구체적으로, 3T3-L1 세포를 12-웰 플레이트에 6×104 cells/mL의 농도로 시딩(seeding)한 후 상기 실시예 1-1에 기재된 방법과 동일한 방법으로 분화를 유도하며, 상기 실험예 1에서 제조한 맨드라미 꽃 추출물을 함께 처리하였다. Real time quantitative PCR was performed to investigate the effect of cockscomb flower extract on the expression of transcription factors related to adipocyte differentiation and energy metabolism. Specifically, after seeding 3T3-L1 cells in a 12-well plate at a concentration of 6×10 4 cells/mL, differentiation is induced by the same method as described in Example 1-1, and the Experimental Example The cockscomb flower extract prepared in 1 was treated together.
이후 분화가 완료된 시점에서 배지를 제거하고 PBS로 세척한 다음 500㎕의 TRIzol 시약(Invitrogen, USA)을 이용하여 RNA를 추출하였다. 이후 100㎕의 클로로폼(chloroform)을 넣어 4℃ 및 12,000rpm 조건에서 20분간 원심분리하여 얻어진 상층액과 동량의 이소프로필알코올을 넣은 후 상온에서 5분 방치한 후 4℃ 및 12,000rpm 조건에서 20분간 원심분리하였다. 상층액을 제거한 펠렛(pallet)은 70% 에탄올로 세척한 후 충분히 건조시켰다. 건조된 펠렛은 RNase-free dH2O에 용해한 후 260nm, 280nm에서 흡광도를 측정하여 OD260/OD280 ratio RNA의 순도(purity)를 알아보고 OD260 값으로 RNA를 정량하였다.After the differentiation was completed, the medium was removed, washed with PBS, and RNA was extracted using 500 μl of TRIzol reagent (Invitrogen, USA). Thereafter, 100 μl of chloroform was added, and the same amount of isopropyl alcohol as the supernatant obtained by centrifugation at 4 ° C and 12,000 rpm for 20 minutes was added, and then left at room temperature for 5 minutes, followed by 20 minutes at 4 ° C and 12,000 rpm. minutes and centrifuged. The pellet from which the supernatant was removed was washed with 70% ethanol and sufficiently dried. The dried pellet was dissolved in RNase-free dH 2 O, and the absorbance was measured at 260 nm and 280 nm to determine the purity of the OD 260 / OD 280 ratio RNA, and the RNA was quantified by the OD 260 value.
추출된 RNA를 DNase가 포함되어있는 RevertAid First Strand cDNA Synthesis Kit(Thermo scientific, USA)를 이용하여 cDNA로 합성하고, TB green(TaKaRa, Japan)과 GAPDH(glyceraldehyde-3-phosphate dehydrogenase), PPARγ, C/EBPα, FABP4 및 Adipoq 프라이머를 이용하여 Real-time PCR(CFX Connect Real-Time System, BIO-RAD, USA)을 수행하였다. 대조군 유전자로는 GAPDH를 사용하였다. 또한, Real-time PCR system을 이용하여 형광 신호를 정량하였다. 데이터는 2-△△CT 방법으로 분석하였으며, 3회 반복 실험하였다. 사용한 유전자의 프라이머 서열은 하기 표 1과 같다.The extracted RNA was synthesized into cDNA using the RevertAid First Strand cDNA Synthesis Kit (Thermo scientific, USA) containing DNase, and TB green (TaKaRa, Japan), GAPDH (glyceraldehyde-3-phosphate dehydrogenase), PPARγ, C Real-time PCR (CFX Connect Real-Time System, BIO-RAD, USA) was performed using /EBPa, FABP4 and Adipoq primers. GAPDH was used as a control gene. In addition, fluorescence signals were quantified using a real-time PCR system. Data were analyzed by the 2 -ΔΔCT method, and the experiment was repeated three times. Primer sequences of the genes used are shown in Table 1 below.
그 결과, 도 4에 나타난 바와 같이, 맨드라미 꽃 추출물은 농도 의존적으로 지방합성 전사인자인 PPARγ(Peroxisome proliferator-activated receptor γ), C/EBPα(CCAAT/enhancer binding protein α) 및 FABP4(Fatty acid binding protein 4)]와 에너지대사 관련 전사인자인 아디포넥틴(Adiponectin; Adipoq) 유전자 발현 억제 효과를 나타내는 것을 확인하였다.As a result, as shown in FIG. 4, the cockscomb flower extract contained the fat synthesis transcription factors PPARγ (Peroxisome proliferator-activated receptor γ), C/EBPα (CCAAT/enhancer binding protein α), and FABP4 (Fatty acid binding protein) in a concentration-dependent manner. 4)] and adiponectin (Adipoq), a transcription factor related to energy metabolism.
[실시예 4] 맨드라미 꽃 추출물의 세포독성 확인[Example 4] Confirmation of cytotoxicity of cockscomb flower extract
상기 실험예 1에서 제조한 맨드라미 꽃 추출물의 세포독성을 WST assay 분석법을 이용하여 평가하였다. 구체적으로, 실험예 2에 기재된 방법으로 3T3-L1 세포가 배양된 100㎠ 배양 플레이트에서 배지액을 제거하고, 1 × PBS로 세척한 후, 트립신(Trypsin)/EDTA를 처리하여 세포를 떼어낸 후 세포배양액으로 중화하고 1200rpm에서 3분 동안 원심분리하였다. 남은 세포의 펠렛에 배양액을 가한 후에, 멸균 피펫으로 반복 흡입하여 단일세포 부유액을 만든 후 세포를 정량하였다. 상기 정량한 3T3-L1 지방전구세포를 96 웰 플레이트에 2×103 cell/well이 되도록 분주하였다. 이를 5% CO2 및 37℃ 조건의 세포 배양기에서 24시간 배양한 후, 맨드라미 꽃 추출물을 농도별로 처리하여 5% CO2 및 37℃ 조건의 배양기에서 24시간 동안 배양하였다. 배양 후 WST 시약을 첨가하여 37℃에서 1시간 동안 반응시킨 후 ELISA reader(TriStar2 LB 942, Berthold technologies, Germany)를 통해 450nm에서 흡광도를 측정하였다.The cytotoxicity of the cockscomb flower extract prepared in Experimental Example 1 was evaluated using the WST assay method. Specifically, by the method described in Experimental Example 2, the medium was removed from the 100 cm 2 culture plate in which 3T3-L1 cells were cultured, washed with 1 × PBS, treated with trypsin/EDTA to remove the cells, and then Neutralized with cell culture medium and centrifuged at 1200 rpm for 3 minutes. After adding the culture medium to the remaining cell pellet, repeated suction with a sterile pipette to make a single cell suspension, and then the cells were quantified. The quantified 3T3-L1 preadipocytes were dispensed in a 96-well plate to be 2×10 3 cells/well. After culturing for 24 hours in a cell incubator under 5% CO 2 and 37° C. conditions, cockscomb flower extracts were treated by concentration and cultured for 24 hours in an incubator under 5% CO 2 and 37° C. conditions. After incubation, WST reagent was added and reacted at 37 ° C. for 1 hour, and then absorbance was measured at 450 nm through an ELISA reader (TriStar2 LB 942, Berthold technologies, Germany).
그 결과, 도 5에 나타난 바와 같이, 맨드라미 꽃 추출물은 3T3-L1 세포에서 독성을 나타내지 않는 것을 확인하였다.As a result, as shown in FIG. 5 , it was confirmed that the cockscomb flower extract was not toxic to 3T3-L1 cells.
[실시예 5] 맨드라미 꽃 추출물의 지방세포의 중성지방 분해효과 확인[Example 5] Confirmation of neutral fat decomposition effect of cockscomb flower extract in adipocytes
맨드라미 꽃 추출물이 지방세포의 중성지방 분해에 미치는 영향을 알아보기 위하여, 3T3-L1 세포에 지방 분화인자를 처리하여 지방세포 분화를 유도한 후, 맨드라미 꽃 추출물을 처리하여 글리세롤(Glycerol) 분석법을 통해 중성지방 분해효과를 확인하였다.In order to investigate the effect of cockscomb flower extract on triglyceride decomposition of adipocytes, 3T3-L1 cells were treated with fat differentiation factor to induce adipocyte differentiation, and then treated with cockscomb flower extract and glycerol assay was performed. The neutral fat decomposition effect was confirmed.
구체적으로, 상기 실험예 2에서 배양한 3T3-L1 세포에 지방세포 분화 유도를 위한 3가지 혼합물질(MDI: 3-Isobutyl-1-methylxanthine(IBMX) 0.5mM, Dexamethasone(Dexa) 1μM 및 인슐린 10㎍/mL)을 포함한 새로운 10% FBS 혈청배지로 교체하여 지방생성자극을 72시간 유지하고, 혈청과 인슐린 10㎍/mL를 포함한 새로운 배지로 5일 동안 지방축적을 유도하였다. 그 다음, 완전히 분화된 3T3-L1 세포를 유리지방산이 제거된 1% 소 혈청 알부민(FFA-free BSA)이 포함된 무혈청 배지로 4시간 starvation 시킨 후 1% FFA-free BSA를 포함한 10% FBS 혈청배지에 상기 실험예 1에서 제조한 맨드라미 꽃 추출물을 농도별로(0, 10, 30 및 50μg/ml) 섞어 세포에 처리하여 세포 내에 생성된 중성지방의 분해를 유도하였다. 이후 배양 배지를 수거하여 70℃에서 5분간 효소를 불활성화시킨 후, 글리세롤이 제거된(free glycerol) 시약(Sigma-Aldrich, USA)과 37℃에서 5분간 반응시켜 590nm로 흡광도를 측정하였다.Specifically, three mixtures (MDI: 3-Isobutyl-1-methylxanthine (IBMX) 0.5mM, Dexamethasone (Dexa) 1μM, and insulin 10μg for inducing adipocyte differentiation were added to the 3T3-L1 cells cultured in Experimental Example 2). /mL), the stimulation of adipogenesis was maintained for 72 hours, and fat accumulation was induced for 5 days with a new medium containing 10 μg/mL of serum and insulin. Then, fully differentiated 3T3-L1 cells were starvated for 4 hours in a serum-free medium containing 1% bovine serum albumin (FFA-free BSA) from which free fatty acids were removed, followed by 10% FBS containing 1% FFA-free BSA. The serum medium was mixed with the cockscomb flower extract prepared in Experimental Example 1 according to concentration (0, 10, 30, and 50 μg/ml) and treated with the cells to induce decomposition of neutral fat produced in the cells. Thereafter, the culture medium was collected and the enzyme was inactivated at 70° C. for 5 minutes, followed by reaction with a free glycerol reagent (Sigma-Aldrich, USA) at 37° C. for 5 minutes, and absorbance was measured at 590 nm.
그 결과, 도 6에 나타난 바와 같이, 맨드라미 꽃 추출물은 농도 의존적으로 지방세포 내의 중성지방 분해효과를 나타내는 것을 확인하였다.As a result, as shown in FIG. 6, it was confirmed that the cockscomb flower extract showed a neutral fat decomposition effect in adipocytes in a concentration-dependent manner.
[[ 실시예Example 6] 고지방식 비만 마우스 동물모델에서 맨드라미 꽃 추출물의 체중 감소 효과 확인 6] Confirmation of weight loss effect of cockscomb flower extract in high fat diet obese mouse animal model
맨드라미 꽃 추출물의 체지방감소 효능을 동물모델에서 검증하기 위하여, 고지방식 비만 마우스 모델(High-fat diet mouse obesity model)을 이용하여 맨드라미 꽃 추출물의 비만 개선 효능을 평가하였다. 동물모델은 4주령 C57BL6/N 마우스를 오리엔트 바이오에서 구매하여 사용하였다. 상기 마우스를 반입하여 순화 과정을 거친 후, 각 개체별 체중을 측정하여 군 간의 유의한 차이가 없도록 군 분리를 시행한 다음, 세포실험에서의 농도를 고려하여 총 3가지 용량(저농도; 25mg/kg/day, 중농도; 50mg/kg/day, 고농도; 100mg/kg/day)의 맨드라미 꽃 추출물을 고지방식이 사료와 혼합한 후, 12주간 섭취시키면서 일주일마다 체중을 측정하였다. 일반식이(Normal diet; 이하 ND라 함)군 및 고지방식이(High-fat diet; 이하 HFD라 함)군을 대조군으로 설정하였다. In order to verify the effect of the cockscomb flower extract on reducing body fat in an animal model, the obesity improvement effect of the cockscomb flower extract was evaluated using a high-fat diet mouse obesity model. As an animal model, 4-week-old C57BL6/N mice were purchased from Orient Bio and used. After the mice were brought in and subjected to the acclimatization process, the weight of each individual was measured and group separation was performed so that there was no significant difference between the groups, and then a total of 3 doses (low concentration; 25 mg/kg) were administered in consideration of the concentration in the cell experiment. /day, medium concentration; 50mg/kg/day, high concentration; 100mg/kg/day) cockscomb flower extract was mixed with a high-fat diet, and then fed for 12 weeks, and body weight was measured every week. A normal diet (hereinafter referred to as ND) group and a high-fat diet (hereinafter referred to as HFD) group were set as a control group.
그 결과, 도 7에 나타난 바와 같이, 섭취 4주차부터 모든 맨드라미 꽃 추출물 섭취군에서 HFD군에 비해 유의적으로 체중이 감소하는 것을 확인하였다.As a result, as shown in FIG. 7, it was confirmed that the body weight decreased significantly compared to the HFD group in all cockscomb flower extract intake groups from the 4th week of intake.
[[ 실시예Example 7] 고지방식 비만 마우스 동물모델에서 맨드라미 꽃 추출물의 7] Effect of cockscomb flower extract in high-fat diet obese mouse animal model 체지방량fat mass 감소 효과 확인 Check the reduction effect
상기 실시예 6에서 확인한 체중감소 효과를 토대로 고지방식 비만 마우스 동물모델에서 맨드라미 꽃 추출물의 체지방량 감소 효과를 확인하기 위하여, 상기 실시예 6의 ND군, HFD군, HFD+맨드라미 꽃 추출물 50mg/kg/day 섭취군(CC+50) 및 HFD+맨드라미 꽃 추출물 100mg/kg/day 섭취군(CC+100)을 EchoMRI™ Body Composition Analyzer(EchoMRI, USA)를 이용하여 체지방량(Fat) 및 지방제외체중(Lean body mass)을 측정하였다.In order to confirm the body fat reduction effect of cockscomb flower extract in a high-fat diet obese mouse animal model based on the weight loss effect confirmed in Example 6, ND group, HFD group, HFD + cockscomb flower extract 50 mg / kg / day of Example 6 The intake group (CC+50) and the HFD+cockscomb flower extract 100mg/kg/day intake group (CC+100) were analyzed using the EchoMRI™ Body Composition Analyzer (EchoMRI, USA) to determine the body fat mass (Fat) and lean body mass (lean body mass). ) was measured.
그 결과, 도 8에 나타난 바와 같이, 맨드라미 꽃 추출물 섭취군에서 HFD군에 비해 체지방량이 감소하였고, 지방제외 체중은 증가하는 것을 확인하였다.As a result, as shown in FIG. 8, it was confirmed that the body fat mass decreased in the cockscomb flower extract intake group compared to the HFD group, and the fat-free body weight increased.
[[ 실시예Example 8] 고지방식 비만 마우스 동물모델에서 맨드라미 꽃 추출물의 8] Effect of cockscomb flower extract in high-fat diet obese mouse animal model 대사능metabolic function 개선 효과 확인 Check the effect of improvement
맨드라미 꽃 추출물이 고지방식 비만 마우스 동물모델에서 나타나는 대사능 감소를 개선시키는지 확인하기 위하여, 상기 실시예 6의 ND군, HFD군, HFD+맨드라미 꽃 추출물 50mg/kg/day 섭취군(CC+50) 및 HFD+맨드라미 꽃 추출물 100mg/kg/day 섭취군(CC+100)을 Phenomaster(TSE system, Germany) 케이지에서 5일간 산소 소비량(VO2), 이산화탄소 소비량(VCO2), 호흡교환율(Respiratory exchange ratio; RER) 및 에너지 소비량(Energy expenditure; EE)을 측정하였다.In order to determine whether the cockscomb flower extract improves the metabolic function reduction in the high-fat diet obese mouse animal model, the ND group, the HFD group, and the HFD + cockscomb flower extract 50 mg / kg / day intake group (CC + 50) of Example 6 and HFD + cockscomb flower extract 100mg/kg/day intake group (CC+100) for 5 days in a Phenomaster (TSE system, Germany) cage, oxygen consumption (VO 2 ), carbon dioxide consumption (VCO 2 ), respiratory exchange rate (Respiratory exchange ratio) ;RER) and energy expenditure (EE) were measured.
그 결과, 도 9에 나타난 바와 같이, 맨드라미 꽃 추출물 섭취군에서 HFD군에 비해 산소 소비량, 이산화탄소 소비량, 호흡교환율 및 에너지 소비량이 증가한 것을 확인하였다.As a result, as shown in FIG. 9, it was confirmed that oxygen consumption, carbon dioxide consumption, respiratory exchange rate, and energy consumption increased in the cockscomb flower extract intake group compared to the HFD group.
[[ 실시예Example 9] 고지방식 비만 마우스 동물모델에서 맨드라미 꽃 추출물의 지방간 및 지방조직 크기 감소 효과 확인 9] Confirmation of effect of cockscomb flower extract on reducing fatty liver and adipose tissue size in high-fat diet obese mouse animal model
맨드라미 꽃 추출물이 고지방식 비만 마우스 동물모델에서 나타나는 지방간 및 지방조직의 비대를 감소시키는지 확인하기 위하여, 상기 실시예 6에서 진행한 마우스의 간 조직 및 복부지방을 채취한 후, 헤마톡실린&에오신(Hematoxylin & eosin; H&E) 염색을 진행하여 간 조직 내 지방공포의 수(Number of lipid vacuoles) 및 지방세포 크기(adipocyte area)를 확인하였다.In order to confirm whether cockscomb flower extract reduces fat liver and adipose tissue hypertrophy in the high-fat diet obese mouse animal model, after collecting the liver tissue and abdominal fat of the mouse in Example 6, hematoxylin & eosin (Hematoxylin &eosin; H&E) staining was performed to confirm the number of lipid vacuoles and adipocyte area in the liver tissue.
그 결과, 도 10에 나타난 바와 같이, 맨드라미 꽃 추출물 섭취군에서 HFD군이 비해, 간 조직 내 지방공포의 수 및 지방세포 크기가 감소한 것을 확인하였다.As a result, as shown in FIG. 10 , it was confirmed that the number of lipovacuoles and the size of adipocytes in liver tissue were reduced in the cockscomb flower extract intake group compared to the HFD group.
[[ 실시예Example 10] 고지방식 비만 마우스 동물모델에서 맨드라미 꽃 추출물의 혈중 간기능지표 및 지질 농도 개선 효과 확인 10] Confirmation of improvement of blood liver function index and lipid concentration of cockscomb flower extract in high-fat diet obese mouse animal model
맨드라미 꽃 추출물의 고지방식 비만 마우스 동물모델에서 나타나는 혈중 간기능지표 및 지질 농도 개선 효과를 확인하기 위하여, 상기 실시예 6의 마우스의 혈액을 EDTA tube에 채취하고, 3000rpm으로 20분 동안 원심분리하여 혈장을 분리하였다. 그 후, 간기능지표인 AST(Aspartate aminotransferase) 및 ALT(Alanine aminotransferase)와 혈중 지질 농도 지표인 트리글리세라이드, 총 콜레스테롤, 저밀도지질단백질(low-density lipoprotein; 이하 LDL이라 함) 및 고밀도지질단백질(high-density lipoprotein; 이하 HDL이라 함)을 Beckman AU480 Chemistry Analyzer(Beckman Coulter, USA)를 이용하여 측정하였다.In order to confirm the effect of cockscomb flower extract on improving liver function indicators and lipid concentration in blood in a high-fat diet obese mouse animal model, the blood of the mouse of Example 6 was collected in an EDTA tube, centrifuged at 3000 rpm for 20 minutes, and plasma was separated. After that, liver function indicators AST (aspartate aminotransferase) and ALT (alanine aminotransferase) and blood lipid concentration indicators such as triglyceride, total cholesterol, low-density lipoprotein (hereinafter referred to as LDL) and high-density lipoprotein (high -density lipoprotein; hereinafter referred to as HDL) was measured using a Beckman AU480 Chemistry Analyzer (Beckman Coulter, USA).
그 결과, 도 11에 나타난 바와 같이, 맨드라미 꽃 추출물 섭취군에서 HFD군 에 비해 AST, ALT, 트리글리세라이드, 총 콜레스테롤 및 LDL은 감소한 반면, HDL은 증가한 것을 확인하였다.As a result, as shown in FIG. 11, it was confirmed that AST, ALT, triglyceride, total cholesterol, and LDL decreased in the cockscomb flower extract intake group compared to the HFD group, while HDL increased.
[[ 실시예Example 11] 고지방식 비만 마우스 동물모델에서 맨드라미 꽃 추출물의 당 대사 기능 개선 효과 확인 11] Confirmation of improvement of sugar metabolism function of cockscomb flower extract in high-fat diet obese mouse animal model
맨드라미 꽃 추출물의 고지방식 비만 마우스 동물모델에서 나타나는 당 대사 기능 개선 효과를 확인하기 위하여, 상기 실시예 6의 마우스에서 경구포도당부하검사(oral glucose tolerance test; 이하 OGTT라 함) 및 인슐린 내성 검사(Insulin tolerance test; 이하 ITT라 함)를 수행하였다. 먼저, OGTT test를 위해 상기 실시예 6의 마우스를 12시간 절식(fasting)시킨 후, 포도당(glucose) 2g/kg을 1회 경구투여(oral gavage)하고, 20분마다 혈액을 채취하여 Gluco Dr. Auto Blood Glucose Monitoring System(Allmedicus, Korea)으로 혈당을 측정하였다. 또한, ITT test를 위해, 상기 실시예 6의 마우스를 6시간 절식시킨 후, 인슐린 0.5U/kg을 1회 복강투여(intraperitoneal injection)하고, 20분마다 혈액을 채취하여 Gluco Dr. Auto Blood Glucose Monitoring System(Allmedicus, Korea)으로 혈당을 측정하였다.In order to confirm the effect of cockscomb flower extract on improving sugar metabolism function in a high-fat diet obese mouse animal model, oral glucose tolerance test (hereinafter referred to as OGTT) and insulin tolerance test (Insulin Resistance Test) in mice of Example 6 A tolerance test; hereinafter referred to as ITT) was performed. First, for the OGTT test, the mice of Example 6 were fasted for 12 hours, and then oral gavage was administered with 2 g/kg of glucose once, and blood was collected every 20 minutes, and Gluco Dr. Blood glucose was measured using an Auto Blood Glucose Monitoring System (Allmedicus, Korea). In addition, for the ITT test, after the mice of Example 6 were fasted for 6 hours, insulin 0.5U/kg was administered once intraperitoneally (intraperitoneal injection), blood was collected every 20 minutes, and Gluco Dr. Blood glucose was measured using an Auto Blood Glucose Monitoring System (Allmedicus, Korea).
그 결과, 도 12에 나타난 바와 같이, 맨드라미 꽃 추출물 투여군에서 HFD군에 비해 당 대사 기능 및 인슐린 저항성이 개선되는 것을 확인하였다.As a result, as shown in FIG. 12, it was confirmed that sugar metabolism function and insulin resistance were improved in the cockscomb flower extract administration group compared to the HFD group.
[[ 실시예Example 12] 고지방식 비만 마우스 동물모델에서 맨드라미 꽃 추출물의 지방세포 분화 관련 전사인자의 발현억제 효과 확인 12] Confirmation of the effect of cockscomb flower extract on the expression of transcription factors related to adipocyte differentiation in a high-fat diet obese mouse animal model
맨드라미 꽃 추출물이 고지방식 비만 마우스 모델에서 나타나는 지방조직 내 지방세포 분화 관련 전사인자의 발현에 미치는 영향을 알아보기 위하여, Real time quantitative PCR을 수행하였다. 구체적으로, 상기 실시예 6의 마우스 지방조직을 500㎕의 TRIzol 시약(Invitrogen, USA)을 이용하여 RNA를 추출하였다. 이후 100㎕의 클로로폼(chloroform)을 넣어 4℃ 및 12,000rpm 조건에서 20분간 원심분리하여 얻어진 상층액과 동량의 이소프로필알코올(isopropyl alcohol)을 넣고, 상온에서 5분 방치한 후, 4℃ 및 12,000rpm 조건에서 20분간 원심분리하였다. 상층액을 제거한 펠렛(pallet)은 70% 에탄올로 세척한 후 충분히 건조시켰다. 건조된 펠렛은 RNase-free dH2O에 용해한 후 260nm 및 280nm에서 흡광도를 측정하여 OD260/OD280 ratio RNA의 순도(purity)를 알아보고, OD260 값으로 RNA를 정량하였다.To investigate the effect of cockscomb flower extract on the expression of transcription factors related to adipocyte differentiation in adipose tissue in a high-fat diet obese mouse model, real time quantitative PCR was performed. Specifically, RNA was extracted from the mouse adipose tissue of Example 6 using 500 μl of TRIzol reagent (Invitrogen, USA). Thereafter, 100 μl of chloroform was added, and the same amount of isopropyl alcohol as the supernatant obtained by centrifugation at 4 ° C and 12,000 rpm for 20 minutes was added, and after leaving at room temperature for 5 minutes, 4 ° C and It was centrifuged for 20 minutes at 12,000 rpm condition. The pellet from which the supernatant was removed was washed with 70% ethanol and sufficiently dried. The dried pellet was dissolved in RNase-free dH 2 O, and then the absorbance was measured at 260 nm and 280 nm to determine the purity of the OD 260 / OD 280 ratio RNA, and the RNA was quantified by the OD 260 value.
추출된 RNA를 DNase가 포함되어있는 RevertAid™ First Strand cDNA Synthesis Kit(Thermo scientific, USA)를 이용하여 cDNA로 합성하고, TB green(TaKaRa, Japan)과 GAPDH(glyceraldehyde-3-phosphate dehydrogenase), PPARγ, C/EBPα 및 FABP4 프라이머를 이용하여 Real-time PCR(CFX Connect Real-Time System, BIO-RAD, USA)을 수행하였다. 대조군 유전자로는 GAPDH를 사용하였다. 또한, Real-time PCR system을 이용하여 형광 신호를 정량하였다. 데이터는 2-△△CT 방법으로 분석하였으며, 3회 반복 실험하였다. 사용한 유전자의 프라이머 서열은 상기 표 1과 같다. The extracted RNA was synthesized into cDNA using RevertAid™ First Strand cDNA Synthesis Kit (Thermo scientific, USA) containing DNase, and TB green (TaKaRa, Japan), GAPDH (glyceraldehyde-3-phosphate dehydrogenase), PPARγ, Real-time PCR (CFX Connect Real-Time System, BIO-RAD, USA) was performed using C/EBPa and FABP4 primers. GAPDH was used as a control gene. In addition, fluorescence signals were quantified using a real-time PCR system. Data were analyzed by the 2 -ΔΔCT method, and the experiment was repeated three times. The primer sequences of the genes used are shown in Table 1 above.
그 결과, 도 13에 나타난 바와 같이, 맨드라미 꽃 추출물은 농도 의존적으로 지방합성 전사인자(PPARγ, C/EBPα 및 FABP4)의 발현 억제 효과를 나타내는 것을 확인하였다.As a result, as shown in FIG. 13, it was confirmed that the cockscomb flower extract exhibited an effect of inhibiting the expression of lip synthesis transcription factors (PPARγ, C/EBPα, and FABP4) in a concentration-dependent manner.
[[ 실시예Example 13] 고지방식 비만 마우스 동물모델에서 맨드라미 꽃 추출물의 체중 감소 효과 확인 13] Confirmation of weight loss effect of cockscomb flower extract in high fat diet obese mouse animal model
상기 실시예 6에서 확인한 고지방식 비만 마우스 모델에서 맨드라미 꽃 추출물의 체중감소 효과를 보다 구체적으로 확인하기 위해, 4주령 마우스를 반입하고 순화 과정을 거쳐 마우스의 각 개체별 체중을 측정하여 군 간의 유의한 차이가 없도록 군 분리를 시행한 다음, 4주간 각각 ND 및 HFD를 4주간 섭취시켰다. 그 다음, 총 2가지 용량(중농도; 50mg/kg/day, 고농도; 100mg/kg/day)의 맨드라미 꽃 추출물을 각각 정상식이 및 고지방식이 사료와 혼합한 후, 8주간 섭취시키면서 일주일마다 체중을 측정하였다.In order to more specifically confirm the weight loss effect of cockscomb flower extract in the high-fat diet obese mouse model confirmed in Example 6, 4-week-old mice were brought in and the weight of each individual mouse was measured through a acclimatization process to determine significant differences between groups. Group separation was performed so that there was no difference, and then ND and HFD were consumed for 4 weeks, respectively. Then, a total of two doses (medium concentration: 50 mg/kg/day, high concentration: 100 mg/kg/day) of cockscomb flower extract were mixed with normal diet and high-fat diet feed, respectively, and then fed for 8 weeks, and the body weight was given every week. was measured.
그 결과, 도 14에 나타난 바와 같이, ND군과 ND 및 맨드라미 꽃 추출물 섭취군(ND+CC50 및 ND+CC100)간의 유의미한 체중변화는 나타나지 않은 반면, HFD 및 맨드라미 꽃 추출물 섭취군(HFD+CC50 및 HFD+CC100)은 HFD군에 비해 유의미한 체중 감소가 나타나는 것을 확인하였다.As a result, as shown in FIG. 14, there was no significant weight change between the ND group and the ND and cockscomb flower extract intake groups (ND + CC50 and ND + CC100), whereas the HFD and cockscomb flower extract intake groups (HFD + CC50 and ND + CC100) HFD+CC100) confirmed a significant weight loss compared to the HFD group.
[[ 실시예Example 14] 맨드라미 꽃 추출물의 고지방식 비만 마우스 동물모델(High-fat diet obesity mouse model)을 지방세포 분화 관련 전사인자의 발현억제 효과 확인 14] Confirmation of inhibition of the expression of transcription factors related to adipocyte differentiation in a high-fat diet obesity mouse model of cockscomb flower extract
상기 실시예 12에서 확인한 고지방식 비만 마우스 모델에서 맨드라미 꽃 추출물의 지방세포 분화 관련 전사인자의 발현억제 효과를 보다 구체적으로 확인하기 위해, Real time quantitative PCR을 수행하였다. 구체적으로, 상기 실시예 13의 마우스 지방조직을 500㎕의 TRIzol 시약(Invitrogen, USA)을 이용하여 RNA를 추출하였다. 이후 100㎕의 클로로폼(chloroform)을 넣어 4℃ 및 12,000rpm 조건에서 20분간 원심분리하여 얻어진 상층액과 동량의 이소프로필알코올(isopropyl alcohol)을 넣고, 상온에서 5분 방치한 후, 4℃ 및 12,000rpm 조건에서 20분간 원심분리하였다. 상층액을 제거한 펠렛(pallet)은 70% 에탄올로 세척한 후 충분히 건조시켰다. 건조된 펠렛은 RNase-free dH2O에 용해한 후 260nm 및 280nm에서 흡광도를 측정하여 OD260/OD280 ratio RNA의 순도(purity)를 알아보고, OD260 값으로 RNA를 정량하였다.In order to more specifically confirm the effect of suppressing the expression of transcription factors related to adipocyte differentiation of cockscomb flower extract in the high-fat diet obese mouse model confirmed in Example 12, Real time quantitative PCR was performed. Specifically, RNA was extracted from the mouse adipose tissue of Example 13 using 500 μl of TRIzol reagent (Invitrogen, USA). Thereafter, 100 μl of chloroform was added, and the same amount of isopropyl alcohol as the supernatant obtained by centrifugation at 4 ° C and 12,000 rpm for 20 minutes was added, and after leaving at room temperature for 5 minutes, 4 ° C and It was centrifuged for 20 minutes at 12,000 rpm condition. The pellet from which the supernatant was removed was washed with 70% ethanol and sufficiently dried. The dried pellet was dissolved in RNase-free dH 2 O, and then the absorbance was measured at 260 nm and 280 nm to determine the purity of the OD 260 / OD 280 ratio RNA, and the RNA was quantified by the OD 260 value.
추출된 RNA를 DNase가 포함되어있는 RevertAid™ First Strand cDNA Synthesis Kit(Thermo scientific, USA)를 이용하여 cDNA로 합성하고, TB green(TaKaRa, Japan)과 GAPDH(glyceraldehyde-3-phosphate dehydrogenase), PPARγ, C/EBPα 및 FABP4 프라이머를 이용하여 Real-time PCR(CFX Connect Real-Time System, BIO-RAD, USA)을 수행하였다. 대조군 유전자로는 GAPDH를 사용하였다. 또한, Real-time PCR system을 이용하여 형광 신호를 정량하였다. 데이터는 2-△△CT 방법으로 분석하였으며, 3회 반복 실험하였다. 사용한 유전자의 프라이머 서열은 하기 표 2와 같다. The extracted RNA was synthesized into cDNA using RevertAid™ First Strand cDNA Synthesis Kit (Thermo scientific, USA) containing DNase, and TB green (TaKaRa, Japan), GAPDH (glyceraldehyde-3-phosphate dehydrogenase), PPARγ, Real-time PCR (CFX Connect Real-Time System, BIO-RAD, USA) was performed using C/EBPa and FABP4 primers. GAPDH was used as a control gene. In addition, fluorescence signals were quantified using a real-time PCR system. Data were analyzed by the 2 -ΔΔCT method, and the experiment was repeated three times. Primer sequences of the genes used are shown in Table 2 below.
그 결과, 도 15에 나타난 바와 같이, 맨드라미 꽃 추출물은 농도 의존적으로 지방합성 전사인자인 PPARγ(Peroxisome proliferator-activated receptor γ), C/EBPα(CCAAT/enhancer binding protein α), FABP4(Fatty acid binding protein 4) 및 FASN(Fatty acid synthase) 유전자 발현 억제 효과를 나타내는 것을 확인하였다.As a result, as shown in FIG. 15, the cockscomb flower extract concentration-dependently expressed the fat synthesis transcription factors PPARγ (Peroxisome proliferator-activated receptor γ), C/EBPα (CCAAT/enhancer binding protein α), and FABP4 (Fatty acid binding protein). 4) and FASN (Fatty acid synthase) gene expression suppression effect was confirmed.
이상으로 본 발명의 특정한 부분을 상세히 기술한 바, 당업계의 통상의 지식을 가진 자에게 있어서 이러한 구체적인 기술은 단지 바람직한 구현 예일 뿐이며, 이에 본 발명의 범위가 제한되는 것이 아닌 점은 명백하다. 따라서, 본 발명의 실질적인 범위는 첨부된 청구항과 그의 등가물에 의하여 정의된다고 할 것이다.Having described specific parts of the present invention in detail above, it is clear that these specific techniques are only preferred embodiments for those skilled in the art, and the scope of the present invention is not limited thereto. Accordingly, the substantial scope of the present invention will be defined by the appended claims and equivalents thereof.
본 발명의 범위는 후술하는 특허청구범위에 의하여 나타내어지며, 특허청구범위의 의미 및 범위 그리고 그 균등개념으로부터 도출되는 모든 변경 또는 변형된 형태가 본 발명의 범위에 포함되는 것으로 해석되어야 한다.The scope of the present invention is indicated by the claims to be described later, and all changes or modifications derived from the meaning and scope of the claims and equivalent concepts thereof should be construed as being included in the scope of the present invention.
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