KR101132174B1 - AMPK activators from Erythrina abyssinica, and compositions for prevention and treatment of metabolic syndromes through activation of AMPK enzyme containing the same as an active ingredients - Google Patents
AMPK activators from Erythrina abyssinica, and compositions for prevention and treatment of metabolic syndromes through activation of AMPK enzyme containing the same as an active ingredients Download PDFInfo
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- KR101132174B1 KR101132174B1 KR1020100013217A KR20100013217A KR101132174B1 KR 101132174 B1 KR101132174 B1 KR 101132174B1 KR 1020100013217 A KR1020100013217 A KR 1020100013217A KR 20100013217 A KR20100013217 A KR 20100013217A KR 101132174 B1 KR101132174 B1 KR 101132174B1
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- obesity
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Abstract
본 발명은 아프리카 식물 에리스리나 아비시니카 (Erythrina abyssinica) 유래의 AMP-활성 단백질키나제 효소(AMP-activated protein kinase; AMPK)를 활성화시키는 화합물 및 이를 유효성분으로 포함하는 조성물에 관한 것으로 상기 조성물은 당뇨, 비만 또는 대사증후군의 예방 및 치료 효과가 있다.The present invention is an African plant Erythrina Abyssinica ( Erythrina). Abyssinica ) relates to a compound for activating AMP-activated protein kinase (AMPK) derived from abyssinica and a composition comprising the same as an active ingredient, the composition has a prevention and treatment effect of diabetes, obesity or metabolic syndrome .
Description
본 발명은 아프리카 식물 에리스리나 아비시니카 (Erythrina abyssinica) 유래의 AMP-활성 단백질 키나제 효소(AMP-activated protein kinase; AMPK)를 활성화시키는 화합물 및 이를 유효성분으로 포함하는 당뇨, 비만 또는 대사증후군(metabolic syndrome)의 예방과 치료용 조성물에 관한 것이다.The present invention is an African plant Erythrina Abyssinica ( Erythrina). It relates to a compound for activating AMP-activated protein kinase (AMPK) derived from abyssinica ) and a composition for preventing and treating diabetes, obesity or metabolic syndrome comprising the same as an active ingredient.
보다 자세하게는 본 발명은 에리스리나 아비시니카를 메탄올 추출한 후 크로마토그래피를 이용하여 순수 분리 정제하여 얻은 AMPK 활성화 화합물과 이를 효율적으로 추출, 정제하여 얻는 화합물을 유효성분으로 함유하는 당뇨, 비만 또는 대사증후군(metabolic syndrome)의 예방과 치료용 조성물에 관한 것이다. More specifically, the present invention is a diabetic, obesity or metabolic syndrome containing an AMPK activating compound obtained by methanol extraction of erythrina abicinica and purified by pure separation using chromatography and a compound obtained by efficiently extracting and purifying it as an active ingredient ( It relates to a composition for the prevention and treatment of metabolic syndrome.
최근 경제발전에 따른 생활수준의 향상으로 위생환경이 개선되고 식생활이 계속적으로 향상되고 있다. 그러나 과도한 음식량으로 섭취 열량은 증가하는 반면 운동 부족 등으로 소비되는 열량이 적어 비만이 증가하는 경향을 보이고 있다. 비만은 젊은이들에게 있어서 마른 체형을 좋아하는 미용적인 모습을 해칠 뿐만 아니라 비만이 지속됨으로서 여러 가지 질환, 즉, 고혈압, 당뇨, 고지혈증, 관상동맥질환 등과 같은 성인병을 비롯하여 유방암, 자궁암 및 대장암 등을 야기하는 것으로 보고되면서 이제는 치명적인 질병으로 취급되고 있다[J. Biol. Chem., 273, 32487-32490 (1998); Nature, 404, 652-660 (2000)].Recently, due to the improvement of living standards according to economic development, the hygiene environment is improved and the dietary life is continuously improved. However, the amount of calories consumed due to excessive food, while the amount of calories consumed due to lack of exercise is showing a tendency to increase obesity. Obesity not only harms young people's skin-like beauty, but also keeps obesity alive, leading to various diseases such as hypertension, diabetes, hyperlipidemia and coronary artery disease, as well as breast cancer, uterine cancer and colon cancer. It is reported to cause it and is now treated as a fatal disease [J. Biol. Chem., 273, 32487-32490 (1998); Nature, 404, 652-660 (2000).
현재 비만을 치료하는 치료제로는 크게 중추 신경계에 작용하여 식욕에 영향을 주는 약제와 위장관에 작용하여 흡수를 저해하는 약물로 나누어 볼 수 있다. 중추 신경계에 작용하는 약물로는 각각의 기전에 따라 세로토닌(5-HT) 신경계를 저해하는 펜플루라민, 덱스펜플루라민 등의 약물, 노르아드레날린 신경계를 통한 에페드린, 카페인 등의 약물, 세로토닌 및 노르아드레날린 신경계에 동시 작용하여 비만을 저해하는 시부트라민 등의 약물들이 시판되고 있다. 이외에도, 위/장관에 작용하여 비만을 저해하는 약물로 장관 리파제를 저해하여 지방의 흡수를 줄여 주는 오를리스타트 등이 대표적인 약물로 사용되고 있다. 그러나 기존에 사용되어온 약물 중 펜플루라민 등의 약물은 부작용으로 원발성 폐고혈압이나 심장 판막병변을 일으켜 최근에 사용이 금지되었으며, 다른 약물들도 혈압감소나 유산산혈증 등의 문제점이 발생하여 심부전, 신질환 등의 환자에는 사용하지 못하는 문제점이 있다.Current treatments for treating obesity can be divided into drugs that affect the central nervous system and affect appetite and drugs that inhibit absorption by acting on the gastrointestinal tract. Drugs that act on the central nervous system include drugs such as fenfluramine and dexfenfluramine that inhibit the serotonin (5-HT) nervous system according to each mechanism, drugs such as ephedrine and caffeine through the noradrenaline nervous system, serotonin and noradrenaline nervous system Drugs such as sibutramine that act and inhibit obesity are commercially available. In addition, orlistat, which inhibits intestinal lipase by acting on gastric / intestinal tract and inhibits obesity, is used as a typical drug. However, drugs such as fenfluramine, which have been used previously, have been banned due to side effects such as primary pulmonary hypertension and heart valve lesions, and other drugs have also caused problems such as decreased blood pressure and lactic acidosis, which can lead to heart failure and kidney disease. The patient has a problem that cannot be used.
따라서 본 발명자는 비만 치료를 위한 보다 개선된 방법을 찾기 위하여 최근 에너지 대사를 조절하는 기전에 관심을 갖게 되었다. 보통 대사증후군 예방 및 치료제는 발병 후 장기간 먹어야 되며 에너지 조절관련 기관이 미토콘드리아이기에 이를 위한 에너지 조절제는 다른 계열의 약물 목표점보다 보다 높은 안전성(낮은 독성)을 가져야 한다는 전제 아래 천연물로부터 AMPK 효소를 활성화하는 약물을 탐색하게 되었다. The present inventors have therefore become interested in the mechanisms of regulating energy metabolism in recent years to find more improved methods for treating obesity. Usually, metabolic syndrome prevention and treatment should be taken for a long time after the onset of the disease, and the energy-regulatory organs are mitochondrial, and the energy regulator for this should be higher safety (low toxicity) than other drug targets. I came to explore.
AMPK는 세포의 영양상태나 운동, 스트레스 등에 의해 변화하는 에너지 상태(ATP/AMP ratio)에 반응하여 활성이 조절되는 인산화 효소로 글루코스 이동(glucose transport), 지방산 합성(fatty acid synthesis), 콜레스테롤 생합성(cholesterol synthesis) 등의 다양한 생리작용에 영향을 미치는 것으로 알려져 있다[Ann. Rev. Pharmacol. Toxicol., 47, 185-210 (2007)]. AMPK is a phosphatase that regulates activity in response to changes in the energy state (ATP / AMP ratio) that is changed by the nutritional state, exercise, or stress of the cell. Glucose transport, fatty acid synthesis, cholesterol biosynthesis ( cholesterol synthesis) and various physiological effects are known [Ann. Rev. Pharmacol. Toxicol., 47, 185-210 (2007).
최근의 보고에 의하면 운동으로 촉진되는 근세포의 글루코오스 흡수(glucose uptake)에 AMPK가 관여하며 이처럼 AMPK는 일반적으로 세포 내에서 에너지 준위를 모니터하는 센서(sensor) 역할을 담당하고 있는 것으로 밝혀졌다. 운동을 하거나 허기진 상태에서 근육세포, 간세포, 지방세포 등은 필요한 에너지를 공급하기 위하여 지방, 글리코겐 등의 합성을 억제하며, 저장물질(지방)로부터 지방분해를 통하여 몸에서 필요한 에너지를 생성하게 하는 역할을 수행하는데 여기에 AMPK가 관여한다는 것이다. 또한, AMPK는 지방세포로부터 분비되는 렙틴(leptin)과 아디포넥틴(adiponectin)의 세포 내 신호전달물질로도 알려져 있다. 특히, 아디포넥틴은 비만인 사람의 혈중에서 정상체중의 사람과 비교하여 낮은 농도로 측정되는 것으로 보아, AMPK가 비만으로 기인한 인슐린 저항성과 높은 관계가 있을 것으로 추정되며, 따라서 AMPK 활성화 물질은 비만의 훌륭한 약물목표점으로 부상하고 있다[Nat. Rev Mol Cell Biol., 8(10), 774-785 (2007)].Recent reports have shown that AMPK is involved in glucose uptake of muscle cells stimulated by exercise, and thus AMPK generally plays a role as a sensor to monitor energy levels in cells. In exercise or hunger, muscle cells, hepatocytes and adipocytes inhibit the synthesis of fat and glycogen to provide the necessary energy, and generate the energy needed by the body through lipolysis from storage materials (fat). AMPK is involved in doing this. AMPK is also known as an intracellular signaling material of leptin and adiponectin secreted from adipocytes. In particular, adiponectin is measured at low concentrations in the blood of obese humans compared to normal weight humans, suggesting that AMPK is highly associated with insulin resistance due to obesity, and therefore AMPK activator is an excellent drug for obesity. Emerging as a target point [Nat. Rev Mol Cell Biol., 8 (10), 774-785 (2007)].
지금까지 경구용 당뇨병 치료용으로 사용하여 왔으나 그 기전을 모르고 있었던 메트포민(metformin)의 약물목표점이 AMPK 활성과 관련성이 있다는 것이 밝혀진 이후부터 많은 기업들은 이들을 목표점으로 약물을 개발하여 왔다. 2008년에 호주의 가르반 의학연구소 팀은 '화학&생물학저널'에 발표한 연구결과로 비터멜론(bitter melon)에서 추출한 4가지 성분이 AMPK를 활성화하여 체내 대사를 조절하는 것으로 보고하였다[Chem Biol., 15(5), 263-273 (2007)].Many companies have been developing drugs targeting these drugs since it has been found that the drug targets of metformin, which have been used to treat oral diabetes but do not know the mechanism, are related to AMPK activity. In 2008, a team published in Australia's Garvan Institute for Medical Research reported that four components derived from bitter melon regulate metabolism in the body by activating AMPK [Chem Biol , 15 (5), 263-273 (2007).
일반적으로 새로운 성분의 약제를 개발하기 위한 여러 가지 방법 중, 기존 약제의 실험적 변형에 의한 약제개발보다는 전통 의학에서 사용되고 있는 천연물 약제들로부터 새로운 활성 성분을 발견하는 것이 약제개발 성공 가능성이 매우 높다. 또한 이러한 활성 성분들은 오랫동안 사용되어 왔기 때문에 약물들에 의한 독성 염려가 적어 바로 약물치료로 사용할 수 있다는 장점이 있다. In general, among the various methods for the development of drugs with new ingredients, finding new active ingredients from natural medicines used in traditional medicine is highly likely to succeed in drug development, rather than the development of drugs by experimental modification of existing drugs. In addition, since these active ingredients have been used for a long time, there is little concern about toxicity due to drugs, and thus there is an advantage that they can be used as a drug treatment.
본 발명의 대상인 에리스리나 아비시니카(Erythrina abyssinica)는 콩과에 속하며 에리스리나 속의 나무는 약 110여 종이나 되는 널리 알려진 식물이다. 에리스리나 속은 열대, 아열대 지역에 걸쳐서 자라며 본 발명의 대상이 되는 에리스리나 아비시니카는 아프리카 중부의 카메룬 지역에 자생하는 나무로 붉은색 꽃을 갖고 있다. 에리스리나 아비시니카의 식물 추출물은 예로부터 아프리카 지역에서 약용식물로 사용하여 왔으며 특히, 항 세균관련 질환에 효능이 있는 것으로 알려져 있다. 본 발명자는 에리스리나 아비시니카로부터 AMPK 효소를 활성화하는 작용을 갖는 7종의 화합물을 분리하여 구조를 확인하였다. 이들 화합물은 코메스탄(coumestan) 계열의 화합물, 프테로카르판(pterocarpan) 계열의 화합물 및 벤조퓨란(Benzofuran) 계열의 화합물이었다. 이들 화합물은 공통적으로 AMPK 효소를 활성화하였으므로 본 발명의 화합물은 비만을 비롯한 대사증후군 예방 및 치료용도로서 사용 가능함을 밝힐 수 있었다. Erythrina abyssinica , which is the subject of the present invention, belongs to the legume and the tree of the genus Erysrina is a well-known plant of about 110 species. The genus Erislina grows across tropical and subtropical regions, and the subject of the present invention is Erislina abyssinica, which is a tree native to Cameroon in central Africa and has red flowers. The plant extract of Erysri abisinica has been used as a medicinal plant in Africa since ancient times, and is known to be particularly effective against antibacterial diseases. The present inventors confirmed the structure by separating seven kinds of compounds having an action of activating the AMPK enzyme from erythrina abysinica. These compounds were coumestan-based compounds, pterocarpan-based compounds and benzofuran-based compounds. Since these compounds commonly activated the AMPK enzyme, it was found that the compounds of the present invention can be used for the prevention and treatment of metabolic syndrome including obesity.
본 발명의 목적은 에리스리나 아비시니카 유래의 AMPK 활성화 작용을 가지며 비만 또는 대사증후군 관련 질환에 예방과 치료 효과를 나타내는 화합물들을 제공하는 데에 있다. An object of the present invention is to provide compounds that have an AMPK activating action derived from erythrina abicinica and exhibit prophylactic and therapeutic effects on obesity or metabolic syndrome-related diseases.
본 발명의 다른 목적은 에리스리나 아비시니카 유래의 AMPK 활성화 작용을 갖는 비만 또는 대사증후군의 예방과 치료 효능을 갖는 화합물들을 각각 혹은 2개 이상 혼합하여 유효성분으로 함유하는 조성물을 제공하는 데에 있다.It is another object of the present invention to provide a composition containing as an active ingredient a mixture of two or more compounds having the prophylactic and therapeutic effect of obesity or metabolic syndrome having an AMPK activating action derived from erythri or abysinica.
본 발명자들은 상기와 같은 점을 감안하여 각종 자생식물 및 한약재를 채집하여 AMPK 활성화 작용을 조사하였으며 최종적으로 에리스리나 아비시니카를 후보식물로 선정하였다. 이 후, 본 식물을 유기용매로 추출하여 AMPK 활성화 작용을 하는 하기 화학식 1로 표시되는 화합물 에리스리비신 F(erythribyssin F, 화합물 1), 에리스리비신 N(erythribyssin N, 화합물 2), 에리스리비신 O(erythribyssin O, 화합물 3), 시그모이딘 K(sigmoidin K, 화합물 4), 이소소자골(isosojagol, 화합물 5), 에리바린 D(eryvarin D, 화합물 6), 에리포에진 F(erypoegin F, 화합물 7)를 추출하였다. In view of the above, the present inventors collected various native plants and herbal medicines to investigate the AMPK activation activity, and finally selected erythrina or abyssinica as candidate plants. Thereafter, the plant is extracted with an organic solvent to act as an AMPK activating compound represented by the following formula (1), erythribysin F (erythribyssin F, compound 1), erythribysin N (erythribyssin N, compound 2), erythribinine Erythribyssin O (compound 3), sigmoidin K (compound 4), isosojagol (compound 5), eryvarin D (compound 6), erypoegin F , Compound 7) was extracted.
상기 화합물은 비만 또는 대사증후군 관련 예방 또는 치료 물질과 AMPK 활성화용 약제 물질 중에서 선택되는 것 중에 적어도 하나의 용도로 사용되는 것을 특징으로 한다. The compound is characterized in that it is used for at least one selected from a prophylactic or therapeutic substance associated with obesity or metabolic syndrome and a pharmaceutical substance for AMPK activation.
상기 화합물은 에리스리나 아비시니카로부터 유래된 것일 수 있다. The compound may be derived from Erysri or Abyssinica.
또한 상기 화합물은 에리스리나 아비시니카의 메탄올 추출물로부터 유래된 것일 수 있다. 메탄올 추출물은 이후 에틸 아세테이트로 추가적으로 분획할 수 있다.In addition, the compound may be derived from the methanol extract of Erysri or Abyssinica. The methanol extract can then be further fractionated with ethyl acetate.
본 발명에 따른 비만 또는 대사증후군 관련 질환의 예방 또는 치료용 조성물은 상기한 화합물들 중 적어도 한 가지 이상의 화합물을 유효성분으로 포함하는 것을 특징으로 한다.The composition for the prevention or treatment of obesity or metabolic syndrome related diseases according to the present invention is characterized in that it comprises at least one compound of the above compounds as an active ingredient.
상기 화합물은,The compound is,
에리스리나 아비시니카를 유기용매로 추출 및 분획하는 단계; Extracting and fractionating erythrina abicinica with an organic solvent;
활성화합물을 크로마토그래피를 이용하여 AMPK를 활성화하는 화합물을 순수하게 분리 정제하는 단계; Purely separating and purifying the compound that activates AMPK using the active compound chromatography;
상기 단계에서 얻은 화합물의 화학구조 및 물리화학적 특성을 조사하는 단계; 및Examining the chemical structure and physicochemical properties of the compound obtained in the step; And
근육 전구세포인 C2C12 세포주를 분화시킨 후 상기 단계의 화합물의 AMPK 활성화를 조사하는 단계;Differentiating a C2C12 cell line, which is a muscle progenitor, and examining AMPK activation of the compound of the above step;
의 과정을 통해 얻어질 수 있다. Can be obtained through the process of.
상기 화합물들의 구조 확인은 물리화학적 특성 및 핵자기공명 스펙트럼의 해석으로부터 확인가능하다. The structural confirmation of the compounds can be confirmed from the interpretation of physicochemical properties and nuclear magnetic resonance spectra.
본 발명에 따른 AMPK 활성화 화합물은 에리스리나 아비시니카로부터 유기용매(알코올, 에테르, 아세톤 등)에 의한 추출, 에틸아세테이트와 물의 분배, 디아이온 HP-20 레진과 같은 흡착수지 사용방법, 칼럼크로마토그래피에 의한 방법 등 식물체 성분의 분리 추출에 이용되는 공지의 방법을 단독 또는 적합하게 조합하여 용이하게 얻을 수가 있다. 조추출물은 필요에 따라서 상법에 따라서 더욱 정제할 수 있다.The AMPK activating compound according to the present invention is extracted from erythrina or abysinica by an organic solvent (alcohol, ether, acetone, etc.), partitioning ethyl acetate and water, using an adsorption resin such as diion HP-20 resin, column chromatography, and the like. A well-known method used for the separate extraction of plant components, such as a method by the above, can be easily obtained by combining individually or suitably. The crude extract can be further purified according to a commercial method as needed.
본 발명에서 사용하는 크로마토그래피에는 실리카겔 칼럼 크로마토그래피(silica gel column chromatography), 엘에이취-20 칼럼 크로마토그래피(LH-20 column chromatography), 박층 크로마토그래피(TLC; thin layer chromatography) 및 고성능 액체 크로마토그래피(high performance liquid chromatography) 등이 이용될 수 있다.The chromatography used in the present invention includes silica gel column chromatography, L-20 column chromatography, thin layer chromatography (TLC) and high performance liquid chromatography (TLC). high performance liquid chromatography) and the like.
본 발명에 따른 화합물은 AMPK 활성화에 작용하므로 비만 또는 대사증후군 관련 예방 또는 치료에 효능이 있으며 생체 내 이용성이 높아서 유리하게 활용할 수 있다. Since the compound according to the present invention acts on AMPK activation, it is effective in preventing or treating obesity or metabolic syndrome and can be advantageously utilized due to its high bioavailability.
본 발명에 따른 화합물은 에리스리나 아비시니카로부터 쉽게 분리할 수 있을 뿐만 아니라 안정도도 높으므로 식품, 의약품의 첨가제로 이용할 수 있다.The compound according to the present invention can be easily separated from erythrica or abyssin and also has high stability, and thus can be used as an additive for food and medicine.
본 발명에 따른 추출물을 포함하는 약학조성물은, 각각 통상의 방법에 따라 산제, 과립제, 정제, 캡슐제, 현탁액, 에멀젼, 시럽, 에어로졸 등의 경구형 제형, 외용제, 좌제 및 멸균 주사용액의 형태로 제형화하여 사용될 수 있다. 추출물을 포함하는 조성물에 포함될 수 있는 담체, 부형제 및 희석제로는 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 들 수 있다. 제제화 할 경우에는 보통 사용하는 충진제, 증량제, 결합제, 습윤제, 붕해제, 계면활성제 등의 희석제 또는 부형제를 사용하여 조제된다. 경구투여를 위한 고형제제에는 정제, 환제, 산제, 과립제, 캡슐제 등이 포함되며, 이러한 고형제제는 상기 추출물에 적어도 하나 이상의 부형제, 예를 들면, 전분, 탄산칼슘, 수크로스 또는 락토오스, 젤라틴 등을 섞어 조제된다. 또한 단순한 부형제 이외에 마그네슘 스테아레이트, 탈크 같은 윤활제들도 사용된다. 경구를 위한 액상 제제로는 현탁제, 내용액제, 유제, 시럽제 등이 해당되는데 흔히 사용되는 단순희석제인 물, 리퀴드 파라핀 이외에 여러 가지 부형제, 예를 들면, 습윤제, 감미제, 방향제, 보존제 등이 포함될 수 있다. 비경구 투여를 위한 제제에는 멸균된 수용액, 비수성용제, 현탁제, 유제, 동결건조 제제, 좌제가 포함된다. 비수성용제, 현탁제로는 프로필렌글리콜, 폴리에틸렌 글리콜, 올리브 오일과 같은 식물성 기름, 에틸올레이트와 같은 주사 가능한 에스테르 등이 사용될 수 있다. 좌제의 기제로는 위텝솔(witepsol), 마크로골, 트윈(tween) 61, 카카오지, 라우린지, 글리세로제라틴 등이 사용될 수 있다. Pharmaceutical compositions comprising extracts according to the invention, in the form of powders, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols and the like, oral preparations, suppositories and sterile injectable solutions, respectively, according to conventional methods. Can be formulated and used. Examples of carriers, excipients and diluents that can be included in the composition containing the extract include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia rubber, alginate, gelatin, calcium phosphate, calcium silicate , Cellulose, methylcellulose, microcrystalline cellulose, polyvinylpyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil. In the case of formulation, a diluent or excipient such as a filler, an extender, a binder, a wetting agent, a disintegrant, or a surfactant is usually used. Solid preparations for oral administration include tablets, pills, powders, granules, capsules, and the like, and such solid preparations include at least one excipient in the extract, for example, starch, calcium carbonate, sucrose or lactose, gelatin, and the like. Are mixed to prepare. In addition to simple excipients, lubricants such as magnesium stearate and talc are also used. Oral liquid preparations include suspensions, solvents, emulsions, and syrups, and may include various excipients, such as wetting agents, sweeteners, fragrances, and preservatives, in addition to commonly used simple diluents such as water and liquid paraffin. have. Formulations for parenteral administration include sterile aqueous solutions, non-aqueous solvents, suspensions, emulsions, lyophilized preparations, suppositories. Examples of the suspending agent include propylene glycol, polyethylene glycol, vegetable oil such as olive oil, injectable ester such as ethyl oleate, and the like. As the base of the suppository, witepsol, macrogol, tween 61, cacao butter, laurin butter, glycerogelatin and the like can be used.
상기 활성성분의 투여량은 치료 받을 대상의 연령, 성별, 체중, 치료할 특정 질환 또는 병리 상태, 질환 또는 병리 상태의 심각도, 투여경로 및 처방자의 판단에 따라 달라질 것이다. 이러한 인자에 기초한 투여량 결정은 당업자의 수준 내에 있으며, 일반적으로 투여량은 0.01㎎/㎏/일 내지 대략 2000㎎/㎏/일의 범위이다. 더 바람직한 투여량은 1㎎/㎏/일 내지 500㎎/㎏/일이다. 투여는 하루에 한 번 투여할 수도 있고, 수 회 나누어 투여할 수도 있다. 상기 투여량은 어떠한 면으로든 본 발명의 범위를 한정하는 것은 아니다. 본 발명의 추출물은 쥐, 가축, 인간 등의 포유동물에 다양한 경로로 투여될 수 있다. 투여의 모든 방식은 예상될 수 있는데, 예를 들면, 경구, 직장 또는 정맥, 근육, 피하, 자궁내 경막 또는 뇌혈관내 주사에 의해 투여될 수 있다. 본 발명의 추출물은 독성 및 부작용은 거의 없으므로 예방 목적으로 장기간 복용시에도 안심하고 사용할 수 있는 약제이다. The dosage of the active ingredient will vary depending on the age, sex, weight of the subject to be treated, the particular disease or pathology to be treated, the severity of the disease or pathology, the route of administration and the judgment of the prescriber. Dosage determination based on these factors is within the level of skill in the art and generally dosages range from 0.01 mg / kg / day to approximately 2000 mg / kg / day. More preferred dosage is 1 mg / kg / day to 500 mg / kg / day. Administration may be once a day or may be divided several times. The dosage does not limit the scope of the invention in any aspect. The extract of the present invention can be administered to mammals such as mice, livestock, humans, etc. by various routes. All modes of administration may be expected, for example, by oral, rectal or intravenous, intramuscular, subcutaneous, intra-uterine dural or intracerebral injection. Since the extract of the present invention has little toxicity and side effects, it is a drug that can be used safely even when taken for long periods of time.
또한, 본 발명은 상기 에리스리나 아비시니카 추출물 및 식품학적으로 허용 가능한 식품보조 첨가제를 포함하는 비만 예방을 위한 건강기능식품을 제공한다. 본 발명의 건강기능식품은 정제, 캡슐제, 환제 또는 액제 등의 형태를 포함하며, 본 발명의 화합물을 첨가할 수 있는 식품으로는, 예를 들어, 각종 식품류, 음료, 껌, 차, 비타민 복합제, 건강기능성식품류 등이 있다. 상세하게는, 본 발명은 에리스리나 아비시니카 추출물을 유효성분으로 함유하는 추출물 및 식품학적으로 허용 가능한 식품보조 첨가제를 포함하는 비만 또는 대사증후군 관련 예방과 치료용 건강 기능 식품을 제공한다. In addition, the present invention provides a health functional food for the prevention of obesity, including the erythrina abicinica extract and a food supplement acceptable food supplement. The health functional food of the present invention includes the form of tablets, capsules, pills or liquids, and the food to which the compound of the present invention can be added, for example, various foods, beverages, gums, teas, vitamin complexes, etc. And health functional foods. In detail, the present invention provides a dietary supplement for the prevention and treatment of obesity or metabolic syndrome, including an extract containing erythrina abicinica extract as an active ingredient and a food supplement acceptable food supplement.
본 발명에 따른 화합물 1 내지 화합물 7을 포함한 조성물은 세포 내에서 AMPK 효소를 활성화하여 에너지 대사과정에 대한 작용을 통하여 비만 또는 대사증후군 관련 예방과 치료의 효과를 기대할 수 있다.
또한 한약재 및 식용차 등의 식품원료로 사용되어 왔던 천연물 에리스리나 아비시니카로부터 추출 분리 정제한 것이므로 세포 독성이 적어 의약품, 화장품 및 식품 산업 등에 매우 유용하게 사용 및 응용될 수 있다. In addition, since it is extracted and purified from the natural product erythrii or abysinica, which has been used as a food raw material such as herbal medicines and edible tea, it has a low cytotoxicity and can be used and applied to medicines, cosmetics, and food industries.
도 1은 에리스리나 아비시니카로부터 얻은 AMP-활성 단백질키나제 효소(AMPK)를 활성화시키는 신규화합물 에리스리비신 N(화합물 1)의 13C-NMR 스펙트럼을 나타낸 것이다.
도 2는 에리스리나 아비시니카로부터 얻은 AMP-활성 단백질키나제 효소를 활성화시키는 신규화합물 에리스리비신 F(화합물 2)의 13C-NMR 스펙트럼을 나타낸 것이다.
도 3은 에리스리나 아비시니카로부터 얻은 AMP-활성 단백질키나제 효소를 활성화시키는 신규화합물 에리스리비신 O(화합물 3)의 13C-NMR 스펙트럼을 나타낸 것이다.
도 4는 에리스리나 아비시니카로부터 얻은 활성 화합물 각각을 분화된 C2C12 세포주에 처리하여 AMPK 효소의 활성을 p-AMPK와 p-ACCs의 발현정도를 통하여 웨스턴 블롯으로 측정한 결과이다.FIG. 1 shows the 13 C-NMR spectrum of a novel compound erythricisin N (Compound 1) activating the AMP-activated protein kinase enzyme (AMPK) obtained from erythrina abysinica.
FIG. 2 shows 13 C-NMR spectra of the novel compound erythrivisin F (Compound 2) activating the AMP-activated protein kinase enzyme obtained from erythrina abysinica.
Figure 3 shows the 13 C-NMR spectrum of the novel compound erythricisin O (Compound 3) activating the AMP-activated protein kinase enzyme obtained from erythrina abysinica.
Figure 4 shows the results of Western blot analysis of the activity of AMPK enzymes through the expression of p-AMPK and p-ACCs by treating each of the active compounds obtained from Erysri or Abysinica in differentiated C2C12 cell lines.
이하 본 발명의 바람직한 실시예를 상세히 설명하기로 한다. 그러나, 본 발명은 여기서 설명되는 실시예에 한정되지 않고 다른 형태로 구체화될 수도 있다. 오히려, 여기서 소개되는 내용이 철저하고 완전해질 수 있도록 그리고 당업자에게 본 발명의 사상이 충분히 전달될 수 있도록 하기 위해 제공되는 것이다. Hereinafter, a preferred embodiment of the present invention will be described in detail. However, the present invention is not limited to the embodiments described herein and may be embodied in other forms. Rather, these embodiments are provided so that this disclosure will be thorough and complete, and will fully convey the concept of the invention to those skilled in the art.
<실시예 1 : 에리스리나 아비시니카로부터 활성화합물의 분리 및 정제>Example 1 Isolation and Purification of the Active Compound from Erysri or Abyssinica
에리스리나 아비시니카의 껍질 5kg을 메탄올 10ℓ를 사용하여 3일씩 3회 실온에서 추출하였다. 상기 메탄올 추출물을 감압 농축한 후 이 추출물 350g을 물로 현탁한 후 n-헥산, 에틸 아세테이트, 부탄올로 순차적으로 용매 분획한 다음 각각의 용매 분획에 대하여 AMPK 활성을 측정한 결과, 에틸 아세테이트 분획에서 강한 활성을 나타내었다. 상기 에틸아세테이트 분획물을 감압농축한 결과 156g의 분획물을 확인할 수 있었다. 에틸아세테이트 분획(45g)은 헥산-아세톤(10:1 → 0:1)의 용매구배 조건으로 실리카겔 컬럼크로마토그래피를 실시하여 5개의 분획을 얻었다(fr.1-5). 분획 F2(2.4g)은 메탄올-물(6:4→1:0)의 용매구배 조건으로 200㎖씩 분취하여 5개의 소분획을 얻었다(fr.2.1-2.5). 소분획 F.2.3은 70% 아세토니트릴(MeCN, acetomitrile)을 용매조건으로 30분간에 걸쳐서 HPLC[Optima Pak C18 column 20×150㎜; 10μm 입자 크기 2㎖/min; UV detection: 254nm]를 실시하여 화합물 1(4.7mg;t R=24.5min)과 화합물 7(27.8mg;t R=26.8min)을 순수하게 분리하였다. 소분획 F.2.4은 78% 아세토니트릴을 용매조건으로 25분 동안 HPLC[Optima Pak C18 column 20×150㎜; 10μm 입자 크기 2㎖/min; UV detection: 254nm]를 실시하여 화합물 6(227.8mg, t R=19.0min)과 화합물 3(5.8mg, t R=22.5min)을 분리하였다. 분획 F3(4g)은 메탄올-물(5:5→1:0)의 용매구배 조건으로 300㎖씩 분취하여 5개의 소분획을 얻었다(fr.3.1-3.5). 소분획 F.3.3은 60% 아세토니트릴을 용매조건으로 HPLC[Optima Pak C18 column 20×150㎜; 10μm 입자 크기 2㎖/min; UV detection: 254nm]를 실시하여 화합물 5(3.7mg,t R=14.5min)와 화합물 2(10.8mg;t R =20.8min)를 얻었다. 소분획 F.3.3은 헥산-아세톤(4:1)의 용매조건으로 실리카겔 컬럼크로마토그래피를 이용하여 화합물 4(15mg)를 순수하게 분리하였다. 5 kg of the shell of erysri abisinica was extracted three times each day at room temperature using 10 liters of methanol. The methanol extract was concentrated under reduced pressure, and then 350 g of the extract was suspended in water, and then solvent fractionation was performed sequentially with n-hexane, ethyl acetate, and butanol, and AMPK activity was measured for each solvent fraction. Indicated. The ethyl acetate fractions were concentrated under reduced pressure, and 156 g of the fractions were confirmed. The ethyl acetate fraction (45 g) was subjected to silica gel column chromatography under a solvent gradient of hexane-acetone (10: 1 to 0: 1) to obtain five fractions (fr.1-5). Fraction F2 (2.4 g) was collected in 200 ml portions under a solvent gradient of methanol-water (6: 4 → 1: 0) to obtain 5 small fractions (fr.2.1-2.5). Small fraction F.2.3 was prepared using HPLC [Optima Pak C 18 column 20 × 150 mm over 30 minutes using 70% acetonitrile (MeCN, acetomitrile); 10
표 1은 에리스리나 아비시니카 추출 용매분획에 대한 AMPK 활성화 측정 결과로서 활성 측정은 실시예 3의 방법을 이용하였다. AMPK 활성화 정도는 에틸아세테이트 분획에서 가장 강하게 나타났다. Table 1 shows the results of measuring the AMPK activation of the erythrina abicinica extract solvent fractions. The degree of AMPK activation was the strongest in the ethyl acetate fraction.
에리스리나 아비시니카 용매분획
Erysrina Abysinica Solvent Fraction
AMPK 활성화 농도 (㎍/㎖)
AMPK activation concentration (µg / ml)
메탄올 추출물 (A 분획)
Methanol Extract (A Fraction)
200
200
n-헥산 (B 분획)
n-hexane (B fraction)
500
500
에틸아세테이트 (C 분획)
Ethyl acetate (C fraction)
50
50
부탄올 (D 분획)
Butanol (D fraction)
300
300
<< 실시예Example 2 : 화합물의 물리화학적 특성 및 화학구조 분석> 2: Physical and chemical properties and chemical structure analysis of compounds>
상기 에리스리나 아비시니카의 껍질로부터 분리된 화합물은 두 쌍의 방향성 수소를 갖는다는 것을 1H, 13C-NMR 분석 결과로부터 확인하였으며 화합물 1 내지 화합물 3은 신규화합물로 밝혀졌다. It was confirmed from the 1 H, 13 C-NMR analysis that the compound isolated from the shell of the erythrina abysinica had two pairs of aromatic hydrogens and
화합물 1은 흰색 분말로 수득되었으며 분자식은 고질량분석기(HRESIMS)에서 350.1154의 측정치로부터 C21H18O5로 결정되었다. 수소 핵자기 공명스펙트럼(1H NMR)은 프레닐기를 존재를 암시하는 δ H 3.68 (2H, d), 5.36 (1H, m), 1.67 (3H, s), 1.91 (3H, s)과 ABX-형태의 방향성 프로톤을 δ H 6.96 (1H, br, s), 7.02 (1H, br, d)와 7.91 (1H, d) 및 한 쌍의 오르소(ortho) 연결된 δ H 7.17 (1H, d, J=8.4Hz)와 7.74 (1H, d, J = 8.4 Hz)를 확인하였다. 각 치환기의 위치는 에치엠비시(HMBC)의 연결로부터 확인하였는데 δ H 3.96에서 측정되는 메톡시 프로톤으로부터 C-9 (δ C 157.3)와 δ H 3.68의 메틸렌 프로톤으로부터 C-9 (δ C 157.3), C-10 (δ C 115.1)과 C-10a (δ C 156.5)의 관찰로부터 이 화합물은 3-hydroxy-9-methoxy- 10-(3-methylbut-2-enyl)coumestan으로 신규화합물 에리스리비신 N (erythriby- ssin N, 화합물 1)으로 명명하였다.
화합물 2는 갈색 분말로 얻어졌으며 UV 흡광스펙트럼(UV spectrum)은 2-아릴벤조퓨란 화합물(2-arylbenzofuran)의 특징인 329nm와 345nm에서 흡수밴드를 보여주었다. 고질량분석기의 측정치인 445.1626으로부터 분자식은 C25H26O6으로 확인하였으며, 탄소핵자기공명스펙트럼(13C NMR)으로부터 2-아릴벤조퓨란의 특징인 올레피닉 4급탄소를 δ C 159.1와 δ C 111.1에서 확인하였다. 수소 핵자기 공명스펙트럼으로부터 오르소 방향족 수소 δ H 7.70 (1H, d, J=7.5, 4-H)과 6.92(1H, d, J=7.5, 5-H), 2개의 단일 방향족 수소를 δ H 6.56 (1H, s, 3′-H)와 7.34 (1H, s, 6′-H)에서 또한 2개의 프레닐(prenyl)기를 확인하였다. 각 치환기의 최종 위치는 에치엠비시(HMBC) 결과인 한 개의 프레닐기는 H-1″로부터 C-6, C-7과 C-8로의 연결로부터 7번에 연결됨을 다른 프레닐기는 H-1″′로부터 C-4′, C-5′ 및 H-6′로부터 C-1″′으로부터 5′에 연결함을 알았다. 화합물 2는 2-[2′,4′-dihydroxy-5′-(3-methylbut-2-enyl)phenyl]-6-hydroxy-7-(3-methylbut- 2-enyl)-1-benzofuran-3-oic acid로 에리스리비신 F(erythribyssin F, 화합물 2)로 명명하였다.
화합물 3은 노란색 분말로 얻어졌으며 그것의 분자량은 350.1154로 측정된 고질량분석기의 결과치로부터 C21H18O5으로 결정하였다. 수소 핵자기 공명스펙트럼으로부터 6번 위치의 프테로카르펜(pterocarpene) 수소인 δ H 5.75 (2H, s)를 확인할 수 있었다. 또한, δ H 6.45와 7.82로부터 방향족 단일수소를 δ H 6.89와 7.18에서 J=8.4Hz를 갖는 방향족 오르소 관계의 수소 및 프레닐기를 확인하였다. 신규화합물 3에 존재하는 알데하이드 기는 수소 핵자기 공명스펙트럼으로부터 δ H 9.94 (1H, s)와 탄소 핵자기 공명스펙트럼으로부터 상응하는 탄소의 측정치를 δ C 196.1에서 확인하였다. 최종적으로 에치엠비시(HMBC) 결과인 알데하이드(δ H 9.94)와 C-2 (δ C 116.6), C-3 (δ C 164.9)의 위치확인을 통하여 구조를 확정하였다. 따라서, 화합물 3은 3,9-dihydroxy-10-prenyl-2-formyl-6a,11a-dehydroxypterocarpan으로 에리스리비신 O(erythribyssin O, 화합물 3)로 명명하였다.
도 1 내지 도 3은 화합물 1 내지 화합물 3의 13C NMR 스펙트럼을 나타낸다.1 to 3 show 13 C NMR spectra of
이전에 보고된 화합물이지만 AMPK 활성화 작용이 처음 밝혀진 화합물 4 내지 화합물 7은 시그모이딘 K(sigmoidin K, 화합물 4), 이소소자골(isosojagol, 화합물 5), 에리바린 D(eryvarin D, 화합물 6) 및 에리포에진 F(erypoegin F, 화합물 7)이었다.
상기 화합물 4 내지 화합물 7은 수소 핵자기 공명스펙트럼, 탄소 핵자기 공명스펙트럼과 질량 분석스펙트럼 및 UV 흡수스펙트럼과의 비교를 통하여 그 구조 및 물리화학적 성질을 확인하였다.
2-1. 에리스리비신 N(erythribyssin N, 화합물 1) 2-1. Erythribyssin N (compound 1)
성상: 흰색 분말Appearance: white powder
분자량: 350.1154 Molecular Weight: 350.1154
분자식: C21H18O5 Molecular Formula: C 21 H 18 O 5
UV 흡광 스펙트럼 (c 0.02, MeOH): λ max nm: 210, 214, 242, 299, 336, 352 nm UV absorption spectrum ( c 0.02, MeOH): λ max nm: 210, 214, 242, 299, 336, 352 nm
수소핵자기공명스펙트럼 (500 MHz, acetone-d 6): δ 7.91(1H, d, J=9.0, H-1), 7.74(1H, d, J=8.4, H-7), 7.17(1H, d, J=8.4, H-8), 7.02(1H, br d, J=7.8, H-2), 6.96(1H, br s, H-4), 5.36(1H, t-like, J=7.2, H-2′), 3.96(3H, 9-OCH3), 3.68(2H, d, J=7.2, H-1′), 1.91(3H, s, H-5′), 1.67(3H, s, H-4′); Hydrogen nuclear magnetic resonance spectrum (500 MHz, acetone- d 6 ): δ 7.91 (1H, d, J = 9.0, H-1), 7.74 (1H, d, J = 8.4, H-7), 7.17 (1H, d, J = 8.4, H-8), 7.02 (1H, br d, J = 7.8, H-2), 6.96 (1H, br s, H-4), 5.36 (1H, t-like, J = 7.2 , H-2 '), 3.96 (3H, 9-OCH 3 ), 3.68 (2H, d, J = 7.2, H-1'), 1.91 (3H, s, H-5 '), 1.67 (3H, s , H-4 ′);
탄소핵자기공명스펙트럼 (125 MHz, acetone-d 6): δ 161.4(C-11a), 162.9(C-3), 158.6(C-6), 157.3(C-9), 156.5(C-10a), 155.5(C-5), 132.9(C-3′), 123.7(C-1), 122.4(C-2′), 119.0(C-7), 117.8(C-6b), 115.1(C-10), 114.7(C-8), 110.2(C-2), 105.7(C-11b), 104.3(C-4), 103.5(C-6a), 25.9(C-4′), 23.4(C-1′), 18.0(C-5′).Carbon nuclear magnetic resonance spectrum (125 MHz, acetone- d 6 ): δ 161.4 (C-11a), 162.9 (C-3), 158.6 (C-6), 157.3 (C-9), 156.5 (C-10a) , 155.5 (C-5), 132.9 (C-3 '), 123.7 (C-1), 122.4 (C-2'), 119.0 (C-7), 117.8 (C-6b), 115.1 (C-10 ), 114.7 (C-8), 110.2 (C-2), 105.7 (C-11b), 104.3 (C-4), 103.5 (C-6a), 25.9 (C-4 '), 23.4 (C-1 ′), 18.0 (C-5 ′).
2-2. 에리스리비신 F(erythribyssin F, 화합물 2) 2-2. Erythribyssin F (compound 2)
성상: 갈색 분말Appearance: Brown Powder
분자량: 445.1626 Molecular Weight: 445.1626
분자식: C25H26O6 Molecular Formula: C 25 H 26 O 6
UV 흡광 스펙트럼 (c 0.025, MeOH): λ max nm: 329, 345 nm UV absorption spectrum ( c 0.025, MeOH): λ max nm: 329, 345 nm
수소핵자기공명스펙트럼 (500 MHz, acetone-d 6): 7.70(1H, d, J=7.5, H-4), 7.34(1H, s, H-5′), 6.92(1H, d, J=7.5, H-5), 6.56(1H, s, H-2′), 5.39(1H, m, H-2″), 5.36(1H, m, H-2″′), 3.59(2H, d, J=7.0, H-1″), 3.31(2H, d, J=7.0, H-1″′), 1.83(3H, s, H-5″), 1.72 (6H, s, H-4″′와 H-5″′), 1.66(3H, s, H-4″); Hydrogen nuclear magnetic resonance spectrum (500 MHz, acetone- d 6 ): 7.70 (1H, d, J = 7.5, H-4), 7.34 (1H, s, H-5 '), 6.92 (1H, d, J = 7.5, H-5), 6.56 (1H, s, H-2 ′), 5.39 (1H, m, H-2 ″), 5.36 (1H, m, H-2 ″ ′), 3.59 (2H, d, J = 7.0, H-1 ″), 3.31 (2H, d, J = 7.0, H-1 ″ ′), 1.83 (3H, s, H-5 ″), 1.72 (6H, s, H-4 ″ ′ And H-5 "'), 1.66 (3H, s, H-4 ");
탄소핵자기공명스펙트럼 (125 MHz, acetone-d 6): δ 168.9(-COOH), 159.1(C-2), 158.9(C-4′), 156.5(C-2′), 154.6(C-8), 153.6(C-6), 132.8(C-6′), 132.5(C-3″′), 132.2(C-3″), 124.0(C-2″′), 123.1(C-2″), 121.1(C-5′), 120.7(C-9), 120.4(C-4), 113.6(C-5), 119.9(C-7), 112.0(C-1′), 111.1(C-3), 105.5(C-3′), 28.4(C-1″′), 26.0(C-4″′), 25.9(C-4″), 23.3(C-1″), 18.1(C-5″), 17.9 (C-5″′).Carbon nuclear magnetic resonance spectrum (125 MHz, acetone- d 6 ): δ 168.9 (-COOH), 159.1 (C-2), 158.9 (C-4 '), 156.5 (C-2'), 154.6 (C-8 ), 153.6 (C-6), 132.8 (C-6 '), 132.5 (C-3 ″'), 132.2 (C-3 ″), 124.0 (C-2 ″ ′), 123.1 (C-2 ″) , 121.1 (C-5 '), 120.7 (C-9), 120.4 (C-4), 113.6 (C-5), 119.9 (C-7), 112.0 (C-1'), 111.1 (C-3 ), 105.5 (C-3 ′), 28.4 (C-1 ″ ′), 26.0 (C-4 ″ ′), 25.9 (C-4 ″), 23.3 (C-1 ″), 18.1 (C-5 ″ ), 17.9 (C-5 ″ ′).
2-3. 에리스리비신 O(erythribyssin O, 화합물 3) 2-3. Erythribyssin O (compound 3)
성상: 노란색 분말Appearance: Yellow Powder
분자량: 350.1154 Molecular Weight: 350.1154
UV 흡광 스펙트럼 (c 0.025, MeOH): λ max nm: 210, 214, 242, 299, 336, 352 nm UV absorption spectrum ( c 0.025, MeOH): λ max nm: 210, 214, 242, 299, 336, 352 nm
수소핵자기공명스펙트럼 (500 MHz, acetone-d 6): δ 9.94(1H, -CHO), 7.82(1H, s, H-1), 7.18(1H, d, J=8.4, H-7), 6.89(1H, d, J=8.4, H-8), 6.45(1H, s, H-4), 5.75(2H, s, H-6), 5.40(1H, m, H-2′), 3.64(2H, d, J=7.2, H-1′), 1.88(3H, s, H-5′), 1.67(3H, s, H-4′); Hydrogen nuclear magnetic resonance spectrum (500 MHz, acetone- d 6 ): δ 9.94 (1H, -CHO), 7.82 (1H, s, H-1), 7.18 (1H, d, J = 8.4, H-7), 6.89 (1H, d, J = 8.4, H-8), 6.45 (1H, s, H-4), 5.75 (2H, s, H-6), 5.40 (1H, m, H-2 ′), 3.64 (2H, d, J = 7.2, H-1 '), 1.88 (3H, s, H-5'), 1.67 (3H, s, H-4 ');
탄소핵자기공명스펙트럼 (125 MHz, acetone-d 6): δ 196.1(2-CHO), 162.9(C-3), 161.4(C-11a), 158.6(C-6), 157.3(C-9), 156.5(C-10a), 155.5(C-4a), 132.9(C-3′), 123.7(C-1), 122.4(C-2′), 119.0(C-7), 117.8(C-6b), 115.1(C-10), 114.7(C-8), 110.2(C-2), 105.7(C-11b), 104.3(C-4), 103.5(C-6a), 25.9(C-5′), 23.4(C-1′), 18.0(C-4′).Carbon nuclear magnetic resonance spectrum (125 MHz, acetone- d 6 ): δ 196.1 (2-CHO), 162.9 (C-3), 161.4 (C-11a), 158.6 (C-6), 157.3 (C-9) , 156.5 (C-10a), 155.5 (C-4a), 132.9 (C-3 '), 123.7 (C-1), 122.4 (C-2'), 119.0 (C-7), 117.8 (C-6b ), 115.1 (C-10), 114.7 (C-8), 110.2 (C-2), 105.7 (C-11b), 104.3 (C-4), 103.5 (C-6a), 25.9 (C-5 ' ), 23.4 (C-1 ′), 18.0 (C-4 ′).
2-4. 시그모이딘 K(sigmoidin K, 화합물 4) 2-4. Sigmoidin K (compound 4)
성상: 갈색 Appearance: Brown
UV 흡광 스펙트럼 (c 0.025, MeOH): λ max nm: 210, 242, 288, 316, 352 nmUV absorption spectrum ( c 0.025, MeOH): λ max nm: 210, 242, 288, 316, 352 nm
수소핵자기공명스펙트럼 (500MHz, acetone-d 6): δ 7.72(1H, s, H-1), 7.59(1H, d, J=8.0, H-7), 7.04(1H, d, J=8.0, H-8), 6.96(1H, s, H-4), 5.44(1H, t-like, J=7.5, H-2″), 5.40 (1H, t-like, J=7.5, H-2′), 3.69(2H, d, J=7.5, H-1′), 3.44(2H, d, J=7.5, H-1″), 1.95(3H, s, H-5′), 1.81(3H, s, H-5″), 1.77(3H, s, H-4″), 1.69(3H, s, H-4′); Hydrogen Nuclear Magnetic Resonance Spectrum (500MHz, acetone- d 6 ): δ 7.72 (1H, s, H-1), 7.59 (1H, d, J = 8.0, H-7), 7.04 (1H, d, J = 8.0 , H-8), 6.96 (1H, s, H-4), 5.44 (1H, t-like, J = 7.5, H-2 ''), 5.40 (1H, t-like, J = 7.5, H-2 ′), 3.69 (2H, d, J = 7.5, H-1 ′), 3.44 (2H, d, J = 7.5, H-1 ″), 1.95 (3H, s, H-5 ′), 1.81 (3H , s, H-5 ″), 1.77 (3H, s, H-4 ″), 1.69 (3H, s, H-4 ′);
탄소핵자기공명스펙트럼 (125 MHz, acetone-d 6): δ 160.8(C-11a), 159.5(C-3), 158.7(C-6), 156.1(C-9), 154.9(C-10a), 154.5(C-4a), 134.1(C-3″), 132.6(C-3′), 127.4(C-2), 122.6(C-2″와 C-2′), 122.2(C-1), 118.9(C-7), 116.8(C-6b), 114.4(C-8), 113.4(C-10), 105.9(C-11b), 103.9(C-6a), 28.4(C-1″), 26.1(C-5″), 26.0(C-4′), 23.5(C-1′), 18.0(C-5′), 17.9(C-4″).Carbon nuclear magnetic resonance spectrum (125 MHz, acetone- d 6 ): δ 160.8 (C-11a), 159.5 (C-3), 158.7 (C-6), 156.1 (C-9), 154.9 (C-10a) , 154.5 (C-4a), 134.1 (C-3 ″), 132.6 (C-3 ′), 127.4 (C-2), 122.6 (C-2 ″ and C-2 ′), 122.2 (C-1) , 118.9 (C-7), 116.8 (C-6b), 114.4 (C-8), 113.4 (C-10), 105.9 (C-11b), 103.9 (C-6a), 28.4 (C-1 ″) , 26.1 (C-5 ″), 26.0 (C-4 ′), 23.5 (C-1 ′), 18.0 (C-5 ′), 17.9 (C-4 ″).
2-5. 이소소자골(isosojagol, 화합물 5) 2-5. Isosojagol (compound 5)
성상: 갈색 분말 Appearance: Brown Powder
UV 흡광 스펙트럼 (c 0.01, MeOH): λ max nm: 208, 242, 316, 343 nmUV absorption spectrum ( c 0.01, MeOH): λ max nm: 208, 242, 316, 343 nm
수소핵자기공명스펙트럼 (500 MHz, acetone-d 6): δ 7.92(1H, d, J=9.0, H-1), 7.02(1H, dd, J=9.0, 2.5, H-2), 6.94(1H, d, J=2.5, H-4), 7.60(1H, d, J=8.5, H-7), 7.05(1H, d,J=8.5, H-8), 5.42(1H, m, H-2′), 3.69(2H, d, J=7.0, H-1′), 1.90(3H, s, H-5′), 1.67(3H, s, H-4′); Hydrogen nuclear magnetic resonance spectrum (500 MHz, acetone- d 6 ): δ 7.92 (1H, d, J = 9.0, H-1), 7.02 (1H, dd, J = 9.0, 2.5, H-2), 6.94 ( 1H, d, J = 2.5, H-4), 7.60 (1H, d, J = 8.5, H-7), 7.05 (1H, d, J = 8.5, H-8), 5.42 (1H, m, H -2 '), 3.69 (2H, d, J = 7.0, H-1'), 1.90 (3H, s, H-5 '), 1.67 (3H, s, H-4');
탄소핵자기공명스펙트럼 (125 MHz, acetone-d 6): δ 162.5(C-3), 161.1(C-11a), 158.9(C-6), 156.6(C-9), 155.9(C-10a), 154.9(C-4a), 132.3(C-3′), 123.2(C-2′), 122.9(C-1), 119.2(C-7), 117.1(C-6b), 114.7(C-10), 114.5(C-8), 111.1(C-2), 105.5(C-11b), 104.0(C-4), 103.7(C-6a), 26.1(C-4′), 23.7(C-1′), 18.0(C-5′).Carbon Nuclear Magnetic Resonance Spectrum (125 MHz, acetone- d 6 ): δ 162.5 (C-3), 161.1 (C-11a), 158.9 (C-6), 156.6 (C-9), 155.9 (C-10a) , 154.9 (C-4a), 132.3 (C-3 '), 123.2 (C-2'), 122.9 (C-1), 119.2 (C-7), 117.1 (C-6b), 114.7 (C-10 ), 114.5 (C-8), 111.1 (C-2), 105.5 (C-11b), 104.0 (C-4), 103.7 (C-6a), 26.1 (C-4 '), 23.7 (C-1 ′), 18.0 (C-5 ′).
2-6. 에리바린 D(eryvarin D, 화합물 6) 2-6. Eryvarin D,
성상: 갈색 분말 Appearance: Brown Powder
수소핵자기공명스펙트럼 (500 MHz, acetone-d 6): δ 8.70 (1H, br s, 3-OH), 7.34 (1H, d, J=8.0, H-1), 7.24(1H, d, J=8.5, H-7), 6.95(1H, d, J=8.5, H-8), 6.53 (1H, d, J=8.0, H-2), 6.44(1H, d, J=2.5, H-4), 5.54 (1H, s, H-6), 5.33 (2H, m, H-2′), 3.89 (3H, 9-OCH3), 3.60 (2H, d, J=7.5, H-1′), 1.87 (3H, s, H-5′), 1.66(3H, s, H-4′);Hydrogen Nuclear Magnetic Resonance Spectrum (500 MHz, acetone- d 6 ): δ 8.70 (1H, br s, 3-OH), 7.34 (1H, d, J = 8.0, H-1), 7.24 (1H, d, J = 8.5, H-7), 6.95 (1H, d, J = 8.5, H-8), 6.53 (1H, d, J = 8.0, H-2), 6.44 (1H, d, J = 2.5, H- 4), 5.54 (1H, s, H-6), 5.33 (2H, m, H-2 ′), 3.89 (3H, 9-OCH 3 ), 3.60 (2H, d, J = 7.5, H-1 ′ ), 1.87 (3H, s, H-5 '), 1.66 (3H, s, H-4');
탄소핵자기공명스펙트럼 (125 MHz, acetone-d 6): δ 159.9(C-3), 156.4(C-4a), 155.9(C-9), 155.4(C-10a), 148.3(C-11a), 132.3(C-3′), 123.0(C-2′), 122.0(C-1), 120.5(C-6b), 116.8(C-7), 114.6(C-10), 109.7(C-11b), 109.5(C-2), 108.9(C-8), 106.7(C-6a), 104.6(C-4), 66.1(C-6), 57.0(9-OCH3), 25.9(C-4′), 23.5(C-1′), 18.0(C-5′)Carbon Nuclear Magnetic Resonance Spectrum (125 MHz, acetone- d 6 ): δ 159.9 (C-3), 156.4 (C-4a), 155.9 (C-9), 155.4 (C-10a), 148.3 (C-11a) , 132.3 (C-3 '), 123.0 (C-2'), 122.0 (C-1), 120.5 (C-6b), 116.8 (C-7), 114.6 (C-10), 109.7 (C-11b ), 109.5 (C-2), 108.9 (C-8), 106.7 (C-6a), 104.6 (C-4), 66.1 (C-6), 57.0 (9-OCH 3 ), 25.9 (C-4 ′), 23.5 (C-1 ′), 18.0 (C-5 ′)
2-7. 에리포에진 F(erypoegin F, 화합물 7) 2-7. Erypoegin F (compound 7)
성상: 갈색 분말Appearance: Brown Powder
UV 흡광 스펙트럼 (c 0.02, MeOH): λ max nm: 219, 289, 331, 346 nmUV absorbance spectrum ( c 0.02, MeOH): λ max nm: 219, 289, 331, 346 nm
수소핵자기공명스펙트럼 (500 MHz, acetone-d 6): 10.17(1H, s, -CHO), 7.91(1H, d, J=8.5, H-4), 7.53(1H, d, J=8.5, H-6′), 7.07(1H, d, J=8.5, H-5), 6.61(1H, dd, J=8.5, 2.0, H-5′), 6.65(1H, d, J=2.0, H-2′), 5.34(1H, t-like, J=7.5, H-2″), 3.59(2H, d, J=7.5, H-1″), 1.81(3H, s, H-5″), 1.64 (3H, s, H-4″); Hydrogen nuclear magnetic resonance spectrum (500 MHz, acetone- d 6 ): 10.17 (1H, s, -CHO), 7.91 (1H, d, J = 8.5, H-4), 7.53 (1H, d, J = 8.5, H-6 ′), 7.07 (1H, d, J = 8.5, H-5), 6.61 (1H, dd, J = 8.5, 2.0, H-5 ′), 6.65 (1H, d, J = 2.0, H -2 '), 5.34 (1H, t-like, J = 7.5, H-2 "), 3.59 (2H, d, J = 7.5, H-1"), 1.81 (3H, s, H-5 ") , 1.64 (3H, s, H-4 ″);
탄소핵자기공명스펙트럼 (125 MHz, acetone-d 6): δ 188.1(-CHO), 164.0(C-2), 162.1(C-4′), 157.9(C-2′), 156.5(C-6), 154.5(C-8), 133.5(C-6′), 132.5(C-3″), 123.5(C-2″), 120.1(C-4), 119.9(C-9), 117.8(C-3), 114.1(C-7), 109.9(C-5), 109.1(C-5′), 109.0(C-1′), 104.2(C-3′), 25.9(C-4″), 23.4(C-1″), 18.0(C-5″).Carbon nuclear magnetic resonance spectrum (125 MHz, acetone- d 6 ): δ 188.1 (-CHO), 164.0 (C-2), 162.1 (C-4 '), 157.9 (C-2'), 156.5 (C-6 ), 154.5 (C-8), 133.5 (C-6 ′), 132.5 (C-3 ″), 123.5 (C-2 ″), 120.1 (C-4), 119.9 (C-9), 117.8 (C -3), 114.1 (C-7), 109.9 (C-5), 109.1 (C-5 '), 109.0 (C-1'), 104.2 (C-3 '), 25.9 (C-4 "), 23.4 (C-1 ″), 18.0 (C-5 ″).
<<
실시예Example
3 : 3:
에리스리나Erisrina
아비시니카로부터From Abyssinica
분리된 화합물 1 내지 화합물 7의 Of
에리스리나 아비시니카로부터 분리 정제한 화합물 1 내지 화합물 7의 AMPK 활성화 효능을 측정하기 위하여 C2C12 근원세포주(myoblast cell line)를 사용하여 웨스턴 블롯을 수행하여 측정하였다. C2C12 세포를 6-웰(wells) 플레이트에 접종한 후 10% 우혈청이 포함된 DMEM 배지를 사용하여 배양시킨 후 분화를 유도하기 위하여 1% FBS를 포함한 DMEM 배지로 치환하였다. 세포의 분화를 확인한 후 16시간 동안 무혈청 상태의 DMEM 배지로 유지한 후에 각 화합물은 최종농도 5μM의 농도로 처리하였으며 양성 대조군으로 아이카(Aicar) 100μM를 각각 처리한 후 2시간 동안 배양한 후에 세포를 수거해 초음파로 파쇄하여 단백질을 얻었다. 아이카(Aicar, aminoimidazole carboxamide ribonucleotide)는 AMPK 활성을 위한 양성대조군으로 사용하였으며 화합물의 용매인 DMSO(세포 배지의 0.1% 이내로 사용)가 음성대조군으로 사용되었다. 이 후, 10% SDS-PAGE 전기영동을 실시하고 PVDF 멤브레인(membrane)에 단백질을 이동시켰다. 이후 5% 탈지유로 1시간 동안 상온에서 유지한 후 인산화된 AMPK(phospho-AMPK, Thr172) 항체를 이용하여 4℃에서 18시간 이상 유지하고 이를 이용하여 단백질 발현량을 확인하였다. 에너지 대사과정에서 AMPK 활성의 증가는 ACCs(acetyl-CoA carboxylase 1 및 2)의 인산화를 증가시키는 것으로 알려져 있으므로 AMPK 활성화를 확인하기 위하여 동일한 방법으로 수득한 단백질을 이용하여 인산화된 ACCs(phospho-ACCs)를 확인하였다.
에리스리나 아비시니카로부터 분리한 화합물 1 내지 화합물 7의 AMPK 활성화 작용을 측정한 결과는 도 4에 나타내었다. The results of measuring the AMPK activating action of
도 4를 참조하면 코메스탄(coumestan) 계열의 화합물인 화합물 1, 화합물 4, 화합물 5가 가장 강한 활성을 보여주었으며 다른 화합물도 AMPK 활성이 강한 것으로 나타났다. Referring to FIG. 4,
<< 실시예Example 4 : 4 : DIODIO (( DietDiet -- InducedInduced ObesityObesity ) 모델에서 ) Model 항비만Anti-obesity 효과 검정> Effect Black>
[1 단계] 시료준비[Step 1] Sample Preparation
항비만 효과를 확인하기 위해 동물실험에 사용된 화합물 2와 화합물 4는 100mg/kg의 농도로 매일 경구투여 하였으며 경구투여 전 투여 약물은 메틸셀룰로오스(Sigmaco.USA) 5% 수용액에 녹여서 준비하였다.
[2 단계] 실험군 설정 및 체중감량 효과 검증[Step 2] Experiment group setting and weight loss effect verification
본 실험을 진행하기 위하여 7주령의 C57BL/6J 수컷 생쥐를 대상으로 군당 10마리씩 준비하였으며, 1주간의 적응기간을 가진 후, 개별 우리에 분리하여 12시간 간격의 낮(오전 7시~오후5시)과 밤의 주기에 따라 관리하였다. 실험군은 1)고지방식이군, 2)고지방식이와 더불어 화합물 2 100mg/kg/day 섭취군, 3)고지방식이와 더불어 화합물 4 100mg/kg/day 섭취군의 총 3개 군으로 나뉘어 1일 1회씩 8주 동안 일정한 시간(오전 10시)에 경구로 투여하였다. 체중은 매주 1회(오전 11시) 측정을 실시하였으며, 투여시작 8주 후에 실험군과 대조군의 최종 체중을 측정하여 분석하였다. 표 2는 각 물질을 경구투여한 후 체중 변화량을 측정한 결과이다.In order to conduct the experiment, 10 rats were prepared per group of 7-week-old male C57BL / 6J mice, and after 1 week of adaptation, they were separated into individual cages and divided into 12-hour daytime (7 am-5pm). ) And nightly cycles. The experimental group was divided into three groups: 1) a high-fat diet group, 2) a high-fat diet and a
그 룹
group
경구투여 후 체중변화량 (g)
Weight change after oral administration (g)
고지방식이
High-fat diet
±0.454.45
± 0.45
±0.236.23
± 0.23
±0.788.56
± 0.78
±0.3410.45
± 0.34
±0.8611.56
± 0.86
±0.2312.32
± 0.23
±0.7613.78
± 0.76
고지방식이
High-fat diet
±0.562.75
± 0.56
±0.753.43
± 0.75
±0.344.19
± 0.34
±0.346.31
± 0.34
±0.347.24
± 0.34
±0.238.21
± 0.23
±0.458.45
± 0.45
고지방식이
High-fat diet
±0.232.62
± 0.23
±0.343.33
± 0.34
±0.454.45
± 0.45
±0.756.43
± 0.75
±0.747.64
± 0.74
±0.648.34
± 0.64
±0.638.23
± 0.63
실험 실시 후 56일 경과 시점에서 각 투여군의 체중을 비교하여 보면, 표 2 에 나타난 바와 같이 고지방식이만 섭취하였던 군에 비해서 화합물 2나 화합물 4를 고지방식이와 함께 섭취한 군의 체중증가가 확연히 낮음을 확인할 수 있다. 고지방식이 투여군의 체중은 13.78g 증가한 반면, 화합물 2 투여군의 체중은 8.45g 증가하였으며 화합물 4의 투여군의 체중은 8.23g이 증가하였다. 이러한 체중 증가량은 고지방식이 투여군과 비교했을 때 95% 신뢰수준에서 통계적으로 유의하게 체중 증가가 억제되었다고 할 수 있다. Comparing the body weight of each administration group at 56 days after the experiment, the weight gain of the
<실시예 5 : 독성실험>Example 5 Toxicity Test
5-1. 급성독성5-1. Acute Toxicity
에리스리나 아비시니카로부터 추출된 활성분획과 화합물 1 내지 화합물 7을 함유한 분획의 단기간에 과량을 섭취하였을 시 급성적(24시간 이내)으로 동물 체내에 미치는 독성을 조사하고, 치사율을 결정하기 위하여 본 실험을 수행하였다. 일반적인 마우스인 ICR 마우스 계통 40 마리를 대조군은 10마리, 실험군은 10마리씩 배정하였다. 대조군에는 30% PEG-400만을 투여하고, 실험군은 에리스리나 아비시니카로부터 추출된 활성분획과 화합물 1 내지 화합물 7을 함유한 분획을 1.0g/㎏의 농도로 각각 경구 투여하였다. 투여 24시간 후에 각각의 치사율을 조사한 결과, 대조군과 1.0g/㎏ 농도의 에리스리나 아비시니카로부터 추출된 활성분획과 화합물 1 내지 화합물 7을 함유한 분획을 투여한 실험군에서는 모두 생존하였다. To investigate the toxicity to animals in acute (within 24 hours) of excessively ingesting the active fraction extracted from Erysri abisinica and the
5-2. 실험군 및 대조군의 장기 및 조직 독성 실험5-2. Long-term and tissue toxicity experiments in experimental and control groups
장기 독성 실험은 C57BL/6J 생쥐를 대상으로 동물의 각 장기(조직)에 미치는 영향을 조사하기 위하여 에리스리나 아비시니카로부터 추출된 활성분획과 화합물 1 내지 화합물 7을 함유한 분획을 투여한 실험군과 용매만을 투여한 대조군의 동물들로부터 8주 후 혈액을 채취하여 GPT(glutamate-pyruvate transferase) 및 BUN(Blood Urea Nitrogen)의 혈액 내 농도를 Select E(Vital Scientific NV, Netherland) 기기를 이용하여 측정하였다. 그 결과, 간독성과 관계있는 것으로 알려진 GPT와 신장독성과 관계있는 것으로 알려진 BUN의 경우, 대조군과 비교하여 실험군은 별다른 차이를 보이지 않았다. 또한, 각 동물로부터 간과 신장을 정취하여 통상적인 조직절편 제작과정을 거쳐 광학현미경으로 조직학적 관찰을 시행하였으며 특이한 이상이 관찰되지 않았다. In the long-term toxicity experiment, C57BL / 6J mice were treated with an active fraction extracted from erythrina abisinica and a
<실시예 6 : 약학적 제제예>Example 6 Pharmaceutical Formulation Example
6-1. 정제의 제조6-1. Manufacture of tablets
본 발명에 따른 에리스리나 아비시니카 추출물 또는 이로부터 분리된 화합물 200g을 락토오스 175.9g, 감자전분 180g 및 콜로이드성 규산 32g과 혼합하였다. 이 혼합물에 10% 젤라틴 용액을 첨가시킨 후, 분쇄해서 14 메쉬체를 통과시켰다. 이것을 건조시키고 여기에 감자전분 160g, 활석 50g 및 스테아린산 마그네슘 5g을 첨가해서 얻은 혼합물을 정제로 만들었다. 200 g of the erythrina abicinica extract according to the present invention or a compound isolated therefrom was mixed with 175.9 g of lactose, 180 g of potato starch, and 32 g of colloidal silicic acid. 10% gelatin solution was added to the mixture, which was then ground and passed through a 14 mesh sieve. It was dried and the mixture obtained by adding 160 g of potato starch, 50 g of talc and 5 g of magnesium stearate was made into a tablet.
6-2. 주사액제의 제조6-2. Preparation of Injection
본 발명에 따른 에리스리나 아비시니카 추출물 또는 이로부터 분리된 화합물을 1g, 염화나트륨 0.6g 및 아스코르브산 0.1g을 증류수에 용해시켜서 100㎖를 만들었다. 이 용액을 병에 넣고 20℃에서 30분간 가열하여 멸균시켰다.1 g, 0.6 g of sodium chloride, and 0.1 g of ascorbic acid were dissolved in distilled water to make 100 ml of the extract of erythrina abicinica or a compound isolated therefrom according to the present invention. The solution was bottled and sterilized by heating at 20 ° C. for 30 minutes.
<실시예 7 : 식품 제조예>Example 7 Food Preparation Example
7-1. 조리용 양념의 제조7-1. Preparation of Cooking Seasonings
본 발명에 따른 에리스리나 아비시니카 추출물 또는 이로부터 분리된 화합물을 각각 0.2~10 중량%로 첨가하여 건강 증진용 조리용 양념을 제조하였다.Erisrina abicinica extract according to the present invention or a compound isolated therefrom was added 0.2 to 10% by weight, respectively, to prepare a cooking seasoning for health promotion.
7-2. 밀가루 식품의 제조7-2. Manufacture of flour food products
본 발명에 따른 에리스리나 아비시니카 추출물 또는 이로부터 분리된 화합물을 각각 0.1~5.0 중량%를 밀가루에 첨가하고, 이 혼합물을 이용하여 빵, 케이크, 쿠키, 크래커 및 면류를 제조하여 건강 증진용 식품을 제조하였다.0.1 to 5.0% by weight of each of the erythri abicinican extract or the compound isolated therefrom is added to the flour, and bread, cake, cookies, crackers and noodles are prepared using the mixture to prepare foods for health promotion. Prepared.
7-3. 스프 및 육즙(gravies)의 제조7-3. Preparation of soups and gravy
본 발명에 따른 에리스리나 아비시니카 추출물 또는 이로부터 분리된 화합물 각각 0.1~1.0 중량%를 스프 및 육즙에 첨가하여 건강 증진용 육가공 제품, 면류의 수프 및 육즙을 제조하였다.0.1-1.0 wt% of erythrina abiciniica extract or a compound isolated therefrom according to the present invention was added to soups and broths to prepare meat products for health promotion, soups and broths of noodles.
7-4. 유제품(dairy products)의 제조7-4. Manufacture of dairy products
본 발명에 따른 에리스리나 아비시니카 추출물 또는 이로부터 분리된 화합물 각각 0.1~1.0 중량%를 우유에 첨가하고, 상기 우유를 이용하여 버터 및 아이스크림과 같은 다양한 유제품을 제조하였다.0.1-1.0% by weight of each of the erythri abicinicar extract or the compound isolated therefrom according to the present invention was added to milk, and various dairy products such as butter and ice cream were prepared using the milk.
<실시예 8 : 음료 제조예>Example 8 Beverage Preparation Example
8-1. 야채쥬스 제조8-1. Vegetable Juice Manufacturing
본 발명에 따른 에리스리나 아비시니카 추출물 또는 이로부터 분리된 화합물 0.5g을 토마토 또는 당근 쥬스 1,000㎖에 가하여 건강 증진용 야채쥬스를 제조하였다.Health promotion vegetable juice was prepared by adding 0.5 g of the erythrina abicinica extract according to the present invention or the compound isolated therefrom to 1,000 ml of tomato or carrot juice.
8-2. 과일쥬스 제조8-2. Fruit juice manufacturing
본 발명에 따른 에리스리나 아비시니카 추출물 또는 이로부터 분리된 화합물 0.1g을 사과 또는 포도 쥬스 1,000㎖에 가하여 건강 증진용 과일쥬스를 제조하였다.Health promotion fruit juice was prepared by adding 0.1 g of erythrina abicinica extract or a compound isolated therefrom to 1,000 ml of apple or grape juice.
Claims (9)
Prevention of obesity or metabolic syndrome characterized in that it contains an extract of Erythrina abyssinica containing at least one of sigmoidin K (compound 4) and isosogol (compound 5) as an active ingredient Therapeutic pharmaceutical composition.
For improvement of obesity or metabolic syndrome, characterized by containing Erythrina abyssinica extract containing at least one of sigmoidin K (compound 4) and isosogol (compound 5) as an active ingredient Health functional food.
상기 약학조성물은 AMP-활성 단백질키나제(AMP-activated protein kinase; AMPK) 효소의 활성을 증가시키는 것을 특징으로 하는 비만 또는 대사증후군의 예방 또는 치료용 약학조성물.The method of claim 1,
The pharmaceutical composition is a pharmaceutical composition for the prevention or treatment of obesity or metabolic syndrome, characterized in that to increase the activity of AMP-activated protein kinase (AMPK) enzyme.
A pharmaceutical composition for preventing or treating obesity or metabolic syndrome, comprising at least one of sigmoidin K (compound 4) and isosogol (compound 5) as an active ingredient.
상기 조성물은 AMP-활성 단백질키나제(AMPK) 효소의 활성을 증가시키는 것을 특징으로 하는 비만 또는 대사증후군의 예방 또는 치료용 약학조성물.The method of claim 8,
The composition is a pharmaceutical composition for the prevention or treatment of obesity or metabolic syndrome, characterized in that to increase the activity of AMP-active protein kinase (AMPK) enzyme.
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KR101994557B1 (en) | 2017-12-28 | 2019-06-28 | 한국생명공학연구원 | Composition for preventing or treating metabolic syndrome comprising extracts of Viburnum stellato-tomentosum (Oerst.) Hemsl., a fraction thereof |
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KR20190073265A (en) | 2017-12-18 | 2019-06-26 | 한국생명공학연구원 | Composition for preventing or treating metabolic syndrome comprising extracts of Selaginella rossii Warb., a fraction thereof |
KR101994557B1 (en) | 2017-12-28 | 2019-06-28 | 한국생명공학연구원 | Composition for preventing or treating metabolic syndrome comprising extracts of Viburnum stellato-tomentosum (Oerst.) Hemsl., a fraction thereof |
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