KR20180029146A - Composition for inhibiting COX-2 and iNOS Aster yomena extract or fractions thereof - Google Patents
Composition for inhibiting COX-2 and iNOS Aster yomena extract or fractions thereof Download PDFInfo
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- KR20180029146A KR20180029146A KR1020160116447A KR20160116447A KR20180029146A KR 20180029146 A KR20180029146 A KR 20180029146A KR 1020160116447 A KR1020160116447 A KR 1020160116447A KR 20160116447 A KR20160116447 A KR 20160116447A KR 20180029146 A KR20180029146 A KR 20180029146A
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Abstract
Description
본 발명은 쑥부쟁이(Aster yomena) 추출물, 또는 이의 분획물을 유효성분으로 포함하는, COX-2의 발현 저해, iNOS의 발현 저해, NF-κB 활성 저해 및 NO 생성 저해에 의한, 염증성 질환의 예방 또는 치료용 약학적 조성물 및 식품 조성물에 관한 것이다.The present invention relates to a method of inhibiting the expression of COX-2, inhibiting the expression of iNOS, inhibiting NF-κB activity and inhibiting NO production, preventing or preventing an inflammatory disease, comprising an Aster yomena extract or a fraction thereof as an active ingredient, And to a pharmaceutical composition for therapeutic use and a food composition.
각종 병원체가 인체에 침입하면 면역 시스템은 생물학적 방어에 관여하게 된다. 염증 반응은 미생물 감염이나 조직 손상에 방어하기 위해 일어나는 현상이고, 이에 의해 조직 구조의 회복이 촉진되게 된다 (MURAKAMI, A. and OHIGASHI, H. 2007. Targeting NOX, INOS and COX-2 in inflammatory cells: chemoprevention using food phytochemicals. Int J Cancer 121(11), 2357-2363). 그러나, 지속되는 염증은 유익하지 않으며, 암을 포함한 다양한 질환의 병리에 관여한다. 미생물 감염이나 조직 손상은 염증 반응을 활성화시키고, 결과적으로 전염증(pro-inflammatory) 단백질의 발현을 유도하게 된다. 유도성 산화 질소(iNOS)와 cyclooxygenase-2(COX-2)는 다양한 염증성 질환과 관련이 있는 주요 효소이다.When various pathogens enter the human body, the immune system becomes involved in biological defense. Inhibition of inflammation is a phenomenon that occurs to defend against microbial infection or tissue damage, thereby promoting the recovery of tissue structure (MURAKAMI, A. and OHIGASHI, H. 2007. Targeting NOX, INOS and COX-2 in inflammatory cells: Chemoprevention using food phytochemicals. Int J Cancer 121 (11), 2357-2363). However, persistent inflammation is not beneficial and is involved in the pathology of various diseases, including cancer. Microbial infection or tissue damage activates the inflammatory response, which in turn leads to the expression of pro-inflammatory proteins. Inducible nitric oxide (iNOS) and cyclooxygenase-2 (COX-2) are major enzymes involved in a variety of inflammatory diseases.
NOS는 NO를 생성하기 위하여, L-아르기닌의 산화적 탈아미노화 반응을 촉매한다. NOS는 세포 유형, 위치, 발현 방식에 따라 세 가지 아형으로 분류된다: 뉴런의 NOS(nNOS), 내피 NOS(eNOS), 및 대식세포 또는 유도성 NOS(iNOS). nNOS와 eNOS 는 신경 조직과 혈관 내피 세포에 각각 본질적으로 발현된다. 반면, iNOS는 다양한 세포에서 감염 또는 전염증성 자극에 의해 유도된다. iNOS는 염증 관련 질환을 가진 환자의 대식세포와 단핵구에서 가장 쉽게 관찰된다. 그러므로, iNOS는 만성 염증성 질환의 치료에 매우 중요한 치료 표적이다.NOS catalyzes the oxidative deamination of L-arginine to produce NO. NOS is classified into three subtypes depending on cell type, location, and mode of expression: neurons (nNOS), endothelial NOS (eNOS), and macrophages or inducible NOS (iNOS). nNOS and eNOS are essentially expressed in nerve tissue and vascular endothelial cells, respectively. On the other hand, iNOS is induced by infection or proinflammatory stimulation in various cells. iNOS is most frequently observed in macrophages and monocytes of patients with inflammatory diseases. Therefore, iNOS is an important therapeutic target for the treatment of chronic inflammatory diseases.
한편, COX의 두가지 동형은 COX-1과 COX-2로, 아라키돈산의 프로스타노이드로의 전환을 촉진하며, 중요한 염증 반응 매개 물질이다. COX-1 효소는 상대적으로 안정적인 수준에서 많은 정상 조직에 널리 분포하고 구조적으로 발현된다. 반면, COX-2는 물리적, 화학적 및 생물학적 자극에 반응하며, 대부분의 정상 포유동물 조직에서 발현되는 유도성 효소이다. COX는 비스테로이드성 항염증성 약물(NSAIDs)의 타겟으로, 통증, 발열 및 염증의 치료에 치료학적인 역할을 하는 것으로 알려져 있다. 따라서, iNOS 및 COX-2 발현의 조절은 특정 염증성 질환의 치료에 있어 중요한 치료학적인 통로(therapeutic avenue)이다. On the other hand, two isoforms of COX are COX-1 and COX-2, which promote the conversion of arachidonic acid to prostanoids and are important inflammatory mediators. The COX-1 enzyme is widely distributed and structurally expressed in many normal tissues at relatively stable levels. On the other hand, COX-2 is an inducible enzyme that responds to physical, chemical and biological stimuli and is expressed in most normal mammalian tissues. COX is the target of non-steroidal anti-inflammatory drugs (NSAIDs) and is known to play a therapeutic role in the treatment of pain, fever and inflammation. Thus, modulation of iNOS and COX-2 expression is an important therapeutic avenue in the treatment of certain inflammatory diseases.
본 발명의 목적은 쑥부쟁이(Aster yomena) 추출물, 또는 이의 분획물을 유효성분으로 포함하는, COX-2의 발현 저해, iNOS의 발현 저해, 및 NO 생성 저해에 의한, 염증성 질환의 예방 또는 치료용 약학적 조성물을 제공하는 것이다.The object of the present invention is to provide a pharmaceutical composition for the prophylaxis or treatment of inflammatory diseases by inhibiting the expression of COX-2, inhibiting the expression of iNOS, and inhibiting NO production, which comprises an Aster yomena extract or a fraction thereof as an active ingredient To provide a composition.
본 발명의 다른 목적은, 쑥부쟁이(Aster yomena) 추출물, 또는 이의 분획물을 유효성분으로 포함하는, COX-2의 발현 저해, iNOS의 발현 저해, 및 NO 생성 저해에 의한, 염증성 질환의 예방 또는 개선용 식품 조성물을 제공하는 것이다.Another object of the present invention is to prevent or ameliorate inflammatory diseases by inhibiting the expression of COX-2, inhibiting the expression of iNOS and inhibiting NO production, comprising an extract of Aster yomena or a fraction thereof as an active ingredient And a food composition.
이에, 본 발명자는 천연물에서 iNOS 및 COX-2 억제제를 찾고자 예의 노력하였으며, 무수히 많은 천연물에 탐색을 통해, 쑥부쟁이의 염화 메틸렌 분획물이 LPS 유도된 iNOS 및 COX-2의 발현을 억제하는 것을 확인하였으며, 또한 NO의 생성을 억제하고, NF-κB의 활성을 저해하는 것을 확인하여, 염증성 질환의 예방 또는 치료에 유용하게 사용될 수 있음을 확인하고 본 발명을 완성하였다. Accordingly, the present inventor has sought to find iNOS and COX-2 inhibitors in natural products and found that the methylene chloride fraction of mugwort was inhibited the expression of LPS-induced iNOS and COX-2 through numerous natural products , Inhibits the production of NO and inhibits the activity of NF-κB. Thus, it has been confirmed that the compound can be effectively used for the prophylaxis or treatment of inflammatory diseases and the present invention has been completed.
상기 목적을 달성하기 위한 하나의 양태로서, 본 발명은 쑥부쟁이(Aster yomena) 추출물, 또는 이의 분획물을 유효성분으로 포함하는, COX-2의 발현 저해, iNOS의 발현 저해, 및 NO 생성 저해에 의한, 염증성 질환의 예방 또는 치료용 약학적 조성물을 제공한다.In order to achieve the above object, the present invention provides a method for inhibiting the expression of COX-2, inhibiting the expression of iNOS, and inhibiting NO production, which comprises an extract of Aster yomena or a fraction thereof as an active ingredient , A pharmaceutical composition for the prophylaxis or treatment of an inflammatory disease.
구체적으로, 본 발명의 염증성 질환의 예방 또는 치료용 약학적 조성물은 쑥부쟁이(Aster yomena) 추출물, 또는 이의 분획물을 포함할 수 있다. Specifically, the pharmaceutical composition for preventing or treating an inflammatory disease of the present invention may comprise an Aster yomena extract, or a fraction thereof.
본 발명에서, 용어 "쑥부쟁이"는 쌍떡잎식물 초롱꽃목 국화과의 여러해살이풀로, 권영초·왜쑥부쟁이·가새쑥부쟁이라고도 한다. 습기가 약간 있는 산과 들에서 자라며, 높이 30∼100cm이다. 뿌리줄기는 옆으로 뻗으며, 원줄기가 처음 나올 때는 붉은빛이 돌지만 점차 녹색 바탕에 자줏빛을 띤다. 뿌리에 달린 잎은 꽃이 필 때 지며, 줄기에 달린 잎은 어긋나고 바소꼴이며 가장자리에 굵은 톱니가 있으며, 겉면은 녹색이고 윤이 나며 위쪽으로 갈수록 크기가 작아진다. 꽃은 7∼10월에 피며, 열매는 수과로서 달걀 모양이고 털이 나며 10∼11월에 익는다. 관모는 길이 약 0.5mm로서 붉은색이며, 번식은 종자나 포기나누기로 한다. In the present invention, the term "Wormwood" is a perennial herb that is a perennial herbaceous plant belonging to the family Asteraceae, and is also referred to as Kwangyoungwoo, wormwood, brachyury. It grows in mountains and fields with little moisture, and is 30-100 cm high. The rootstock extends sideways. When the main stem comes out for the first time, it is reddish, but it gradually becomes purple on the green background. The leaves on the roots are blossomed, and the leaves on the stem are slanting and bulbous, with coarse sawtooth on the edge, the surface is green and glazed, and the size becomes smaller toward the top. Flowers bloom in July-October, fruit is ovate, egg-shaped, hairy, ripe in October-November. The tangents are about 0.5mm in length and are red, and the breeding is done by seeding or giving up.
본 발명에서 용어, "쑥부쟁이(Aster yomena) 추출물"은 쑥부쟁이(Aster yomena)를 추출하여 수득한 추출물을 의미한다. 상기 쑥부쟁이 추출물은 쑥부쟁이 분쇄물을 건조 중량의 약 2 내지 20배, 바람직하게는 약 8 내지 10배에 달하는 부피의 물, 메탄올, 에탄올 및 부탄올 등과 같은 탄소수 1(C1) 내지 4(C4)의 알코올 또는 이들의 혼합용매를 용출 용매로써 사용하고, 추출 온도는 20 내지 100℃, 바람직하게는 60 내지 90℃에서, 추출 기간은 약 2시간 내지 4일, 바람직하게는 2 내지 6시간 동안 열수 추출, 냉침 추출, 환류 냉각 추출 또는 초음파 추출 등의 추출방법을 사용하여 추출할 수 있으나, 염증성 질환의 예방 또는 치료 활성이 있는 물질을 추출하는 방법이라면 제한없이 이용될 수 있다. 바람직하게는 열수추출로 1회 내지 5회 연속 추출하여 감압여과하고, 그 여과추출물을 진공회전농축기로 20 내지 100℃에서 감압 농축하여 물, 저급 알콜 또는 이들의 혼합용매에 가용한 쑥부쟁이 조추출물을 수득한 결과물이 될 수 있으나, 본 발명의 염증성 질환의 예방 또는 치료 활성을 나타낼 수 있는 한, 이에 제한되지는 않고, 추출액, 추출액의 희석액 또는 농축액, 추출액을 건조하여 얻어지는 건조물, 또는 이들 조정제물 또는 정제물을 모두 포함할 수 있다. 상기 쑥부쟁이 추출물은 천연, 잡종, 변종식물의 다양한 기관으로부터 추출될 수 있고, 예를 들어, 뿌리, 지상부, 줄기, 잎, 열매 또는 식물 조직 배양물 등으로부터 추출 가능하며, 특히 쑥부쟁이의 건조된 잎으로부터 추출될 수 있다.In the present invention, the term " Aster yomena extract" means an extract obtained by extracting Aster yomena . The mugwort berry extract has a volume of water ranging from about 2 to 20 times, preferably about 8 to 10 times the dry weight of mugwort pulverized water, a water soluble organic solvent having 1 to 4 carbon atoms (C 1 to 4) such as methanol, ethanol, 4 ) alcohol or a mixed solvent thereof is used as an elution solvent and the extraction temperature is 20 to 100 ° C, preferably 60 to 90 ° C, the extraction period is about 2 hours to 4 days, preferably 2 to 6 hours Extraction can be carried out using an extraction method such as hot water extraction, cold extraction, reflux cooling extraction, or ultrasonic extraction, but any method can be used without limitation as long as it is a method for extracting a substance having an activity of preventing or treating inflammatory diseases. Preferably, the extract is continuously extracted 1 to 5 times by hot water extraction, and filtered under reduced pressure. The filtrate extract is concentrated under reduced pressure at 20 to 100 캜 in a vacuum rotary condenser, and then extracted with water, a lower alcohol or a mixed solvent thereof, But the present invention is not limited thereto and may be a dried product obtained by drying an extract, a diluted solution of the extract, a concentrated solution or an extract, or a dried product obtained by drying the concentrated solution or the adjusted product Or purified water. The mugwort extract can be extracted from various organs of natural, hybrid, and variant plants and extracted from, for example, root, ground, stem, leaf, fruit or plant tissue culture, It can be extracted from leaves.
본 발명에서 용어, "분획물"은 다양한 구성성분을 포함하는 혼합물로부터 특정 성분 또는 특정 그룹을 분리하는 분획방법에 의하여 얻어진 결과물을 의미한다. 본 발명의 쑥부쟁이 분획물은 쑥부쟁이 추출물을 현탁한 후, 물, 탄소수 1(C1) 내지 4(C4)의 알코올, 염화 메틸렌, 클로로포름, 에틸 아세테이트, 헥산, 부탄올 또는 이들의 혼합용매를 사용하여 분획함으로써 분획물을 수득할 수 있다. 구체적으로, 쑥부쟁이 조추출물을 증류수 등에 현탁한 후, 현탁액의 약 1 내지 100배, 바람직하게는 약 1 내지 5배 부피의 물, 탄소수 1(C1) 내지 4(C4)의 알코올, 염화 메틸렌, 클로로포름, 에틸 아세테이트, 헥산, 부탄올 또는 이들의 혼합용매를 가하여 1회 내지 10회, 바람직하게는 2회 내지 5회에 걸쳐 극성 또는 비극성 용매 가용층을 추출, 분리하여 수득할 수 있다.The term "fraction" in the present invention means a product obtained by a fractionation method for separating a specific component or a specific group from a mixture containing various constituents. After Aster ridden fractions of the present invention is suspended Aster ivy extract, water, carbon number 1 (C 1) to 4 (C 4) alcohol, methylene chloride, chloroform, ethyl acetate, hexane, butanol, or the use of such a mixed solvent of Followed by fractionation to obtain a fraction. Specifically, after extracting the mugwort juvenile extract, it is suspended in distilled water or the like, and then water, about 1 to 100 times, preferably about 1 to 5 times the volume of the suspension, the alcohol having 1 to (C 1 ) to 4 (C 4 ) Methylene, chloroform, ethyl acetate, hexane, butanol or a mixed solvent thereof, and extracting and separating the polar or non-polar solvent
본 발명의 일 실시예에서는 쑥부쟁이의 건조된 잎(1kg)을 50 % 에탄올(9 L)로 87℃에서 4시간 동안 3번 추출하여 쑥부쟁이 50% 에탄올 추출물을 수득하였으며, 45℃의 진공에서 농축시켰다. 또한, 상기 쑥부쟁이의 건조 추출물(12.1g)을 물(100 ml)에 현탁시키고, n-헥산, 메틸렌 클로라이드(염화 메틸렌), 에틸 아세테이트, 및 물을 이용하여 분획물(fraction)을 제조하였다. 이후, 본 발명의 일실시예에서는 상기 쑥부쟁이의 에탄올 추출물, 헥산 분획물, 에틸 아세테이트 분획물, 염화 메틸렌, 부탄올 분획물이 NF-κB 활성을 억제하는 지를 조사하였다. 그 결과, 쑥부쟁이 에탄올 추출물, 헥산 분획물, 에틸 아세테이트 분획물, 부탄올 분획물은 NF-κB 활성을 억제하지 않았으나, 쑥부쟁이의 염화 메틸렌 분획물만이 LPS에 의해 유도된 NF-κB 활성화를 억제하는 것을 확인하였다(도 1). 이에 따라, 이후의 실험에서는 쑥부쟁이 염화 메틸렌 분획물을 사용하였다. In one embodiment of the present invention, the dried leaf (1 kg) of mugwort was extracted with 50% ethanol (9 L) for 3 hours at 87 ° C for 3 hours to obtain a 50% ethanol extract of Mugwort mugwort, Lt; / RTI > The dried extract (12.1 g) was suspended in water (100 ml), and a fraction was prepared using n-hexane, methylene chloride (methylene chloride), ethyl acetate and water. Then, in one embodiment of the present invention, it was examined whether the ethanol extract, hexane fraction, ethyl acetate fraction, methylene chloride or butanol fraction inhibited NF-κB activity of the mugwort. As a result, it was confirmed that the mugwort extract, hexane fraction, ethyl acetate fraction, and butanol fraction did not inhibit NF-κB activity, but only the methylene chloride fraction of mugwort was inhibited by LPS-induced NF-κB activation (Fig. 1). Thus, in the subsequent experiments, the methylene chloride fraction of mugwort was used.
본 발명에 따른 쑥부쟁이(Aster yomena) 추출물, 또는 이의 분획물은 염증관련 인자로 알려진 COX-2와 iNOS의 발현을 억제하고, 염증 관련 전사인자로 알려진 NF-κB의 활성을 저해하고, NO 생성을 억제하는 것을 확인함으로써 염증성 질환의 예방 또는 치료용도로 사용될 수 있음을 확인하였다(실험예 1, 내지 3 및 도 1 내지 4).The Aster yomena extract or its fractions according to the present invention inhibit the expression of COX-2 and iNOS, known as inflammation-related factors, inhibit the activity of NF-κB, an inflammatory-related transcription factor, (Experimental Examples 1 to 3 and Figs. 1 to 4). As shown in Fig.
구체적으로, NF-κB는 염증과 관련이 있는 전사조절인자인데, NF-κB 활성화에 대한 쑥부쟁이(Aster yomena) 추출물 또는 이의 분획물의 효과를 규명하기 위하여, NF-κB 루시퍼라아제 리포터 분석법을 이용한 결과, 쑥부쟁이(Aster yomena) 염화 메틸렌 분획물은 LPS에 의해 유도된 NF-κB 활성화를 억제하는 것을 확인하였으며(도 2B), 쑥부쟁이(Aster yomena) 염화 메틸렌 분획물은 LPS에 의해 유도된 IκBα의 분해 역시 억제하는 것을 확인하였다(도. 2C). Specifically, NF-κB is a transcriptional regulator associated with inflammation. To investigate the effect of Aster yomena extract or its fractions on NF-κB activation, NF-κB luciferase reporter assay As a result, Aster yomena methylene chloride fraction inhibited LPS-induced NF-κB activation (Fig. 2B). The methylene chloride fraction of Aster yomena inhibited LPS-induced IκBα degradation (Fig. 2C).
또한, COX-2는 대식 세포에서 NF-κB의 활성화를 통해 조절되는 타겟 유전자 중의 하나인데, 쑥부쟁이 염화 메틸렌 분획물(FAY)이 COX-2 발현을 조절하는 지를 평가하였다. 그 결과, COX-2 루시퍼라제 리포터 분석과 면역블랏 분석에 의해 확인된 바와 같이, 상기 쑥부쟁이 염화 메틸렌 분획물은 RAW264.7 세포에서 COX-2의 발현을 억제하는 것을 확인하였다(도 3A 및 3B). In addition, COX-2 is one of the target genes regulated through the activation of NF-κB in macrophages, evaluating whether the methylene chloride fraction (FAY) regulates COX-2 expression. As a result, it was confirmed that the above-mentioned mugwort methylene chloride fraction inhibited the expression of COX-2 in RAW264.7 cells (Fig. 3A and 3B), as confirmed by COX-2 luciferase reporter analysis and immunoblot analysis .
다음으로, 쑥부쟁이 염화 메틸렌 분획물(FAY)이 NF-κB의 활성화를 통해 조절되는 다른 타겟 유전자인 iNOS의 발현을 조절하는 지를 조사하였다. 그 결과, iNOS의 루시퍼라제 리포터 및 면역블랏 분석에 의해 확인된 바와 같이, 쑥부쟁이 염화 메틸렌 분획물(FAY)은 RAW264.7 세포에서 iNOS의 발현을 억제하는 것을 확인하였다(도 4A 및 4B).Next, we examined whether mugwort methylene chloride fraction (FAY) regulates the expression of iNOS, another target gene regulated through activation of NF-κB. As a result, it was confirmed that the mugwort methylene fraction (FAY) inhibited the expression of iNOS in RAW264.7 cells (Fig. 4A and 4B), as confirmed by the luciferase reporter and immunoblot analysis of iNOS.
또한, 쑥부쟁이 염화 메틸렌 분획물(FAY)이 LPS 유도된 NO 생성을 억제하는 지를 평가하였다. 그 결과, 쑥부쟁이 염화 메틸렌 분획물(FAY)이 LPS 유도된 니트라이트(nitrite) 생성을 억제하여, NO 생성을 억제하는 것을 확인하였다(도 4C). In addition, it was evaluated whether the methylene chloride fraction (FAY) inhibited LPS - induced NO production. As a result, it was confirmed that the methylene chloride fraction (FAY) of mugwort buckwheat inhibited LPS-induced nitrite production and inhibited NO production (FIG. 4C).
본 발명에서 용어, "염증성 질환"은 염증을 주병변으로 하는 질병을 총칭하는 의미로서, 이에 제한되지는 않으나 구체적으로 천식, 만성폐쇄성 폐질환, 알레르기, 전신성 홍반성 루푸스, 경피증, 궤양성 대장염, 크론병, 아토피성 피부염, 건선, 아나필락시스, 피부염, 당뇨병성 망막증, 망막염, 황반 변성, 포도막염, 결막염, 관절염, 류마티스성 관절염, 강직성 척추염, 골관절염, 골다공증, 당뇨, 당뇨성 신장병, 신염, 신장염, 쇼그렌 증후군, 크론씨 병, 자가 면역 췌장염, 치주질환, 이식편 대 숙주 질환, 만성 골반 염증 질환, 자궁내막염, 비염, 편도염, 중이염, 인후염, 방광염 및 만성 전립선염로 이루어진 군으로부터 선택되는 어느 하나에 해당할 수 있으나, 이에 제한되는 것은 아니다.The term "inflammatory disease" in the present invention means a general disease of inflammation as a main lesion, and includes, but is not limited to, asthma, chronic obstructive pulmonary disease, allergy, systemic lupus erythematosus, scleroderma, ulcerative colitis, Diabetic retinopathy, retinitis, macular degeneration, uveitis, conjunctivitis, arthritis, rheumatoid arthritis, ankylosing spondylitis, osteoarthritis, osteoporosis, diabetes, diabetic nephropathy, nephritis, nephritis, Sjogren's syndrome Wherein the disease is selected from the group consisting of chronic obstructive pulmonary disease, autoimmune pancreatitis, periodontal disease, graft versus host disease, chronic pelvic inflammatory disease, endometritis, rhinitis, tonsillitis, otitis media, sore throat, cystitis and chronic prostatitis. But is not limited thereto.
본 발명에서 용어, "예방"은 상기 조성물의 투여로 염증성 질환의 발병을 억제 또는 지연시키는 모든 행위를 의미하며, "치료"는 상기 조성물에 의해 염증성 질환에 의한 증세가 호전되거나 이롭게 변경되는 모든 행위를 의미한다.In the present invention, the term "prevention" means any action that inhibits or delays the onset of an inflammatory disease upon administration of the composition, and "treatment" .
본 발명의 쑥부쟁이 추출물, 또는 이의 분획물을 포함하는 약학적 조성물은 약학적 조성물의 제조에 통상적으로 사용하는 적절한 담체, 부형체 또는 희석제를 추가로 포함할 수 있다. 이때, 상기 조성물에 포함되는 쑥부쟁이 추출물, 또는 이의 분획물은 특별히 이에 제한되지 않으나, 조성물 총 중량에 대하여 0.001 중량% 내지 99 중량%로, 바람직하게는 0.01 중량% 내지 50 중량%를 포함할 수 있다.The pharmaceutical compositions comprising the mugwort extract of the present invention, or fractions thereof, may further comprise suitable carriers, adducts or diluents conventionally used in the manufacture of pharmaceutical compositions. At this time, the composition of the mugwort extract or the fraction thereof contained in the composition is not particularly limited, but it may contain 0.001% by weight to 99% by weight, preferably 0.01% by weight to 50% by weight, based on the total weight of the composition .
상기 약학적 조성물은 정제, 환제, 산제, 과립제, 캡슐제, 현탁제, 내용액제, 유제, 시럽제, 멸균된 수용액, 비수성용제, 현탁제, 유제, 동결 건조제 및 좌제로 이루어진 군으로부터 선택되는 어느 하나의 제형을 가질 수 있으며, 경구 또는 비경구의 여러 가지 제형일 수 있다. 제제화할 경우에는 보통 사용하는 충진제, 증량제, 결합제, 습윤제, 붕해제, 계면활성제 등의 희석제 또는 부형제를 사용하여 조제된다. The pharmaceutical composition may be any one selected from the group consisting of tablets, pills, powders, granules, capsules, suspensions, solutions, emulsions, syrups, sterilized aqueous solutions, nonaqueous solvents, suspensions, emulsions, And may be oral or parenteral formulations of various forms. 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.
경구투여를 위한 고형제제에는 정제, 환제, 산제, 과립제, 캡슐제 등이 포함되며, 이러한 고형제제는 적어도 하나 이상의 부형제 예를 들면, 전분, 탄산칼슘, 수크로오스(sucrose) 또는 락토오스(lactose), 젤라틴 등을 섞어 조제될 수 있다. 또한, 단순한 부형제 이외에 스테아린산 마그네슘, 탈크 등과 같은 윤활제들도 사용될 수 있다. 경구투여를 위한 액상제제로는 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. 비경구투여를 위한 제제에는 멸균된 수용액, 비수성용제, 현탁제, 유제, 동결건조 제제, 좌제가 포함된다. 비수성용제, 현탁용제로는 프로필렌글리콜(propylene glycol), 폴리에틸렌 글리콜, 올리브 오일과 같은 식물성 기름, 에틸올레이트와 같은 주사 가능한 에스테르 등이 사용될 수 있다. 좌제의 기제로는 위텝솔(witepsol), 마크로골, 트윈(tween) 61, 카카오지, 라우린지, 글리세로젤라틴 등이 사용될 수 있다.Solid formulations for oral administration include tablets, pills, powders, granules, capsules and the like, which may contain at least one excipient such as starch, calcium carbonate, sucrose or lactose, gelatin And the like. In addition to simple excipients, lubricants such as magnesium stearate, talc, and the like may also be used. Liquid preparations for oral administration include suspensions, solutions, emulsions, syrups and the like. Various excipients such as wetting agents, sweeteners, fragrances, preservatives and the like may be included in addition to water and liquid paraffin, which are simple diluents commonly used. have. Formulations for parenteral administration include sterilized aqueous solutions, non-aqueous solutions, suspensions, emulsions, freeze-dried preparations, and suppositories. Propylene glycol, polyethylene glycol, vegetable oil such as olive oil, injectable ester such as ethyl oleate, and the like can be used as the non-aqueous solvent and suspension agent. Examples of the suppository base include witepsol, macrogol, tween 61, cacao paper, laurin, glycerogelatin and the like.
본 발명의 약학적 조성물은 약학적으로 유효한 양으로 투여할 수 있다. 본 발명에서 용어, "약학적으로 유효한 양"은 의학적 치료에 적용 가능한 합리적인 수혜/위험 비율로 질환을 치료하기에 충분한 양을 의미하며, 유효 용량 수준은 개체 종류 및 중증도, 연령, 성별, 질병의 종류, 약물의 활성, 약물에 대한 민감도, 투여 시간, 투여 경로 및 배출 비율, 치료기간, 동시 사용되는 약물을 포함한 요소 및 기타 의학 분야에 잘 알려진 요소에 따라 결정될 수 있다. 본 발명의 조성물은 개별 치료제로 투여하거나 다른 치료제와 병용하여 투여될 수 있고 종래의 치료제와는 순차적 또는 동시에 투여될 수 있다. 그리고 단일 또는 다중 투여될 수 있다. 상기 요소를 모두 고려하여 부작용없이 최소한의 양으로 최대 효과를 얻을 수 있는 양을 투여하는 것이 중요하며, 당업자에 의해 용이하게 결정될 수 있다.The pharmaceutical composition of the present invention may be administered in a pharmaceutically effective amount. The term "pharmaceutically effective amount" as used herein means an amount sufficient to treat a disease at a reasonable benefit / risk ratio applicable to medical treatment, and the effective dose level will vary depending on the species and severity, age, sex, The type of drug, the activity of the drug, the sensitivity to the drug, the time of administration, the route of administration and the rate of release, the duration of the treatment, factors including co-administered drugs, and other factors well known in the medical arts. The composition of the present invention may be administered as an individual therapeutic agent or in combination with other therapeutic agents, and may be administered sequentially or simultaneously with conventional therapeutic agents. And can be administered singly or multiply. It is important to take into account all of the above factors and to administer the amount in which the maximum effect can be obtained in a minimal amount without adverse effect, and can be easily determined by those skilled in the art.
본 발명의 약학적 조성물은 염증성 질환을 목적으로 하는 개체이면 특별히 한정되지 않고, 어떠한 것이든 적용가능하다. 예를 들면, 원숭이, 개, 고양이, 토끼, 모르모트, 랫트, 마우스, 소, 양, 돼지, 염소 등과 같은 비인간동물, 인간, 조류 및 어류 등 어느 것이나 사용할 수 있으며, 상기 약학적 조성물은 비 경구, 피하, 복강 내, 폐 내 및 비강 내로 투여될 수 있고, 국부적 치료를 위해, 필요하다면 병변 내 투여를 포함하는 적합한 방법에 의하여 투여될 수 있다. 본 발명의 상기 약학적 조성물의 바람직한 투여량은 개체의 상태 및 체중, 질병의 정도, 약물형태, 투여경로 및 기간에 따라 다르지만, 당업자에 의해 적절하게 선택될 수 있다. 예를 들어, 경구, 직장 또는 정맥, 근육, 피하, 자궁내 경막 또는 뇌혈관 내 주사에 의해 투여될 수 있으나, 이에 제한되는 것은 아니다. The pharmaceutical composition of the present invention is not particularly limited as long as it is an object for an inflammatory disease, and any of them can be applied. For example, any non-human animal such as a monkey, a dog, a cat, a rabbit, a guinea pig, a rat, a mouse, a cattle, a sheep, a pig or a goat can be used. Subcutaneous, intraperitoneal, intrapulmonary, and intranasal, and may be administered by a suitable method, including localized administration, if necessary, for localized treatment. The preferred dosage of the pharmaceutical composition of the present invention varies depending on the condition and body weight of the individual, the degree of disease, the type of drug, the route of administration and the period of time, but can be appropriately selected by those skilled in the art. For example, by oral, rectal or intravenous, intramuscular, subcutaneous, intra-uterine dural or intracerebral injection.
적합한 총 1일 사용량은 올바른 의학적 판단범위 내에서 처치의에 의해 결정될 수 있으며, 일반적으로 0.001 내지 1000 mg/kg의 양, 바람직하게는 0.05 내지 200 mg/kg, 보다 바람직하게는 0.1 내지 100 mg/kg의 양을 일일 1회 내지 수회로 나누어 투여할 수 있다.Suitable total daily doses may be determined by the treatment within the scope of sound medical judgment and are generally in the range of 0.001 to 1000 mg / kg, preferably 0.05 to 200 mg / kg, more preferably 0.1 to 100 mg / kg can be administered once or several times a day.
본 발명은 다른 하나의 양태로서, 쑥부쟁이(Aster yomena) 추출물, 또는 이의 분획물을 유효성분으로 포함하는, COX-2의 발현 저해, iNOS의 발현 저해, 및 NO 생성 저해에 의한, 염증성 질환의 예방 또는 개선용 식품 조성물을 제공한다. In another aspect, the present invention provides a method of inhibiting the expression of COX-2, inhibiting the expression of iNOS, inhibiting NO production, inhibiting inflammatory diseases, comprising an extract of Aster yomena or a fraction thereof as an active ingredient Or improving food composition.
상기 쑥부쟁이(Aster yomena), 이의 추출물, 및 이의 분획물 및 염증성 질환에 대해서는 상기에서 설명한 바와 같다.The above-mentioned Aster yomena , its extract, its fractions and inflammatory diseases are as described above.
본 발명에서의 용어, "개선"은 쑥부쟁이(Aster yomena) 추출물, 또는 이의 분획물을 유효성분으로 포함하는 조성물을 이용하여 예방 또는 치료되는 염증성 질환과 같은 질환의 의심 및 발병 개체의 증상이 호전되거나 이롭게 되는 모든 행위를 말한다.The term "improvement" in the present invention refers to the use of a composition containing an Aster yomena extract or a fraction thereof as an active ingredient to prevent or treat a disease such as an inflammatory disease to be prevented or treated, It refers to all actions that are benefited.
구체적으로, 본 발명의 쑥부쟁이(Aster yomena) 추출물, 또는 이의 분획물을 염증성 질환의 예방 또는 개선을 목적으로 식품 조성물에 첨가할 수 있다.Specifically, the Aster yomena extract of the present invention, or a fraction thereof, can be added to a food composition for the purpose of preventing or improving an inflammatory disease.
본 발명의 식품 조성물은 환제, 분말, 과립, 침제, 정제, 캡슐 또는 액제 등의 형태를 포함할 수 있으며, 본 발명의 쑥부쟁이(Aster yomena) 추출물, 또는 이의 분획물을 첨가할 수 있는 식품의 종류에는 별다른 제한이 없으며, 예를 들어 각종 음료, 껌, 차, 비타민 복합제, 건강보조 식품류 등이 있다.The food composition of the present invention may be in the form of pills, powders, granules, infusions, tablets, capsules or liquid preparations and may be in the form of a food to which the Aster yomena extract of the present invention or its fractions can be added There is no particular limitation, and examples thereof include various drinks, gum, tea, vitamin complex, and health supplement foods.
상기 식품 조성물에는 쑥부쟁이(Aster yomena) 추출물, 또는 이의 분획물 이외에도 다른 성분을 추가할 수 있으며, 그 종류는 특별히 제한되지 않는다. 예를 들어, 통상의 식품과 같이 여러 가지 생약 추출물, 식품학적으로 허용가능한 식품보조첨가제 또는 천연 탄수화물 등을 추가 성분으로서 함유할 수 있으며, 이에 제한되지 않는다.In addition to the Aster yomena extract or the fraction thereof, other components may be added to the food composition, and the kind thereof is not particularly limited. For example, it may contain various herbal medicine extracts, food-acceptable food-aid additives or natural carbohydrates such as ordinary food, but is not limited thereto.
본 발명에서 용어, "식품보조첨가제"란 식품에 보조적으로 첨가될 수 있는 구성요소를 의미하며, 각 제형의 건강기능식품을 제조하는데 첨가되는 것으로서 당업자가 적절히 선택하여 사용할 수 있다. 식품보조첨가제의 예로는 여러 가지 영양제, 비타민, 광물(전해질), 합성 풍미제 및 천연 풍미제 등의 풍미제, 착색제 및 충진제, 펙트산 및 그의 염, 알긴산 및 그의 염, 유기산, 보호성 콜로이드 증점제, pH 조절제, 안정화제, 방부제, 글리세린, 알코올, 탄산음료에 사용되는 탄산화제 등이 포함되지만, 상기 예들에 의해 본 발명의 식품보조첨가제의 종류가 제한되는 것은 아니다.The term "food supplementary additive " in the present invention means a component which can be added to foods in a supplementary manner, and is appropriately selected and used by those skilled in the art as added to produce health functional foods of each formulation. Examples of food-aid additives include flavors such as various nutrients, vitamins, minerals (electrolytes), synthetic flavors and natural flavors, colorants and fillers, pectic acid and its salts, alginic acid and its salts, organic acids, , a pH adjusting agent, a stabilizer, a preservative, a glycerin, an alcohol, and a carbonating agent used in a carbonated beverage. However, the types of the food auxiliary additives of the present invention are not limited by the above examples.
상기 천연 탄수화물의 예는 포도당, 과당 등의 단당류; 말토스, 수크로스 등의 이당류; 및 덱스트린, 시클로덱스트린 등의 다당류와, 자일리톨, 소르비톨, 에리트리톨 등의 당알콜이 있으며, 상기한 것 이외의 향미제로서 천연 향미제(타우마틴 등), 스테비아 추출물(레바우디오시드 Ａ, 글리시르히진 등) 및 합성 향미제(사카린, 아스파르탐 등)를 유리하게 사용할 수 있다.Examples of the natural carbohydrate include monosaccharides such as glucose and fructose; Disaccharides such as maltose, sucrose and the like; And polysaccharides such as dextrin and cyclodextrin and sugar alcohols such as xylitol, sorbitol and erythritol. In addition to the above, natural flavorings (such as tau mart), stevia extracts (rebaudioside A, Etc.) and synthetic flavoring agents (saccharin, aspartame, etc.) can be advantageously used.
본 발명의 식품 조성물에는 건강기능성 식품이 포함될 수 있다. 본 발명에서 사용된 용어 "건강기능성 식품"이란 인체에 유용한 기능성을 가진 원료나 성분을 사용하여 정제, 캅셀, 분말, 과립, 액상 및 환 등의 형태로 제조 및 가공한 식품을 말한다. 여기서 기능성이라 함은 인체의 구조 및 기능에 대하여 영양소를 조절하거나 생리학적 작용 등과 같은 보건 용도에 유용한 효과를 얻는 것을 의미한다. 본 발명의 건강기능성 식품은 당업계에서 통상적으로 사용되는 방법에 의하여 제조가능하며, 상기 제조시에는 당업계에서 통상적으로 첨가하는 원료 및 성분을 첨가하여 제조할 수 있다. 또한 일반 약품과는 달리 식품을 원료로 하여 약품의 장기 복용 시 발생할 수 있는 부작용 등이 없는 장점이 있고, 휴대성이 뛰어날 수 있다.The food composition of the present invention may include a health functional food. The term " health functional food " as used in the present invention refers to foods prepared and processed in the form of tablets, capsules, powders, granules, liquids and circles by using raw materials and components having useful functions in the human body. Here, the term "functionality" means that the structure and function of the human body are controlled to obtain nutritional effects or effects useful for health use such as physiological actions. The health functional food of the present invention can be manufactured by a method commonly used in the art and can be prepared by adding raw materials and ingredients which are conventionally added in the art. Also, unlike general medicine, there is an advantage that there is no side effect that can occur when a medicine is used for a long time by using food as a raw material, and it is excellent in portability.
유효성분의 혼합양은 사용 목적(예방, 건강 또는 치료적 처치)에 따라 적합하게 결정될 수 있다. 일반적으로, 식품의 제조 시에 본 발명의 쑥부쟁이(Aster yomena) 추출물, 또는 이의 분획물은 원료 조성물 중 1 내지 50 중량%, 바람직하게는 5 내지 10 중량%의 양으로 첨가될 수 있으나, 이에 제한되는 것은 아니다. 그러나 건강 및 위생을 목적으로 하거나 또는 건강 조절을 목적으로 하는 장기간의 섭취의 경우에는 상기 양은 상기 범위 이하로도 사용될 수 있다.The amount of the active ingredient to be mixed can be suitably determined according to the intended use (prevention, health or therapeutic treatment). In general, the Aster yomena extract of the present invention, or a fraction thereof, can be added in an amount of 1 to 50% by weight, preferably 5 to 10% by weight, in the raw material composition, It is not. However, in the case of long-term ingestion intended for health and hygiene purposes or for the purpose of controlling health, the amount can also be used in the above-mentioned range.
상기 식품의 종류에는 특별한 제한은 없다. 상기 물질을 첨가할 수 있는 식품의 예로는 육류, 소세지, 빵, 쵸코렛, 캔디류, 스넥류, 과자류, 피자, 라면, 기타 면류, 껌류, 아이스크림류를 포함한 낙농제품, 각종 스프, 음료수, 차, 드링크제, 알코올 음료 및 비타민 복합제 등이 있으며, 통상적인 의미에서의 건강기능성 식품을 모두 포함한다.There is no particular limitation on the kind of the food. Examples of the food to which the above substances can be added include dairy products including meat, sausage, bread, chocolate, candy, snack, confectionery, pizza, ramen, other noodles, gums, ice cream, various soups, drinks, tea, Alcoholic beverages, and vitamin complexes, all of which include health functional foods in a conventional sense.
본 발명의 쑥부쟁이(Aster yomena) 추출물, 또는 이의 분획물은 오랫동안 천연약재로 사용되어온 천연물에서 유래되어 부작용이 없으면서도, 염증관련 인자인 COX-2와 iNOS의 발현을 억제하고, 염증 관련 전사인자로 알려진 NF-κB의 활성을 저해하고, NO 생성을 억제하는 효과가 우수하므로, 염증성 질환의 예방 또는 치료에 있어 유용하게 사용될 수 있다.The Aster yomena extract of the present invention or its fractions are derived from natural products that have been used for a long time as natural medicines and have no side effects and inhibited the expression of COX-2 and iNOS, which are inflammation-related factors, Inhibits the activity of the known NF-kB and has an excellent effect of inhibiting NO production, and thus can be usefully used for the prophylaxis or treatment of inflammatory diseases.
도 1은, RAW264.7 세포는 NF-κB 루시퍼라제 리포터 플라스미드로 트랜스펙션하였으며, 쑥부쟁이 50% 에탄올 추출물, 헥산 분획물, 염화 메틸렌 분획물, 에틸 아세테이트 분획물, 부탄올 분획물을 50 또는 100 ㎍/㎖로 1시간 동안 전처리하였으며, 이후, LPS(10 ng/㎖)로 추가 8시간 동안 처리하였다. 세포 용해물(lysates)은 제조되었으며, 루시퍼라제 효소 활성은 측정되었다
도 2는 쑥부쟁이 에탄올 추출물(FAY)이 LPS-유도된 NF-κB 활성을 억제하는 효과를 나타낸다. (A) RAW264.7 세포는 FAY(50, 100, 200 ㎍/㎖)로 4 시간 동안 처리하였다. CellTiter 96 AQueous One Solution Reagent는 배양 웰에 직접 넣었다. 상기 플레이트는 습윤된 5 % CO2 분위기에서 4시간 동안 37℃에서 배양 하였다. 흡광도는 96웰 플레이트 리더로 490 nm에서 기록하였다. (B) RAW264.7 세포는 NF-κB루시퍼라제 리포터 플라스미드로 트랜스펙션하였으며, FAY 50 또는 100 ㎍/㎖로 1시간 동안 전처리하였으며, 이후, LPS(10 ng/㎖)로 추가 8시간 동안 처리하였다. 세포 용해물(lysates)은 제조되었으며, 루시퍼라제 효소 활성은 측정되었다.
값은 평균±SEM으로 표현했다(n = 3). *는 LPS 단독과 유의한 차이가 있으며, P<0.05 (*)를 의미한다. (C) RAW264.7 세포는 FAY 50 또는 100 ㎍/㎖로 1시간 동안 전처리하였으며, 추가적으로, LPS(10 ng/㎖)를 8시간 동안 자극하였다. 세포 용해물(lysates)은 면역블랏에 의해 IκBα와 β-actin 단백질을 분석하였다. Veh; Vehicle; FAY, 쑥부쟁이의 염화 메틸렌 추출물.
도 3은 FAY가 LPS에 의해 유도된 COX-2 발현을 억제하는 결과를 나타낸다. (A) RAW264.7 세포는 COX-2 루시퍼라제 리포터 플라스미드로 트랜스펙션하였으며, 50 또는 100 ㎍/㎖ FAY를 1시간 동안 전처리하였으며, 추가 8시간 동안 LPS(10 ng/㎖) 을 처리하였다. 세포 용해물은 제조되었으며, 루시퍼라제 효소 활성은 측정되었다. 값은 평균±SEM으로 표현했다(n = 3). *는 LPS 단독과 유의한 차이가 있으며, P<0.05 (*)를 의미한다. (B) RAW264.7 세포는 FAY 50 또는 100 ㎍/㎖로 1시간 동안 전처리하였으며, 추가적으로, LPS(10 ng/㎖)를 8시간 동안 자극하였다. 세포 용해물(lysates)은 면역블랏에 의해 COX-2와 β-actin 단백질을 분석하였다. Veh; Vehicle; FAY, 쑥부쟁이의 염화 메틸렌 분획물.
도 4는 FAY가 LPS에 의해 유도된 iNOS 발현을 억제하는 결과를 나타낸다. (A) RAW264.7 세포는 iNOS 루시퍼라제 리포터 플라스미드로 트랜스펙션하였으며, 50 또는 100 ㎍/㎖ FAY를 1시간 동안 전처리하였으며, 추가 8시간 동안 LPS(10 ng/㎖) 을 처리하였다. 세포 용해물은 제조되었으며, 루시퍼라제 효소 활성은 측정되었다. 값은 평균±SEM으로 표현했다(n = 3). *는 LPS 단독과 유의한 차이가 있으며, P<0.05 (*)를 의미한다. (B) RAW264.7 세포는 FAY 50 또는 100 ㎍/㎖로 1시간 동안 전처리하였으며, 추가적으로, LPS(10 ng/㎖)를 8시간 동안 자극하였다. 세포 용해물(lysates)은 면역블랏에 의해 iNOS와 β-actin 단백질을 분석하였다. (C) RAW264.7 세포는 FAY 50 또는 100 ㎍/㎖로 1시간 동안 전처리하였으며, 추가적으로, LPS(10 ng/㎖)를 20시간 동안 자극하였다. 상등액 내의 니트라이트(nitrite)의 양은 Griess reagent를 이용하여 측정하였다. 값은 평균±SEM으로 표현했다(n = 3). +는 LPS 단독과 유의한 차이가 있으며, P<0.001 (++)를 의미한다 Veh; Vehicle; FAY, 쑥부쟁이의 염화 메틸렌분획물.1 shows that RAW 264.7 cells were transfected with NF-κB luciferase reporter plasmid and 50% ethanol extract, hexane fraction, methylene chloride fraction, ethylacetate fraction and butanol fraction of
FIG. 2 shows the effect of inhibiting LPS-induced NF-.kappa.B activity of a mugwort ethanol extract (FAY). (A) RAW 264.7 cells were treated with FAY (50, 100, 200 / / ml) for 4 hours. The CellTiter 96 AQueous One Solution Reagent was loaded directly into the culture wells. The plates in a wet atmosphere, 5% CO 2 for 4 hours and incubated at 37 ℃. Absorbance was recorded at 490 nm with a 96-well plate reader. (B) RAW264.7 cells were transfected with NF-κB luciferase reporter plasmid and pretreated with
Values were expressed as mean ± SEM (n = 3). * Is significantly different from LPS alone, which means P <0.05 (*). (C) RAW264.7 cells were pretreated with
Figure 3 shows that FAY inhibits COX-2 expression induced by LPS. (A) RAW264.7 cells were transfected with the COX-2 luciferase reporter plasmid and pretreated with 50 or 100 μg / ml FAY for 1 hour and treated with LPS (10 ng / ml) for an additional 8 hours. Cell lysates were prepared and the luciferase enzyme activity was measured. Values were expressed as mean ± SEM (n = 3). * Is significantly different from LPS alone, which means P <0.05 (*). (B) RAW 264.7 cells were pretreated with
Figure 4 shows that FAY inhibits LPS-induced iNOS expression. (A) RAW264.7 cells were transfected with an iNOS luciferase reporter plasmid and pretreated with 50 or 100 μg / ml FAY for 1 hour and treated with LPS (10 ng / ml) for an additional 8 hours. Cell lysates were prepared and the luciferase enzyme activity was measured. Values were expressed as mean ± SEM (n = 3). * Is significantly different from LPS alone, which means P <0.05 (*). (B) RAW 264.7 cells were pretreated with
이하, 본 발명을 실시예에 의해 보다 상세히 설명한다. 단, 하기 실시예는 본 발명을 예시하는 것일 뿐, 본 발명의 내용이 하기의 실시예에 한정되는 것은 아니다. Hereinafter, the present invention will be described in more detail by way of examples. However, the following examples are illustrative of the present invention, and the contents of the present invention are not limited to the following examples.
<A: 실험 재료 및 방법><A: Materials and Methods>
실시예Example 1: 쑥부쟁이( 1: Aster Aster yomenayomena ) 추출물 및 이의 ) Extracts and their 분획물의Fraction 제조 Produce
쑥부쟁이(Aster yomena) 잎은 전라남고 구례군 구례읍의 농업기술센터에서 구입하였다. 상기 식물은 순천향대학교 식물학과에서 인증되었으며, 바우처 샘플(바우처 SCH0722)로 기탁되었다(deposite). 쑥부쟁이의 건조된 잎(1kg)은 50 % 에탄올(9 L)로 87℃에서 4시간 동안 3번 추출하였다. 상기 쑥부쟁이 50% 에탄올 추출물은 45℃의 진공에서 농축시켰다. 상기 건조 추출물(12.1g)은 물(100 ml)에 현탁시키고, n- 헥산, 메틸렌 클로라이드(염화메틸렌), 에틸 아세테이트, 및 물을 이용하여 분리시키고 이들의 분획물을 제조하였다. Aster yomena leaves were purchased at the Agricultural Technology Center in Gurseup , Guryeong-gun. The plant was certified at the Soonchunhyang University Botany Department and was deposited with a voucher sample (voucher SCH0722). Dried leaves (1 kg) of mulberry wort were extracted with 50% ethanol (9 L) three times at 87 ℃ for 4 hours. The above-mentioned 50% ethanol extract of Mugwort was concentrated in a vacuum at 45 ° C. The dried extract (12.1 g) was suspended in water (100 ml) and separated using n-hexane, methylene chloride (methylene chloride), ethyl acetate, and water, and fractions thereof were prepared.
실시예Example 2: 시약 2: Reagent
LPS는 List Biological Laboratories (San Jose, CA, USA)로부터 얻었다. 모든 다른 시약은 달리 명시되지 않는 한 시그마 알드리치로부터 구입하였다.LPS was obtained from List Biological Laboratories (San Jose, Calif., USA). All other reagents were purchased from Sigma-Aldrich unless otherwise stated.
실시예Example 3: 세포배양 3: Cell culture
RAW264.7 세포 (쥣과의 단핵구 세포주; ATCC는 TIB-71)는 10% (v/v)의 소 태아혈청, 100 units/ml의 페니실린, 100 μg/ml의 스트렙토마이신을 포함하는 Dulbecco's modified Eagle's 배지에서 배양하였다. 상기 세포는 5% CO2/95% 공기 환경에서 37℃에서 유지했다.RAW264.7 cells (monocyte cell line with ATCC, TIB-71) were cultured in Dulbecco's modified Eagle's medium containing 10% (v / v) fetal bovine serum, 100 units / ml penicillin, 100 μg / ml streptomycin Lt; / RTI > The cells were maintained at 37 ° C in a 5% CO 2 /95% air environment.
실시예Example 4: 세포 생존력 시험 4: Cell viability test
세포 생존 능력은 3-(4,5-디메틸티아졸-2-일)-5(3-카르복시메톡시페닐)-2-(4-술포페닐)-2H-테트라졸륨(MTS)-기반의 비색 분석법을 사용하였다. 생존력 테스트는 CellTiter 96 AQueous One Solution reagent (Promega, Madison, WI, USA) 소량을 배양 웰에 직접 첨가하고 4시간 동안 배양하여 수행하였으며, 96-웰-플레이트 판독기로 490 nm에서 흡광도를 측정하였다.Cell viability was determined by measuring the fluorescence intensity of 3- (4,5-dimethylthiazol-2-yl) -5 (3-carboxymethoxyphenyl) -2- (4-sulfophenyl) -2H-tetrazolium Analysis method was used. Viability testing was performed by adding a small amount of CellTiter 96 AQueous One Solution reagent (Promega, Madison, Wis., USA) directly to culture wells and incubating for 4 hours and measuring absorbance at 490 nm with a 96-well-plate reader.
실시예Example 5: 5: 트랜스펙션과Transactions and 루시퍼라제Luciferase 리포터 유전자 분석 Reporter gene analysis
공지된 논문(PARK, H.J. and YOUN, H.S. 2013. Mercury induces the expression of cyclooxygenase-2 and inducible nitric oxide synthase. Toxicol Ind Health 29(2), 169-174)에 보고된 바와 같이 분석을 수행하였다. 세포는 루시퍼라제 플라스미드와 내부 대조군으로, 열 충격단백질 (HSP)70-β-갈락토시다제를 포함하는 플라스미드로 SuperFect transfection reagent(Qiagen, Valencia, CA, USA)를 이용하여 제조자의 지시에 따라 코트랜스펙션했다. 제조자의 지시에 따라 루시퍼 라제 효소 활성은 상업용 루시퍼라제 분석시스템(Promega)을 사용하여 측정하였다. 루시퍼라제 활성은 β-갈락토시다제 활성을 표준화하였다. Toxicol Ind Health 29 (2), 169-174) was performed as described in a well-known paper (PARK, H.J. and YOUN, H. S. 2013. Mercury induces the expression of cyclooxygenase-2 and inducible nitric oxide synthase. Cells were treated with luciferase plasmid and internal control using a SuperFect transfection reagent (Qiagen, Valencia, Calif., USA) as a plasmid containing heat shock protein (HSP) 70-β-galactosidase I had LAN SPEED. The luciferase enzyme activity was measured using a commercial luciferase assay system (Promega) according to the manufacturer's instructions. Luciferase activity normalized? -Galactosidase activity.
실시예Example 6: 6: 웨스턴Western 블롯Blot 분석 analysis
공지된 논문(AHN, S.I., LIM, S.J., GU, G.J., HONG, C.Y., KIM, J.S., JEONG, H.J., KOH, K.O., MANG, J.Y., KIM, D.Y. and YOUN, H.S. 2015. Suppressive effects of 1-[4-fluoro-2-(2-nitrovinyl)phenyl]pyrrolidine on the Toll-like receptor signaling pathways. Int Immunopharmacol 24(1), 36-4)에 기재된 바와 같이, 웨스턴 블랏을 실시했다.Suppressive effects of 1- (1-thiophen-2-yl) pyrimidin-2-yl] -1H- Western blotting was carried out as described in Int Immunopharmacol 24 (1), 36-4).
세포 추출물의 동일한 양을 8 %의 도데실 셀페이드-폴리아크릴아미드 겔 전기영동에 제공했으며, 상기 분리된 단백질은 폴리비닐리덴 디플루오라이드 막에 옮겼다.The same amount of cell extract was subjected to 8% dodecyl cell fade-polyacrylamide gel electrophoresis, and the separated proteins were transferred to a polyvinylidene difluoride membrane.
상기 막은 0.1 %의 Tween-20, 3 %의 무지방 건조된 밀크를 포함하는 인산 완충 생리 식염수를 이용하여, 항체의 비특이적 결합을 방지하기 위해 블로킹하였다. 면역블랏팅은 1차 항체와 horseradish peroxidase 컨쥬게이트된 2차 항체(Amersham Biosciences, Arlington Heights, IL, USA)를 사용하여 수행하였다. 반응 밴드는 강화된 화학 발광 검출 시약(Intron, Seongnam, Gyeonggi-do, South Korea)와 Fusion Solo 화학 발광 검출 시스템(Fisher Biotec, Wembley, WA, Australia)을 이용하여 시각화하였다. The membrane was blocked with phosphate buffered saline containing 0.1% Tween-20, 3% nonfat dryed milk to prevent nonspecific binding of the antibody. Immunoblotting was performed using a primary antibody and a secondary antibody conjugated with horseradish peroxidase (Amersham Biosciences, Arlington Heights, IL, USA). The reaction band was visualized using an enhanced chemiluminescence detection reagent (Intron, Seongnam, Gyeonggi-do, South Korea) and a Fusion Solo chemiluminescence detection system (Fisher Biotec, Wembley, WA, Australia).
실시예Example 7: 니트라이트(nitrite) 분석 7: Nitrite analysis
RAW264.7 세포로부터 방출된 산화질소(Nitric oxide, NO)은 배양 상등액에서 니트라이트(nitrite) 농도를 측정하여 평가하였다. 96 웰 마이크로 플레이트에서 배양 배지의 샘플 (100 μL)은 150 μL의 Griess 시약(2.5 % 인산 용액 내에 1 % 술파닐아미드 및 0.1 % 나프틸에틸렌 디아민 함유)으로 실온에서 10분 동안 배양하였다. 540 nm에서의 흡광도를 플레이트 판독기를 이용하여 판독하였으며, NO의 농도는 표준 검량선을 이용하여 결정하였으며, 표준으로서 니트라이트(nitrite) 나트륨을 사용하였다. Nitric oxide (NO) released from RAW264.7 cells was assessed by measuring the nitrite concentration in the culture supernatant. Samples (100 μL) of the culture medium in 96-well microplates were incubated with 150 μL of Griess reagent (containing 1% sulfanilamide and 0.1% naphthylethylenediamine in 2.5% phosphoric acid solution) for 10 minutes at room temperature. Absorbance at 540 nm was read using a plate reader, the concentration of NO was determined using a standard calibration curve, and sodium nitrite was used as a standard.
실시예Example 8: 데이터 분석 8: Data Analysis
데이터는 세번의 실험으로부터 얻었다. 값은 평균±평균의 표준 에러(SEM)로 표현하였다. 데이터의 차이는 Student't 테스트를 이용하여 평가하였다. P<0.05의 값은 통계적으로 유의한 차이를 나타낸다. Data were obtained from three experiments. Values are expressed as mean ± standard error (SEM). Data differences were assessed using the Student ' t test. Values of P <0.05 indicate statistically significant differences.
<B: <B: 실험예Experimental Example > >
실험예Experimental Example 1: 쑥부쟁이 추출물과 이의 1: Extract and its object 분획물을The fraction 이용한 Used LPSLPS -유도된 - Induced NFNF -- κBκB 활성을 억제하는 효과 Effect to inhibit activity
NF-κB는 150 개 이상의 유전자를 조절하는 가장 결정적인 전사 인자 중 하나로, 염증과 관련이 있다. 각종 병원체로부터의 전염증성 자극에 의한 NF-κB 활성은 사이토카인, COX-2 및 iNOS를 포함한 염증성 유전자 산물의 발현을 증가시키는 것으로 알려져 있다. 이에, 본 발명에서는 NF-κB 활성화에 대한 쑥부쟁이 에탄올 추출물, 헥산 분획물, 염화 메틸렌 분획물, 에틸 아세테이트 분획물, 부탄올 분획물의 효과를 규명하기 위하여, NF-κB 루시퍼라아제 리포터 분석법을 이용하였다.NF-κB is one of the most crucial transcription factors controlling over 150 genes and is associated with inflammation. NF-κB activation by proinflammatory stimuli from various pathogens is known to increase the expression of inflammatory gene products including cytokines, COX-2 and iNOS. In this invention, NF-κB luciferase reporter assay was used to examine the effects of the extracts of Mugwort bark extract, hexane fraction, methylene chloride fraction, ethyl acetate fraction and butanol fraction on NF-κB activation.
먼저, RAW 264.7 세포에서 쑥부쟁이 50% 에탄올 추출물, 헥산 분획물, 염화 메틸렌 분획물, 에틸 아세테이트 분획물, 부탄올 분획물을 50, 또는 100 ㎍/㎖ 처리하고, LPS-유도된 NF-κB 활성을 억제하는 지를 조사하였다. First, 50 or 100 μg / ml of 50% ethanol extract, hexane fraction, methylene chloride fraction, ethylacetate fraction and butanol fraction were treated with RAW 264.7 cells to determine whether LPS-induced NF-κB activity was inhibited Respectively.
도 1은, RAW264.7 세포는 NF-κB 루시퍼라제 리포터 플라스미드로 트랜스펙션하였으며, 쑥부쟁이 50% 에탄올 추출물, 헥산 분획물, 염화 메틸렌 분획물, 에틸 아세테이트 분획물, 부탄올 분획물을 50 또는 100 ㎍/㎖로 1시간 동안 전처리하였으며, 이후, LPS(10 ng/㎖)로 추가 8시간 동안 처리하였다. 세포 용해물(lysates)은 제조되었으며, 루시퍼라제 효소 활성은 측정되었다. 그 결과, 쑥부쟁이 에탄올 추출물, 헥산 분획물, 에틸 아세테이트 분획물, 부탄올 분획물은 NF-κB 활성을 억제하지 않았으나, 쑥부쟁이의 염화 메틸렌 분획물만이 LPS에 의해 유도된 NF-κB 활성화를 억제하는 것을 확인하였다(도 1). 이에 따라, 이후의 실험에서는 쑥부쟁이 염화 메틸렌 분획물을 사용하였다. 1 shows that RAW 264.7 cells were transfected with NF-κB luciferase reporter plasmid and 50% ethanol extract, hexane fraction, methylene chloride fraction, ethylacetate fraction and butanol fraction of
실험예Experimental Example 2: 쑥부쟁이 염화 메틸렌 2: methylene chloride 분획물이The fraction LPSLPS -유도된 - Induced NFNF -- κBκB 활성을 억제하는 효과 Effect to inhibit activity
RAW 264.7 세포에서 쑥부쟁이 염화 메틸렌 분획물 (FAY)의 세포 독성 특성을 평가하기 위해, 3-(4,5-디메틸티아졸-2-일)-5(3-카르복시메톡시페닐)-2-(4-술포페닐)-2H-테트라졸륨(MTS)가 포르마잔으로 변환되는 원리에 기초한 잘 확립된 생존력 분석법을 사용하여 새포독성을 평가하였다.To evaluate the cytotoxic properties of the Aster ridden methylene chloride fraction (FAY) from RAW 264.7 cells, 3- (4,5-dimethylthiazol-2-yl) -5- (3-carboxy-methoxyphenyl) -2- ( The well-established viability assay based on the principle that 4-sulfophenyl) -2H-tetrazolium (MTS) is converted to formazan was used to evaluate pore toxicity.
도 2A에서, RAW264.7 세포는 FAY(50, 100, 200 ㎍/㎖)로 4 시간 동안 처리하였으며, CellTiter 96 AQueous One Solution Reagent는 배양 웰에 직접 넣었다. 상기 플레이트는 습윤된 5 % CO2 분위기에서 4시간 동안 37℃에서 배양하였으며, 흡광도는 96웰 플레이트 리더로 490 nm에서 기록 하였다.In Figure 2A, RAW 264.7 cells were treated with FAY (50, 100, 200 ug / ml) for 4 hours and CellTiter 96 AQueous One Solution Reagent directly into culture wells. The plates were incubated for 4 hours at 37 ° C in a humidified 5% CO 2 atmosphere and absorbance was recorded at 490 nm with a 96-well plate reader.
그 결과, 100 ㎍/㎖까지의 쑥부쟁이 염화 메틸렌 분획물은 상기 RAW 264.7 세포에 독성이 없었다. 그러나, 200 ㎍/㎖의 쑥부쟁이 염화 메틸렌 분획물은 82%까지 세포의 생존력을 감소시켰다(도 2A). 이에 이후의 실험은 100 ㎍/㎖ 이하의 FAY를 이용했다.As a result, the mugwort fraction of methylene chloride up to 100 / / ml was not toxic to the RAW 264.7 cells. However, the mugwort fraction of methylene chloride at 200 [mu] g / ml reduced cell viability by 82% (Fig. 2A). Subsequent experiments used less than 100 μg / ml FAY.
다음으로는, NF-κB 활성화에 대한 FAY의 효과를 규명하기 위하여, NF-κB 루시퍼라아제 리포터 분석법과 면역블랏을 실시하였다. 도 2B에서, RAW264.7 세포는 NF-κB 루시퍼라제 리포터 플라스미드로 트랜스펙션하였으며, FAY 50 또는 100 ㎍/㎖로 1시간 동안 전처리하였으며, 이후, LPS(10 ng/㎖)로 추가 8시간 동안 처리하였다. 세포 용해물(lysates)은 제조되었으며, 루시퍼라제 효소 활성은 측정되었다. 그 결과, 쑥부쟁이 염화 메틸렌 분획물(FAY)은 LPS에 의해 유도된 NF-κB 활성화를 억제하는 것을 확인하였다(도 2B). 도 2C에서, RAW264.7 세포는 FAY 50 또는 100 ㎍/㎖로 1시간 동안 전처리하였으며, 추가적으로, LPS(10 ng/㎖)를 8시간 동안 자극하였다. 면역블랏에 의해 세포 용해물(lysates)에서 IκBα와 β-actin 단백질을 분석하였다. 그 결과, FAY은 LPS에 의해 유도된 IκBα의 분해 역시 억제하는 것을 확인하였다(도. 2C).Next, NF-κB luciferase reporter assay and immunoblotting were performed to determine the effect of FAY on NF-κB activation. In FIG. 2B, RAW 264.7 cells were transfected with NF-κB luciferase reporter plasmid and pretreated with
실험예 3: 쑥부쟁이의 염화 메틸렌 분획물이 LPS -유도된 COX-2와 iNOS 발현을 억제하는 효과 The methylene chloride fraction of Aster ridden: Experiment 3 Effect of inhibiting LPS -induced expression of COX-2 and iNOS
다음으로, 쑥부쟁이 염화 메틸렌 분획물(FAY)이 COX-2 발현을 조절하는 지를 평가하였다. COX-2는 대식 세포에서 NF-κB의 활성화를 통해 조절되는 타겟 유전자 중의 하나이다. 도 3A에서, RAW264.7 세포는 COX-2 루시퍼라제 리포터 플라스미드로 트랜스펙션하였으며, 50 또는 100 ㎍/㎖ FAY를 1시간 동안 전처리하였으며, 추가 8시간 동안 LPS(10 ng/㎖)을 처리하였다. 세포 용해물은 제조되었으며, 루시퍼라제 효소 활성은 측정되었다. 그 결과, COX-2 루시퍼라제 리포터 분석에 의해 측정된 바와 같이, 상기 쑥부쟁이 염화 메틸렌 분획물은 RAW264.7 세포에서 COX-2의 발현을 억제하였다(도 3A). Next, it was evaluated whether the methylene chloride fraction (FAY) regulates COX-2 expression. COX-2 is one of the target genes regulated through the activation of NF-κB in macrophages. In FIG. 3A, RAW 264.7 cells were transfected with a COX-2 luciferase reporter plasmid and pretreated with 50 or 100 μg / ml FAY for 1 hour and treated with LPS (10 ng / ml) for an additional 8 hours . Cell lysates were prepared and the luciferase enzyme activity was measured. As a result, the mugwort fraction of methylene chloride, as determined by COX-2 luciferase reporter assay, inhibited the expression of COX-2 in RAW264.7 cells (Fig. 3A).
도 3B에서, RAW264.7 세포는 FAY 50 또는 100 ㎍/㎖로 1시간 동안 전처리하였으며, 추가적으로, LPS(10 ng/㎖)를 8시간 동안 자극하였다. 면역블랏에 의해 세포 용해물(lysates)에서 COX-2와 β-actin 단백질을 분석하였다. 그 결과, COX-2 면역불랏 분석에 의해 측정된 바와 같이, 상기 쑥부쟁이 염화 메틸렌 분획물은 RAW264.7 세포에서 COX-2의 발현을 억제하였다(도 3B). In FIG. 3B, RAW264.7 cells were pretreated with
다음으로, 쑥부쟁이 염화 메틸렌 분획물(FAY)이 NF-κB의 활성화를 통해 조절되는 다른 타겟 유전자인 iNOS의 발현을 조절하는 지를 조사하였다. Next, we examined whether mugwort methylene chloride fraction (FAY) regulates the expression of iNOS, another target gene regulated through activation of NF-κB.
도 4A에서, RAW264.7 세포는 iNOS 루시퍼라제 리포터 플라스미드로 트랜스펙션하였으며, 50 또는 100 ㎍/㎖ FAY를 1시간 동안 전처리하였으며, 추가 8시간 동안 LPS(10 ng/㎖) 을 처리하였다. 세포 용해물은 제조되었으며, 루시퍼라제 효소 활성은 측정되었다. 그 결과, iNOS의 루시퍼라제 리포터 분석에 의해 확인된 바와 같이, 쑥부쟁이 염화 메틸렌 분획물(FAY)은 RAW264.7 세포에서 iNOS의 발현 억제을 억제하는 것을 확인하였다(도 4A).In FIG. 4A, RAW 264.7 cells were transfected with iNOS luciferase reporter plasmid and pretreated with 50 or 100 μg / ml FAY for 1 hour and treated with LPS (10 ng / ml) for an additional 8 hours. Cell lysates were prepared and the luciferase enzyme activity was measured. As a result, it was confirmed that the mugwort microbial methylene fraction (FAY) inhibited the inhibition of iNOS expression in RAW264.7 cells (Fig. 4A), as confirmed by the luciferase reporter assay of iNOS.
도 4B에서, RAW264.7 세포는 FAY 50 또는 100 ㎍/㎖로 1시간 동안 전처리하였으며, 추가적으로, LPS(10 ng/㎖)를 8시간 동안 자극하였다. 면역블랏에 의해 세포 용해물(lysates)에서 iNOS와 β-actin 단백질을 분석하였다. 그 결과, iNOS의 면역블랏 분석에 의해 확인된 바와 같이, 쑥부쟁이 염화 메틸렌 분획물(FAY)은 RAW264.7 세포에서 iNOS의 발현 억제을 억제하였다(도 4B).In FIG. 4B, RAW 264.7 cells were pretreated with
또한, 쑥부쟁이 염화 메틸렌 분획물(FAY)이 LPS 유도된 NO 생성을 억제하는 지를 평가하였다. 방출된 NO의 농도는 니트라이트(nitrite)의 형태로 Griess 방법(Green, L. C.; Wagner, D. A.; Glogowski,J.; Skipper, P. L.; Wishnok, J. S.; Tannenbaum, S. R. Anal. Biochem. 1982, 126, 131-138)으로 분석하였다. 도 3C에서, RAW264.7 세포는 FAY 50 또는 100 ㎍/㎖로 1시간 동안 전처리하였으며, 추가적으로, LPS(10 ng/㎖)를 20시간 동안 자극하였다. 상등액 내의 니트라이트(nitrite)의 양은 Griess reagent를 이용하여 측정하였다. 그 결과, 쑥부쟁이 염화 메틸렌 추출물(FAY)이 LPS 유도된 니트라이트(nitrite) 생성을 억제하는 것을 확인하였다(도 4C). In addition, it was evaluated whether the methylene chloride fraction (FAY) inhibited LPS - induced NO production. The concentration of released NO was measured in the form of nitrite using the Griess method (Green, LC; Wagner, DA; Glogowski, J .; Skipper, PL; Wishnok, JS; Tannenbaum, SR Anal. Biochem. -138). In FIG. 3C, RAW 264.7 cells were pretreated with
상기 결과를 요약하면, 쑥부쟁이 염화 메틸렌 분획물(FAY)이 NF-κB의 활성을 억제하고, 이에 의해 COX-2와 iNOS와 같은 표적 유전자의 발현 억제하고, NO 생성을 억제함으로써 항염증 치료제로 사용할 수 있음을 의미한다. The results are summarized as follows: Methylene chloride methylene fraction (FAY) inhibits the activity of NF-κB, thereby inhibiting expression of a target gene such as COX-2 and iNOS and inhibiting NO production to be used as an anti-inflammatory drug .
이상의 설명으로부터, 본 발명이 속하는 기술분야의 당업자는 본 발명이 그 기술적 사상이나 필수적 특징을 변경하지 않고서 다른 구체적인 형태로 실시될 수 있다는 것을 이해할 수 있을 것이다. 이와 관련하여, 이상에서 기술한 실시 예들은 모든 면에서 예시적인 것이며 한정적인 것이 아닌 것으로서 이해해야만 한다. 본 발명의 범위는 상기 상세한 설명보다는 후술하는 특허 청구범위의 의미 및 범위 그리고 그 등가 개념으로부터 도출되는 모든 변경 또는 변형된 형태가 본 발명의 범위에 포함되는 것으로 해석되어야 한다.From the above description, it will be understood by those skilled in the art that the present invention may be embodied in other specific forms without departing from the spirit or essential characteristics thereof. In this regard, it should be understood that the above-described embodiments are to be considered in all respects as illustrative and not restrictive. The scope of the present invention should be construed as being included in the scope of the present invention without departing from the scope of the present invention as defined by the appended claims.
Claims (7)
A pharmaceutical composition for inhibiting the expression of COX-2, inhibiting the expression of iNOS and inhibiting NO production, comprising an Aster yomena extract or a fraction thereof as an active ingredient.
The method of claim 1 wherein the extract is extracted using alcohol or a mixed solvent of water, carbon number 1 (C 1) to 4 (C 4), the pharmaceutical compositions.
The pharmaceutical composition according to claim 1, wherein the extract is extracted with ethanol.
The method of claim 1, wherein the fraction is used for the ethanol extract of Aster ridden water, carbon number 1 (C 1) to 4 alcohol, methylene chloride, chloroform, ethyl acetate, hexane, butanol, or a mixed solvent of (C 4) ≪ / RTI > by fractionation.
2. The pharmaceutical composition according to claim 1, wherein the fraction is fractionated with methylene chloride.
The method of claim 1, wherein the inflammatory disease is selected from the group consisting of asthma, chronic obstructive pulmonary disease, allergy, systemic lupus erythematosus, scleroderma, ulcerative colitis, Crohn's disease, atopic dermatitis, psoriasis, anaphylaxis, dermatitis, diabetic retinopathy, Or a pharmaceutically acceptable salt thereof, for the manufacture of a medicament for the treatment and / or prophylaxis of diabetic nephropathy, diabetic nephropathy, nephritis, Sjogren's syndrome, Crohn's disease, autoimmune pancreatitis, periodontal disease, graft- A disease, endometritis, rhinitis, tonsillitis, otitis media, sore throat, cystitis, and chronic prostatitis.
A food composition for preventing or ameliorating an inflammatory disease by inhibiting expression of COX-2, inhibiting the expression of iNOS, and inhibiting NO production, comprising an extract of Aster yomena or a fraction thereof as an active ingredient.
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| KR20200072619A (en) * | 2018-12-12 | 2020-06-23 | 대한민국(농촌진흥청장) | Fermented product of lactic acid bacteria with improved physiological activity |
| CN111514217A (en) * | 2020-06-24 | 2020-08-11 | 卢戚开 | Medicine for treating rhinitis and using method thereof |
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