KR101303693B1 - Compositions for Improving Lipid Metabolism Disease, Menopause Disease or Cardiovascular Disease - Google Patents
Compositions for Improving Lipid Metabolism Disease, Menopause Disease or Cardiovascular Disease Download PDFInfo
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- KR101303693B1 KR101303693B1 KR1020110064994A KR20110064994A KR101303693B1 KR 101303693 B1 KR101303693 B1 KR 101303693B1 KR 1020110064994 A KR1020110064994 A KR 1020110064994A KR 20110064994 A KR20110064994 A KR 20110064994A KR 101303693 B1 KR101303693 B1 KR 101303693B1
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Abstract
본 발명은 세잎승마(Cimicifuga heracleifolia) 추출물, 눈빛승마(Cimicifuga davurica) 추출물, 왜승마(Cimicifuga japonia) 추출물 및 촛대승마(Cimicifuga simplex) 추출물로 구성된 군으로부터 선택되는 최소 하나의 천연 추출물을 유효성분으로 포함하는 지방 대사 질환, 폐경기 질환 또는 심혈관질환 개선용 식품 조성물에 관한 것으로, 세잎승마 추출물, 눈빛승마 추출물, 왜승마 추출물 및 촛대승마 추출물로 구성된 군으로부터 선택되는 최소 하나의 천연 추출물을 유효성분으로 포함하는 지방 대사 질환, 폐경기 질환 또는 심혈관질환 개선용 식품 조성물 및 예방 또는 치료용 약제학적 조성물을 제공한다. 본 발명의 세잎승마 추출물, 눈빛승마 추출물, 왜승마 추출물 및 촛대승마 추출물, 특히 자생종 식물인 세잎승마 추출물의 지방 대사 질환, 폐경기 질환 또는 심혈관질환의 개선에 대한 신규한 용도를 제시한다. 또한 세잎승마 추출물의 혈중 지질개선 효과는 현재 임상적으로 사용하고 있는 아메리카승마 추출물과 St. John's wort 추출물의 혼합물보다도 높으며, 종래의 아메리카승마 추출물과 유사한 혈관이완작용을 나타내며 이는 심혈관질환의 치료에 이용될 수 있음을 보여준다. 본 발명의 추출물은 폐경기 질환의 예방 또는 치료에 이용될 수 있으며, 여성호르몬 대체제로 이용될 수 있으며, 아메리카승마 수입 대체를 통한 외화절감 효과가 기대된다.The present invention comprises at least one natural extract selected from the group consisting of three leaf ( Cicmicifuga heracleifolia ) extract, Cimicifuga davurica extract, Cimicifuga japonia extract and Cimicifuga simplex extract as an active ingredient The present invention relates to a food composition for improving fat metabolism disease, menopausal disease or cardiovascular disease, comprising: at least one natural extract selected from the group consisting of three-leaf horseback riding, eye riding horse riding, horseback riding and candlestick riding Provided are food compositions for improving fat metabolism disease, menopausal disease or cardiovascular disease, and pharmaceutical compositions for preventing or treating. The present invention proposes a novel use for the improvement of fat metabolism disease, menopausal disease or cardiovascular disease of the three-leaf horse riding extract, eye horseback riding extract, horseback riding extract and candlestick horse riding extract, in particular, three leaf horseback riding extract, a native plant. In addition, the lipid-improving effects of three-leaf horseback riding extracts were similar to those of the American horseback riding extracts currently used clinically. It is higher than the mixture of John's wort extract and shows similar vasorelaxant action as the conventional horseback riding extract, which can be used for the treatment of cardiovascular diseases. Extract of the present invention can be used for the prevention or treatment of menopausal diseases, can be used as a female hormone replacement, and is expected to reduce foreign currency through the replacement of horse riding horses in America.
Description
본 발명은 세잎승마(Cimicifuga heracleifolia) 추출물, 눈빛승마(Cimicifuga davurica) 추출물, 왜승마(Cimicifuga japonia) 추출물 및 촛대승마(Cimicifuga simplex) 추출물로 구성된 군으로부터 선택되는 최소 하나의 천연 추출물을 유효성분으로 포함하는 지방 대사 질환, 폐경기 질환 또는 심혈관질환 개선용 식품 조성물에 관한 것이다.
The present invention is a three- wheeled horse riding ( Cimicifuga heracleifolia extract, Riding Horse ( Cimicifuga) davurica extract, Cimicifuga It relates to a food composition for improving fat metabolism disease, menopause disease or cardiovascular disease comprising at least one natural extract selected from the group consisting of japonia ) extract and Cimicifuga simplex extract as an active ingredient.
승마속(Cimicifuga L.)은 미나리아재비과에 속하는 식물로 전 세계적으로 20여종이 분포하는 것으로 보고되어 있다(1). 본 속에 속하는 식물들은 삼출복엽, 원추상 또는 총상의 꽃차례에 많은 꽃이 달리는 점, 열매인 골돌과의 형태적 차이를 통해 미나리아재비과내 다른 속과 구별된다(1). 본 속에 속하는 식물들은 인도의 캐시미르(Kashmir)에서부터 동쪽으로 히말라야, 중국, 만주, 아무르, 한반도 및 일본을 거쳐 캄챠카, 시베리아의 알타이, 바이칼 및 치타에 이르는 아시아 지역과 북아베리카의 동부와 서부의 일부 지역, 그리고 독일, 헝가리, 폴란드, 루마니아 및 우크라이나를 포함하는 동부 유럽 등 북위 25°에서 60°사이의 북반구 온대지역에 분포하는 것으로 알려져 있다(2). 한반도에는 왜승마(C. japonica (Thunb.) Spreng.), 개승마(C. biternara (Siebold & Zucc.) Miquel), 눈빛승마(C. dahurica (Turcz. ex Fischer & Meyer) Maxim.), 황새승마(C. foetida L.), 승마(C. heracleifolia Komarov), 촛대승마(C. simplex (Mormsk. ex DC.) Turcz.) 및 승마의 변종인 세잎승마(C. eracleifolia var. bifida Nakai)가 분포하는 것으로 보고되었으나 이 중 개승마는 한반도에 분포하지 않고, 황새승마는 한반도 북부의 고산지대에 분포하는 식물로 알려져 있어 휴전선 이남에는 분포하지 않는 것으로 알려져 있다(3). Cimicifuga L. is a plant belonging to the Buttercup family, and it is reported that 20 species are distributed worldwide (1). Plants belonging to the genus are distinguished from other genus in the buttercup family by morphological differences between the exudative, conical or gunshot inflorescences and the fruit of godol (1). Plants belonging to this genus are from the region of Kashmir in India to the east through the Himalayas, China, Manchuria, Amur, the Korean Peninsula and Japan, to Kamchatka, Altai in Siberia, Baikal and Chita, and in the eastern and western parts of North Aberica It is known to be distributed in temperate regions of the northern hemisphere between 25 ° and 60 ° latitudes, including some regions and eastern Europe, including Germany, Hungary, Poland, Romania and Ukraine (2). On the Korean Peninsula, horseback riding ( C. japonica (Thunb.) Spreng.), Horseback riding ( C. biternara (Siebold & Zucc.) Miquel), snow riding ( C. dahurica (Turcz. Ex Fischer & Meyer) Maxim.), Storks Riding (C. foetida L.), horseback riding (C. heracleifolia Komarov), candlesticks and horseback riding (C. simplex (Mormsk. ex DC .) Turcz.) and variants trefoil Riding (C. eracleifolia var. bifida Nakai) is riding Although it is reported to be distributed, the horse riding horses are not distributed on the Korean peninsula, and the stork horses are known to be distributed in the alpine region of the northern part of the Korean peninsula, so it is not known to be distributed below the ceasefire line (3).
한반도 승마속 식물에 대한 연구는 대부분 한약재로 사용되는 승마의 약리학적인 연구, 성분분석, 생리활성물질의 탐색 등이 주를 이루고 있으며 한반도에 인접한 중국, 일본 및 러시아(극동)등의 연구 또한 약리학적 연구 및 생리활성물질 탐색이 주를 이루고 있다. 이러한 승마 속 식물에 대한 생리활성물질의 탐색과 연구, 약재로의 사용은 북아메리카에서도 이루어지며 이 경우는 C. racemosa (L.) Nutt.(아메리카승마)가 주 대상이 되고 있다. 아메리카승마는 블랙 코호시(black cohosh)로 알려져 있으며 전통적으로 폐경기 여성의 폐경관련 증상완화에 사용되어왔고, 다양한 임상적 연구 결과들에 따라 여성호르몬 대체제로서 유럽 및 북미에서 활용이 증가하였다. 또한, 이제까지 블랙 코호시의 효과는 주로 여성호르몬 결핍에 의해 나타나는 안면홍조 및 우울감의 완화 등에 초점이 맞추어져 왔으나(4,5) 최근 들어 이의 여성호르몬으로서의 기능이 없다는 연구보고들이 증가하고 있어 그 효능에 대한 논란이 일고 있다(6-8). 그러나, 일부에서는 아메리카 승마 추출물이 폐경기 여성의 여러 가지 증상에 효과적으로 작용을 나타내어 폐경기 여성의 중요한 문제 중 하나인 심혈관질환에 영향을 미칠 수 있는 혈중 지질 농도의 개선이나, 복부지방 축적의 억제 등이 보고되고 있다(9,10). 국내에서는 이러한 효능을 나타내는 것으로 보고된 블랙 코호시(아메리카승마)를 수입하여 여성호르몬 대체제를 제조 및 판매하고 있으며 그 시장이 1년에 약 386억원에 이르고 있다. 그러나, 우리나라에서도 블랙 코호시와 같은 Cimicifuga 종 식물이 자생하고 있으며, 이의 효과가 블랙 코호시와 유사한 경우 자생종 승마의 재배를 통한 블랙 코호시의 대체가 가능하여 아메리카승마 수입대체를 통한 외화절감과 더불어 자생승마 재배유도를 통한 농가 수익증대도 기대할 수 있을 것으로 사료된다. 따라서 본 연구에서는 폐경기 여성의 여성호르몬 결핍에 따른 주요 후유증의 하나인 혈관기능 저하에 대한 효과를 블랙 코호시와 자생종 승마 추출물을 이용, 비교한 후 난소를 절제한 폐경유도 모델동물에서 자생종 승마 및 블랙 코호시 추출물의 투여가 혈중지질농도에 미치는 효과를 비교하여 자생종 승마의 블랙 코호시 대체제로서의 개발가능성을 확인하였다.
Most studies on horseback riding in the Korean peninsula mainly consist of pharmacological research, ingredient analysis, and search for physiologically active substances, which are used as herbal medicines. Research and the search for bioactive substances are the main focus. The exploration, research and use of physiologically active substances on plants in horseback riding are also carried out in North America. In this case, C. racemosa (L.) Nutt. American horseback riding, known as black cohosh, has traditionally been used to relieve menopause-related symptoms in postmenopausal women, and has been increasingly used in Europe and North America as female hormone replacements, according to various clinical studies. In addition, the effects of black cohosh have been focused mainly on the relief of hot flashes and depression caused by female hormone deficiency (4,5). There is controversy over (6-8). However, some reported that horseback riding extracts were effective in treating various symptoms of postmenopausal women, and thus improved blood lipid levels and suppression of abdominal fat accumulation, which could affect cardiovascular disease, one of the important problems of postmenopausal women. (9,10). In Korea, black cohosh (American Riding Horse), which has been reported to show such efficacy, is imported and manufactured and sold as a female hormone substitute. The market reaches about KRW 38.6 billion a year. However, in Korea, Cimicifuga species such as black cohosh grow naturally, and if its effect is similar to black cohosh, it is possible to replace black cohosh by cultivating native horse riding, and to reduce foreign currency through import substitution of American horseback riding. It is also expected to increase farm income through induction of indigenous riding. In this study, we compared the effects of vascular function, one of the main sequelae of postmenopausal women, with black cohosh and indigenous horseback riding extracts. By comparing the effects of cohosh extract on blood lipid concentration, the possibility of development of black cohosh as a substitute for native horse riding was confirmed.
본 명세서 전체에 걸쳐 다수의 논문 및 특허문헌이 참조되고 그 인용이 표시되어 있다. 인용된 논문 및 특허문헌의 개시 내용은 그 전체로서 본 명세서에 참조로 삽입되어 본 발명이 속하는 기술 분야의 수준 및 본 발명의 내용이 보다 명확하게 설명된다.
Numerous papers and patent documents are referenced and cited throughout this specification. The disclosures of the cited papers and patent documents are incorporated herein by reference in their entirety to better understand the state of the art to which the present invention pertains and the content of the present invention.
본 발명자들은 지방 대사 질환, 폐경기 질환 또는 심혈관질환 개선 효과가 있는 천연물을 개발하고자 노력하였다. 그 결과, 세잎승마 추출물, 눈빛승마 추출물, 왜승마 추출물 및 촛대승마 추출물이 지방 대사 질환, 폐경기 질환 또는 심혈관질환 개선 효과가 우수함을 규명함으로써 본 발명을 완성하게 되었다. The present inventors have tried to develop a natural product having an effect of improving fat metabolism disease, menopause disease or cardiovascular disease. As a result, the present invention was completed by elucidating that the three-leaf horseback riding, eye riding, horseback riding, and candlestick riding were excellent in improving fat metabolism, menopause, or cardiovascular disease.
따라서 본 발명의 목적은 지방 대사 질환, 폐경기 질환 또는 심혈관질환 개선용 식품 조성물을 제공하는데 있다.Accordingly, an object of the present invention is to provide a food composition for improving fat metabolism disease, menopause disease or cardiovascular disease.
본 발명의 다른 목적은 지방 대사 질환, 폐경기 질환 또는 심혈관질환의 예방 또는 치료용 약제학적 조성물을 제공하는데 있다.
Another object of the present invention to provide a pharmaceutical composition for the prevention or treatment of adipose metabolism disease, menopause disease or cardiovascular disease.
본 발명의 다른 목적 및 이점은 하기의 발명의 상세한 설명, 청구범위 및 도면에 의해 보다 명확하게 된다.
Other objects and advantages of the present invention will become more apparent from the following detailed description of the invention, claims and drawings.
본 발명의 일 양태에 따르면, 본 발명은 세잎승마 추출물, 눈빛승마 추출물, 왜승마 추출물 및 촛대승마 추출물로 구성된 군으로부터 선택되는 최소 하나의 천연 추출물을 유효성분으로 포함하는 지방 대사 질환, 폐경기 질환 또는 심혈관질환 개선용 식품 조성물을 제공한다.
According to one aspect of the present invention, the present invention comprises at least one natural extract selected from the group consisting of three-leaf horse riding, eye riding horse, horse riding horse and horse riding horse extract as an active ingredient fat metabolism disease, menopausal diseases or It provides a food composition for improving cardiovascular disease.
본 발명자들은 지방 대사 질환, 폐경기 질환 또는 심혈관질환 개선용 천연물을 개발하고자 노력하였다. 그 결과, 자생종인 세잎승마 추출물, 눈빛승마 추출물, 왜승마 추출물 및 촛대승마 추출물이 지방 대사 질환, 폐경기 질환 또는 심혈관질환의 개선 효과가 우수함을 규명하였다.The present inventors have tried to develop natural products for improving fat metabolism disease, menopause disease or cardiovascular disease. As a result, it was found that the three-leaf horseback riding, snow horseback riding, horseback riding and candlestick riding, which are native species, have an excellent effect of improving fat metabolism disease, menopause disease or cardiovascular disease.
본 명세서에서 세잎승마, 눈빛승마, 왜승마 및 촛대승마을 언급하면서 사용되는 용어 ‘추출물’은 세잎승마, 눈빛승마, 왜승마 및 촛대승마에 추출용매를 처리하여 얻은 추출 결과물뿐만 아니라 세잎승마, 눈빛승마, 왜승마 및 촛대승마 자체를 동물에게 투여할 수 있도록 제형화(예컨대, 분말화)된 세잎승마, 눈빛승마, 왜승마 및 촛대승마 가공물도 포함하는 의미를 갖는다.The term 'extract' used in the present specification while referring to three-leaf horseback riding, eye riding, horseriding and candlestick riding, as well as three leaf horseback riding, eye riding, horse riding and candle riding, as well as the extraction result obtained by treating the extraction solvent , Horseback riding and candlestick horseback riding itself is meant to include the three-wheeled horse riding, eye riding, horseriding and candlestick riding products formulated (eg, powdered) for administration to animals.
본 발명의 조성물에서 이용되는 세잎승마, 눈빛승마, 왜승마 및 촛대승마 추출물을 세잎승마, 눈빛승마, 왜승마 및 촛대승마에 추출용매를 처리하여 얻는 경우에는, 다양한 추출용매가 이용될 수 있다. 바람직하게는, 극성 용매 또는 비극성 용매를 이용할 수 있다. 극성 용매로서 적합한 것은, (i) 물, (ii) 알코올(바람직하게는, 메탄올, 에탄올, 프로판올, 부탄올, 노말-프로판올, 이소-프로판올, 노말-부탄올, 1-펜탄올, 2-부톡시에탄올 또는 에틸렌글리콜), (iii) 아세트산, (iv) DMFO(dimethyl-formamide) 및 (v) DMSO(dimethyl sulfoxide)를 포함한다. 비극성 용매로서 적합한 것은, 아세톤, 아세토나이트릴, 에틸 아세테이트, 메틸 아세테이트, 플루오로알칸, 펜탄, 헥산, 2,2,4-트리메틸펜탄, 데칸, 사이클로헥산, 사이클로펜탄, 디이소부틸렌, 1-펜텐, 1-클로로부탄, 1-클로로펜탄, o-자일렌, 디이소프로필 에테르, 2-클로로프로판, 톨루엔, 1-클로로프로판, 클로로벤젠, 벤젠, 디에틸 에테르, 디에틸 설파이드, 클로로포름, 디클로로메탄, 1,2-디클로로에탄, 어닐린, 디에틸아민, 에테르, 사염화탄소 및 THF(Tetrahydrofuran)를 포함한다.When the three-horse riding, snow riding, horse riding and candle riding horse extract used in the composition of the present invention is obtained by treating the extraction solvent on the three horse riding, snow riding, horse riding and candle riding, various extraction solvents can be used. Preferably, a polar solvent or a nonpolar solvent can be used. Suitable polar solvents include (i) water, (ii) alcohols (preferably methanol, ethanol, propanol, butanol, normal-propanol, iso-propanol, normal-butanol, 1-pentanol, 2-butoxyethanol Or ethylene glycol), (iii) acetic acid, (iv) dimethyl-formamide (DMFO) and (v) dimethyl sulfoxide (DMSO). Suitable as nonpolar solvents are acetone, acetonitrile, ethyl acetate, methyl acetate, fluoroalkane, pentane, hexane, 2,2,4-trimethylpentane, decane, cyclohexane, cyclopentane, diisobutylene, 1- Pentene, 1-chlorobutane, 1-chloropentane, o-xylene, diisopropyl ether, 2-chloropropane, toluene, 1-chloropropane, chlorobenzene, benzene, diethyl ether, diethyl sulfide, chloroform, dichloro Methane, 1,2-dichloroethane, anneal, diethylamine, ether, carbon tetrachloride and THF (Tetrahydrofuran).
보다 바람직하게는, 본 발명에서 이용되는 추출용매는 (a) 물, (b) 탄소수 1-4의 무수 또는 함수 저급 알코올 (메탄올, 에탄올, 프로판올, 부탄올 등), (c) 상기 저급 알코올과 물과의 혼합용매, (d) 아세톤, (e) 에틸 아세테이트, (f) 클로로포름, (g) 부틸아세테이트, (h) 1,3-부틸렌글리콜, (i) 헥산 및 (j) 디에틸에테르를 포함한다. 가장 바람직하게는, 본 발명의 추출물은 물, 에탄올, 메탄올 또는 프로판올을 세잎승마, 눈빛승마, 왜승마 또는 촛대승마에 처리하여 수득한 것이다.More preferably, the extraction solvent used in the present invention is (a) water, (b) anhydrous or hydrated lower alcohol having 1 to 4 carbon atoms (methanol, ethanol, propanol, butanol, etc.) (E) ethyl acetate, (f) chloroform, (g) butyl acetate, (h) 1,3-butylene glycol, (i) hexane and (j) diethyl ether. . Most preferably, the extract of the present invention is obtained by treating water, ethanol, methanol or propanol with three-horse riding, snow riding, horse riding or candle riding.
바람직하게는 본 발명의 조성물은 세잎승마 추출물을 포함한다.Preferably the composition of the present invention comprises a three-leaf horse riding extract.
본 명세서에서 사용되는 용어 ‘추출물’은 상술한 바와 같이 당업계에서 조추출물(crude extract)로 통용되는 의미를 갖지만, 광의적으로는 추출물을 추가적으로 분획(fractionation)한 분획물도 포함한다. 즉, 세잎승마, 눈빛승마, 왜승마 및 촛대승마 추출물은 상술한 추출용매를 이용하여 얻은 것뿐만 아니라, 여기에 정제과정을 추가적으로 적용하여 얻은 것도 포함한다. 예컨대, 상기 추출물을 일정한 분자량 컷-오프 값을 갖는 한외 여과막을 통과시켜 얻은 분획, 다양한 크로마토그래피 (크기, 전하, 소수성 또는 친화성에 따른 분리를 위해 제작된 것)에 의한 분리 등, 추가적으로 실시된 다양한 정제 방법을 통해 얻어진 분획도 본 발명의 세잎승마, 눈빛승마, 왜승마 및 촛대승마 추출물에 포함되는 것이다.As used herein, the term " extract " means that it is used in the art as a crude extract as described above, but broadly includes fractions obtained by further fractionating the extract. That is, three-leaf horseback riding, eye riding, horseback riding and candlestick horseback riding are not only obtained by using the above-mentioned extraction solvent, but also include those obtained by additionally applying a purification process. For example, fractions obtained by passing the extract through an ultrafiltration membrane having a constant molecular weight cut-off value, separation by various chromatography (manufactured for separation according to size, charge, hydrophobicity or affinity), etc. The fraction obtained through the purification method is also included in the three-horse riding, eye riding, horse riding and candlestick riding.
본 발명에서 이용되는 세잎승마, 눈빛승마, 왜승마 및 촛대승마 추출물은 감압 증류 및 동결 건조 또는 분무 건조 등과 같은 추가적인 과정에 의해 분말 상태로 제조될 수 있다.The three-horse riding, snow riding, horse riding and candle riding horse extract used in the present invention may be prepared in powder form by an additional process such as vacuum distillation and freeze drying or spray drying.
본 명세서에서 용어 ‘유효성분으로 포함하는’이란 하기의 세잎승마, 눈빛승마, 왜승마 및 촛대승마의 효능 또는 활성을 달성하는 데 충분한 양을 포함하는 것을 의미한다. 본 발명은 천연식물재료인 세잎승마, 눈빛승마, 왜승마 및 촛대승마로부터 추출한 조성물로서 과량 투여하여도 인체에 부작용이 없으므로 세잎승마 추출물, 눈빛승마 추출물, 왜승마 추출물 및 촛대승마 추출물이 본 발명의 조성물에 포함된 양적 상한은 당업자가 적절한 범위 내에서 선택하여 실시할 수 있다.As used herein, the term 'comprising as an active ingredient' means to include an amount sufficient to achieve the efficacy or activity of the following three horse riding, eye riding, horse riding and candle riding. The present invention is a composition extracted from natural plant material, three-leaf horseback riding, eye riding, horse riding and candle riding horse riding, so there is no side effect to the human body even when the overdose three leaf riding, eye riding horse riding, horse riding and candle riding horse extract of the present invention The upper limit of the amount contained in the composition can be carried out by those skilled in the art selected within the appropriate range.
본 발명에 의해 예방 또는 치료되는 질환은 지방 대사 질환, 폐경기 질환 또는 심혈관질환이다. Diseases that are prevented or treated by the present invention are fatty metabolic diseases, menopausal diseases or cardiovascular diseases.
바람직하게는, 본 발명의 조성물에 의해 예방 또는 치료되는 지방 대사 질환은 비만, 고지혈증 또는 지방간이다.Preferably, the fat metabolism disease prevented or treated by the composition of the present invention is obesity, hyperlipidemia or fatty liver.
하기의 실시예에서 입증된 바와 같이, 세잎승마 추출물의 혈중 지질개선 효과는 현재 임상적으로 사용하고 있는 아메리카승마 추출물과 St. John's wort 추출물의 혼합물보다도 높다.As demonstrated in the following examples, the effect of three-leaf horseback riding on the lipid-improving effect of the three-wheeled horseback riding was similar to that of the American horseback riding extract currently used clinically. Higher than a mixture of John's wort extract.
바람직하게는, 본 발명의 조성물에 의해 예방 또는 치료되는 심혈관질환은 고혈압, 협심증, 급성 관상동맥 증후군, 동맥경화증, 아테롬성 동맥경화증, 경동맥경화증, 뇌혈관 질환, 울혈성 심부전, 선천성 심장병, 관상동맥 질환, 이상지질단백혈증, 혈관내피세포 기능장애, 간헐성파행, 허혈재관류 손상, 허혈 심장질환, 심근경색증, 말초혈관질환, 재협착, 신동맥 죽상경화증 또는 혈전증이다.Preferably, the cardiovascular disease prevented or treated by the composition of the present invention is hypertension, angina, acute coronary syndrome, arteriosclerosis, atherosclerosis, carotid arteriosclerosis, cerebrovascular disease, congestive heart failure, congenital heart disease, coronary artery disease , Dyslipidemia, vascular endothelial dysfunction, intermittent claudication, ischemic reperfusion injury, ischemic heart disease, myocardial infarction, peripheral vascular disease, restenosis, renal artery atherosclerosis or thrombosis.
하기의 실시예에서 입증된 바와 같이, 세잎승마 추출물, 눈빛승마 추출물, 왜승마 추출물 및 촛대승마 추출물, 특히 세잎승마 추출물은 우수한 혈관이완작용을 나타내며, 이는 내피세포에서 나이트릭 옥사이드의 생성을 촉진하는 NO/cGMP 경로가 관여하는 기전을 통해 나타난다. 또한, 세잎승마 추출물의 혈관이완작용에는, 막 전위 조절에 관여하는 포타슘 채널 중 특히 내향성 정류 채널이 관여하는 것으로 판단된다.As demonstrated in the following examples, three-leaf horseback riding, eye riding, horseback riding, and candle riding horseback, in particular three-horse riding, exhibit excellent vasorelaxation, which promotes the production of nitric oxide in endothelial cells. It appears through the mechanism by which the NO / cGMP pathway is involved. In addition, it is considered that the inward rectifying channel is involved in the vascular relaxation action of the three-leaf horseback riding extract.
본 명세서에서 용어 “폐경기 질환”은 전폐경(perimenopausal), 폐경기 및 후폐경(postmenopausal) 시기에 발생되는 모든 증상을 의미한다. 전폐경은 실제적인 폐경이 시작되기 전의 시기이다. 이 전폐경 시기에서 에스트로겐의 생성이 불규칙하게 되며, 여성의 가임능력이 크게 감소한다. 전폐경은 몇 개월 또는 몇 년 동안 지속될 수 있다. 이 전폐경 시기에서도 갱년기(climacteric) 증상이 나타난다.As used herein, the term "menopausal disease" refers to all symptoms that occur during the period of perimenopausal, menopause and postmenopausal. Premenopausal is the period before actual menopause begins. During this premenopausal period, the production of estrogens is irregular and the fertility of women is greatly reduced. Premenopause can last for months or years. Menopausal symptoms also occur during this premenopausal period.
바람직하게는, 본 발명의 조성물에 의해 예방 또는 치료되는 폐경기 질환은 성교통증, 질건조증(vaginal dryness), 수면 장애(sleep disorder), 집중력 이상(mental awareness problem), 관절통, 근골격 질환, 소화불량, 요실금, 피로, 혈관 운동 난조로 인한 신열, 안면 홍조, 야간의 발한, 심계항진(palpitations), 우울증, 불안증(anxiety) 및 과민성(irritability) 등의 갱년기(climacteric) 증상, 골다공증, 비뇨생식기계 질환, 심혈관계 질환, 치매, 치아손실 및 피부 콜라겐 손실을 포함한다.Preferably, the menopausal disease prevented or treated by the composition of the present invention is dyspareunia, vaginal dryness, sleep disorder, mental awareness problem, joint pain, musculoskeletal disorders, indigestion, Urinary incontinence, fatigue, fever due to vascular dystrophy, hot flashes, night sweats, palpitations, depression, anxiety, and irritability, such as climacteric symptoms, osteoporosis, genitourinary system diseases, cardiovascular system Diseases, dementia, tooth loss and skin collagen loss.
하기의 실시예에서 입증된 바와 같이, 세잎승마 추출물의 투여는 난소를 절제하여 폐경을 유도하고, 고콜레스테롤 식이를 섭취한 쥐에서 체중의 증가를 억제하고, 혈중 총 콜레스테롤 및 LDL-콜레스테롤의 농도를 감소시키며 HDL-콜레스테롤의 농도는 저하시키지 않는다. 이와 같은 실험 데이터는 본 발명의 조성물이 폐경기 질환의 예방 또는 치료에 이용될 수 있으며, 여성호르몬 대체제로 이용될 수 있음을 보여주는 것이다.As demonstrated in the examples below, administration of the three-leaf equestrian extract induces menopause by ablation of the ovary, inhibits gain in body weight, and increases blood cholesterol and LDL-cholesterol levels in rats fed a high cholesterol diet. Decreases and does not lower the concentration of HDL-cholesterol. These experimental data show that the composition of the present invention can be used for the prevention or treatment of menopausal diseases, and can be used as a female hormone replacement.
본 발명의 식품 조성물은 유효성분으로서 세잎승마 추출물, 눈빛승마 추출물, 왜승마 추출물 및 촛대승마 추출물뿐만 아니라, 식품 제조 시에 통상적으로 첨가되는 성분을 포함할 수 있으며, 예를 들어, 단백질, 탄수화물, 지방, 영양소, 조미제 및 향미제를 포함한다. 상술한 탄수화물의 예는 모노사카라이드, 예를 들어, 포도당, 과당 등; 디사카라이드, 예를 들어 말토스, 슈크로스, 올리고당 등; 및 폴리사카라이드, 예를 들어 덱스트린, 사이클로덱스트린 등과 같은 통상적인 당 및 자일리톨, 소르비톨, 에리트리톨 등의 당알콜이다. 향미제로서 천연 향미제 [타우마틴, 스테비아 추출물 (예를 들어 레바우디오시드 A, 글리시르히진 등]) 및 합성 향미제(사카린, 아스파르탐 등)를 사용할 수 있다. 예컨대, 본 발명의 식품 조성물이 드링크제로 제조되는 경우에는 본 발명의 세잎승마 추출물, 눈빛승마 추출물, 왜승마 추출물 및 촛대승마 추출물 이외에 구연산, 액상과당, 설탕, 포도당, 초산, 사과산, 과즙, 두충 추출액, 대추 추출액, 감초 추출액 등을 추가로 포함시킬 수 있다.
The food composition of the present invention may include, as an active ingredient, three-leaf horseback riding, eye riding, horseback riding, and horseback riding, as well as components that are commonly added during food production, for example, proteins, carbohydrates, Fats, nutrients, seasonings and flavoring agents. Examples of the above carbohydrates include monosaccharides such as glucose, fructose and the like; Disaccharides such as maltose, sucrose, oligosaccharides and the like; And sugars such as conventional sugars such as polysaccharides such as dextrin, cyclodextrin and the like and xylitol, sorbitol, erythritol. As flavoring agents, natural flavoring agents (tauumatin, stevia extract (for example rebaudioside A, glycyrrhizin, etc.)) and synthetic flavoring agents (saccharin, aspartame, etc.) can be used. For example, when the food composition of the present invention is prepared with a drink, in addition to the three-leaf horse riding, eye riding, horse riding and candle riding horse extract of the present invention citric acid, liquid fructose, sugar, glucose, acetic acid, malic acid, fruit juice, tofu extract , Jujube extract, licorice extract and the like may be further included.
본 발명의 다른 양태에 따르면, 본 발명은 세잎승마 추출물, 눈빛승마 추출물, 왜승마 추출물 및 촛대승마 추출물로 구성된 군으로부터 선택되는 최소 하나의 천연 추출물을 유효성분으로 포함하는 지방 대사 질환, 폐경기 질환 또는 심혈관질환의 예방 또는 치료용 약제학적 조성물을 제공한다.According to another aspect of the present invention, the present invention comprises at least one natural extract selected from the group consisting of three-leaf horse riding, eye riding, horse riding and candle riding horse extract as an active ingredient fat metabolism disease, menopausal diseases or It provides a pharmaceutical composition for the prevention or treatment of cardiovascular diseases.
본 발명의 약제학적 조성물은 약제학적으로 허용되는 담체를 포함한다. 상기 약제학적으로 허용되는 담체는 제제시에 통상적으로 이용되는 것으로서, 락토스, 덱스트로스, 수크로스, 솔비톨, 만니톨, 전분, 아카시아 고무, 인산 칼슘, 알기네이트, 젤라틴, 규산 칼슘, 미세결정성 셀룰로스, 폴리비닐피롤리돈, 셀룰로스, 물, 시럽, 메틸 셀룰로스, 메틸히드록시벤조에이트, 프로필히드록시벤조에이트, 활석, 스테아르산 마그네슘 및 미네랄 오일 등을 포함하나, 이에 한정되는 것은 아니다. 본 발명의 약제학적 조성물은 상기 성분들 이외에 윤활제, 습윤제, 감미제, 향미제, 유화제, 현탁제, 보존제 등을 추가로 포함할 수 있다. 적합한 약제학적으로 허용되는 담체 및 제제는 Remington's Pharmaceutical Sciences (19th ed., 1995)에 상세히 기재되어 있다.The pharmaceutical composition of the present invention includes a pharmaceutically acceptable carrier. The pharmaceutically acceptable carrier is conventionally used in the preparation, lactose, dextrose, sucrose, sorbitol, mannitol, starch, acacia rubber, calcium phosphate, alginate, gelatin, calcium silicate, microcrystalline cellulose, Polyvinylpyrrolidone, cellulose, water, syrup, methyl cellulose, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil, and the like. In addition to the above components, the pharmaceutical composition of the present invention may further include a lubricant, a humectant, a sweetener, a flavoring agent, an emulsifier, a suspending agent, a preservative, and the like. Suitable pharmaceutically acceptable carriers and formulations are described in detail in Remington ' s Pharmaceutical Sciences (19th ed., 1995).
본 발명의 약제학적 조성물은 경구 또는 비경구로 투여할 수 있고, 비경구 투여인 경우에는 정맥내 주입, 피하 주입, 근육 주입, 복강 주입, 경피 투여 등으로 투여할 수 있으며, 바람직하게는 경구 투여이다.The pharmaceutical composition of the present invention may be administered orally or parenterally, and in the case of parenteral administration, it may be administered by intravenous injection, subcutaneous injection, intramuscular injection, intraperitoneal injection, transdermal administration, and preferably, oral administration. .
본 발명의 약제학적 조성물의 적합한 투여량은 제제화 방법, 투여 방식, 환자의 연령, 체중, 성, 병적 상태, 음식, 투여 시간, 투여 경로, 배설 속도 및 반응 감응성과 같은 요인들에 의해 다양하며, 보통으로 숙련된 의사는 소망하는 치료 또는 예방에 효과적인 투여량을 용이하게 결정 및 처방할 수 있다. 본 발명의 바람직한 구현예에 따르면, 본 발명의 약제학적 조성물의 1일 투여량은 0.001-10000 ㎎/㎏이다.The appropriate dosage of the pharmaceutical composition of the present invention varies depending on factors such as the formulation method, administration method, age, body weight, sex, pathological condition, food, administration time, administration route, excretion rate and responsiveness of the patient, Usually, a skilled physician can readily determine and prescribe dosages effective for the desired treatment or prophylaxis. According to a preferred embodiment of the present invention, the daily dose of the pharmaceutical composition of the present invention is 0.001-10000 mg / kg.
본 발명의 약제학적 조성물은 당해 발명이 속하는 기술분야에서 통상의 지식을 가진 자가 용이하게 실시할 수 있는 방법에 따라, 약제학적으로 허용되는 담체 및/또는 부형제를 이용하여 제제화 함으로써 단위 용량 형태로 제조되거나 또는 다용량 용기 내에 내입시켜 제조될 수 있다. 이때 제형은 오일 또는 수성 매질중의 용액, 현탁액 또는 유화액 형태이거나 엑스제, 분말제, 과립제, 정제 또는 캅셀제 형태일 수도 있으며, 분산제 또는 안정화제를 추가적으로 포함할 수 있다.
The pharmaceutical composition of the present invention may be formulated into a unit dose form by formulating it using a pharmaceutically acceptable carrier and / or excipient according to a method which can be easily carried out by a person having ordinary skill in the art to which the present invention belongs. Or by intrusion into a multi-dose container. The formulations may be in the form of solutions, suspensions or emulsions in oils or aqueous media, or in the form of excipients, powders, granules, tablets or capsules, and may additionally contain dispersing or stabilizing agents.
본 발명의 특징 및 이점을 요약하면 다음과 같다: The features and advantages of the present invention are summarized as follows:
(a) 본 발명은 세잎승마 추출물, 눈빛승마 추출물, 왜승마 추출물 및 촛대승마 추출물, 특히 자생종 식물인 세잎승마 추출물의 지방 대사 질환, 폐경기 질환 또는 심혈관질환의 개선에 대한 신규한 용도를 제시한다.(a) The present invention proposes a novel use for the improvement of fat metabolism disease, menopausal disease or cardiovascular diseases of the three-leaf horse riding extract, eye horse riding, horse riding and candlestick horse riding, in particular, the three leaf horse riding, a native plant.
(b) 본 발명의 추출물, 특히 세잎승마 추출물의 혈중 지질개선 효과는 현재 임상적으로 사용하고 있는 아메리카승마 추출물과 St. John's wort 추출물의 혼합물보다도 높다.(b) The blood lipid improvement effect of the extract of the present invention, in particular, the three-leaf horseback riding extract, is currently clinically used in the American horseback riding extract and St. Higher than a mixture of John's wort extract.
(c) 본 발명의 추출물은 종래의 아메리카승마 추출물과 유사한 혈관이완작용을 나타내며 이는 심혈관질환의 치료에 이용될 수 있음을 보여준다.(c) The extract of the present invention shows a vasorelaxant effect similar to that of the conventional horseback riding extract, which shows that it can be used for the treatment of cardiovascular diseases.
(d) 본 발명의 추출물은 폐경기 질환의 예방 또는 치료에 이용될 수 있으며, 여성호르몬 대체제로 이용될 수 있다.(d) The extract of the present invention may be used for the prevention or treatment of menopausal diseases, and may be used as a female hormone replacement agent.
(e) 본 발명의 조성물은 아메리카승마 수입 대체를 통한 외화절감 효과가 기대된다. (e) The composition of the present invention is expected to reduce the foreign currency effect by replacing the American riding horse.
(f) 본 발명의 자생종 승마를 재배하여 농가 수익 증대를 기대할 수 있다.
(f) It is expected to increase farm income by cultivating the native riding of the present invention.
도 1은 세잎승마, 눈빛승마, 왜승마 또는 촛대승마를 각각 물, 80% 에탄올, 앱솔루트 메탄올 또는 40% 2-프로판올로 추출용매를 달리한 승마 4종의 혈관이완작용을 나타내는 그래프이다. CH는 세잎승마를 CS는 촛대승마, CD는 눈빛승마, CJ는 왜승마를 나타낸다.
도 2는 내피세포의 존재유무에 따른 자생종 세잎승마 추출물(A, CH) 및 아메리카 승마 추출물(B, BC)의 혈관이완작용을 비교한 결과이다.
도 3은 자생종 세잎승마 추출물(CH) 및 아메리카승마 추출물(BC)의 농도에 따른(0.3-3.0 ㎎/㎖) 내피세포 의존적 혈관이완작용을 비교한 결과이다.(n=4-7) *은 대조군과 비교하여 p<0.05에서, **은 대조군과 비교하여 p<0.01에서 유의적 차이가 있음(LSD-post hoc test)을 의미한다.
도 4는 자생종 세잎승마 추출물(A, CH) 및 아메리카 승마 추출물(B, BC)(1.0 ㎎/㎖)의 내피세포의존적 혈관이완작용 기전을 비교한 결과를 보여준다.(n=4-7) ***은 대조군과 비교하여 p<0.001에서 유의적 차이가 있음(LSD-post hoc test)을 의미한다.
도 5는 자생종 세잎승마 추출물(A, CH)과 아메리카승마 추출물(B, BC)의 내피세포 의존적 혈관이완작용에서 에스트로겐 수용체와의 연관성을 비교한 결과를 보여준다.(n=4-7)
도 6은 자생종 세잎승마 추출물(A, CH) 및 아메리카승마 추출물(B, BC)(1.0 ㎎/㎖)의 내피세포의존적 혈관이완작용에 대한 세포막 수용체의 연관성을 비교한 결과이다.(n=4-7) *은 대조군과 비교하여 p<0.05에서 유의적 차이가 있음(LSD-post hoc test)을 의미한다.
도 7은 자생종 세잎승마 추출물(A, CH) 및 아메리카승마 추출물(B, BC)(1.0 ㎎/㎖)의 혈관이완작용에서 포타슘 채널의 연관성을 비교한 결과를 보여준다.(n=4-7) *은 대조군과 비교하여 p<0.05에서 유의적 차이가 있음(LSD-post hoc test)을 의미한다.
도 8은 자생종 승마 추출물 및 아메리카 승마 추출물과 SJW 추출물의 복합물 투여가 쥐의 체중변화에 미치는 영향을 나타낸 결과이다. BC는 아메리카코호시, CH는 세입승마, CS는 촛대승마, SJW는 St. John's wort를 가리킨다.
도 9는 자생종 승마 추출물 및 아메리카 승마 추출물과 SJW 추출물의 복합물 투여가 쥐의 체지방(A) 및 자궁무게(B)에 미치는 영향을 나타낸 결과이다. BC는 아메리카코호시, CH는 세입승마, CS는 촛대승마, SJW는 St. John's wort를 가리킨다. 그래프의 a, b 및 ab는 Duncan의 다중비교법에 의하여 같은 알파벳이 부여된 군의 측정치는 유의적으로 차이가 나지 않음을 표시한 것이다.
도 10은 자생종 승마 추출물 및 아메리카 승마와 SJW 추출물의 복합물 투여가 쥐의 골밀도에 미치는 영향을 나타낸 그래프이다. BC는 아메리카코호시, CH는 세입승마, CS는 촛대승마, SJW는 St. John's wort를 가리킨다.
도 11은 자생종 승마 추출물 및 아메리카승마 추출물과 SJW 추출물의 복합물 투여가 쥐의 혈중 지질 프로필에 미치는 영향을 나타낸 결과이다. BC는 아메리카코호시, CH는 세입승마, CS는 촛대승마, SJW는 St. John's wort를 가리킨다.
도 12는 27-디옥시액테인 및 각 승마종의 UPLC 분석 결과를 보여준다.
도 13은 27-디옥시액테인 및 각 승마종의 질량 분석법 분석결과를 보여준다.1 is a graph showing the three-horse riding, eye riding, horseback riding or horseback riding, four vessels of the horse riding with different extraction solvents with water, 80% ethanol, absolute methanol or 40% 2-propanol, respectively. CH represents three-leaf riding, CS represents candle riding, CD represents eye riding, and CJ represents horse riding.
Figure 2 is a result of comparing the vasorelaxation effect of the native leaf riding horse extract (A, CH) and the American horse riding extract (B, BC) according to the presence or absence of endothelial cells.
Figure 3 is a result of comparing the endothelial cell-dependent vascular relaxation effect according to the concentration of native leaf leaf riding horse (CH) and American horse riding extract (BC) (0.3-3.0 mg / ㎖) (n = 4-7) At p <0.05 compared to the control, ** means significant difference at p <0.01 compared to the control (LSD-post hoc test).
Figure 4 shows the results of comparing the endothelial cell-dependent vascular relaxation mechanism of the native leaf leaf riding horse (A, CH) and the American horse riding extract (B, BC) (1.0 mg / ㎖) (n = 4-7) * ** means significant difference (LSD-post hoc test) at p <0.001 compared to the control.
FIG. 5 shows the result of comparing the association with estrogen receptor in endothelial cell-dependent vasorelaxation of native horseshoe leaf extract (A, CH) and American horseback extract (B, BC). (N = 4-7)
FIG. 6 shows the results of comparing the association of cell membrane receptors with endothelial cell-dependent vasorelaxation of native horseshoe leaf extract (A, CH) and American horseback extract (B, BC) (1.0 mg / ml). (N = 4 -7) * means significant difference (LSD-post hoc test) at p <0.05 compared to the control.
FIG. 7 shows the results of comparing the association of potassium channels in vasorelaxation of native species three-wheeled horse riding extract (A, CH) and American horse-riding extract (B, BC) (1.0 mg / ml). (N = 4-7) * Means significant difference (LSD-post hoc test) at p <0.05 compared to the control.
8 is a result showing the effect of the combination of the native horse riding extract and the American horse riding extract and SJW extract administration on the weight change of the rat. BC is America Koho City, CH is Revenue Horseriding, CS is Candlestick Horseriding, SJW is St. Point to John's wort.
9 is a result showing the effect on the body fat (A) and uterine weight (B) of rats of the indigenous horse riding extract and the combination of the American horse riding extract and SJW extract. BC is America Koho City, CH is Revenue Horseriding, CS is Candlestick Horseriding, SJW is St. Point to John's wort. A, b and ab of the graphs indicate that the measurements of the groups given the same alphabet by Duncan's multiple comparison method are not significantly different.
Figure 10 is a graph showing the effect of the combination of the native horse riding extract and the American horse riding and SJW extract administration on the bone mineral density of the rat. BC is America Koho City, CH is Revenue Horseriding, CS is Candlestick Horseriding, SJW is St. Point to John's wort.
11 is a result showing the effect of the combination of the native horse riding extract and the American horse riding extract and SJW extract administration on the blood lipid profile of the rat. BC is America Koho City, CH is Revenue Horseriding, CS is Candlestick Horseriding, SJW is St. Point to John's wort.
12 shows the results of UPLC analysis of 27-dioxyactin and each riding species.
Figure 13 shows the mass spectrometry analysis of 27-deoxyactin and each riding species.
이하, 실시예를 통하여 본 발명을 더욱 상세히 설명하고자 한다. 이들 실시예는 오로지 본 발명을 보다 구체적으로 설명하기 위한 것으로, 본 발명의 요지에 따라 본 발명의 범위가 이들 실시예에 의해 제한되지 않는다는 것은 당업계에서 통상의 지식을 가진 자에 있어서 자명할 것이다.
Hereinafter, the present invention will be described in more detail with reference to Examples. It is to be understood by those skilled in the art that these embodiments are only for describing the present invention in more detail and that the scope of the present invention is not limited by these embodiments in accordance with the gist of the present invention .
실시예Example
시료sample
자생승마는 강원도 일대에서 채취한 한반도에서 자생하는 것으로 알려진 4종 즉, 눈빛승마(Cimicifuga davurica, CD), 왜승마(C. japonica, CJ), 세잎승마(C. heracleifolia var. vifida, CH) 및 촛대승마(C. simplex, CS)를 한국자생식물원(강원도 평창군)으로부터 제공받아 근경부위를 자연건조 시킨 후 푸드 믹서로 분말을 제조하여 데시케이터에 보관하며 사용하였다. 각 승마 종 건조분말에 20배 량의 증류수, 80% 에탄올, 앱솔루트 메탄올 및 40% 2-프로판올을 가하여 고압균질기(Ultra-Turrax T-25 basic, IKA Werke GmbH & Co. KG, Staufen, 독일)로 추출한 후 원심분리(3,700 xg, Sorvall RC50, GMI Inc., WA, USA), 여과한 여과액을 37-40℃에서 감압건고(rotary evaporator RE121, B, Switzerland) 및 동결건조하여 눈빛승마의 물추출물(CD-W); 에탄올추출물(CD-E); 메탄올추출물(CD-M); propanol추출물(CD-P), 왜승마의 물추출물(CJ-W); 에탄올추출물(CJ-E); 메탄올추출물(CJ-M); propanol추출물(CJ-P), 세잎승마의 물추출물(CH-W); 에탄올추출물(CH-E); 메탄올추출물(CH-M); propanol추출물(CH-P) 및 촛대승마의 물추출물(CS-W); 에탄올추출물(CS-E); 메탄올추출물(CS-M); propanol추출물(CS-P)을 얻었다. 모든 추출물은 -20℃에 보관하면서 실험에 사용하였고, 사용 시 물추출물은 물에, 그 외 용매 추출물은 50% 에탄올에 녹여 사용하였다. 각 추출물의 증거 표본(voucher specimen, CD-W001, CD-E001, CD-M001, CD-P001, CJ-W001, CJ-E001, CJ-M001, CJ-P001, CH-W001, CH-E001, CH-M001, CH-P001, CS-W001, CS-E001, CS-M001, CS-P001)은 한국식품연구원(경기도)에 보관하였다. 또한, 블랙 코호시는 현재 임상적으로 사용되고 있는 임상추출물(clinical extract, BC)을 미국 일리노이 대학교(시카고)의 NIH 센터의 식물성 식사 보충 연구소(Botanical Dietary Supplements Research)의 Dr. Norman Farnsworth로부터 제공받아 사용하였다. 또한 폐경을 유도한 동물모델에서의 승마와 블랙 코호시 추출물의 효과비교를 위해서는 현재 임상적으로 사용되고 있는 승마 추출물을 동국제약으로부터 제공받아 사용하였다.
There are four species of native horses known to grow wild on the Korean Peninsula, Gangwon-do, namely, snow riding ( Cimicifuga davurica , CD), horse riding ( C. japonica , CJ), three horse riding ( C. heracleifolia var. Vifida , CH) and Candlestick horseback riding ( C. simplex , CS) was provided from Korea Botanic Garden (Pyeongchang, Gangwon-do), and the roots were naturally dried, and then powder was prepared using a food mixer and stored in a desiccator. Dry powder of each riding species was added high pressure homogenizer (Ultra-Turrax T-25 basic, IKA Werke GmbH & Co. KG, Staufen, Germany) by adding 20 times distilled water, 80% ethanol, absolute methanol and 40% 2-propanol. After extraction with centrifugation (3,700 xg, Sorvall RC50, GMI Inc., WA, USA), the filtrate was dried under reduced pressure (rotary evaporator RE121, B, Switzerland) and freeze-dried at 37-40 ° C. Extract (CD-W); Ethanol extract (CD-E); Methanol extract (CD-M); propanol extract (CD-P), dwarf horse extract (CJ-W); Ethanol extract (CJ-E); Methanol extract (CJ-M); propanol extract (CJ-P), three-horse riding water extract (CH-W); Ethanol extract (CH-E); Methanol extract (CH-M); propanol extract (CH-P) and candlestick horseback water extract (CS-W); Ethanol extract (CS-E); Methanol extract (CS-M); Propanol extract (CS-P) was obtained. All extracts were used in experiments while being stored at -20 ° C. Water extracts were dissolved in water and other solvent extracts were used in 50% ethanol. Evidence specimens of each extract (voucher specimen, CD-W001, CD-E001, CD-M001, CD-P001, CJ-W001, CJ-E001, CJ-M001, CJ-P001, CH-W001, CH-E001, CH -M001, CH-P001, CS-W001, CS-E001, CS-M001, CS-P001) were stored at Korea Food Research Institute (Gyeonggi-do). In addition, Black Cohosh was using the clinical extract (BC) from the Botanical Dietary Supplements Research at the NIH Center at the University of Illinois (Chicago). Used by Norman Farnsworth. To compare the effects of horseback riding and black cohosh extract in menopause-induced animal models, the horse riding extract currently being used clinically was provided from Dongkuk Pharmaceutical.
실시예 1: 혈관이완 효능 및 기전분석 Example 1: Vasorelaxation Efficacy and Mechanism Analysis
동맥이완 작용 측정Measurement of arterial relaxation
스프래그-다우리(Sprague-Dawley) 랫트(230-250 g)을 기절시킨 후 즉시 방혈하고 하행흉부대동맥(thoracic aorta)을 분리하여 길이 약 2-3 ㎜의 링 형태로 잘라 3 ㎖ 생리식염수(Physiological salt solution: PSS, NaCl 136.9 mM, KCl 5.4 mM, CaCl2 1.5 mM, MgCl2 1.0 mM, NaHCO3 23.8 mM, 글루코오스 5.5 mM 및 EDTA 0.01 mM가 포함된 장기 배스(organ bath)에 현수 시킨 후 1 g의 장력으로 60분간 평형화시키고 72 mM KCl 및 PSS를 번갈아 투여하여 혈관수축반응을 안정화시켰다. 혈관의 수축반응이 안정화되면 300 nM 노르에피네프린(norepinephrine: NE)을 투여하여 혈관수축을 유도한 후 최대수축상태에서 자생종 승마 추출물 또는 블랙 코호시 임상추출물을 투여하였다. 장기 배스의 용액은 37℃, pH 7.5, 95% O2-5% CO2 통기상태로 유지시켰으며, 혈관의 장력은 force-displacement transducer(FT3, Grass, RI, USA)가 연결된 폴리그래프 시스템(RPS212, Grass, RI, 미국) 및 컴퓨터 분석기(Power Lab 400, MacLab system, Castle Hill, 호주)로 측정하였다.Sprague-Dawley rats (230-250 g) were stunned and immediately bled, and the descending thoracic aorta was separated and cut into rings of about 2-3 mm in length and 3 ml saline solution ( Physiological salt solution: Suspended in an organ bath containing PSS, NaCl 136.9 mM, KCl 5.4 mM, CaCl 2 1.5 mM, MgCl 2 1.0 mM, NaHCO 3 23.8 mM, glucose 5.5 mM and EDTA 0.01
혈관벽 내피세포의존성 혈관이완 효능기전 분석Vascular Wall Endothelial Cell Dependent Vascular Relaxation Efficacy Mechanism Analysis
내피가 온전한 혈관에 내피세포에서 유래되는 이완인자(endothelium-derived relaxing factor, EDRF)에 대한 각종 저해제, 즉 나이트릭 옥사이드(nitric oxide: NO) 합성저해제인 L-NNA(10 μM), 프로스타사이클린(prostacyclin) 생성 억제제 인도메타신(indomethacin, 10 μM) 및 구아닐레이트 사이클라제 억제제(guanylate cyclase inhibitor)인 메틸린 블루(methylene blue, 1 μM)을 NE로 혈관의 수축을 유도하기 약 20분 전에 장기 배스에 투여하고, 혈관수축 유도 후 자생종 승마 및 블랙 코호시 추출물을 투여하여 이들의 혈관확장 저해작용을 분석, EDRF 방출기전을 확인하였다. 또한 내피의존성 혈관이완작용의 에스트로겐 수용기 매개활성 확인을 위하여 에스트로겐 수용기 특이적 안타고니스트인 ICI 182,780을 NE에 의한 혈관수축 유도 20분전에 organ bath에 투여한 후 혈관수축을 유도하고 자생종승마 및 블랙 코호시 추출물을 투여하여 그 영향을 분석하였다.
Inhibitors of endothelial-derived relaxing factor (EDRF) in endothelial intact blood vessels, namely L-NNA ( 10 μM), prostacyclin, which inhibits nitric oxide (NO) synthesis Prostacyclin production inhibitor indomethacin ( 10 μM) and guanylate cyclase inhibitor methylene blue (1 μM) are about 20 minutes to induce vasoconstriction with NE After the administration to the long-term bath, after the induction of vasoconstriction, the autologous horse riding and black cohosh extract was administered to analyze their vasodilation inhibitory effect, confirming the EDRF release mechanism. In addition, ICI 182,780, an estrogen receptor-specific antagonist, was administered to the
혈관평활근 직접작용에 의한 By direct action of vascular smooth muscle 혈관이완효능Vascular Relaxation Effect 및 기전 분석 And mechanism analysis
각 추출물의 혈관벽 내피세포 의존적 이완작용 뿐 아니라 내피세포 비의존적 이완작용기전 또한 분석하였다. 혈관이완작용 측정밥법에 따라 적출한 혈관 내부를 면봉으로 부드럽게 문질러 내피를 제거한 혈관을 실험에 사용하였다. 추출물의 K+ 채널 억제제를 사용하여 혈관평활근의 K+ 채널 매개 동맥확장기전을 확인하였다. 즉, 내피를 제거한 혈관의 수축 유도 20분 전에 각종 K+ 채널 억제제를 투여한 후 NE로 혈관수축을 유도하고 자생종승마 및 블랙 코호시 추출물을 투여하였다. 이때 ATP-민감성 K+ 채널 차단제로 글리벤크라마이드(3 μM), 전압-의존적 K+ 채널 차단제로 4-아미노피리딘(1 mM), 내향성 정류 K+ 채널 차단제로 바륨 클로라이드(20 μM), 저-전도 Ca2 +-활성 K+ 채널 차단제로 아파민(10 nM)을 사용하였다(11).
The endothelial cell independent relaxation mechanism of each extract was analyzed as well as endothelial cell independent relaxation mechanism. Vascular relaxation action The blood vessels from which the endothelium was removed by gently scrubbing the inside of the blood vessels extracted by the method were used in the experiment. The K + channel inhibitor of the extract was used to confirm the K + channel mediated artery dilated mechanism of vascular smooth muscle. In other words, various K + channel inhibitors were administered 20 minutes before the induction of endothelial vascular contraction, and then vascular contraction was induced by NE and autologous horseriding and black cohosh extracts were administered. At this time, as ATP- sensitive K + channel blockers article riben Klein polyimide (3 μM), voltage-dependent K + channel blocker 4-aminopyridine (1 mM), ingrown barium chloride (20 μM) to the rectifying K + channel blocker, low It was used for sick min (10 nM) to the activity K + channel blockers (11) conductive Ca + 2.
실시예Example 2: 난소를 절제한 모델동물에서 승마 및 블랙 2: Riding and Black on Ovariectomized Animals 코호시Cohosh 투여에 따른 효과 Effect of Dosing
8주령의 SD 자성 쥐를 실험실 환경에서(22±2℃, 상대습도 59±1%, 12시간 명/암 주기(명주기, 07:00-09:00)) 1주일간 적응시킨 후 케타민(70 ㎎/㎏)과 자이라진(10 ㎎/㎏) 복합제제를 근육주사하여 마취시키고 복부를 절개한 후 난소를 절제한 난소적출(ovariectomized: OVX) 그룹과 난소절제 없이 절개부분을 봉합한 대조군으로 나누었다. 수술 후 2주간 회복시키고, 모든 군에 고 콜레스테롤 식이를 섭취시키면서 난소를 절제한 쥐를 다시 5군으로 나누어 매일 같은 시간에 블랙 코호시(BC) 추출물(23 ㎎/㎏/day), 세잎승마 추출물(각 23 ㎎/㎏/day), 촛대승마 추출물(각 23 ㎎/㎏/day), St. John's wort 추출물(SJW, 280 ㎎/㎏/day) 및 BC와 SJW 혼합물(BC 23 ㎎/㎏/day + SJW 280 ㎎/㎏/day)을 경구투여하면서 10일간 사육하며 체중의 변화를 측정하고, 10일 경과 후 희생시켜 혈중 지질의 농도, 체지방량, 자궁위축 및 골밀도를 측정하였다.
8-week-old SD female rats were acclimated in a laboratory setting (22 ± 2 ° C, 59 ± 1% relative humidity, 12 hours light / dark cycle (light cycle, 07: 00-09: 00)) for 1 week before ketamine (70 Mg / kg) and ziragin (10 mg / kg) combinations were intramuscularly injected into anesthesia, incised abdomen, and divided into ovariectomized (OVX) group and ovarian-dissected ovarian resected group. . After recovery for 2 weeks, the rats whose ovaries were removed while ingesting a high cholesterol diet in all groups were divided into 5 groups and black cohosh (BC) extract (23 mg / kg / day) and three-horse riding extract at the same time every day. (23 mg / kg / day each), Candlestick Riding extract (23 mg / kg / day each), John's wort extract (SJW, 280 mg / kg / day) and BC and SJW mixture (BC 23 mg / kg / day +
실시예Example 3: 승마 추출물의 지표물질 분석 3: Indicator Material Analysis of Horse Riding Extract
현재 사용되는 아메리카 승마 임상 추출물의 지표물질은 트리테르핀 글리코시드(triterpene glycoside)의 하나인 27-디옥시액테인(deoxyactein)로 알려져 있다. 따라서 자생종 승마의 아메리카 승마 대체가능성을 확인하기 위하여 자생종승마 4종 추출물의 27-디옥시액테인 함량을 UPLC-Q-TOF 질량 분석법를 이용하여 분석하였다. 이때 각 승마 추출물을 100% 메탄올에 녹인 후 12,000 rpm으로 15분간 원심분리하고 0.22 μm 필터로 여과 후 분석하였다. UPLC 분석 시 ACQUITYM 1.7 ㎛ C18 컬럼(φ 2.1 mm×10 ㎝)을 사용하였고, 분석온도는 40℃로 하였다. 이동상은 0.1% 개미산(formic acid)를 함유한 물과 아세토나이트릴(acetonitrile) 혼합물 농도구배하여 사용하였으며(아세토나이트릴 40%-100%/8분) 유속는 0.3 ㎖/분, 주사 용량은 5 ㎕였으며 203 nm에서 확인하였다. 질량 분석법 분석은 대기압 전기분무 양성 이온(atmospheric pressure electrospray positive ion, ESI+) 모드로 수행하였으며, 모세관 및 샘플링 콘은 3000 및 100 V로 검출기는 1900 V로 하였고 스캔 범위는 100-1000 Da(스캔 시간: 0.2초, 스캔 간 지연: 0.02초)으로 하였다.
The indicator used in the American equestrian clinical extract currently used is known as 27-deoxyactein, one of the triterpene glycosides. Therefore, the 27-dioxyactin content of four species of native horseback riding was analyzed using UPLC-Q-TOF mass spectrometry to confirm the possibility of native horseback riding. At this time, each riding extract was dissolved in 100% methanol and centrifuged at 12,000 rpm for 15 minutes, and filtered after 0.22 μm filter. For UPLC analysis, an ACQUITYM 1.7 μm C 18 column (φ 2.1 mm × 10 cm) was used, and the analysis temperature was 40 ° C. The mobile phase was used with a concentration gradient of acetonitrile mixture with water containing 0.1% formic acid (
통계분석Statistical analysis
모든 실험결과는 평균±표준오차로 표기하였다. 실험에서 서로 다른 쥐로부터 얻어진 혈관의 수 및 동일 실험군에 해당하는 쥐의 수를 n으로 표기하였다. 혈관이완작용은 NE에 의해 유도되는 최대수축에서의 감소정도로 표시하였다. 실험결과는 SAS 프로그램을 이용하여 분산분석(one-way ANOVA)을 수행, 유의차를 검증하였고, 분산분석에 의해 차이가 유의적인 경우 혈관실험의 경우 LSD 사후검증(post-hoc test)을 하였으며 혈중지질개선 효과에서는 Duncan의 다중비교법에 의하여 α=0.05 수준에서 검정하였다.
All experimental results are expressed as mean ± standard error. In the experiment, the number of blood vessels obtained from different mice and the number of mice corresponding to the same experimental group were denoted by n. Vasorelaxation was expressed as a decrease in maximal contraction induced by NE. The results were analyzed by one-way ANOVA using SAS program, and the significant differences were verified. In case of significant differences by variance analysis, LSD post-hoc test was performed in blood vessels. Lipid improvement effect was tested at α = 0.05 level by Duncan's multiple comparison method.
실험결과Experiment result
자생종 승마와 블랙 Native horse riding and black 코호시Cohosh 추출물의 Extract 혈관이완작용Vasorelaxation
내피가 온전한 쥐의 대동맥에 NE를 투여하여 최대 수축을 유도한 후 자생종 승마 4종(세잎승마, 촛대승마, 눈빛승마 및 왜승마)의 용매별 추출물 및 블랙 코호시 추출물을 투여하여 혈관이완작용을 검토하였다. 4종의 자생종 승마 추출물 및 블랙 코호시 추출물 모두 추출물 투여 직후 나타나는 순간이완작용이 일어났으며 이는 승마 종과는 관련이 없었다. 반면 이들의 추출에 사용한 용매에 의해서는 영향을 받아 물 추출의 경우 촛대승마는 이완작용을 나타내지 않았으며 80% 에탄올은 촛대승마와 눈빛승마에서 활성을 나타내지 않았다(도 1). 반면 메탄올과 40% 2-프로판올 추출물의 경우 높은 활성을 나타내었으며, 특히 한반도에서만 자라는 것으로 알려진 세잎승마는 메탄올 추출물이 가장 높은 활성을 나타내었다. 따라서 세잎승마의 메탄올 추출물과 현재 사용되고 있는 블랙 코호시의 임상추출물의 혈관이완작용을 1 ㎎/㎖의 농도로 비교한 결과 세잎승마 메탄올 추출물이 좀 더 낮은 이완작용을 나타내었다(도 2). 그러나 이들 추출물의 농도를 변화시키며 혈관이완작용을 측정한 결과 두 가지 추출물 모두 농도 증가에 따라 작용이 증가하는 농도 의존성을 나타내었으며 낮은 농도에서는 블랙 코호시 추출물이 혈관이완작용이 세잎승마 추출물보다 유의적으로 높았으나 농도가 증가함에 따라 활성의 차이가 유의적으로 감소하였다(도 3). 이러한 차이는 블랙 코호시 추출물은 현재 임상적으로 사용가능한 임상 추출물인데 반하여 자생종 승마 추출물은 실험용 추출물인 것에 따라 나타나는 것으로 추정되며, 그럼에도 불구하고 농도 증가 시 유의적인 차이가 감소되는 것으로 미루어 자생종 세잎 승마 또한 블랙 코호시에 비견할 만한 활성을 나타낼 수 있을 것으로 사료되었다. 자생종 승마는 메탄올과 2-프로판올 추출물이 모두 활성을 나타내었으므로 이후의 혈관이완작용 기전 비교 실험에서는 특히 한반도에서 자생하는 세잎승마 메탄올 추출물을 이용, 실험을 수행하였다.
Induced maximal contraction by administering NE to the endothelial intact rat aorta, followed by solvent-extracted extracts and black cohosh extracts from four species of autologous horseback riding (Trifolium, Candlestick, Eye and Horse) Reviewed. All four native horse riding and black cohosh extracts had a momentary relaxation effect immediately after the administration of the extract, which was not associated with the riding species. On the other hand, it was influenced by the solvents used for their extraction, and in the case of water extraction, the candlestick riding showed no relaxation effect and 80% ethanol showed no activity in the candleriding and eye riding. On the other hand, methanol and 40% 2-propanol extract showed high activity. Especially, three-leaf horseback riding, which is known to grow only on the Korean peninsula, showed the highest activity. Therefore, when comparing the vascular relaxation activity of the methanol extract of the three-wheeled horse riding and the clinical extract of currently used black cohosh at a concentration of 1 mg / ml, the three-leafed horseriding methanol extract showed a lower relaxation effect (FIG. 2). However, as a result of measuring the vasorelaxation effect by varying the concentrations of these extracts, both extracts showed a concentration dependence, which increased with increasing concentrations. It was higher, but the difference in activity was significantly decreased as the concentration was increased (Fig. 3). The difference is that black cohosh extracts are currently clinically available clinical extracts, whereas native horse riding extracts appear to be experimental extracts. Nevertheless, a significant difference decreases with increasing concentrations. It was thought that the black cohosh could show comparable activity. The native horse riding showed that both methanol and 2-propanol extracts were active. Thus, in the comparative experiments of vascular relaxation mechanism, experiments were carried out using methanol extracts that are native to the Korean Peninsula.
자생종 승마와 아메리카 승마 추출물의 Of endemic equestrian and American equestrian extracts NONO -- cGMPcGMP 계 system 혈관이완작용Vasorelaxation 분석 analysis
내피세포의존성 혈관이완작용의 주요 경로 중 하나로는 내피세포로부터 분비되는 내피세포의존성 혈관확장물질(endothelium-derived relaxing factor; EDRF)로 알려져 있으며 다양한 EDRF 중 가장 대표적인 것이 나이트릭 옥사이드이다(12). NO는 혈관내피세포에서 분비된 후 혈관의 평활근세포에 확산되어 구아닐레이트 사이클라제를 활성화시켜 cGMP의 형성을 증가시킴으로 인해 혈관의 이완작용을 나타내는 것으로 알려져 있다(13). 따라서 내피가 온전한 혈관에 NO 합성억제제인 L-NNA(10 μM), L-NNA와 함께 NO 합성의 전구체인 L-아르기닌 및 수용성 구아닐레이트 사이클라제 억제제인 메틸린 블루(1 μM)를 각각 첨가한 후(14) NE로 혈관수축을 유도하고 세잎승마 메탈올 추출물(CH-M) 및 블랙 코호시 임상추출물(BC)를 투여, 내피세포 의존적인 혈관이완작용인 NO-cGMP계 관련성을 분석하였다. 실험결과 CH-M 및 BC에 의한 혈관이완작용은 모두 L-NNA에 처리에 의해 유의적으로 감소하였고 L-NNA와 L-아르기닌을 동시 처리 시 혈관이완작용의 억제효과는 나타나지 않아 블랙 코호시와 자생종 세잎승마 추출물 모두 NO가 관여하는 내피세포 의존적 혈관이완작용을 나타냄을 알 수 있었다(도 4a 및 b). 메틸린 블루 또한 CH-M과 BC 모두에서 혈관이완작용을 유의적으로 억제시켜 자생종 CH-M이 BC와 같은 NO-cGMP계의 작용에 의해 혈관이완작용을 나타내는 것으로 추정되었다. One of the major pathways of endothelial cell-dependent vasorelaxation is known as the endothelial cell-derived relaxing factor (EDRF) secreted from endothelial cells, the most representative of which is nitric oxide (12). NO is released from vascular endothelial cells and then diffuses into smooth muscle cells of blood vessels, thereby activating guanylate cyclase to increase the formation of cGMP. Therefore, L-NNA (10 μM), a NO synthesis inhibitor, L-arginine, a precursor of NO synthesis, and methylin blue (1 μM), a water-soluble guanylate cyclase inhibitor, were added to endothelial vessels. Induced vasoconstriction with NE after administration (14) and administration of three-leaved horseriding metalol extract (CH-M) and black cohosh clinical extract (BC) to analyze NO-cGMP-related relationship of endothelial cell-dependent vascular relaxation It was. Experimental results showed that CH-M and BC were significantly decreased by treatment with L-NNA, and simultaneous treatment with L-NNA and L-arginine did not show inhibition of vascular relaxation. It was found that all three leaf equestrian extracts showed endothelial cell dependent vasorelaxation involving NO (FIGS. 4A and B). Methyl blue also significantly inhibited vasodilation in both CH-M and BC, suggesting that native CH-M exhibits vasorelaxation by the action of NO-cGMP, such as BC.
또한 이들 추출물이 나타내는 혈관이완작용의 에스트로겐 수용기(Estrogen Receptor: ER)와의 관련성을 검토하기 위하여 ER 특이적 안타고니스트 ICI182,780을 상기의 실험과 동일한 방법으로 전처리하여 그 영향을 분석한 결과 CH-M과 BC에 의해 유도되는 내피세포의존적 혈관이완작용은 모두 ICI182,780 전처리로 유의적인 변화를 나타내지 않아 에스트로겐 수용기를 매개하지 않는 것으로 나타났다(도 5). 결과적으로 자생종 세잎승마 및 블랙 코호시가 동일한 기전에 의해 내피세포 의존적 혈관이완작용을 나타냄으로 인하여 세잎승마의 아메리카승마 대체소재로서의 활용 가능성이 대두되었다.
In addition, ER-specific antagonist ICI182,780 was pretreated in the same manner as the above experiment to examine the relationship between the vascular relaxation effect of the extract and the estrogen receptor (ER). The endothelial cell-dependent vasorelaxation induced by BC did not show any significant change with ICI182,780 pretreatment and thus did not mediate estrogen receptor (FIG. 5). As a result, the endocrine cell-dependent vasorelaxation effect of the three-wheeled horse riding and black cohosh showed the possibility that the three-horse riding could be used as a substitute material for the American horse riding.
자생종 승마와 아메리카 승마 추출물의 세포막 수용체와의 관련성Association between Endemic Horse Riding and American Horse Riding Extracts on Membrane Receptors
자생종 세잎승마 및 블랙 코호시 임상 추출물의 혈관이완작용이 내피세포에서 유래된 NO에 의한 혈관평활근세포의 구아닐레이트 사이클라제를 활성화하여 cGMP 형성을 유도하는 것으로 확인된 바 내피세포에서 NO의 발생을 유도하는 것으로 보고 되어있는 내피세포 막 수용체와의 관련성을 측정하였다(15,16). 내피가 온전한 혈관에 선별적 무스카린성 수용체 안타고니스트, 아트로핀(atropin, 100 nM), substance P 수용체 안타고니스트, [D-Pro2, D-Trp7 ,9] substance P (5 μM), β-아드레날린성 수용체 안타고니스트, 프로프라놀롤(propanolol, 10 μM) 및 선별적 히스타민 H1-수용체 안타고니스트, 다이페닐하이드라민(diphenylhydramin, 10 μM)을 전처리하고 NE로 혈관수축 후 CH-M 및 BC를 투여한 결과 세잎승마 추출물 및 블랙 코호시 임상추출물에 의해 유도되는 혈관이완작용은 아트로핀과 다이페닐하이드라민 처리에 의해 유의적으로 감소하였다(도 6).
Endothelial NO in endothelial cells has been shown to induce cGMP formation by activating guanilate cyclase of vascular smooth muscle cells by NO derived from endothelial cells. The association with endothelial membrane receptors reported to induce was determined (15, 16). Selective muscarinic receptor antagonists, atropin (100 nM), substance P receptor antagonists, [D-Pro 2 , D-Trp 7 , 9 ] substance P (5 μM), β-adrenergic to endothelial intact blood vessels Pre-treatment with receptor antagonist, propanolol (10 μM) and selective histamine H 1 -receptor antagonist, diphenylhydramin (diphenylhydramin, 10 μM) followed by CH-M and BC after vasoconstriction with NE Vasorelaxation induced by black cohosh clinical extracts was significantly reduced by atropine and diphenylhydramine treatment (FIG. 6).
자생종 승마와 아메리카 승마 추출물의 혈관평활근 직접작용에 의한 K+ K + by Direct Action of Vascular Smooth Muscle of Native Horse Riding and American Riding Extracts channelchannel 조절 효능 평가 Regulatory efficacy assessment
혈관의 이완은 내피세포 뿐 아니라 평활근세포에 의해서도 나타나며 이 경우 혈관의 이완에 영향을 미치는 것으로 세포막 전위가 대표적이고, 이러한 세포막 전위의 조절에는 포타슘 채널이 중요한 역할을 하는 것으로 알려져 있다(17,18). 따라서 평활근 의존적인 이완작용이 나타나는 것으로 나타난 세잎승마 추출물 및 블랙 코호시 추출물의 포타슘 채널과의 관련성을 측정하였다. 세포내 포타슘 채널은 여러 가지가 알려져 있으며, 본 연구에서는 ATP-민감성 포타슘 채널 저해제인 글리벤 클라마이드(gliben clamide), 전압-의존성 포타슘 채널 저해제인 4-아미노피리딘, 소 전도도(small conductance) Ca2 +-활성 포타슘 채널 저해제인 아파민 및 내향성 정류 K+ 채널 차단제인 바륨 클로라이드를 전처리한 결과 블랙 코호시 추출물의 혈관이완작용은 바륨 클로라이드에 의해 저해를 받았고, 자생종 세잎승마 추출물의 이완작용은 저해되는 것으로 보이나 유의적인 차이가 없었다(도 7). 그 외의 다른 모든 포타슘 채널 저해제는 블랙 코호시와 자생종 세잎승마 추출물 모두 효과가 없었다. 따라서 아메리카승마 추출물은 내향성 정류 K+ 채널의 활성화에 관여하여 혈관평활근세포의 이완작용을 매개함을 알 수 있으며, 자생종 세잎승마 추출물 또한 통계적 유의서은 없으나 동일한 포타슘 채널의 작용에 일부 관여하는 것으로 추정할 수 있었다.
Vascular relaxation may be caused by not only endothelial cells but also smooth muscle cells. In this case, it is known that cell membrane potential is representative, and that potassium channel plays an important role in the regulation of cell membrane potential (17, 18). . Therefore, the relationship between potassium horseshoe leaf extract and black cohosh extract showed smooth muscle-dependent relaxation. Various intracellular potassium channels are known. In this study, ATP-sensitive potassium channel inhibitor gliben clamide, voltage-dependent potassium channel inhibitor 4-aminopyridine, small conductance Ca 2 + - activated potassium channel inhibitors Apa min and inward rectifier K + channel blocker After a pretreatment of barium chloride black cohosh vasodilator when extract action was given a inhibited by barium chloride, native species relaxing action of the trefoil riding extract inhibited It appears that there was no significant difference (FIG. 7). All other potassium channel inhibitors were ineffective in both black cohosh and native leaf riding. Therefore, it can be seen that the American horse riding extract mediates the activation of inward rectifying K + channels and mediates the relaxation of vascular smooth muscle cells. there was.
난소를 절제한 모델동물에서 승마 및 블랙 Riding an ovary model animal and black 코호시Cohosh 투여에 따른 효과 Effect of Dosing
혈관실험결과 자생종 승마 추출물이 블랙 코호시 추출물과 유사한 기전에 의하여 혈관이완작용을 나타냄을 알 수 있었다. 따라서 이의 생체 내에서의 작용 및 현재 사용 중인 블랙 코호시 대체제로서의 사용가능성을 알아보기 위하여 난소를 절제하여 폐경을 유도한 동물 모델에서의 영향을 비교하였다. 실험을 위하여 현재 임상적으로는 블랙 코호시의 2-프로판올 추출물에 St. John's wort 추출물(SJW)을 혼합한 제재가 사용되고 있어 블랙 코호시 추출물과 자생종 승마(세잎승마 및 촛대승마) 추출물, 블랙 코호시와 St. John's wort 혼합물의 효과를 모두 비교하였다. As a result of the vascular test, the native horse riding extract exhibited vasorelaxant action by a mechanism similar to that of the black cohosh extract. Therefore, we compared the effects of ovarian ablation in animal models that induced menopause in order to examine its in vivo function and its potential as a black cohosh substitute in use. For the experiment, clinically, 2-propanol extract of Black Cohosh was st. A blend of John's wort extracts (SJW) is used, with black cohosh extracts and native horse riding (triple and candlestick horses) extracts, black cohosh and st. The effects of John's wort mixtures were all compared.
CH-P, CS-P, BC, SJW를 단독 및 BC와 SJW 복합물의 투여에 따른 쥐의 체중변화를 측정한 결과 난소를 절제하고 시료를 투여하지 않은 기간 동안은 모든 군에서 유사하게 체중이 증가한 반면 CH-P 추출물 투여군에서 시료를 투여하는 기간 동안 체중증가가 가장 낮은 경향을 보였다(도 8). The weight change of rats following CH-P, CS-P, BC, and SJW alone and the BC and SJW combinations were measured. Body weight gain was similar in all groups during ovarian ablation and no sample administration. On the other hand, the weight gain tended to be the lowest during the period of administration of the sample in the CH-P extract administration group (FIG. 8).
또한 각 군의 쥐의 체지방량과 자궁무게를 비교한 결과 승마 및 SJW 단독 투여군 중에서는 CH-P 투여군의 체지방량이 가장 낮았고(도 9a), 이는 BC와 SJW 복합물보다는 높았으나 유의적인 차이는 없었다. 자궁 무게는 BC 투여군에서 가장 높은 경향을 보였으나 역시 유의적인 차이는 나타나지 않았다(도 9b). In addition, as a result of comparing the fat mass and uterine weight of the rats in each group, the body fat amount of the CH-P-treated group was the lowest among the horse riding and SJW-only group (Fig. 9a), which was higher than the BC and SJW complex, but there was no significant difference. Uterine weight showed the highest tendency in BC-administered group, but also no significant difference (FIG. 9B).
각 실험군의 쥐에서 분리한 다리뼈의 골밀도 또한 실험군간에 유의적인 차이가 없었다(도 10). 난소를 절제한 후 에스트로겐의 투여는 골밀도의 증가를 나타낸다는 연구결과들도 보고되고 있으나, 본 연구는 실험기간이 짧아 시료의 투여가 골밀도에까지 영향을 미치지는 못하는 것으로 생각되며, 향후 좀 더 장기간의 투여실험을 통하여 확인이 필요할 것으로 사료되었다.Bone mineral density of leg bones isolated from rats of each experimental group was also not significantly different between the experimental groups (FIG. 10). Although studies have shown that the administration of estrogen after ablation of ovaries indicates an increase in bone mineral density, this study suggests that the administration of the sample does not affect bone mineral density due to the short duration of the experiment. It may be necessary to confirm the results through dosing experiments.
또한, 각 승마 추출물의 투여가 혈중 지질 프로필에 미치는 효과를 측정한 결과 시료투여군이 TC 및 LDL-C에서 대조군에 비해 낮은 경향을 나타내었으며, HDL-C는 대조군이 낮았고 TG는 차이가 없었다. 특히 CH-P 투여군의 TC 및 LDL-C는 BC와 SJW 혼합물 투여군보다도 낮은 경향을 나타내어 모든 군 중 가장 낮았고, HDL-C또한 BC 투여군과 유사한 수준으로 높았다(도 11). TG는 BC와 SJW 혼합물 투여군이 가장 낮았으나 유의적인 차이는 없었다. 폐경기 여성에서 에스트로겐의 투여는 TC 및 LDL-C를 낮추고, HDL-C를 높이는 것으로 항아테롬성 효과(antiatherogenic effects)를 나타내는 반면 TG의 농도는 높이는 반면 랄록시펜(raloxifene)를 비롯한 선별적 에스트로겐 수용체 모듈레이터는 TC 및 LDL-C를 낮추는 반면 HDL-C와 TG의 농도에는 크게 영향을 미치지 않는다고 하였다(19-21). 본 실험에서도 이와 동일한 효과가 나타났고, BC 및 CH와 BC와 SJW의 혼합물 투여 시 TC 및 LDL-C를 낮추고 TG의 농도에서는 변화를 나타내지 않음으로 인하여 폐경이후의 심혈관 위험 요소의 증가에 대한 보호작용을 나타낼 수 있을 것으로 사료되었다. 결과적으로 자생종, 특히 세잎승마 추출물은 폐경을 유도하고 고 콜레스테롤 식이를 투여한 동물의 혈중 지질에서 단기간의 투여로도 블랙 코호시 추출물이나 현재 사용되고 있는 BC와 SJW의 혼합물보다도 유의적으로 혈중 지질 프로필의 개선에 효과적인 것으로 나타낼 수 있는 것으로 사료되었다.
In addition, as a result of measuring the effect of each riding extract on the lipid profile in the blood, the sample group showed a lower tendency in the TC and LDL-C than the control group, and the HDL-C had a lower control group and no difference in the TG. In particular, TC and LDL-C of the CH-P administration group showed a lower tendency than the BC and SJW mixture administration group, the lowest among all groups, HDL-C was also similar to the BC administration group (Fig. 11). TG was lowest in the BC and SJW-treated groups, but there was no significant difference. In postmenopausal women, the administration of estrogen lowers TC and LDL-C, and raises HDL-C, resulting in antiatherogenic effects, while increasing TG levels, while selective estrogen receptor modulators, including raloxifene, result in TC And lower LDL-C, but did not significantly affect the concentration of HDL-C and TG (19-21). The same effect was observed in this experiment, and the effect of lowering TC and LDL-C and no change in the concentration of TG when BC and CH and BC and SJW were administered, thus protecting against the increase of cardiovascular risk factors after menopause. It is thought to be able to indicate. As a result, autologous species, especially the three-leaf horseback extract, were significantly lower in blood lipid profile than black cohosh extracts and the current mixtures of BC and SJW, even with short-term administration of blood lipids in animals that induce menopause and had a high cholesterol diet. It is thought to be effective for improvement.
UPLCUPLC -Q--Q- TOFTOF 질량 mass 분석법를Method 이용한 각 Used angle 승마종의Horseback riding 27- 27- 디옥시액테인Deoxyactin 함량 content
화학적으로 블랙 코호시 추출물은 액테인이나 27-디옥시액테인 같은 트리테르핀 글리코시드와 페룰산(ferulic acid)과 이소페룰산(isoferulic acid) 같은 페놀릭 화합물을 함유하고 있다(22-24). 그 중에서도 현재 임상적으로 여성호르몬 대체제로 사용하고 있는 BC는 그 지표물질로 27-디옥시액테인의 함량을 측정하여 나타내고 있다. 따라서 본 연구에서도 임상적으로 사용되는 BC와 자생종 승마 추출물내의 27-디옥시액테인의 함량을 비교, 분석하였다. 분석조건에 따라 27-디옥시액테인 스탠다드와 아메리카 승마(BC) 및 4종의 자생종승마를 UPLC로 분석한 결과 약 2.9분에서 27-디옥시액테인 최고치가 나타났으며, BC의 함량이 가장 많았고, CH, CS 및 CD에는 2.9분에 최고치가 관찰되었으나 CJ는 거의 없었다(도 12).Chemically, black cohosh extracts contain triterpin glycosides such as actane or 27-dioxyactin and phenolic compounds such as ferulic acid and isoferulic acid (22-24). . Among them, BC, which is currently used as a female hormone replacement agent, is measured and indicated the content of 27-dioxyactane as an indicator. Therefore, this study also compared and analyzed the contents of 27-dioxyactane in clinically used BC and native species equestrian extract. According to the analysis conditions, 27-dioxyactin standard, American horse riding (BC) and four native species riding horses were analyzed by UPLC, and the highest content of BC was found in 2.9 minutes at 27-deoxyactin. The highest value was observed at 2.9 minutes in CH, CS and CD, but there was almost no CJ (FIG. 12).
이를 다시 질량 분석법으로 분석한 결과 UPLC의 결과와 같이 BC에의 함량이 가장 많았으며(도 13), 자생종 승마 중에서는 CH의 함량이 가장 높고, 그다음으로는 CS, 그리고 CD와 CJ의 함량은 낮았다. 특히, CH는 BC의 27-디옥시액테인 함량과 유의적인 차이가 없는 것으로 나타나 아메리카승마 대체제로서의 사용가능성이 높을 것으로 사료되었다. 스탠다드 및 각 승마종을 0.5 ㎎/㎖의 농도로 분석한 결과 질량 분석법에서의 측정 정도는 표 1에 나타내었다.As a result of mass spectrometry analysis, the content of BC was the highest as shown in UPLC (Fig. 13). Among native horse riding, CH content was the highest, followed by CS, and CD and CJ contents were low. In particular, CH was not found to be significantly different from BC's 27-dioxyactin content, and therefore, it may be considered to be highly applicable as an alternative to horseback riding. As a result of analyzing the standard and each riding species at a concentration of 0.5 mg / ml, the measurement accuracy in the mass spectrometry is shown in Table 1.
결론conclusion
한반도 자생종 승마와 아메리카승마의 혈관이완활성 및 폐경을 유도한 동물모델에서의 혈중 지질농도의 개선효과를 비교한 결과 자생종 승마 중 특히 한반도에만 자생하는 것으로 알려진 세잎승마 추출물이 현재 임상적으로 사용되고 있는 아메리카 승마 추출물과 유사한 활성을 나타내는 것을 알 수 있었다. 특히, 혈중 지질 개선효과에서는 세잎승마 추출물 투여 시 폐경기여성의 호르몬 대체제로서 사용되고 있는 아메리카승마와 St. John's wort 혼합물보다도 높은 활성을 나타내어 효능면에서 자생종승마의 아메리카 승마 대체 가능성이 대두되었다. 뿐만 아니라, 현재 사용되는 아메리카승마의 지표물질인 27-디옥시-액테인의 함량 또한 한반도 자생종인 세잎승마 추출물이 아메리카 승마보다는 낮으나 다른 승마 종 보다는 현저히 높아, 아메리카 승마 대체소재로의 활용가능성이 높을 것으로 사료되었다.
A comparison of the effect of improving blood lipid concentrations on the vasorelaxant activity and postmenopausal animal models of native horseback riding and American horseback riding in the Korean peninsula showed that the three-leaf horseback riding extract, which is known to grow only on the Korean peninsula, is currently used clinically. It was found to exhibit similar activity to the equestrian extract. In particular, the effect of improving lipids in blood was that horseriding and St. It showed higher activity than John's wort mixture, and thus the possibility of replacing native horse riding with native horse riding appeared. In addition, the content of 27-dioxy-actin, an indicator of American riding, is also lower than that of American riding, but significantly higher than that of other riding horses. Was considered to be.
이상으로 본 발명의 특정한 부분을 상세히 기술하였는바, 당업계의 통상의 지식을 가진 자에게 있어서 이러한 구체적인 기술은 단지 바람직한 구현예일 뿐이며, 이에 본 발명의 범위가 제한되는 것이 아닌 점은 명백하다. 따라서 본 발명의 실질적인 범위는 첨부된 청구항과 그의 등가물에 의하여 정의된다고 할 것이다.
While the present invention has been particularly shown and described with reference to exemplary embodiments thereof, it is to be understood that the same is by way of illustration and example only and is not to be construed as limiting the scope of the present invention. It is therefore intended that the scope of the invention be defined by the claims appended hereto and their equivalents.
참조 문헌References
1. 이현우, 박종욱. 1994. Cimicifuga foetida L. Complex 및 근연종(미나리아재비과)에 대한 분류학적 연구. 한국식물학회지, 37(1): 111-124 Lee Hyun-woo, Park Jong-wook. 1994. Taxonomic Study on Cimicifuga foetida L. Complex and Near Species. Korean Journal of Plant Science, 37 (1): 111-124
2. 박종욱. 1994. 세계산 승마속 식물의 계통과 진화:비교형태학적, 세포학적 및 화학적 접근. 과학재단 용역과제 보고서2. Park Jong Wook. 1994. Lineage and Evolution of World Riding Plants: A Comparative Morphological, Cytologic and Chemical Approach. Science Foundation Service Project Report
3. 이현우. 2000. 승마속(미나리아재비과)식물의 유전적 분기. 서울대학교 대학원 생명과학부 박사학위 논문 3. Lee Hyun-woo. 2000. Genetic divergence of Equestrian genus. Seoul National University, Ph.D.
4. Foster S. 1999. black cohosh: Cimicifuga racemosa. A literature review. Herbalgram, 45: 35-504. Foster S. 1999. black cohosh: Cimicifuga racemosa. A literature review. Herbalgram, 45: 35-50
5. Borrelli F, Ernst E. 2002. Cimicifuga racemosa: a systemic review of its clinical efficacy. European Journal of Clinical Pharmacology, 58: 235-241Borrelli F, Ernst E. 2002. Cimicifuga racemosa: a systemic review of its clinical efficacy. European Journal of Clinical Pharmacology, 58: 235-241
6. Kennelly EJ, Baggett S, Nuntanakorn P, Ososki AL, Mori SA, Duke J, Coleton M, Kronenberg F. Analysis of thirteen populations of black cohosh for formononetin. Phytomedicine, 9: 4671-4676. Kennelly EJ, Baggett S, Nuntanakorn P, Ososki AL, Mori SA, Duke J, Coleton M, Kronenberg F. Analysis of thirteen populations of black cohosh for formononetin. Phytomedicine, 9: 4671-467
7. Liske E, Hanggi W, Henneicke-von Zeplin HH, Boblitz N, Wustenberg P, Rahlfs VW. Physiological investigation of a unique extract of black cohosh (Cimicifuga racemosa rhizome): a 6-month clinical study demonstrates no systemic estrogenic effect. Journal of Womens Health Gender-Based Medicine, 11: 163-1747. Liske E, Hanggi W, Henneicke-von Zeplin HH, Boblitz N, Wustenberg P, Rahlfs VW. Physiological investigation of a unique extract of black cohosh (Cimicifuga racemosa rhizome): a 6-month clinical study demonstrates no systemic estrogenic effect. Journal of Womens Health Gender-Based Medicine, 11: 163-174
8. Pinea B, Garcia-Perez MA, Vazques F, Juia MD, Tarin JJ, Hermenegildo C, Cano A. No effect of Cimicifuga racemosa extract on serum interleukin-6 levels and prostacyclin production by human endothelial cells. European Journal of Obstetrics and Gynecology and Reproductive Biology, 144: 93-94Pinea B, Garcia-Perez MA, Vazques F, Juia MD, Tarin JJ, Hermenegildo C, Cano A. No effect of Cimicifuga racemosa extract on serum interleukin-6 levels and prostacyclin production by human endothelial cells. European Journal of Obstetrics and Gynecology and Reproductive Biology, 144: 93-94
9. Seidlova-Wuttke D, Jarry H, Becker T, Christoffel V, Wuttke W. Pharmacology of Cimicifuga racemosa extract BNO 1055 in rats: bone, fat and uterus. Maturitas, 137: S39-S509.Seidlova-Wuttke D, Jarry H, Becker T, Christoffel V, Wuttke W. Pharmacology of Cimicifuga racemosa extract BNO 1055 in rats: bone, fat and uterus. Maturitas, 137: S39-S50
10. Rachon D, Vortherms T, Seidlova-Wuttke D, Wuttke W. Effects of black cohosh extract on body weight gain, intra-abdominal fat accumulation, plasma lipids and glucose tolerance in ovariectomized Sprague-Dawley rats. Maturitas, 60: 209-21510. Rachon D, Vortherms T, Seidlova-Wuttke D, Wuttke W. Effects of black cohosh extract on body weight gain, intra-abdominal fat accumulation, plasma lipids and glucose tolerance in ovariectomized Sprague-Dawley rats. Maturitas, 60: 209-215
11. Brayden JE. Potassium channel in vascular smooth muscle. Clinical and Experimental Pharmacology and Physiology, 23: 1069-107611. Brayden JE. Potassium channel in vascular smooth muscle. Clinical and Experimental Pharmacology and Physiology, 23: 1069-1076
12. Vanhoutte PM. 2004. Endothelium-dependent hyperpolarizations: the history. Pharmacological Research, 49: 503-50812. Vanhoutte PM. 2004. Endothelium-dependent hyperpolarizations: the history. Pharmacological Research, 49: 503-508
13. Moncada S, Higgs A. 1993. The L-arginine-nitric oxide pathway. New England Journal of Medicine, 329: 2002-201213. Moncada S, Higgs A. 1993. The L-arginine-nitric oxide pathway. New England Journal of Medicine, 329: 2002-2012
14. Raggazzi E, Chinellato A, Pandolfo L. 1995. Endothelial nucleotide-mediated aorta relaxation in aged Watanabe heritable hyperlipidemic rabbits. Journal of Cardiovascular Pharmacology, 26: 119-12614. Raggazzi E, Chinellato A, Pandolfo L. 1995. Endothelial nucleotide-mediated aorta relaxation in aged Watanabe heritable hyperlipidemic rabbits. Journal of Cardiovascular Pharmacology, 26: 119-126
15. Szar다 JL, Bailly DA, Stewart NL, Gruetter CA. 1992. Histamine H1-receptor mediated endothelium-dependent relaxaiton of rat isolated pulmonary arteries. Pulmonary Pharmacology, 5: 67-7415. Szar JL, Bailly DA, Stewart NL, Gruetter CA. 1992. Histamine H1-receptor mediated endothelium-dependent relaxaiton of rat isolated pulmonary arteries. Pulmonary Pharmacology, 5: 67-74
16. Kysela S, Torok J. 1996. Histamine H1-receptor antagonists do not prevent the appearance of endothelium-dependent relaxation to acetylcholine in pulmonary artery. Physiological Research, 45: 345-35016. Kysela S, Torok J. 1996. Histamine H1-receptor antagonists do not prevent the appearance of endothelium-dependent relaxation to acetylcholine in pulmonary artery. Physiological Research, 45: 345-350
17. Nelson MT, Quayle JM. 1995. Physiological roles and properties of potassium channels in arterial smooth muscle. American Journal of Physiology, 268: C799-C82217. Nelson MT, Quayle JM. 1995. Physiological roles and properties of potassium channels in arterial smooth muscle. American Journal of Physiology, 268: C799-C822
18. Standen NB, Quayle JM. 1998. K+ channel modulation in arterial smooth muscle. Acta Physiologica Scandinavica, 164: 549-55718. Standen NB, Quayle JM. 1998. K + channel modulation in arterial smooth muscle. Acta Physiologica Scandinavica, 164: 549-557
19. Walsh BW, Kuller LH, Wild RA, Paul S, Farmer M. Lawrence JB, Shah AS, Anderson PW. 1998. Effects of raloxifene on serum lipids and coagulation factors in healthy posmenopausal women. The Journal of the American Medical Association, 279: 1445-1451.19. Walsh BW, Kuller LH, Wild RA, Paul S, Farmer M. Lawrence JB, Shah AS, Anderson PW. 1998. Effects of raloxifene on serum lipids and coagulation factors in healthy posmenopausal women. The Journal of the American Medical Association, 279: 1445-1451.
20. Herrington DM, Pusser BE, Riley WA, Thuren TY, Brosnihan KB, Brinton EA, MacLean DB. 2000. Cardiovascular effects of droloxifene, a new selective estrogen receptor modulator, in healthy postmenopausal women. Arteriosclerosis Thrombosis and Vascular Biology, 20: 1606-161220. Herrington DM, Pusser BE, Riley WA, Thuren TY, Brosnihan KB, Brinton EA, MacLean DB. 2000. Cardiovascular effects of droloxifene, a new selective estrogen receptor modulator, in healthy postmenopausal women. Arteriosclerosis Thrombosis and Vascular Biology, 20: 1606-1612
21. Sutherlan MK, Brady H, Gayo-Fung LM, Leisten J, Lippes SG, McKie JA, O'Leary E, Patnaik N, Anderson, DW, Bhagwat SS, Stein B. 2003. Effects of SP500263, a novel selective estrogen receptor modulator, on bone, uterus, and serum cholesterol in the ovariectomized rat. Calcification Tissue International, 72: 710-716Sutherlan MK, Brady H, Gayo-Fung LM, Leisten J, Lippes SG, McKie JA, O'Leary E, Patnaik N, Anderson, DW, Bhagwat SS, Stein B. 2003. Effects of SP500263, a novel selective estrogen receptor modulator, on bone, uterus, and serum cholesterol in the ovariectomized rat. Calcification Tissue International, 72: 710-716
22. Shao Y, Harris A, Wang M, Zhang H, Cordell GA, Bowman M, Lemmo E. 2000. Triterpene glycosides from Cimicifuga racemosa. Journal of Natural Products, 63: 905-91022. Shao Y, Harris A, Wang M, Zhang H, Cordell GA, Bowman M, Lemmo E. 2000. Triterpene glycosides from Cimicifuga racemosa. Journal of Natural Products, 63: 905-910
23. He K, Zheng B, Kim CH, Rogers L, Zheng Q. 2000. Direct analysis and identification of triterpene glycosides by LC/MS in black cohosh, Cimicifuga racemosa, and in several commercially available black cohosh products. Planta Medica, 66: 635-64023. He K, Zheng B, Kim CH, Rogers L, Zheng Q. 2000. Direct analysis and identification of triterpene glycosides by LC / MS in black cohosh, Cimicifuga racemosa, and in several commercially available black cohosh products. Planta Medica, 66: 635-640
24. Kruse SO, Lohning A, Pauli GF, Winterhoff H, Nahrstedt A. 1999. Fukiic and Piscidic acid esters from rhizome of Cimicifuga racemosa and the in vitro estrogenic activity of fukinolic acid. Planta Medica, 65: 763-76424. Kruse SO, Lohning A, Pauli GF, Winterhoff H, Nahrstedt A. 1999. Fukiic and Piscidic acid esters from rhizome of Cimicifuga racemosa and the in vitro estrogenic activity of fukinolic acid. Planta Medica, 65: 763-764
Claims (8)
Food composition for menopausal disease improvement comprising the three-leaf horseriding extract as an active ingredient.
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