KR20210030858A - Composition for preventing and treating brain diseases caused by fine dust containing Ecklonia cava extract - Google Patents
Composition for preventing and treating brain diseases caused by fine dust containing Ecklonia cava extract Download PDFInfo
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- KR20210030858A KR20210030858A KR1020200095180A KR20200095180A KR20210030858A KR 20210030858 A KR20210030858 A KR 20210030858A KR 1020200095180 A KR1020200095180 A KR 1020200095180A KR 20200095180 A KR20200095180 A KR 20200095180A KR 20210030858 A KR20210030858 A KR 20210030858A
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Abstract
Description
본 발명은 감태 (Ecklonia cava) 추출물을 유효성분으로 포함하는 미세먼지로 인한 뇌질환의 예방, 개선 및 치료용 조성물에 관한 것이다. 더욱 구체적으로는 감태 추출물을 포함하는 초미세먼지로 인한 뇌질환 중 뇌 신경 질환의 예방, 개선 및 치료용 조성물에 관한 것이다.The present invention relates to a composition for preventing, improving, and treating brain diseases caused by fine dust comprising an Ecklonia cava extract as an active ingredient. More specifically, it relates to a composition for preventing, improving, and treating neurological diseases of the brain among brain diseases caused by ultrafine dust containing Ecklonia cava extract.
본 발명은 감태 (Ecklonia cava) 추출물을 유효성분으로 포함하는 미세먼지로 인한 뇌질환의 예방, 개선 및 치료용 조성물에 관한 것으로서, 더욱 상세하게는 감태 추출물을 포함하는 초미세먼지로 인한 뇌 신경 질환의 예방, 개선 및 치료용 조성물에 관한 것이다. 상기 뇌 신경 질환의 종류로는 뇌졸중, 알츠하이머 병 (Alzheimer’s disease; AD), 치매 (dementia) 및 파킨슨병 등이 있다.The present invention relates to a composition for the prevention, improvement and treatment of brain diseases caused by fine dust containing Ecklonia cava extract as an active ingredient, and more particularly, brain neurological diseases due to ultrafine dust containing Ecklonia cava extract It relates to a composition for the prevention, improvement and treatment of. The types of neurological disorders in the brain include stroke, Alzheimer's disease (AD), dementia, and Parkinson's disease.
한편, 최근 미세먼지 (particulate matter, PM)의 농도가 증가하고 지속기간이 증가됨에 따라 미세먼지에 의한 인체영향성에 대한 관심이 증가되고 있는 추세이다 (Kim 등, 2017). 미세먼지는 우리나라의 오랜 역사와 함께 해왔으며, 예로부터 몽고와 중국 사막지역 및 황화강 유역에서 발원된 황사의 영향을 받았고, 최근에는 우리나라 및 동북아시아 국가들의 급격한 산업화가 미세먼지의 주요 발생 원인으로 보고되고 있다 (Myung, 2016).Meanwhile, as the concentration of particulate matter (PM) increases and the duration of the particulate matter (PM) increases, interest in the effects of fine dust on the human body is increasing (Kim et al., 2017). Fine dust has been associated with Korea's long history, and has been influenced by yellow dust originating from the desert areas of Mongolia and China, as well as the Huanghua River basin. Recently, the rapid industrialization of Korea and Northeast Asian countries is a major cause of fine dust. Reported (Myung, 2016).
초미세먼지 (PM2.5)는 공기역학적 지름이 2.5 μm 이하인 미세먼지를 의미하며, 대기 오염 발생원에서 직접 배출되어지는 1차오염 물질과 대기에서 반응하여 생성되는 2차 대기오염 물질 (NO3 -, SO4 -, NH4-, polyacromatichydrocarbon (PAH), quinone등)이 주를 이룬다 (Kim 등, 2017). 세계보건기구 (World Health Organization, 2013)에 의하면, PM10 (공기역학적 지름이 10 μm 이하인 미세먼지)에 장기 노출될 경우 호흡기관 관련 질환과 사망률이 증가하게 되는데, PM2.5는 이보다 더 강한 위험 인자로 작용한다고 보고하였다.Ultra fine particles (PM 2.5) is the aerodynamic diameter refers to fine particles less than 2.5 μm, and the secondary air pollutants produced by reaction in the primary pollutants and air being discharged directly from the air pollution sources (NO 3 -, SO 4 -, NH4 -, polyacromatichydrocarbon (PAH), quinone , etc.) constitute the two weeks (Kim et al., 2017). According to the World Health Organization (2013), long-term exposure to PM 10 (fine dust with an aerodynamic diameter of 10 μm or less) increases respiratory tract-related diseases and mortality. PM 2.5 is a stronger risk factor. Reported to act as.
지름 5~10 μg/m3이하의 먼지는 코 점막을 통해 체내에 흡수가 가능하며 2~5 μg/m3이하는 기도 (호흡기)를 통과하고, 0.1~1 μg/m3는 폐포 손상까지 유발하게 된다. 미세먼지가 인체에 흡입되었을 경우, 충돌·중력침강·확산·정전기적 흡착 등과 같은 다양한 기전에 의해서 조직에 침착될 수 있으며, 일부는 혈액을 따라서 전신을 순환하기도 한다. Dust with a diameter of 5-10 μg/m 3 or less can be absorbed into the body through the nasal mucosa, and 2-5 μg/m 3 or less pass through the airways (respiratory system), and 0.1 to 1 μg/m 3 can damage the alveoli. Will cause. When fine dust is inhaled into the human body, it can be deposited in tissues by various mechanisms such as collision, gravitational sedimentation, diffusion, and electrostatic adsorption, and some circulate throughout the body along the blood.
특히, 체내에 침착된 미세먼지는 산화적 스트레스와 염증 반응을 유도하고 호흡계 및 순환계 질환의 급성 악화 등을 유발하는 것으로 보고되고 있다 (Myung, 2016). 또한, 후각상피세포를 거치면 혈관 뇌 장벽 (Blood-Brain Barrier; BBB)을 거치지 않고도 뇌로 직접 도달 할 수 있으며, 자성을 띄는 입자의 경우 뇌 조직에 직접 침착 됨으로써 미세아교세포 (Microglia)를 활성화 하여 pro-inflammatory cytokines (IL-1, TNF-a 및 IFN-r) 등을 생산함으로써 뇌신경 염증을 유도하고 더 나아가 인지장애를 유도하는 것으로 보고되었다 (Block, 2004). 따라서, 이러한 미세먼지로 유도될 수 있는 인체 내 산화적 스트레스 억제 및 염증반응을 억제시켜 줄 수 있는 천연 식품 소재에 대한 연구가 필요하다고 사료된다.In particular, it has been reported that fine dust deposited in the body induces oxidative stress and inflammatory reactions and causes acute exacerbation of respiratory and circulatory diseases (Myung, 2016). In addition, through olfactory epithelial cells, it can reach the brain directly without going through the blood-brain barrier (BBB), and magnetic particles are deposited directly in the brain tissue, activating microglia and pro It has been reported to induce cranial nerve inflammation and further cognitive impairment by producing -inflammatory cytokines (IL-1, TNF-a and IFN-r) (Block, 2004). Therefore, it is considered that there is a need for research on natural food materials that can suppress oxidative stress and inflammatory reactions in the human body that can be induced by such fine dust.
한편, 감태 (Ecklonia cava)는 다시마목 미역과에 속하는 갈조류의 일종으로, 한반도와 일본 등 온대 연안에서 분포하며 우리나라에서는 제주도에서 풍부하게 생산된다 (Heo 등, 2005). 감태에는 펩타이드 (peptides), 다당류 (polysaccharides), 카로티노이드 (carotenoids), 푸코이단 (fucoidan) 및 플로로탄닌 (phlorotannins)과 같은 생리활성물질을 포함되어 있다 (Wijesinghe과 Jeon, 2012).On the other hand, Ecklonia cava is a type of brown algae belonging to the kelp seaweed family. It is distributed in temperate coasts such as the Korean Peninsula and Japan, and is abundantly produced in Jeju Island in Korea (Heo et al., 2005). Ecklonia cava contains bioactive substances such as peptides, polysaccharides, carotenoids, fucoidan and phlorotannins (Wijesinghe and Jeon, 2012).
특히, 갈조류에서 주로 발견되는 주요한 생리활성물질인 플로로탄닌; phlorotannins (eckol, dieckol, 6,6′- bieckol 및 eckstolonol)은 뛰어난 항산화, 항염증, 항알레르기, 주름 생성 억제 및 모발 생성 촉진 효과 등으로 인하여 건강기능식품 및 기능성 화장품과 같은 다양한 산업분야에서 화학 합성물 대체제로 주목을 받고 있다 (sanjeewa 등, 2016).In particular, fluorotannin, a major physiologically active substance mainly found in brown algae; Phlorotannins (eckol, dieckol, 6,6′-bieckol and eckstolonol) are chemical compounds in various industries such as health functional foods and functional cosmetics due to their excellent antioxidant, anti-inflammatory, anti-allergic, anti-wrinkle and hair growth promoting effects. It is attracting attention as a substitute (sanjeewa et al., 2016).
또한, 갈조류에 주로 함유된 다당류의 일종인 푸코이단은 혈중 지질억제, 종양세포의 성장 저해효과 뿐만 아니라, 다당류들이 구성하고 있는 카르복실기와 황산기는 유해 중금속 및 양이온의 배출 효과가 있는 것으로도 보고되고 있다 (Kim 등, 2000). 다만, 이와 같은 해조류의 다양한 생리활성 기능에도 불구하고 미세먼지와 관련된 연구는 매우 미흡한 수준이다.In addition, it has been reported that fucoidan, a type of polysaccharide mainly contained in brown algae, has not only the effect of inhibiting blood lipids and inhibiting the growth of tumor cells, but also has the effect of releasing harmful heavy metals and cations. Kim et al., 2000). However, despite the various physiologically active functions of such algae, studies related to fine dust are inadequate.
따라서, 본 연구에서는 뇌 신경 세포에서 발생되는 세포 독성에 대한 세포보호 효과를 검증하였고, 동물실험을 통해 감태 추출물을 포함하는 조성물이 초미세먼지로 인한 뇌질환에 대해 예방, 개선 및 치료용 조성물로 사용될 수 있음을 확인하여 본 발명을 완성하기에 이르렀다.Therefore, in this study, the cytoprotective effect on cytotoxicity generated in brain neurons was verified, and a composition containing Ecklonia cava extract was used as a composition for preventing, improving and treating brain diseases caused by ultrafine dust through animal experiments. By confirming that it can be used, it came to complete the present invention.
본 발명은 상기와 같은 문제를 해결하기 위해, 감태 (Ecklonia cava) 추출물을 유효성분으로 포함하는 미세먼지로 인한 뇌질환의 예방, 개선 및 치료용 조성물을 제공하는 것을 목적으로 하며, 더욱 상세하게는 감태 추출물이 뇌 신경 세포에서 발생되는 세포 독성에 대한 세포보호 효과를 검증하였으며, 동물실험을 통해 직접적으로 초미세먼지로 인한 뇌질환의 예방, 개선 및 치료 효능을 확인하여 본 발명을 완성하였다.In order to solve the above problems, the present invention aims to provide a composition for preventing, improving and treating brain diseases caused by fine dust containing an Ecklonia cava extract as an active ingredient, and more specifically The present invention was completed by verifying the cytoprotective effect of Ecklonia cava extract on cytotoxicity generated in brain nerve cells, and directly confirming the efficacy of preventing, improving, and treating brain diseases caused by ultrafine dust through animal experiments.
상기한 과제를 해결하기 위하여, 본 발명은 감태 추출물을 유효성분으로 포함하는, 미세먼지로 인한 뇌질환 예방 및 개선용 건강기능성식품 조성물을 제공한다. 보다 바람직하게는, 초미세먼지로 인한 뇌질환 예방 및 개선용 건강기능성식품 조성물을 제공한다.In order to solve the above problems, the present invention provides a health functional food composition for preventing and improving brain diseases caused by fine dust, comprising an Ecklonia cava extract as an active ingredient. More preferably, it provides a functional food composition for preventing and improving brain diseases caused by ultrafine dust.
본 발명의 일 실시예에 있어서, 본 발명은 물을 이용할 수 있고, 또는 휘발성 용제를 이용하여 유기용매 추출법에 의해 추출될 수 있으며, 바람직하게는 물 또는 50 내지 80% 에탄올을 이용할 수 있으나 이에 한정되는 것은 아니다.In one embodiment of the present invention, the present invention may use water, or may be extracted by an organic solvent extraction method using a volatile solvent, preferably water or 50 to 80% ethanol, but limited thereto. It does not become.
본 발명의 일 실시예에 있어서, 본 발명의 뇌질환은 뇌 신경 질환인 것을 특징으로 하며, 상기 뇌 신경 질환은 뇌졸중, 알츠하이머 병 (Alzheimer’s disease; AD), 치매 (dementia) 및 파킨슨병 중 어느 하나인 것으로 하는 것을 특징으로 할 수 있으나, 이에 한정되는 것은 아니다.In one embodiment of the present invention, the brain disease of the present invention is characterized in that the brain neurological disease, the brain neurological disease is any one of stroke, Alzheimer's disease (AD), dementia and Parkinson's disease It may be characterized as being, but is not limited thereto.
본 발명의 일 실시예에 있어서, 감태 추출물은 뇌 조직 내 ABTS 라디칼 소거 활성 또는 DPPH 라디칼 소거 활성이 증가된 것을 특징으로 할 수 있으나 이에 한정되는 것은 아니다.In one embodiment of the present invention, Ecklonia cava extract may be characterized by an increase in ABTS radical scavenging activity or DPPH radical scavenging activity in brain tissue, but is not limited thereto.
본 발명의 일 실시예에 있어서, 감태 추출물은 초미세먼지로 유도된 뇌 조직 내 에서의 지방질과산화물인 말론디알데히드 (Malondialdehyde, MDA)의 생성을 억제하는 효과를 특징으로 할 수 있으나 이에 한정되는 것은 아니다.In one embodiment of the present invention, Ecklonia cava extract may be characterized by an effect of inhibiting the production of malondialdehyde (MDA), which is a lipid peroxide in brain tissue induced by ultrafine dust, but is limited thereto. no.
본 발명의 일 실시예에 있어서, 감태 추출물은 초미세먼지로 유도된 뇌 조직 내 에서의 활성산소 (reactive oxygen species, ROS)의 생성을 억제시키는 효과를 특징으로 할 수 있으나 이에 한정되는 것은 아니다.In one embodiment of the present invention, Ecklonia cava extract may be characterized by an effect of inhibiting the production of reactive oxygen species (ROS) in brain tissue induced by ultrafine dust, but is not limited thereto.
본 발명의 일 실시예에 있어서, 감태 추출물은 초미세먼지로 유도된 뇌 조직 내 에서의 세포사멸을 억제시키는 효과를 특징으로 할 수 있으나 이에 한정되는 것은 아니다.In one embodiment of the present invention, Ecklonia cava extract may be characterized by an effect of inhibiting apoptosis in brain tissue induced by ultrafine dust, but is not limited thereto.
본 발명의 일 실시예에 있어서, 감태 추출물은 초미세먼지로 유도된 뇌 조직 내 에서의 염증반응에 대한 조직보호 효과를 특징으로 할 수 있으나 이에 한정되는 것은 아니다.In one embodiment of the present invention, Ecklonia cava extract may be characterized by a tissue protective effect against inflammatory reactions in brain tissue induced by ultrafine dust, but is not limited thereto.
본 발명의 일 실시예에 있어서, 감태 추출물은 초미세먼지로 인한 공간인지력 저하를 개선시키는 것을 특징으로 할 수 있으나 이에 한정되는 것은 아니다.In one embodiment of the present invention, the Ecklonia cava extract may be characterized in that it improves spatial cognitive decline due to ultrafine dust, but is not limited thereto.
본 발명의 일 실시예에 있어서, 감태 추출물은 초미세먼지로 인해 저하된 단기 학습 및 단기 기억력을 개선시키는 것을 특징으로 할 수 있으나 이에 한정되는 것은 아니다.In one embodiment of the present invention, Ecklonia cava extract may be characterized by improving short-term learning and short-term memory reduced due to ultrafine dust, but is not limited thereto.
본 발명의 일 실시예에 있어서, 감태 추출물은 초미세먼지로 인해 저하된 장기 학습 및 장기 기억력을 개선시키는 것을 특징으로 할 수 있으나 이에 한정되는 것은 아니다.In one embodiment of the present invention, the Ecklonia cava extract may be characterized in that it improves long-term learning and long-term memory reduced due to ultrafine dust, but is not limited thereto.
본 발명의 일 실시예에 있어서, 감태 추출물은 초미세먼지로 인해 뇌 조직에서의 인지기능 저하를 개선시키는 것을 특징으로 할 수 있으나 이에 한정되는 것은 아니다.In one embodiment of the present invention, Ecklonia cava extract may be characterized in that it improves cognitive decline in brain tissue due to ultrafine dust, but is not limited thereto.
본 발명의 일 실시예에 있어서, 감태 추출물은 초미세먼지로 인한 뇌 조직에서 콜린성 시스템의 기능저하를 개선시키는 것을 특징으로 할 수 있으나 이에 한정되는 것은 아니다.In one embodiment of the present invention, Ecklonia cava extract may be characterized in that it improves the deterioration of the cholinergic system in brain tissues caused by ultrafine dust, but is not limited thereto.
또한, 본 발명은 감태 추출물을 유효성분으로 포함하는, 미세먼지로 인한 뇌질환 예방 및 개선용 식품 조성물을 제공한다. 보다 바람직하게는, 초미세먼지로 인한 뇌질환 예방 및 개선용 식품 조성물을 제공한다.In addition, the present invention provides a food composition for preventing and improving brain diseases caused by fine dust, comprising an Ecklonia cava extract as an active ingredient. More preferably, it provides a food composition for preventing and improving brain diseases caused by ultrafine dust.
또한, 본 발명은 감태 (Ecklonia cava)로부터 추출된 추출물을 유효성분으로 포함하는, 미세먼지로 인한 뇌질환 예방 및 치료용 약학적 조성물을 제공한다. 보다 바람직하게는, 초미세먼지로 인한 뇌질환 예방 및 치료용 약학적 조성물을 제공한다.In addition, the present invention provides a pharmaceutical composition for preventing and treating brain diseases caused by fine dust, comprising an extract extracted from Ecklonia cava as an active ingredient. More preferably, it provides a pharmaceutical composition for preventing and treating brain diseases caused by ultrafine dust.
아울러, 본 발명은 감태 추출물을 유효성분으로 포함하는, 미세먼지로 인한 뇌질환 예방 및 개선용 화장료 조성물을 제공한다. 보다 바람직하게는, 초미세먼지로 인한 뇌질환 예방 및 개선용 화장료 조성물을 제공한다.In addition, the present invention provides a cosmetic composition for preventing and improving brain diseases caused by fine dust, comprising an Ecklonia cava extract as an active ingredient. More preferably, it provides a cosmetic composition for preventing and improving brain diseases caused by ultrafine dust.
본 발명의 감태 (Ecklonia cava) 추출물은 초미세먼지로 인한 뇌질환에 대해 예방, 개선 및 치료 효과가 뛰어나므로 초미세먼지로 인한 뇌질환 특히 뇌 신경 질환에 대한 예방 및 개선용 건강기능성식품 조성물, 초미세먼지로 인한 뇌질환 특히 뇌 신경 질환에 대한 예방 및 개선용 식품 조성물, 초미세먼지로 인한 뇌질환 특히 뇌 신경 질환에 대한 예방 및 치료용 약학적 조성물 또는 초미세먼지로 인한 뇌질환 특히 뇌 신경 질환에 대한 예방 및 개선용 화장료 조성물로 유용하게 이용할 수 있다. The Ecklonia cava extract of the present invention is excellent in preventing, improving, and treating brain diseases caused by ultrafine dust, so a health functional food composition for preventing and improving brain diseases, especially brain neurological diseases caused by ultrafine dust, Food composition for preventing and improving brain diseases caused by ultrafine dust, especially cranial nerve diseases, pharmaceutical composition for preventing and treating brain diseases, especially brain neurological diseases caused by ultrafine dust, or brain diseases due to ultrafine dust, especially brain It can be usefully used as a cosmetic composition for preventing and improving neurological diseases.
도 1은 본 발명의 감태 추출물의 ABTS 라디칼 소거 활성(A), DPPH 라디칼 소거 활성(B) , 말론디알데히드 (MDA) 억제(C) 효과를 나타낸 도이다.
도 2는 본 발명의 감태 추출물이 뇌 신경 세포에서의 세포 내 활성산소 (reactive oxygen species, ROS)의 생성 억제 효과를 나타낸 도이다.
도 3은 본 발명의 감태 추출물이 뇌 신경 세포에서의 세포사멸을 억제시키는 효과를 나타낸 도이다.
도 4는 실험동물의 무게 변화 및 식이량을 측정한 결과를 나타낸 도이다.
도 5는 동물행동분석에 대한 결과를 나타낸 도이다.
도 6은 본 발명의 감태 추출물이 뇌 조직 내 지질과산화 억제 효과를 나타낸 도이다.
도 7은 초미세먼지에 노출된 뇌 조직에서의 미토콘드리아 기능평가 결과를 측정하여 나타낸 도이다.
도 8은 뇌 조직에서의 인지기능 저하와 관련된 단백질의 변화 측정 결과를 나타낸 도이다.
도 9는 뇌 조직에서의 사이토카인을 분석한 결과를 나타낸 도이다.
도 10은 콜린성 시스템 (cholinergic system) 평가에 대한 결과를 나타낸 도이다.
도 11은 본 발명의 감태 추출물의 페놀성 화합물을 분석한 도이다.Figure 1 is a diagram showing the ABTS radical scavenging activity (A), DPPH radical scavenging activity (B), malondialdehyde (MDA) inhibition (C) effect of the Ecklonia cava extract of the present invention.
Figure 2 is a diagram showing the effect of the Ecklonia cava extract of the present invention inhibiting the production of intracellular reactive oxygen species (ROS) in brain neurons.
Figure 3 is a diagram showing the effect of inhibiting apoptosis in brain nerve cells of the Ecklonia cava extract of the present invention.
Figure 4 is a diagram showing the results of measuring the weight change and dietary amount of the experimental animal.
5 is a diagram showing the results of animal behavior analysis.
Figure 6 is a diagram showing the effect of the Ecklonia cava extract of the present invention inhibiting lipid peroxidation in brain tissue.
7 is a diagram showing results of measuring mitochondrial function evaluation results in brain tissue exposed to ultrafine dust.
8 is a diagram showing the results of measuring changes in proteins related to cognitive decline in brain tissue.
9 is a diagram showing the results of analyzing cytokines in brain tissue.
10 is a diagram showing the results of the cholinergic system evaluation.
11 is a diagram analyzing the phenolic compound of the Ecklonia cava extract of the present invention.
본 발명은 감태 (Ecklonia cava)로부터 추출된 추출물을 유효성분으로 포함하는, 미세먼지로 인한 뇌질환 예방 및 개선용 건강기능성식품 조성물 제공을 목적으로 한다. 보다 바람직하게는, 초미세먼지로 인한 뇌질환 예방 및 개선용 건강기능성식품 조성물 제공을 목적으로 한다.An object of the present invention is to provide a health functional food composition for preventing and improving brain diseases caused by fine dust, comprising an extract extracted from Ecklonia cava as an active ingredient. More preferably, it is for the purpose of providing a health functional food composition for preventing and improving brain diseases caused by ultrafine dust.
또한, 본 발명은 감태 추출물을 유효성분으로 포함하는, 미세먼지로 인한 뇌질환 예방 및 개선용 식품 조성물 제공을 목적으로 한다. 보다 바람직하게는, 초미세먼지로 인한 뇌질환 예방 및 개선용 식품 조성물 제공을 목적으로 한다.In addition, an object of the present invention is to provide a food composition for preventing and improving brain diseases caused by fine dust, comprising an Ecklonia cava extract as an active ingredient. More preferably, it is intended to provide a food composition for preventing and improving brain diseases caused by ultrafine dust.
또한, 본 발명은 감태 추출물을 유효성분으로 포함하는, 미세먼지로 인한 뇌질환 예방 및 치료용 약학적 조성물 제공을 목적으로 한다. 보다 바람직하게는, 초미세먼지로 인한 뇌질환 예방 및 치료용 약학적 조성물 제공을 목적으로 한다.In addition, an object of the present invention is to provide a pharmaceutical composition for preventing and treating brain diseases caused by fine dust, comprising an Ecklonia cava extract as an active ingredient. More preferably, it is intended to provide a pharmaceutical composition for preventing and treating brain diseases caused by ultrafine dust.
마지막으로, 본 발명은 감태 추출물을 유효성분으로 포함하는, 미세먼지로 인한 뇌질환 예방 및 개선용 화장료 조성물 제공을 목적으로 한다. 보다 바람직하게는, 초미세먼지로 인한 뇌질환 예방 및 개선용 화장료 조성물 제공을 목적으로 한다.Finally, an object of the present invention is to provide a cosmetic composition for preventing and improving brain diseases caused by fine dust, comprising an Ecklonia cava extract as an active ingredient. More preferably, it is intended to provide a cosmetic composition for preventing and improving brain diseases caused by ultrafine dust.
이하, 첨부된 도면을 참조하여 본 발명의 구현예로 본 발명을 상세히 설명하기로 한다. 다만, 하기 구현 예는 본 발명에 대한 예시로 제시되는 것으로, 당업자에게 주지 저명한 기술 또는 구성에 대한 구체적인 설명이 본 발명의 요지를 불필요하게 흐릴 수 있다고 판단되는 경우에는 그 상세한 설명을 생략할 수 있고, 이에 의해 본 발명이 제한되지는 않는다. 본 발명은 후술하는 특허 청구범위의 기재 및 그로부터 해석되는 균등 범주 내에서 다양한 변형 및 응용이 가능하다.Hereinafter, the present invention will be described in detail as an embodiment of the present invention with reference to the accompanying drawings. However, the following implementation examples are presented as examples of the present invention, and if it is determined that a detailed description of a technique or configuration well known to those skilled in the art may unnecessarily obscure the subject matter of the present invention, the detailed description may be omitted. However, the present invention is not limited thereby. The present invention is capable of various modifications and applications within the scope of equality interpreted from the description of the claims to be described later and therefrom.
또한, 본 명세서에서 사용되는 용어 (terminology)들은 본 발명의 바람직한 실시 예를 적절히 표현하기 위해 사용된 용어들로서, 이는 사용자, 운용자의 의도 또는 본 발명이 속하는 분야의 관례 등에 따라 달라질 수 있다. 따라서 본 용어들에 대한 정의는 본 명세서 전반에 걸친 내용을 토대로 내려져야 할 것이다. 명세서 전체에서, 어떤 부분이 어떤 구성요소를 “포함”한다고 할 때, 이는 특별히 반대되는 기재가 없는 한 다른 구성요소를 제외하는 것이 아니라 다른 구성 요소를 더 포함할 수 있는 것을 의미한다.In addition, terms used in the present specification are terms used to properly express preferred embodiments of the present invention, which may vary depending on the intention of users or operators, or customs in the field to which the present invention belongs. Therefore, definitions of these terms should be made based on the contents throughout the present specification. Throughout the specification, when a part "includes" a certain component, it means that other components may be further included rather than excluding other components unless specifically stated to the contrary.
본 명세서 전체에 걸쳐, 특정 물질의 농도를 나타내기 위하여 사용되는 '%'는 별도의 언급이 없는 경우, 고체/고체는 (w/w) %, 고체/액체는 (w/v) %, 그리고 액체/액체는 (v/v) %이다.Throughout this specification,'%' used to indicate the concentration of a specific substance is (w/w)% for solids/solids, (w/v)% for solids/liquids, and Liquid/liquid is (v/v) %.
일 측면에서, 감태 추출물을 유효성분으로 포함하는, 초미세먼지로 인한 뇌질환 예방 및 개선용 건강기능성식품 조성물 또는 감태 추출물을 유효성분으로 포함하는, 초미세먼지로 인한 뇌질환 예방 및 개선용 식품 조성물에 관한 것이다.In one aspect, a health functional food composition for preventing and improving brain diseases due to ultrafine dust, or a food for preventing and improving brain diseases due to ultrafine dust, comprising an Ecklonia cava extract as an active ingredient It relates to the composition.
본 발명에 따른 추출물은 당업계에 공지된 추출 및 분리방법을 사용하여 천연으로부터 추출 및 분리하여 수득한 것을 사용할 수 있으며, 본 발명에서 정의된 "추출물"은 적절한 용매를 이용하여 감태로부터 추출한 것이며, 예를 들어, 조추출물, 극성용매 가용 추출물 또는 비극성용매 가용 추출물을 모두 포함한다. 상기 감태로부터 추출물을 추출하기 위한 적절한 용매로는 식품학적으로 또는 약학적으로 허용되는 유기용매라면 어느 것을 사용해도 무방하며, 물 또는 유기용매를 사용할 수 있으며, 이에 제한되지는 않으나, 예를 들어, 정제수, 메탄올 (methanol), 에탄올 (ethanol), 프로판올 (propanol), 이소프로판올 (isopropanol), 부탄올 (butanol) 등을 포함하는 탄소수 1 내지 4의 알코올, 아세톤 (acetone), 에테르 (ether), 벤젠 (benzene), 클로로포름 (chloroform), 에틸아세테이트 (ethyl acetate), 메틸렌클로라이드 (methylene chloride), 헥산 (hexane) 및 시클로헥산 (cyclohexane) 등의 각종 용매를 단독으로 혹은 혼합하여 사용할 수 있다. 추출 방법으로는 열수추출법, 냉침추출법, 환류냉각추출법, 용매추출법, 수증기증류법, 초음파추출법, 용출법, 압착법 등의 방법 중 어느 하나를 선택하여 사용할 수 있다. 또한, 목적하는 추출물은 추가로 통상의 분획 공정을 수행할 수도 있으며, 통상의 정제 방법을 이용하여 정제될 수도 있다.The extract according to the present invention may be obtained by extraction and separation from nature using an extraction and separation method known in the art, and the "extract" as defined in the present invention is extracted from Ecklonia cava using an appropriate solvent, For example, it includes all of a crude extract, a polar solvent-soluble extract, or a non-polar solvent-soluble extract. As a suitable solvent for extracting the extract from Ecklonia cava, any organic solvent that is food wise or pharmaceutically acceptable may be used, and water or an organic solvent may be used, but is not limited thereto, for example, Alcohols having 1 to 4 carbon atoms, including purified water, methanol, ethanol, propanol, isopropanol, butanol, acetone, ether, benzene ), chloroform, ethyl acetate, methylene chloride, hexane, and cyclohexane may be used alone or in combination. As the extraction method, any one of methods such as hot water extraction, cold precipitation extraction, reflux cooling extraction, solvent extraction, steam distillation method, ultrasonic extraction method, elution method, and compression method may be used. In addition, the desired extract may be further subjected to a conventional fractionation process, or may be purified using a conventional purification method.
본 발명의 추출물의 제조방법에는 제한이 없으며, 공지되어 있는 어떠한 방법도 이용될 수 있다. 예를 들면, 본 발명의 조성물에 포함되는 추출물은 상기한 열수 추출 또는 용매 추출법으로 추출된 1차 추출물을, 감압 증류 및 동결 건조 또는 분무 건조 등과 같은 추가적인 과정에 의해 분말상태로 제조할 수 있다. 또한 상기 1차 추출물을 실리카겔 컬럼 크로마토그래피 (silica gel column chromatography), 박층 크로마토그래피 (thin layer chromatography), 고성능 액체 크로마토그래피 (high performance liquid chromatography) 등과 같은 다양한 크로마토그래피를 이용하여 추가로 정제된 분획을 얻을 수도 있다. 따라서 본 발명에 있어서 추출물은 추출, 분획 또는 정제의 각 단계에서 얻어지는 모든 추출액, 분획 및 정제물, 그들의 희석액, 농축액 또는 건조물을 모두 포함하는 개념이다.There is no limitation on the method for preparing the extract of the present invention, and any known method may be used. For example, the extract included in the composition of the present invention may be prepared in a powder state by an additional process such as distillation under reduced pressure and freeze drying or spray drying of the primary extract extracted by the hot water extraction or solvent extraction method described above. In addition, the primary extract was further purified using various chromatography such as silica gel column chromatography, thin layer chromatography, high performance liquid chromatography, etc. You can also get it. Therefore, in the present invention, the extract is a concept including all extracts, fractions, and purified products obtained in each step of extraction, fractionation, or purification, their dilutions, concentrates or dried products.
본 발명의 식품 조성물은 유효성분인 추출물을 함유하는 것 외에 통상의 식품 조성물과 같이 여러 가지 향미제 또는 천연 탄수화물 등을 추가 성분으로서 함유할 수 있다.In addition to containing the extract as an active ingredient, the food composition of the present invention may contain various flavoring agents or natural carbohydrates as an additional ingredient, like a conventional food composition.
상술한 천연 탄수화물의 예는 모노사카라이드, 예를 들어, 포도당, 과당 등; 디사카라이드, 예를 들어 말토스, 슈크로스 등; 및 폴리사카라이드, 예를 들어 덱스트린, 시클로덱스트린 등과 같은 통상적인 당, 및 자일리톨,소르비톨, 에리트리톨 등의 당알콜이다. 상술한 향미제는 천연 향미제 (타우마틴), 스테비아 추출물 (예를 들어 레바우디오시드 A, 글리시르히진 등) 및 합성 향미제 (사카린, 아스파르탐 등)를 유리하게 사용할 수 있다. 본 발명의 식품 조성물은 상기 약학적 조성물과 동일한 방식으로 제제화되어 기능성 식품으로 이용하거나, 각종 식품에 첨가할 수 있다. 본 발명의 조성물을 첨가할 수 있는 식품으로는 예를 들어, 음료류, 육류, 초코렛, 식품류, 과자류, 피자, 라면, 기타 면류, 껌류, 사탕류, 아이스크림류, 알코올 음료류, 비타민 복합제 및 건강보조식품류 등이 있다.Examples of the above-described natural carbohydrates include monosaccharides such as glucose, fructose, and the like; Disaccharides such as maltose, sucrose, and the like; And polysaccharides, for example, common sugars such as dextrin and cyclodextrin, and sugar alcohols such as xylitol, sorbitol, and erythritol. The above-described flavoring agent may advantageously be used a natural flavoring agent (taumatin), a stevia extract (eg, rebaudioside A, glycyrrhizin, etc.), and a synthetic flavoring agent (saccharin, aspartame, etc.). The food composition of the present invention may be formulated in the same manner as the pharmaceutical composition and used as a functional food or added to various foods. Foods to which the composition of the present invention can be added include, for example, beverages, meat, chocolate, foods, confectionery, pizza, ramen, other noodles, gums, candy, ice cream, alcoholic beverages, vitamin complexes and health supplements, etc. There is this.
또한, 상기 식품 조성물은 유효성분인 추출물 외에 여러 가지 영양제, 비타민, 광물 (전해질), 합성 풍미제 및 천연 풍미제 등의 풍미제, 착색제 및 중진제 (치즈, 초콜릿 등), 펙트산 및 그의 염, 알긴산 및 그의 염, 유기산, 보호성 콜로이드 증점제, pH 조절제, 안정화제, 방부제, 글리세린, 알콜, 탄산음료에 사용되는 탄산화제 등을 함유할 수 있다. 그밖에 본 발명의 식품 조성물은 천연 과일 쥬스 및 과일 쥬스 음료 및 야채 음료의 제조를 위한 과육을 함유할 수 있다.In addition, the food composition includes various nutrients, vitamins, minerals (electrolytes), flavoring agents such as synthetic and natural flavoring agents, coloring agents and heavy weight agents (cheese, chocolate, etc.), pectic acid and salts thereof, in addition to the active ingredient extract. , Alginic acid and salts thereof, organic acids, protective colloidal thickeners, pH adjusters, stabilizers, preservatives, glycerin, alcohols, carbonates used in carbonated beverages, and the like. In addition, the food composition of the present invention may contain flesh for the production of natural fruit juice and fruit juice beverages and vegetable beverages.
본 발명의 건강기능성식품 조성물은, 정제, 캅셀, 분말, 과립, 액상, 환 등의 형태로 제조 및 가공될 수 있다. 본 발명에서 '건강기능성식품 조성물'이라 함은 건강기능식품에 관한 법률 제6727호에 따른 인체에 유용한 기능성을 가진 원료나 성분을 사용하여 제조 및 가공한 식품을 말하며, 인체의 구조 및 기능에 대하여 영양소를 조절하거나 생리학적 작용 등과 같은 보건용도에 유용한 효과를 얻을 목적으로 섭취하는 것을 의미한다. 본 발명의 건강기능성식품은 통상의 식품 첨가물을 포함할 수 있으며, 식품 첨가물로서의 적합 여부는 다른 규정이 없는 한, 식품의약품안전청에 승인된 식품 첨가물 공전의 총칙 및 일반시험법 등에 따라 해당 품목에 관한 규격 및 기준에 의하여 판정한다. 상기 '식품 첨가물 공전'에 수재된 품목으로는 예를 들어, 케톤류, 글리신, 구연산칼슘, 니코틴산, 계피산 등의 화학적 합성물; 감색소, 감초추출물, 결정셀룰로오스, 고량색소, 구아검 등의 천연첨가물; L-글루타민산나트륨 제제, 면류첨가알칼리제, 보존료 제제, 타르색소제제 등의 혼합제제류 등을 들 수 있다. 예를 들어, 정제 형태의 건강기능성식품은 본 발명의 유효성분을 부형제, 결합제, 붕해제 및 다른 첨가제와 혼합한 혼합물을 통상의 방법으로 과립화한 다음, 활택제 등을 넣어 압축성형하거나, 상기 혼합물을 직접 압축 성형할 수 있다. 또한 상기 정제 형태의 건강기능성식품은 필요에 따라 교미제 등을 함유할 수도 있다. 캅셀 형태의 건강기능성식품 중 경질 캅셀제는 통상의 경질 캅셀에 본 발명의 유효성분을 부형제 등의 첨가제와 혼합한 혼합물을 충진하여 제조할 수 있으며, 연질 캅셀제는 본 발명의 유효성분을 부형제 등의 첨가제와 혼합한 혼합물을 젤라틴과 같은 캅셀기제에 충진하여 제조할 수 있다. 상기 연질 캅셀제는 필요에 따라 글리세린 또는 소르비톨 등의 가소제, 착색제, 보존제 등을 함유할 수 있다. 환 형태의 건강기능성식품은 본 발명의 유효성분과 부형제, 결합제, 붕해제 등을 혼합한 혼합물을 기존에 공지된 방법으로 성형하여 조제할 수 있으며, 필요에 따라 백당이나 다른 제피제로 제피할 수 있으며, 또는 전분, 탈크와 같은 물질로 표면을 코팅할 수도 있다. 과립 형태의 건강기능성식품은 본 발명의 유효성분의 부형제, 결합제, 붕해제 등을 혼합한 혼합물을 기존에 공지된 방법으로 입상으로 제조할 수 있으며, 필요에 따라 착향제, 교미제 등을 함유할 수 있다.The health functional food composition of the present invention may be manufactured and processed in the form of tablets, capsules, powders, granules, liquids, pills, and the like. In the present invention, the term'health functional food composition' refers to a food manufactured and processed using raw materials or ingredients having useful functions for the human body pursuant to the Health Functional Food Act No.6727, and with respect to the structure and function of the human body. It means ingestion for the purpose of obtaining useful effects for health use such as controlling nutrients or physiological effects. The health functional food of the present invention may contain ordinary food additives, and whether or not it is suitable as a food additive is determined according to the general rules and general test methods of food additives approved by the Food and Drug Administration, unless otherwise specified. It is judged according to the standards and standards. Examples of the items listed in the'Food Additives Code' include chemical compounds such as ketones, glycine, calcium citrate, nicotinic acid, and cinnamic acid; Natural additives such as reduced pigment, licorice extract, crystalline cellulose, high color pigment, and guar gum; Mixed preparations, such as a sodium L-glutamate preparation, an alkali additive for noodles, a preservative preparation, and a tar color preparation, etc. are mentioned. For example, in the health functional food in the form of a tablet, a mixture obtained by mixing the active ingredient of the present invention with an excipient, a binder, a disintegrant, and other additives is granulated by a conventional method, and then compression molded by putting a lubricant or the like, or The mixture can be directly compression molded. In addition, the health functional food in the form of a tablet may contain a mating agent or the like, if necessary. Among the health functional foods in the form of capsules, hard capsules can be prepared by filling a mixture of the active ingredient of the present invention with additives such as excipients in a conventional hard capsule, and the soft capsules contain the active ingredient of the present invention with additives such as excipients. The mixture mixed with can be prepared by filling in a capsule base such as gelatin. The soft capsule may contain a plasticizer such as glycerin or sorbitol, a colorant, a preservative, and the like, if necessary. The cyclic health functional food can be prepared by molding a mixture of the active ingredient of the present invention, an excipient, a binder, a disintegrant, etc. by a conventionally known method, and can be coated with a white sugar or other coating agent if necessary, Alternatively, the surface may be coated with a material such as starch or talc. The health functional food in the form of granules can be prepared in granular form by a mixture of the excipients, binders, disintegrants, etc. of the active ingredients of the present invention by a known method, and if necessary, may contain flavoring agents, flavoring agents, etc. I can.
일 측면에서, 감태 (Ecklonia cava)로부터 추출된 추출물을 유효성분으로 포함하는, 초미세먼지로 인한 뇌질환 예방 및 치료용 약학적 조성물에 관한 것이다.In one aspect, it relates to a pharmaceutical composition for preventing and treating brain diseases caused by ultrafine dust, comprising an extract extracted from Ecklonia cava as an active ingredient.
본 발명의 약학 조성물에는 유효성분 이외에 보조제 (adjuvant)를 추가로 포함할 수 있다. 상기 보조제는 당해 기술분야에 알려진 것이라면 어느 것이나 제한 없이 사용할 수 있으나, 예를 들어 프로인트 (Freund)의 완전 보조제 또는 불완전 보조제를 더 포함하여 본 발명의 효과를 증가시킬 수 있다.The pharmaceutical composition of the present invention may further include an adjuvant in addition to the active ingredient. Any of the adjuvants known in the art may be used without limitation, but, for example, Freund's complete adjuvant or incomplete adjuvant may be further included to increase the effect of the present invention.
본 발명에 따른 약학 조성물은 유효성분을 약학적으로 허용된 담체에 혼입시킨 형태로 제조될 수 있다. 여기서, 약학적으로 허용된 담체는 제약 분야에서 통상 사용되는 담체, 부형제 및 희석제를 포함한다. 본 발명의 약학 조성물에 이용할 수 있는 약학적으로 허용된 담체는 이들로 제한되는 것은 아니지만, 락토스, 덱스트로스, 수크로스, 솔비톨, 만니톨, 자일리톨, 에리스리톨, 말티톨, 전분, 아카시아 고무, 알지네이트, 젤라틴, 칼슘 포스페이트, 칼슘 실리케이트, 셀룰로스, 메틸 셀룰로스, 폴리비닐 피롤리돈, 물, 메틸히드록시벤조에이트, 프로필히드록시벤조에이트, 탈크, 마그네슘 스테아레이트 및 광물유를 들 수 있다.The pharmaceutical composition according to the present invention may be prepared in a form in which an active ingredient is incorporated in a pharmaceutically acceptable carrier. Here, the pharmaceutically acceptable carrier includes carriers, excipients, and diluents commonly used in the pharmaceutical field. Pharmaceutically acceptable carriers that can be used in the pharmaceutical composition of the present invention are not limited thereto, but lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, gum acacia, alginate, gelatin, Calcium phosphate, calcium silicate, cellulose, methyl cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate, and mineral oil.
본 발명의 약학 조성물은 각각 통상의 방법에 따라 산제, 과립제, 정제, 캡슐제, 현탁액, 에멀전, 시럽, 에어로졸 등의 경구형 제형, 외용제, 좌제 또는 멸균 주사용액의 형태로 제형화하여 사용될 수 있다.The pharmaceutical compositions of the present invention can be formulated and used in the form of oral dosage forms such as powders, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols, etc., external preparations, suppositories, or sterile injectable solutions according to a conventional method. .
제제화할 경우에는 통상 사용하는 충진제, 증량제, 결합제, 습윤제, 붕해제, 계면활성제 등의 희석제 또는 부형제를 사용하여 조제될 수 있다. 경구투여를 위한 고형제제에는 정제, 환제, 산제, 과립제, 캡슐제 등이 포함되며, 그러한 고형 제제는 유효성분에 적어도 하나 이상의 부형제, 예를 들면 전분, 칼슘 카르보네이트, 수크로스, 락토오스, 젤라틴 등을 섞어 조제될 수 있다. 또한, 단순한 부형제 이외에 마그네슘 스테아레이트, 탈크 같은 윤활제들도 사용될 수 있다. 경구투여를 위한 액상 제제로는 현탁제, 내용액제, 유제, 시럽제 등이 해당되는데, 일반적으로 사용되는 희석제인 물, 리퀴드 파라핀 이외에 여러 가지 부형제, 예를 들면 습윤제, 감미제, 방향제, 보존제 등이 포함될 수 있다. 비경구 투여를 위한 제제에는 멸균된 수용액, 비수용성용제, 현탁제, 유제, 동결건조 제제 및 좌제가 포함된다. 비수용성용제, 현탁제로는 프로필렌 글리콜, 폴리에틸렌 글리콜, 올리브유와 같은 식물성 기름, 에틸올레이트와 같은 주사 가능한 에스테르 등이 사용될 수 있다. 좌제의 기제로는 위텝솔 (witepsol), 트윈 (tween) 61, 카카오지, 라우린지, 글리세로젤라틴 등이 사용될 수 있다.In the case of formulation, it may be prepared using diluents or excipients such as fillers, extenders, binders, wetting agents, disintegrants, and surfactants that are commonly used. Solid preparations for oral administration include tablets, pills, powders, granules, capsules, and the like, and such solid preparations include at least one excipient in the active ingredient, such as starch, calcium carbonate, sucrose, lactose, gelatin. It can be prepared by mixing and the like. In addition, in addition to simple excipients, lubricants such as magnesium stearate and talc may also be used. Liquid preparations for oral administration include suspensions, liquid solutions, emulsions, syrups, and various excipients, such as wetting agents, sweeteners, fragrances, and preservatives, in addition to water and liquid paraffin, which are commonly used diluents. I can. Formulations for parenteral administration include sterile aqueous solutions, non-aqueous solutions, suspensions, emulsions, lyophilized formulations, and suppositories. As the non-aqueous solvent and suspension, propylene glycol, polyethylene glycol, vegetable oil such as olive oil, injectable ester such as ethyl oleate, and the like may be used. As a base for suppositories, witepsol, tween 61, cacao butter, laurin paper, glycerogelatin, and the like can be used.
본 발명에 따른 약학 조성물은 개체에 다양한 경로로 투여될 수 있다. 투여의 모든 방식이 예상될 수 있는데, 예를 들면 경구, 정맥, 근육, 피하, 복강내 주사에 의해 투여될 수 있다.The pharmaceutical composition according to the present invention can be administered to a subject by various routes. All modes of administration can be expected, for example oral, intravenous, intramuscular, subcutaneous, intraperitoneal injection.
상기 약학 조성물은 다양한 경구 또는 비경구 투여 형태로 제형화될 수 있다. The pharmaceutical composition may be formulated in various oral or parenteral dosage forms.
경구 투여용 제형으로는 예를 들면 정제, 환제, 경질, 연질 캅셀제, 액제, 현탁제, 유화제, 시럽제, 과립제 등이 있는데, 이들 제형은 유효성분 이외에 희석제 (예: 락토즈, 덱스트로즈, 수크로즈, 만니톨, 솔비톨, 셀룰로즈 및/또는 글리신), 활택제 (예: 실리카, 탈크, 스테아르산 및 그의 마그네슘 또는 칼슘염 및/ 또는 폴리에틸렌 글리콜)를 추가로 포함할 수 있다. 또한, 상기 정제는 마그네슘 알루미늄 실리케이트, 전분 페이스트, 젤라틴, 트라가칸스, 메틸셀룰로즈, 나트륨 카복시메틸셀룰로즈 및/또는 폴리비닐피롤리딘과 같은 결합제를 함유할 수 있으며, 경우에 따라 전분, 한천, 알긴산 또는 그의 나트륨 염과 같은 붕해제 또는 비등 혼합물 및/또는 흡수제, 착색제, 향미제 및 감미제를 함유할 수 있다. 상기 제형은 통상적인 혼합, 과립화 또는 코팅 방법에 의해 제조될 수 있다.Formulations for oral administration include, for example, tablets, pills, hard, soft capsules, solutions, suspensions, emulsifiers, syrups, granules, etc. These formulations include diluents (e.g., lactose, dextrose, water) in addition to the active ingredients. Croze, mannitol, sorbitol, cellulose and/or glycine), lubricants (eg silica, talc, stearic acid and magnesium or calcium salts thereof and/or polyethylene glycol). In addition, the tablet may contain a binder such as magnesium aluminum silicate, starch paste, gelatin, tragacanth, methylcellulose, sodium carboxymethylcellulose and/or polyvinylpyrrolidine, and in some cases starch, agar, alginic acid Or a disintegrant or boiling mixture and/or absorbent, colorant, flavoring and sweetening agent such as its sodium salt. The formulation can be prepared by conventional mixing, granulating or coating methods.
또한, 비경구 투여용 제형의 대표적인 것은 주사용 제제이며, 주사용 제제의 용매로서 물, 링거액, 등장성 생리식염수 또는 현탁액을 들 수 있다. 상기 주사용 제제의 멸균 고정 오일은 용매 또는 현탁 매질로서 사용할 수있으며 모노-, 디-글리세라이드를 포함하여 어떠한 무자극성 고정오일도 이러한 목적으로 사용될 수 있다.In addition, a representative formulation for parenteral administration is a formulation for injection, and as a solvent for the formulation for injection, water, Ringer's solution, isotonic physiological saline, or a suspension may be mentioned. The sterile fixed oil of the injectable preparation can be used as a solvent or suspension medium, and any non-irritating fixed oil including mono- and di-glycerides can be used for this purpose.
또한, 상기 주사용 제제는 올레산과 같은 지방산을 사용할 수 있다.In addition, the formulation for injection may use a fatty acid such as oleic acid.
일 측면에서, 감태 추출물을 유효성분으로 포함하는, 초미세먼지로 인한 뇌질환 예방 및 개선용 화장료 조성물에 관한 것이다.In one aspect, it relates to a cosmetic composition for preventing and improving brain diseases caused by ultrafine dust, comprising an Ecklonia cava extract as an active ingredient.
본 발명의 “화장료 조성물”은 상술한 본 발명의 감태에서 추출한 추출물의 화장품학적 유효량 (cosmetically effective amount) 및 화장품학적으로 허용되는 담체를 포함하여 제조할 수 있다.The "cosmetic composition" of the present invention can be prepared including a cosmetically effective amount of the extract extracted from Ecklonia cava of the present invention and a cosmetically acceptable carrier.
본 명세서에서 용어 “화장품학적 유효량”은 상술한 본 발명의 조성물의 표피 각질형성세포의 증식을 통한 피부 재생 효능을 달성하는 데 충분한 양을 의미한다.As used herein, the term "cosmetically effective amount" means an amount sufficient to achieve the skin regeneration effect through the proliferation of epidermal keratinocytes of the composition of the present invention described above.
화장료 조성물의 외형은 화장품학 또는 피부과학적으로 허용 가능한 매질 또는 기제를 함유한다. 이는 국소적용에 적합한 모든 제형으로, 예를 들면, 용액, 겔, 고체, 반죽 무수 생성물, 수상에 유상을 분산시켜 얻은 에멀젼, 현탁액, 마이크로에멀젼, 마이크로캡슐, 미세과립구 또는, 이온형 (리포좀) 및 비이온형의 소낭 분산제의 형태로, 또는 크림, 스킨, 로션, 파우더, 연고, 스프레이 또는 콘실 스틱의 형태로 제공될 수 있다. 이들 조성물은 당해 분야의 통상적인 방법에 따라 제조될 수 있다. 본 발명에 따른 조성물은 또한 포말 (foam)의 형태로 또는 압축된 추진제를 더 함유한 에어로졸 조성물의 형태로도 사용될 수 있다.The cosmetic composition contains a cosmetically or dermatologically acceptable medium or base. These are all formulations suitable for topical application, such as solutions, gels, solids, dough anhydrous products, emulsions obtained by dispersing the oil phase in an aqueous phase, suspensions, microemulsions, microcapsules, microgranules or, ionic (liposomes) and It may be provided in the form of a nonionic vesicle dispersant, or in the form of a cream, skin, lotion, powder, ointment, spray or conceal stick. These compositions can be prepared according to conventional methods in the art. The composition according to the invention can also be used in the form of a foam or in the form of an aerosol composition further containing a compressed propellant.
본 발명의 일 실시예에 따른 상기 화장료 조성물은 그 제형에 있어서 특별히 한정되는 바가 없으며, 예를 들면, 유연화장수, 수렴화장수, 영양화장수, 영양크림, 마사지크림, 에센스, 아이크림, 아이에센스, 클렌징크림, 클렌징폼, 클렌징워터, 팩, 파우더, 바디로션, 바디크림, 바디오일 및 바디에센스 등의 화장품으로 제형화될 수 있다.The cosmetic composition according to an embodiment of the present invention is not particularly limited in its formulation, for example, softening lotion, astringent lotion, nourishing lotion, nourishing cream, massage cream, essence, eye cream, eye essence, cleansing It can be formulated into cosmetics such as cream, cleansing foam, cleansing water, pack, powder, body lotion, body cream, body oil and body essence.
본 발명의 화장료 조성물의 제형이 페이스트, 크림 또는 겔인 경우에는 담체 성분으로서 동물섬유, 식물섬유, 왁스, 파라핀, 전분, 트라칸트, 셀룰로오스 유도체, 폴리에틸렌 글리콜, 실리콘, 벤토나이트, 실리카, 탈크 또는 산화아연 등이 이용될 수 있다.When the formulation of the cosmetic composition of the present invention is a paste, cream or gel, as a carrier component, animal fiber, plant fiber, wax, paraffin, starch, tracant, cellulose derivative, polyethylene glycol, silicone, bentonite, silica, talc or zinc oxide, etc. Can be used.
본 발명의 화장료 조성물의 제형이 파우더 또는 스프레이인 경우에는 담체 성분으로서 락토스, 탈크, 실리카, 알루미늄히드록시드, 칼슘 실리케이트 또는 폴리아미드 파우더가 이용될 수 있고, 특히 스프레이인 경우에는 추가적으로 클로로플루오로히드로카본, 프로판/부탄 또는 디메틸 에테르와 같은 추진체를 포함할 수 있다.When the formulation of the cosmetic composition of the present invention is a powder or spray, lactose, talc, silica, aluminum hydroxide, calcium silicate or polyamide powder may be used as a carrier component. Propellants such as carbon, propane/butane or dimethyl ether.
본 발명의 화장료 조성물의 제형이 용액 또는 유탁액의 경우에는 담체 성분으로서 용매, 용매화제 또는 유탁화제가 이용되고, 예컨대 물, 에탄올, 이소프로판올, 에틸 카보네이트, 에틸 아세테이트, 벤질 알코올, 벤질 벤조에이트, 프로필렌글리콜, 1,3-부틸글리콜 오일, 글리세롤 지방족 에스테르, 폴리에틸렌 글리콜 또는 소르비탄의 지방산 에스테르가 있다.When the formulation of the cosmetic composition of the present invention is a solution or emulsion, a solvent, solvating agent or emulsifying agent is used as a carrier component, such as water, ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene Glycol, 1,3-butylglycol oil, glycerol aliphatic ester, polyethylene glycol or fatty acid ester of sorbitan.
본 발명의 화장료 조성물의 제형이 현탁액인 경우에는 담체 성분으로서 물, 에탄올 또는 프로필렌 글리콜과 같은 액상 희석제, 에톡실화 이소스테아릴 알코올, 폴리옥시에틸렌 소르비톨 에스테르 및 폴리옥시에틸렌 소르비탄 에스테르와 같은 현탁제, 미소결정성 셀룰로오스, 알루미늄 메타히드록시드, 벤토나이트, 아가 또는 트라칸트 등이 이용될 수 있다.When the formulation of the cosmetic composition of the present invention is a suspension, as a carrier component, a liquid diluent such as water, ethanol or propylene glycol, an ethoxylated isostearyl alcohol, a suspending agent such as polyoxyethylene sorbitol ester and polyoxyethylene sorbitan ester, Microcrystalline cellulose, aluminum metahydroxide, bentonite, agar or tracant, and the like may be used.
본 발명의 화장료 조성물의 제형이 계면-활성제 함유 클린징인 경우에는 담체 성분으로서 지방족 알코올 설페이트, 지방족 알코올 에테르 설페이트, 설포숙신산 모노에스테르, 이세티오네이트, 이미다졸리늄 유도체, 메틸타우레이트, 사르코시네이트, 지방산 아미드 에테르 설페이트, 알킬아미도베타인, 지방족 알코올, 지방산 글리세리드, 지방산 디에탄올아미드, 식물성 유, 리놀린 유도체 또는 에톡실화 글리세롤 지방산 에스테르 등이 이용될 수 있다.When the formulation of the cosmetic composition of the present invention is a surfactant containing cleansing, as a carrier component, aliphatic alcohol sulfate, aliphatic alcohol ether sulfate, sulfosuccinic acid monoester, isethionate, imidazolinium derivative, methyltaurate, sarcosinate , Fatty acid amide ether sulfate, alkylamidobetaine, fatty alcohol, fatty acid glyceride, fatty diethanolamide, vegetable oil, linoline derivative or ethoxylated glycerol fatty acid ester, and the like may be used.
본 발명의 화장료 조성물은 스킨, 로션, 크림, 에센스, 팩, 파운데이션, 색조화장품, 선크림, 투웨이케이크, 페이스파우더, 콤팩트, 메이크업베이스, 스킨커버, 아이쉐도우, 립스틱, 립글로스, 립픽스, 아이브로우 펜슬, 화장수 등의 화장품 및 샴푸, 비누 등의 세정제에 적용될 수 있다.The cosmetic composition of the present invention is skin, lotion, cream, essence, pack, foundation, color cosmetics, sun cream, two-way cake, face powder, compact, makeup base, skin cover, eye shadow, lipstick, lip gloss, lip fix, eyebrow pencil , It can be applied to cosmetics such as lotion and detergents such as shampoo and soap.
본 발명의 일 실시예에 따른 화장료 조성물에는 상기 감태에서 추출한 추출물 이외에 기능성 첨가물 및 일반적인 화장료 조성물에 포함되는 성분이 추가로 포함될 수 있다. 상기 기능성 첨가물로는 수용성 비타민, 유용성 비타민, 고분자 펩티드, 고분자 다당, 스핑고 지질 및 해초 엑기스로 이루어진 군에서 선택된 성분을 포함할 수 있다.In addition to the extract extracted from Ecklonia cava, the cosmetic composition according to an embodiment of the present invention may further include functional additives and ingredients included in general cosmetic compositions. The functional additive may include a component selected from the group consisting of water-soluble vitamins, oil-soluble vitamins, polymer peptides, polymer polysaccharides, sphingo lipids, and seaweed extract.
본 발명의 화장료 조성물에는 또한, 상기 기능성 첨가물과 더불어 필요에 따라 일반적인 화장료 조성물에 포함되는 성분을 배합해도 된다. 이외에 포함되는 배합 성분으로서는 유지 성분, 보습제, 에몰리엔트제, 계면 활성제, 유기 및 무기 안료, 유기 분체, 자외선 흡수제, 방부제, 살균제, 산화 방지제, 식물 추출물, pH 조정제, 알콜, 색소, 향료, 혈행 촉진제, 냉감제, 제한 (制汗)제, 정제수 등을 들 수 있다.In addition to the above functional additives, the cosmetic composition of the present invention may further contain components contained in a general cosmetic composition, if necessary. Other ingredients included include oils and fats, moisturizers, emollients, surfactants, organic and inorganic pigments, organic powders, ultraviolet absorbers, preservatives, fungicides, antioxidants, plant extracts, pH adjusters, alcohols, pigments, fragrances, blood circulation Accelerators, cooling agents, limiting agents, and purified water.
이하, 실시예를 통하여 본 발명을 보다 자세히 설명한다. 다만, 상기 실시예 및 실험예는 본 발명에 대한 예시로 제시되는 것으로, 당업자에게 주지 저명한 기술 또는 구성에 대한 구체적인 설명이 본 발명의 요지를 불필요하게 흐릴 수 있다고 판단되는 경우에는 그 상세한 설명을 생략할 수 있고, 이에 의해 본 발명이 제한되지는 않는다. 본 발명은 후술하는 특허청구범위의 기재 및 그로부터 해석되는 균등 범주 내에서 다양한 변형 및 응용이 가능하다.Hereinafter, the present invention will be described in more detail through examples. However, the above embodiments and experimental examples are presented as examples of the present invention, and if it is determined that a detailed description of a technique or configuration well known to those skilled in the art may unnecessarily obscure the subject matter of the present invention, the detailed description thereof will be omitted. And the invention is not limited thereby. The present invention is capable of various modifications and applications within the scope of equality interpreted from the description of the claims to be described later and therefrom.
[in-vitro] 실험에 대하여About the [in-vitro] experiment
[준비예 1] 시약 및 실험 재료[Preparation Example 1] Reagents and Experimental Materials
실험에 사용된 폴린시오칼토 페놀시약 (Folin-Ciocalteu's phenol reagent), 갈산 (gallic acid), 다이에틸렌글리콜, 루틴, 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), 트라이클로로아세트산(trichloroacetic acid), 싸이오바비투르산 (thiobarbituric acid), 아스코브산, 카테킨, 2',7'-dichlorofluorescein diacetate (DCF-DA), 3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), 소태아혈청 (fetal bovine serum), Roswell Park Memorial Institute (RPMI) 1640, Dulbecco modified Eagle Medium (DMEM), Minimum Essential Medium (MEM), 페니실린, 스트렙토마이신은 Sigma-Aldrich Chemical Co. (St. Louis, MO, USA) 제품을 구입하였으며, 그 외 사용된 용매 및 시약은 모두 일급 이상의 등급을 사용하였다.Folin-Ciocalteu's phenol reagent used in the experiment, gallic acid, diethylene glycol, lutein, 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) , Trichloroacetic acid, thiobarbituric acid, ascorbic acid, catechin, 2',7'-dichlorofluorescein diacetate (DCF-DA), 3-(4,5-dimethyl-thiazol- 2-yl)-2,5-diphenyltetrazolium bromide (MTT), fetal bovine serum, Roswell Park Memorial Institute (RPMI) 1640, Dulbecco modified Eagle Medium (DMEM), Minimum Essential Medium (MEM), penicillin, Streptomycin is Sigma-Aldrich Chemical Co. (St. Louis, MO, USA) product was purchased, and all other solvents and reagents used were of the first grade or higher.
[준비예 2] 감태 추출물의 제조[Preparation Example 2] Preparation of Ecklonia cava extract
본 실험에 사용된 감태 (Ecklonia cava)는 2018년 2월에 제주시에서 채취된 것을 구입하여 사용하였다. 감태의 염분 및 불순물 제거를 위하여 흐르는 물에 수세하고, 냉동 건조기 (Ilshin Lab Co., Ltd., Yangju, Korea)에서 건조시킨 후 분말화하여 냉동 보관 (-20°C)하였다. 감태 추출물은 건조물 20 g에 물과 에탄올 (80%) 각 1 L를 첨가하여 40°C에서 환류 냉각 하에 2시간 동안 추출하였다. Ecklonia cava used in this experiment was purchased and used in Jeju City in February 2018. To remove salt and impurities from Ecklonia cava, it was washed with running water, dried in a freeze dryer (Ilshin Lab Co., Ltd., Yangju, Korea), powdered, and stored frozen (-20 °C). Ecklonia cava extract was extracted for 2 hours under reflux cooling at 40 °C by adding 1 L of water and ethanol (80%) to 20 g of the dried product.
감태 추출물은 No.2 거름종이 (Whatman Inc, Kent, UK)로 여과하여 진공농축기 (N-N series, EYELA Co., Tokyo, Japan)를 이용해서 농축하였다. 농축된 추출물은 냉동 건조 후 냉동 보관 (-20°C)하여 실험에 사용하였다.Ecklonia cava extract was filtered through No.2 filter paper (Whatman Inc, Kent, UK) and concentrated using a vacuum concentrator (N-N series, EYELA Co., Tokyo, Japan). The concentrated extract was freeze-dried and stored frozen (-20 °C) to be used in the experiment.
[준비예 3] 실험에 사용된 세포 배양[Preparation Example 3] Cell culture used in the experiment
본 실험에 사용된 뇌 신경 세포 (MC-IXC)는 American Type Culture Collection (ATCC, Manasas, VA, USA)로부터 구매하여 사용하였다. Brain neurons (MC-IXC) used in this experiment were purchased from American Type Culture Collection (ATCC, Manasas, VA, USA) and used.
MC-IXC 세포는 10% 소태아혈청, 1% 50 units/mL 페니실린 및 100 μg/mL 스트렙토마이신이 포함된 MEM 배지를 배양액으로 하여 37°C에서 5% CO2조건으로 배양하였다.MC-IXC cells were cultured in MEM medium containing 10% fetal bovine serum, 1% 50 units/mL penicillin, and 100 μg/mL streptomycin as a culture medium at 37°C under 5% CO 2 conditions.
[실시예 1] 감태 추출물의 총 페놀성 화합물 및 총 플라보노이드 함량 측정[Example 1] Measurement of total phenolic compound and total flavonoid content of Ecklonia cava extract
1.1 실험 방법1.1 Experiment method
총 페놀성 화합물 함량은 감태 추출물 1 mL에 3차 증류수 9 mL와 폴린시오칼토 페놀시약 1 mL을 혼합하였다. 혼합물은 25°C에서 5분 동안 반응시키고, 7% 탄산소듐 용액 10 mL과 3차 증류수 4 mL 첨가하여 25°C에서 2시간 동안 반응시켰다. 최종 반응물은 분광광도계 (spectrophotometer, Shimadzu UV-1601, Tokyo, Japan)를 이용하여 760 nm에서 흡광도를 측정하였고, 갈산을 사용하여 작성된 보정선에 대입하여 총 폴리페놀 함량을 계산하였으며 이를 갈산 당량 (mg GAE (gallic acid equivalent)/g of dried weight)으로 나타냈다.The total phenolic compound content was mixed with 9 mL of tertiary distilled water and 1 mL of foliniciocalto phenol reagent to 1 mL of Ecklonia cava extract. The mixture was reacted at 25 °C for 5 minutes, 10 mL of a 7% sodium carbonate solution and 4 mL of tertiary distilled water were added and reacted at 25 °C for 2 hours. For the final reactant, absorbance was measured at 760 nm using a spectrophotometer (Shimadzu UV-1601, Tokyo, Japan), and the total polyphenol content was calculated by substituting it into a calibration line prepared using gallic acid. It is expressed as GAE (gallic acid equivalent)/g of dried weight).
또한, 총 플라보노이드 함량 측정은 감태 추출물 1 mL에 다이에틸렌글리콜 10 mL와 수산화소듐 1 mL를 혼합한 후, 30℃에서 60분동안 반응시켰다. 최종반응물은 420 nm에서 흡광도를 측정하였고, 루틴을 사용하여 작성된 보정선에 대입하여 총 플라보노이드 함량을 계산하였고, 이를 루틴 당량 (mg RE (rutin equivalent)/g of dried weight)으로 나타냈다.In addition, to measure the total flavonoid content, 10 mL of diethylene glycol and 1 mL of sodium hydroxide were mixed with 1 mL of Ecklonia cava extract, and then reacted at 30° C. for 60 minutes. The final reactant was measured absorbance at 420 nm, and the total flavonoid content was calculated by substituting it into the calibration line prepared using rutin, and this was expressed as rutin equivalent (mg RE (rutin equivalent)/g of dried weight).
모든 실험은 3회 반복 실행 후, mean±SD로 나타냈으며, 각 평균값에 대한 유의성 검증은 SAS software 9.4 (SAS Institute Inc., Cary, NC, USA)을 실시하고, Duncan의 다중범위검정법 (Duncan’s multiple range test)으로 각 시료 간의 유의차를 5% 수준에서 검증하였다.All experiments were repeated three times, and then expressed as mean±SD. To verify the significance of each mean value, SAS software 9.4 (SAS Institute Inc., Cary, NC, USA) was performed, and Duncan's multiple range test was performed. range test), the significant difference between each sample was verified at the 5% level.
1.2 실험 결과1.2 Experimental results
감태 80% 에탄올 추출물의 총 페놀성 화합물 함량 및 총 플라보노이드 함량은 각각 418.08 mg GAE/g of dried weight 및 111.22 mg RE/g of dried weight으로 물 추출물 189.25 mg GAE/g of dried weight 및 44.93 mg RE/g of dried weight 대비 상대적으로 높은 함량을 나타냈다.The total phenolic compound content and total flavonoid content of
[실시예 2] 뇌 조직에서의 라디칼 소거 활성 및 지방질과산화물 생성 억제 효과[Example 2] Radical scavenging activity and inhibition of lipid peroxide production in brain tissue
2.1 실험 방법2.1 Experimental method
ABTS (2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) 라디칼 소거 활성은 150 mM 염화소듐을 포함한 100 mM 인산 완충용액 (pH 7.4)에 2.45 mM ABTS와 1.0 mM [2,2'-azobis-(2-amidinopropane)·HCl] (AAPH)를 혼합하여 68℃의 항온 수조에서 30분간 가열한 뒤, 4°C에서 24시간 동안 냉장보관 하여, ABTS 라디칼을 생성시켜 사용하였다.ABTS (2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) radical scavenging activity was 2.45 mM ABTS and 1.0 mM [2,2] in 100 mM phosphate buffer (pH 7.4) containing 150 mM sodium chloride. '-azobis-(2-amidinopropane)·HCl] (AAPH) was mixed and heated in a constant temperature water bath at 68° C. for 30 minutes, and then stored refrigerated at 4° C. for 24 hours to generate and use ABTS radicals.
ABTS 라디칼용액은 734 nm에서 흡광도 값 (0.70±0.02)을 조정하였고, 시료 20 μL에 980 μL를 혼합하여 37℃에서 10분 동안 반응시켰다. 반응물은 분광광도계를 이용하여 734 nm에서 흡광도를 측정하여 라디칼 소거 활성을 계산하였다.In the ABTS radical solution, the absorbance value (0.70±0.02) was adjusted at 734 nm, and 980 μL was mixed with 20 μL of the sample and reacted at 37° C. for 10 minutes. The reactant was measured for absorbance at 734 nm using a spectrophotometer to calculate the radical scavenging activity.
DPPH 라디칼 소거활성은 80% 메탄올에 녹인 0.1 mM DPPH 용액을 517 nm에서 흡광도 값이 1.00±0.02가 되도록 조정하였고, 추출물 0.1 mL에 2.9 mL을 첨가하여 실온에서 30분간 반응시켰다. 최종반응물은 분광광도계를 이용하여 흡광도를 측정하였다.For DPPH radical scavenging activity, a 0.1 mM DPPH solution dissolved in 80% methanol was adjusted to have an absorbance value of 1.00±0.02 at 517 nm, and 2.9 mL was added to 0.1 mL of the extract, followed by reaction at room temperature for 30 minutes. The final reactant was measured for absorbance using a spectrophotometer.
마우스 뇌 조직을 이용한 지방질과산화물 (Malondialdehyde, MDA) 생성 억제 효과는 ICR (institute of cancer research) 마우스 (male, 4 weeks)를 실험동물 공급업체 (Samtako, Osan, Korea)로부터 구입 후, 뇌를 적출하여 실험에 사용하였다. 본 동물실험은 경상대학교 동물윤리심의위원회 승인 후 진행하였다 (경상대학교 동물실험 인가번호: GNU-120831-M0067).To inhibit the production of lipid peroxide (Malondialdehyde, MDA) using mouse brain tissue, ICR (institute of cancer research) mice (male, 4 weeks) were purchased from laboratory animal suppliers (Samtako, Osan, Korea), and the brain was removed. It was used in the experiment. This animal experiment was conducted after approval by the Animal Ethics Review Committee of Gyeongsang National University (Gyeongsang National University Animal Experiment License Number: GNU-120831-M0067).
뇌 조직 무게 10배의 20 mM 트리스 염산 완충용액 (pH 7.4)를 첨가하여 조직파쇄기 (Next Advance Inc., NY, USA)를 사용하여 균질화하였다. 균질화 된 뇌 조직은 원심분리 (10,000xg, 20분, 4°C)하였고, 그 상층액을 실험에 사용하였다. 추출물 0.2 mL에 뇌 조직 상층액 0.1 mL, 10 μM 황산철(Ⅱ) 0.1 mL, 0.1 mM 아스코브산 0.1 mL을 혼합하여 37°C에서 1시간 동안 배양하였다. 배양 후, 30% 트라이클로로아세트산 0.1 mL과 1% 싸이오바비투르산 0.3 mL를 첨가하여 95℃의 항온 수조에서 20분 동안 가열하였다. 최종 반응물은 원심분리 (10,000xg, 10 min)하여 상층액을 532 nm에서 흡광도를 측정하였다.The brain tissue was homogenized using a tissue breaker (Next Advance Inc., NY, USA) by adding 20 mM tris hydrochloric acid buffer solution (pH 7.4) of 10 times the weight of the brain tissue. The homogenized brain tissue was centrifuged (10,000xg, 20 minutes, 4°C), and the supernatant was used in the experiment. In 0.2 mL of the extract, 0.1 mL of brain tissue supernatant, 0.1 mL of 10 μM iron(II) sulfate, and 0.1 mL of 0.1 mM ascorbic acid were mixed and incubated at 37°C for 1 hour. After incubation, 0.1 mL of 30% trichloroacetic acid and 0.3 mL of 1% thiobabituric acid were added, followed by heating in a constant temperature water bath at 95° C. for 20 minutes. The final reactant was centrifuged (10,000xg, 10 min), and the supernatant was measured for absorbance at 532 nm.
모든 실험은 3회 반복 실행 후, mean±SD로 나타냈으며, 각 평균값에 대한 유의성 검증은 SAS software 9.4 (SAS Institute Inc., Cary, NC, USA)을 실시하고, Duncan의 다중범위검정법 (Duncan’s multiple range test)으로 각 시료 간의 유의차를 5% 수준에서 검증하였다.All experiments were repeated three times, and then expressed as mean±SD. To verify the significance of each mean value, SAS software 9.4 (SAS Institute Inc., Cary, NC, USA) was performed, and Duncan's multiple range test was performed. range test), the significant difference between each sample was verified at the 5% level.
2.2 실험 결과2.2 Experiment results
감태 추출물의 마우스 뇌 조직에서의 ABTS 라디칼 소거 활성을 측정한 결과는 도 1(A)와 같다. 물 추출물과 80% 에탄올 추출물 모두 농도가 증가함에 따라 ABTS 라디칼 소거 활성이 증가하는 경향을 나타냈으며, 양성대조군으로 사용 된 비타민 C와 동일 농도 (200 μg/mL; 83.52%, IC50=123.72μg/mL)에서 물 추출물 (83.04%)은 유의적인 결과를 나타냈으며 80% 에탄올 추출물 (90.83%)에서는 상대적으로 우수한 ABTS 라디칼 소거활성을 나타냈다. 또한, 80% 에탄올 추출물의 IC50값은 101.94 μg/mL로 물 추출물 (IC50=114.17μg/mL) 대비 상대적으로 높은 ABTS 소거활성을 가지는 것으로 나타났다.The result of measuring the ABTS radical scavenging activity in mouse brain tissue of Ecklonia cava extract is shown in FIG. 1(A). Both the water extract and the 80% ethanol extract showed a tendency to increase the ABTS radical scavenging activity as the concentration increased, and the same concentration as vitamin C used as the positive control (200 μg/mL; 83.52%, IC 50 =123.72 μg/) mL), water extract (83.04%) showed significant results, and 80% ethanol extract (90.83%) showed relatively excellent ABTS radical scavenging activity. In addition, the IC 50 value of the 80% ethanol extract was 101.94 μg/mL, which was found to have a relatively high ABTS scavenging activity compared to the water extract (IC 50 =114.17 μg/mL).
도 1(B)에서와 같이 DPPH 라디칼 소거 활성을 측정한 결과는 양성대조군으로 사용된 비타민 C (200 μg/mL; 95.50%) 대비 물 추출물 (37.38%)과 80% 에탄올 추출물 (41.96%) 모두 상대적으로 낮은 DPPH 소거 활성을 나타냈다. 감태 물 추출물과 80% 에탄올 추출물 모두 ABTS 라디칼 소거 활성이 상대적으로 높게 나타났는데, 이러한 결과는 ABTS 라디칼 제거 측정방법이 친수성 및 소수성 화합물 모두의 산화방지 활성을 측정할 수 있는 기전에서 기인된 것으로 사료된다.As shown in Fig. 1(B), DPPH radical scavenging activity was measured. Both water extract (37.38%) and 80% ethanol extract (41.96%) compared to vitamin C (200 μg/mL; 95.50%) used as a positive control group were shown. It showed a relatively low DPPH scavenging activity. Both Ecklonia cava water extract and 80% ethanol extract showed relatively high ABTS radical scavenging activity. This result is thought to be due to the mechanism by which the ABTS radical scavenging method can measure the antioxidant activity of both hydrophilic and hydrophobic compounds. .
지방질과산화 중간생성물인 MDA 생성 억제 효과를 측정한 결과는 도 1(C)와 같다. 감태 물 추출물은 100 μg/mL 농도에서 77.18%, 80% 에탄올 추출물은 89.12%의 생성 억제 효과를 나타냈으며, 이러한 결과는 양성대조군으로 사용한 카테킨 (100 μg/mL; 71.03%, IC50=16.54μg/mL)과 비교 시에도 유의적으로 우수한 결과임을 확인 할 수 있었다. 반면, 80% 에탄올 추출물의 IC50값은 29.06 μg/mL로 나타났으며 물 추출물 (59.76 μg/mL) 대비 상대적으로 우수한 MDA 생성 억제 효과를 나타내는 것으로 확인되었다.The results of measuring the inhibitory effect of MDA production, which is an intermediate product of lipid peroxidation, are shown in FIG. Ecklonia cava water extract showed 77.18% at the concentration of 100 μg/mL, and the 80% ethanol extract showed 89.12% inhibition of production, and these results showed that the catechin used as a positive control (100 μg/mL; 71.03%, IC 50 =16.54 μg) /mL), it was confirmed that the result was significantly superior. On the other hand, the IC 50 value of the 80% ethanol extract was 29.06 μg/mL, and it was confirmed to exhibit a relatively superior MDA production inhibitory effect compared to the water extract (59.76 μg/mL).
이러한 결과들을 고려할 때, 감태 추출물의 마우스 뇌 조직에서 나타나는 우수한 항산화 활성은 실시예 1의 총 페놀성 화합물의 함량과의 상관관계에서 기인된 것이며, 산화적 스트레스로 인하여 발생되는 세포의 기능적 손상을 감소시켜 보호하는데 도움이 될 것으로 판단된다.Considering these results, the excellent antioxidant activity that appears in mouse brain tissue of Ecklonia cava extract is due to the correlation with the content of the total phenolic compound of Example 1, and reduces functional damage to cells caused by oxidative stress. It is believed that it will help to protect it.
[실시예 3] 감태 추출물의 뇌 신경 세포에서의 초미세먼지 (PM[Example 3] Ultrafine dust in brain nerve cells of Ecklonia cava extract (PM 2.52.5 ) 유도성 산화적 스트레스의 세포 내 생성 억제 효과) Inhibitory effect of induced oxidative stress on intracellular production
3.1 세포 내 산화적 스트레스 측정 방법3.1 Method for measuring oxidative stress in cells
세포 내 산화적스트레스 측정은 DCF-DA dye를 이용하여 진행하였다. 96 well plate에 1x104cells/well로 분주하고, 24시간동안 배양하였다. 배양된 세포에 감태 추출물을 처리하고 30분 뒤에 초미세먼지 (PM2.5) 100μg/mL농도가 되도록 전처리하여 37°C에서 5% CO2배양기에서 반응을 시켰다. Intracellular oxidative stress was measured using DCF-DA dye. Dispense into a 96 well plate at 1×10 4 cells/well and incubate for 24 hours. The cultured cells were treated with Ecklonia cava extract and pretreated to a concentration of 100 μg/mL of ultrafine dust (PM 2.5 ) 30 minutes later, and reacted in a 5% CO 2 incubator at 37°C.
24시간 후, 50 μM DCF-DA를 처리하여 40분간 배양하고 형광광도계 (Infinite F200, Tecan, Switzerland)를 사용하여 들뜸 파장 (excitation wave) 485 nm 및 방출 파장 (emission wave) 535 nm에서 형광광도를 측정하였다.After 24 hours, 50 μM DCF-DA was treated, incubated for 40 minutes, and fluorescence intensity was measured at 485 nm excitation wave and 535 nm emission wave using a fluorescence photometer (Infinite F200, Tecan, Switzerland). It was measured.
모든 실험은 3회 반복 실행 후, mean±SD로 나타냈으며, 각 평균값에 대한 유의성 검증은 SAS software 9.4 (SAS Institute Inc., Cary, NC, USA)을 실시하고, Duncan의 다중범위검정법 (Duncan’s multiple range test)으로 각 시료 간의 유의차를 5% 수준에서 검증하였다.All experiments were repeated three times, and then expressed as mean±SD. To verify the significance of each mean value, SAS software 9.4 (SAS Institute Inc., Cary, NC, USA) was performed, and Duncan's multiple range test was performed. range test), the significant difference between each sample was verified at the 5% level.
3.2 실험 결과3.2 Experiment results
도2의 경우 뇌 신경 세포 (MC-IXC)에서 초미세먼지 처리군은 대조군(100.00%) 대비 332.94%로 증가된 세포 내 ROS 함량을 나타냈으며 양성대조군인 비타민 C는 76.69%로 유의적으로 높은 세포내 ROS 생성 억제효과를 나타냈다. 감태 물 추출물은 20 μg/mL (102.70%)에서 대조군과 유사한 결과를 나타내었으며, 80% 에탄올 추출물은 10 μg/mL (85.59%)에서 유의적으로 우수한 ROS 생성 억제 효과를 나타냈다.In the case of Fig. 2, the ultrafine dust-treated group in brain neurons (MC-IXC) showed an increased intracellular ROS content of 332.94% compared to the control group (100.00%), and the positive control vitamin C was significantly higher at 76.69%. It showed the inhibitory effect of intracellular ROS production. Ecklonia cava water extract showed similar results to the control at 20 μg/mL (102.70%), and 80% ethanol extract showed significantly superior ROS production inhibitory effect at 10 μg/mL (85.59%).
[실시예 4] 감태 추출물의 뇌 신경 세포에서의 초미세먼지 (PM[Example 4] Ultrafine dust in brain nerve cells of Ecklonia cava extract (PM 2.52.5 ) 유도성 세포사멸 억제 효과) Induced apoptosis inhibitory effect
4.1 세포 내 산화적 스트레스 측정 방법4.1 How to measure oxidative stress in cells
세포 생존율 측정은 전처리된 세포에 10 mg/mL MTT stock 용액을 처리하여 37℃에서 2시간 동안 반응시켰다. 반응 후, 생성된 crystal 함량 측정을 위하여, 배지는 모두 제거하고 이메틸 일산화항 (dimethyl sulfoxide; DMSO)를 첨가하여 20분간 상온에서 반응시킨 뒤 570 nm (determination wave)와 690 nm (reference wave)에서 흡광도를 측정하였다.Cell viability was measured by treating the pretreated cells with a 10 mg/mL MTT stock solution and reacting at 37° C. for 2 hours. After the reaction, in order to measure the crystal content generated, all the medium was removed, dimethyl sulfoxide (DMSO) was added and reacted at room temperature for 20 minutes, and then at 570 nm (determination wave) and 690 nm (reference wave). The absorbance was measured.
모든 실험은 3회 반복 실행 후, mean±SD로 나타냈으며, 각 평균값에 대한 유의성 검증은 SAS software 9.4 (SAS Institute Inc., Cary, NC, USA)을 실시하고, Duncan의 다중범위검정법 (Duncan’s multiple range test)으로 각 시료 간의 유의차를 5% 수준에서 검증하였다.All experiments were repeated three times, and then expressed as mean±SD. To verify the significance of each mean value, SAS software 9.4 (SAS Institute Inc., Cary, NC, USA) was performed, and Duncan's multiple range test was performed. range test), the significant difference between each sample was verified at the 5% level.
4.2 실험 결과4.2 Experimental results
초미세먼지는 세포 내에 산화적 스트레스를 증가시키고 염증반응을 촉진 시킴으로써 세포의 기능 저하 및 사멸을 유도하는 것으로 알려져 있으며 (Guo 등, 2015), 감태 추출물의 뇌 신경 세포에서의 초미세먼지 유도성 세포사멸 억제 효과를 측정한 결과는 도 3과 같다.Ultrafine dust is known to induce cell function decline and death by increasing oxidative stress within cells and promoting inflammatory reactions (Guo et al., 2015). The result of measuring the killing inhibitory effect is shown in FIG. 3.
도 3은 뇌 신경 세포 (MC-IXC)에서 초미세먼지 처리군 (64.95%)에서는 대조군 (100.00%) 대비 약 35.05% 감소된 세포 생존율을 나타냈으며, 양성대조군인 비타민 C처리군 (71.32%)에서는 6.37% 증가된 생존율을 나타냈다. 감태 물 추출물 (96.74%) 및 80% 에탄올 추출물 (101.23%)은 100 μg/mL 농도 처리 시 대조군과 통계적으로 우수한 뇌 신경 세포 생존율을 나타내는 것으로 확인되었다.3 shows a cell survival rate reduced by about 35.05% compared to the control group (100.00%) in the ultrafine dust-treated group (64.95%) in brain neurons (MC-IXC), and the vitamin C-treated group (71.32%), which is a positive control group. Showed a 6.37% increase in survival rate. Ecklonia cava water extract (96.74%) and 80% ethanol extract (101.23%) were found to show statistically superior brain neuron survival rate compared to the control group when treated at a concentration of 100 μg/mL.
초미세먼지의 노출에 의한 세포기능 저하는 다양한 메커니즘에 의한 것으로 그 중심에는 염증반응의 활성화와 관련된 것으로 보고되고 있다 (Øvrevik 등, 2015). 초미세먼지는 세포막에서 직접적으로 반응하는데, lysosomal leakage 및 세포 표면 수용체인 toll-like 수용체와의 결합은 NACHT, LRR and PYD domains-containing protein 3 (NLRP3) inflammasome의 형성을 유도한다. 이는 다시 IL-1β의 방출을 유도하게 되고 nuclear factor-κB (NF-κB) 및 mitogen-ctivated protein kinase (MAPK) 경로를 활성화 시킴으로써 세포 내 ROS의 생성 유도 및 pro-inflammatory cytokine (IL-1 family, TNF-α 및 IL-18) 분비를 촉진하게 된다. 뿐만 아니라, 초미세먼지는 세포표면에서 직접적으로 반응할 수 있으며, PAH 및 quinone과 같은 물질들은 산화-환원 관련 대사의 활성화를 통하여 ROS 및 반응성이 큰 친전자성 대사산물 (O2 ·-,H2O2,O2 ·-및 ·OH)들을 생성함으로써 미토콘드리아의 손상을 유발하고, 세포의 기능 저하를 초래하게 된다 (Guo 등, 2015; Øvrevik 등, 2015; Yan 등, 2016). Cellular function degradation caused by exposure to ultrafine dust is due to various mechanisms and is reported to be related to the activation of inflammatory reactions at the center (Øvrevik et al., 2015). Ultrafine dust reacts directly in the cell membrane, and lysosomal leakage and binding to toll-like receptors, cell surface receptors, induce the formation of NACHT, LRR and PYD domains-containing protein 3 (NLRP3) inflammasomes. This induces the release of IL-1β again and activates the nuclear factor-κB (NF-κB) and mitogen-ctivated protein kinase (MAPK) pathways, thereby inducing the production of intracellular ROS and pro-inflammatory cytokines (IL-1 family, TNF-α and IL-18) secretion is promoted. In addition, ultrafine dust can react directly on the cell surface, and substances such as PAH and quinone are ROS and highly reactive electrophilic metabolites (O 2 ·- ,H) through activation of oxidation-reduction-related metabolism. 2 O 2 ,O 2 ·- and · OH) induce mitochondrial damage and deterioration of cell function (Guo et al., 2015; Øvrevik et al., 2015; Yan et al., 2016).
본 실험의 결과에서 나타난 감태 추출물의 뇌 세포 내 ROS 생성 억제효과 및 세포사멸 억제 효과는 감태에 함유되어 있는 다양한 생리활성물질에 의한 것으로 사료된다. 이러한 결과들을 종합해 볼 때, 감태 추출물은 뇌 신경 세포에서 초미세먼지로 유도될 수 있는 세포 손상으로부터 기능 개선 및 치료에 도움을 줄 수 있는 건강기능성식품 조성물, 식품 조성물, 약학적 조성물 또는 화장료 조성물로서의 활용 가능성이 기대된다.In the results of this experiment, the effect of Ecklonia cava extract on inhibiting ROS production and apoptosis in brain cells is believed to be due to various physiologically active substances contained in Ecklonia cava. Taking these results together, Ecklonia cava extract is a health functional food composition, food composition, pharmaceutical composition, or cosmetic composition that can help improve function and treatment from cell damage that can be induced by ultrafine dust in brain nerve cells. It is expected to be used as a product.
[in-vivo] 실험에 대하여About the [in-vivo] experiment
[준비예 4] 감태 추출물의 제조[Preparation Example 4] Preparation of Ecklonia cava extract
본 실험에 사용된 감태 (Ecklonia cava; E. cava)는 2018년 2월에 제주시에서 채취된 것을 구입하여 사용하였다. 염분 및 불순물 제거하고, 동결건조기 (Ilshin Lab Co., Ltd., Yangju, Korea)에서 건조시킨 후 분말화하여 냉동 보관 (-20°C)하였다. 건조분말 20 g에 물 (증류수)을 1 L를 첨가하여 40°C에서 환류 냉각 하에 2시간동안 추출하였다. 감태 물 추출물은 No.2 거름종이 (Whatman Inc, Kent, UK)로 여과하여 진공농축기 (N-N series, EYELA Co., Tokyo, Japan)를 이용해서 농축하였다. 농축된 추출물은 동결건조하여 사용하였다. Ecklonia cava (E. cava ) used in this experiment was purchased and used in Jeju City in February 2018. Salt and impurities were removed, dried in a freeze dryer (Ilshin Lab Co., Ltd., Yangju, Korea), powdered, and stored frozen (-20 °C). 1 L of water (distilled water) was added to 20 g of the dry powder, followed by extraction under reflux cooling at 40 °C for 2 hours. Ecklonia cava water extract was filtered through No.2 filter paper (Whatman Inc, Kent, UK) and concentrated using a vacuum concentrator (NN series, EYELA Co., Tokyo, Japan). The concentrated extract was used after lyophilization.
[실시예 5] 동물실험 디자인 및 실험동물의 몸무게 변화 및 식이량 개선효과[Example 5] Animal experiment design and effect of weight change and dietary improvement of experimental animals
5.1 동물실험 디자인5.1 Animal testing design
본 실험에 사용된 동물은 6주령의 수컷 BALB/c 마우스 (Samtako, Osan, Korea)로부터 구입하였으며, 온도 22±2°C, 상대습도 50±5%를 유지하며 충분한 물과 사료를 지급하는 일정한 사육환경을 유지하였다. 모든 실험은 경상대학교 동물실험 윤리위원회 (IACUC 승인번호: GNU-180927-M0050)의 승인하에 수행하였다. 실험동물은 반입 1주일 동안의 적응 기간을 거친 뒤 정상대조군 (Normal control; NC), 초미세먼지 노출군 (PM2.5)및 감태 추출물 식이군으로 나누어 사육하였다. 초미세먼지 군과 감태 추출물 식이군은 whole body exposure 챔버 내에서 초미세먼지에 노출시켰으며, 정상 대조군은 여과된 공기를 주입시켰다. 감태 물 추출물 식이 군 (water extract from E. cava; WEE)은 음용수에 녹인 후, 노출 전 50, 100, 200 mg/kg of body weight 농도 (WEE 50, WEE 100, WEE 200)로 경구 투여하였다. 그리고, 실험동물의 몸무게와 식이량은 4주에 1번씩 측정하였다.The animals used in this experiment were purchased from 6-week-old male BALB/c mice (Samtako, Osan, Korea), maintaining a temperature of 22±2°C and a relative humidity of 50±5%, and supplying sufficient water and feed. The breeding environment was maintained. All experiments were performed under the approval of Gyeongsang National University Animal Experiment Ethics Committee (IACUC approval number: GNU-180927-M0050). Experimental animals were reared by dividing into a normal control group (Normal control; NC), an ultrafine dust exposure group (PM 2.5 ), and an Ecklonia cava extract diet group after an adaptation period for 1 week. The ultrafine dust group and the Ecklonia cava extract diet group were exposed to ultrafine dust in the whole body exposure chamber, and the normal control group was injected with filtered air. Water extract from E. cava (WEE) was dissolved in drinking water and administered orally at 50, 100, 200 mg/kg of body weight concentration (
5.2 실험동물의 몸무게 변화 및 식이량 개선효과5.2 Effect of weight change and dietary improvement in experimental animals
실험동물의 무게 변화 및 식이량을 측정한 결과는 도 4와 같다. 초미세먼지의 노출로 인한 생체내 신진대사의 변화로 인하여, 노출 8주차부터 PM2.5노출군은 정상대조군 대비 통계적 유의적인 변화가 관찰되기 시작하였다. 특히, 노출 12주차에서 PM2.5노출군 (25.71 g, 6.25 g weight gain)은 정상 대조군 (29.36 g, 9.06 g weight gain) 대비 상대적으로 감소된 몸무게를 나타냈다 (도 4a 및 도 4b). 감태 물 추출물 식이군 (WEE 200; 29.14 g, 8.88 g weight gain)은 정상대조군과 유의적인 수준으로 보호하는 것으로 나타났다. 또한, 노출 12주차에서 PM2.5노출군 (3.96 g/day)은 정상 대조군 (4.44 g/day) 대비 약 10.81% 감소된 식이량를 나타냈다 (도 4c). 감태 물 추출물의 식이는 WEE 100 (4.28 g/day) 과 WEE 200 (4.64 g/day)에서 정상 대조군 수준으로 회복되는 것으로 나타났다.The results of measuring the weight change and dietary amount of the experimental animals are shown in FIG. 4. Due to the change in metabolism in vivo due to exposure to ultrafine dust, statistically significant changes began to be observed in the PM 2.5 exposure group from the 8th week of exposure compared to the normal control group. In particular, at 12 weeks of exposure, the PM 2.5 exposure group (25.71 g, 6.25 g weight gain) showed a relatively reduced body weight compared to the normal control group (29.36 g, 9.06 g weight gain) (FIGS. 4A and 4B). Ecklonia cava water extract diet group (
[실시예 6] 뇌질환 개선효과를 보기위한 동물행동분석[Example 6] Animal behavior analysis to see the effect of improving brain disease
6.1 공간인지능력 평가 실험 (Y-maze)6.1 Spatial cognitive ability evaluation experiment (Y-maze)
공간인지능력을 실험하기 위하여 Y-maze를 실시하였고, 3개의 arm (길이; 33 cm, 높이; 15 cm, 너비; 10 cm)으로 이루어진 검은색 플라스틱으로 제작한 Y-maze를 실험에 사용하였다. 각 arm을 각각 A와 B, C로 정한 후, 8분 동안 마우스가 움직인 경로를 smart 3.0 video tracking system (Panlab, Barcelona, Spain)으로 기록하였다. 변경 행동력 (alter-nation behavior)은 총 통과횟수 (total arm entry) 대비 3개의 서로 다른 arm으로 들어갔을 경우 1점 (actual alternation)을 부여하여 계산하였다.Y-maze was performed to test spatial perception ability, and a Y-maze made of black plastic consisting of three arms (length; 33 cm, height; 15 cm, width; 10 cm) was used in the experiment. Each arm was set to A, B, and C, respectively, and the path of the mouse movement for 8 minutes was recorded with a smart 3.0 video tracking system (Panlab, Barcelona, Spain). Alter-nation behavior was calculated by giving 1 point (actual alternation) when entering 3 different arms compared to the total arm entry.
공간인지력 평가 결과는 모든 그룹에서 arm을 통과한 횟수 (평균 27.00)는 유의적인 차이를 나타내지 않았으며, 이러한 결과는 기본적인 운동능력에는 큰 차이를 나타내지 않는 것으로 나타났다 (도 5a). 반면, PM2.5노출군 (3.96 g/day)에서는 정상 대조군 (4.44 g/day) 대비 공간 인지력 저하가 나타났으며, 감태 물 추출물의 식이 (WEE 50; 60.73%, WEE 100; 64.42%, WEE 200; 61.43%)는 효과적으로 공간인지력을 개선시키는 것으로 나타났다 (도 5a 및 도 5b).The spatial cognitive evaluation results showed no significant difference in the number of passes through the arm (average 27.00) in all groups, and these results showed no significant difference in basic exercise capacity (FIG. 5A). On the other hand, in the PM 2.5 exposure group (3.96 g/day), spatial perception was lowered compared to the normal control group (4.44 g/day), and the diet of Ecklonia delicacy water extract (
6.2 단기 학습 및 기억 능력 평가 실험 (Passive avoidance)6.2 Short-term learning and memory ability evaluation experiment (Passive avoidance)
단기 학습 및 기억 능력을 평가하기 위하여 Passive avoidance 실험을 진행하였고, 2개의 구역 (밝은 챔버 및 어두운 챔버)으로 나누어져 있는 장치를 실험에 사용하였다. 우선, 마우스를 밝은 챔버에서 조명을 켜지 않은 채 1분간 적응시킨 뒤 조명을 켜고 2분 동안 환경을 인지시킨 다음 마우스가 어두운 챔버로 들어가게 되면 전기충격 (0.5 mA, 1초)을 가하였다. 24시간 후, 각각의 마우스를 밝은 챔버에 마우스를 놓고 어두운 챔버로 마우스의 네 발이 모두 들어가는 데 걸리는 시간 (latency time: 머무름 시간)을 최대 300초까지 측정하였다.In order to evaluate short-term learning and memory ability, a passive avoidance experiment was conducted, and a device divided into two zones (bright chamber and dark chamber) was used in the experiment. First, the mouse was acclimated for 1 minute without turning on the light in a bright chamber, then turned on the light and recognized the environment for 2 minutes, and then an electric shock (0.5 mA, 1 second) was applied when the mouse entered the dark chamber. After 24 hours, each mouse was placed in a bright chamber, and the time required for all four feet of the mouse to enter the dark chamber (latency time: retention time) was measured for up to 300 seconds.
단기 학습 및 기억력을 평가한 결과, PM2.5노출군 (26.83 s)에서는 정상 대조군 (260 s) 대비 약 89.68% 감소된 결과를 나타냈으며, 감태 물 추출물 군은 (WEE 50; 94.17 s, WEE 100; 99.33s, WEE 200; 144.67 s) 효과적으로 단기 학습 및 기억력을 개선시키는 것으로 나타났다 (도 5c).As a result of evaluating short-term learning and memory, the PM 2.5 exposure group (26.83 s) showed a decrease of about 89.68% compared to the normal control group (260 s), and the Ecklonia cava extract group (
6.3 장기 학습 및 기억 능력 평가 실험 (Morris water maze)6.3 Long-term learning and memory ability evaluation experiment (Morris water maze)
장기 학습 및 기억 능력을 평가하기 위하여 Morris water maze 실험을 실시하였고, 실험에 사용된 장치는 원형으로 된 수조 (지름 150 cm, 높이 60 cm)에 깨끗한 물을 30 cm 높이로 채운 뒤 (20±2°C), 수조 사분면의 한 구역에 escape platform을 설치하고 식용 오징어 먹물 (Cebesa, Valencia, Spain)을 녹였다. 실험이 시작된 첫 번째 날은 수조에서 마우스가 escape platform이 보이도록 설치한 후, 찾아가는 훈련을 실시하였다. 이 후, 4일 동안은 platform을 수면 아래로 1 cm로 놓고 보이지 않도록 설정한 원형 수조에서 입수하는 위치 (N, S, E, W zone)를 다르게 하고 하루 3번씩 반복하여 진행하였으며 smart 3.0 video tracking system을 이용하여 기록하였다 (hidden trial). 마우스가 60초 안에 platform에 도달하는 경우에는 10초간 platform 위에 머물게 하였으며, platform을 찾지 못할 경우에는 손으로 위치를 안내해주어 platform에 위치하도록 하고 20초간 위치를 인지하도록 하였다. 실험 5일째 (probe trial)에는 platform을 제거하고 working memory를 측정하기 위해 60초간 platform이 있었던 구역에 머무르는 시간을 기록하는 probe test를 진행하였다.Morris water maze experiment was conducted to evaluate long-term learning and memory ability, and the device used in the experiment was filled with clean water to a height of 30 cm (20±2 cm) in a circular water tank (
장기 학습 및 기억력을 평가한 결과에서는 hidden platform 훈련기간동안 모든 그룹에서 찾아가는 시간이 감소되는 경향을 나타냈다 (도 5d). 훈련 4일차에서는 PM2.5노출군 (45.95 s)에서는 정상 대조군 (32.75 s) 대비 찾아가는 시간이 오래 걸리는 것을 확인할 수 있었으며, 감태 물 추출물 식이군 (WEE 200; 37.54 s)은 PM2.5노출군 대비 찾아가는 시간이 감소했음을 확인할 수 있었다. Platform이 있었던 구역에 대한 머무르는 시간을 측정한 결과 (도 5e 및 도 5f)는 PM2.5노출군이 13.60 s로 정상대조군 (41.01s) 대비 약 66.84 % 감소된 결과를 나타냈다. 반면, 감태 물 추출물 식이군 (WEE 200)은 37.54 s의 머무른 시간을 나타냄으로써, 정상대조군와 유사한 수준으로 장기 학습 및 기억력을 개선시키는 것으로 나타났다.In the results of evaluating long-term learning and memory, the time to visit in all groups during the hidden platform training period tended to decrease (FIG. 5D). On the 4th day of training, it was found that the PM 2.5 exposure group (45.95 s) took longer to visit compared to the normal control group (32.75 s), and the Ecklonia water extract diet group (
[실시예 7] 뇌 조직 내 지질과산화 억제 효과[Example 7] Inhibitory effect of lipid peroxidation in brain tissue
뇌 조직에서의 지질과산화 정도를 평가하기 위하여, malondialhehyde (MDA)함량을 측정하였다. 마우스 조직 무게의 10배에 해당하는 PBS를 넣고 균질화한 후 원심분리 (6,000xg, 10분, 4°C) 하여 상등액을 취해 실험에 사용하다. 추출한 마우스 뇌 조직 균질액에 1% phosphoric acid를 혼합한 후 0.67% thiobarbituric acid를 넣고 95°C에서 1시간 동안 반응시켰다. 해당 반응액은 532 nm에서 흡광도를 측정하였으며, MDA 함량은 mg protein 당 μmole의 농도로 표시하였다.To evaluate the degree of lipid peroxidation in brain tissue, the content of malondialhehyde (MDA) was measured. After adding PBS corresponding to 10 times the weight of the mouse tissue, homogenizing, centrifugation (6,000xg, 10 minutes, 4 °C) to take the supernatant and use in the experiment. After mixing 1% phosphoric acid in the extracted mouse brain tissue homogenate, 0.67% thiobarbituric acid was added and reacted at 95 °C for 1 hour. The reaction solution was measured for absorbance at 532 nm, and the MDA content was expressed as the concentration of μmole per mg protein.
뇌 조직에서의 감태 물 추출물 (WEE)의 초미세먼지 유도성 조직의 산화적 손상 지표로써 MDA 함량을 측정한 결과는 도 6과 같다. 뇌 조직에서의 MDA 함량은 PM2.5노출군 (18.71 μmole/mg of protein)은 정상대조군 (13.56 μmole/mg of protein) 대비 증가된 함량을 나타냈으며, 감태 물 추출물 식이군 (WEE 50; 14.28, WEE 100; 12.65, WEE 200; 10.62 μmole/mg of protein)에서는 농도가 증가함에 따라 효과적으로 조직내 지질과산화를 억제하는 것으로 나타났다 (도 6).The results of measuring MDA content as an index of oxidative damage to ultrafine dust-inducing tissues of Ecklonia cava water extract (WEE) in brain tissue are shown in FIG. 6. The MDA content in brain tissue was increased in the PM 2.5 exposure group (18.71 μmole/mg of protein) compared to the normal control (13.56 μmole/mg of protein), and the Ecklonia cava extract diet group (
[실시예 8] 미토콘드리아 기능 개선 효과[Example 8] Mitochondrial function improvement effect
8.1 뇌 조직 내 미토콘드리아 분리8.1 Isolation of mitochondria in brain tissue
뇌 조직에서의 미토콘드리아를 분리하기 위하여 1 mM ethylene glycol tetraacetic acid (EGTA)가 포함된 isolation buffer [215 mM mannitol, 75 mM sucrose, 0.1% BSA, 20 mM HEPES(Na+),pH7.2]를 첨가하여 균질화 한다. 균질화 된 뇌 조직은 원심분리 (1,300xg, 5분, 4°C)하고, 상층액을 다시 원심분리 (13,000xg, 10분, 4°C)하였다. Pellet에 1 mM EGTA와 0.1% digitonin이 포함된 isolation buffer를 첨가하여 5분동안 얼음 위에서 반응시키고, 원심분리 (13,000xg, 10분, 4°C)하였다. Pellet에 isolation buffer를 첨가하여 원심분리 (10,000xg, 15분, 4°C)하여 최종 pellet을 뇌 조직의 미토콘드리아로 활용하여 실험하였다.To separate mitochondria from brain tissue, an isolation buffer containing 1 mM ethylene glycol tetraacetic acid (EGTA) [215 mM mannitol, 75 mM sucrose, 0.1% BSA, 20 mM HEPES(Na + ), pH7.2] was added. To homogenize. The homogenized brain tissue was centrifuged (1,300xg, 5 minutes, 4°C), and the supernatant was centrifuged again (13,000xg, 10 minutes, 4°C). An isolation buffer containing 1 mM EGTA and 0.1% digitonin was added to the pellets, reacted on ice for 5 minutes, and centrifuged (13,000xg, 10 minutes, 4°C). Isolation buffer was added to the pellet, centrifuged (10,000xg, 15 minutes, 4°C), and the final pellet was used as a mitochondria of brain tissue for experiments.
8.2 초미세먼지에 노출된 뇌 조직에서의 미토콘드리아 기능평가 (미토콘드리아 내 Reactive oxygen species; ROS 함량 측정)8.2 Evaluation of mitochondrial function in brain tissue exposed to ultrafine dust (reactive oxygen species in mitochondria; ROS content measurement)
미토콘드리아 ROS 함량은 뇌 조직으로부터 분리된 미토콘드리아 추출물을 KCl-based respiration buffer [125 mM 염화칼륨, 2 mM 인산칼륨, 20 mM HEPES, 1 mM 염화마그네슘, 500μM EGTA, 2.5 mM malate 및 5 mM pyruvate]와 25 μM DCF-DA를 20분간 반응시킨 후, 형광광도계를 이용하여 excitation wave 485 nm와 emission wave 535 nm에서 형광강도를 측정함으로써 평가하였다.For mitochondrial ROS content, the mitochondrial extract isolated from brain tissue was used in a KCl-based respiration buffer [125 mM potassium chloride, 2 mM potassium phosphate, 20 mM HEPES, 1 mM magnesium chloride, 500 μM EGTA, 2.5 mM malate and 5 mM pyruvate] and 25 μM. After reacting DCF-DA for 20 minutes, it was evaluated by measuring the fluorescence intensity at excitation wave 485 nm and emission wave 535 nm using a fluorescence photometer.
감태 추출물의 초미세먼지 노출에 대한 뇌 조직의 미토콘드리아 손상에 대한 기능평가 결과는 도 7과 같다. 뇌 조직에서의 미토콘드리아 ROS 함랑을 측정한 결과 PM2.5노출군 (132.83%)은 정상 대조군 (100.00%) 대비 상대적으로 증가된 결과를 나타냈다. 반면, 감태 물 추출물 식이군 (WEE 200)은 98.10 %으로 미토콘드리아 내 ROS을 효과적으로 억제시키는 것으로 나타났다 (도 7a).The results of functional evaluation of mitochondrial damage in brain tissues in response to exposure to ultrafine dust of Ecklonia cava extract are shown in FIG. 7. As a result of measuring mitochondrial ROS content in brain tissue, the PM 2.5 exposure group (132.83%) showed a relatively increased result compared to the normal control group (100.00%). On the other hand, Ecklonia cava water extract diet group (WEE 200) was found to effectively inhibit ROS in mitochondria at 98.10% (Fig. 7a).
8.3 초미세먼지에 노출된 뇌 조직에서의 미토콘드리아 기능평가 (미토콘드리아 막 전위 측정 Mitochondria membrane potential; MMP)8.3 Evaluation of mitochondrial function in brain tissue exposed to ultrafine dust (measurement of mitochondria membrane potential Mitochondria membrane potential; MMP)
미토콘드리아 막 전위 (MMP) 측정은 분리된 미토콘드리아에 assay 용액 [5 mM pyruvate, 5 mM malate in isolation buffer]과 1 μM 5,5′,6,6′-tetrachloro-1,1′,3,3′-tetraethylbenzimidazolcarbocyanine iodide (JC-1) dye를 black 96 well에서 혼합하여, 암실에서 20분간 반응시킨다. 반응 후, 형광광도계를 이용하여 530 nm (excitation wave) 및 590 nm (emission wave)에서 형광강도를 측정하였다.Mitochondrial membrane potential (MMP) measurement was performed on the isolated mitochondria with an assay solution [5 mM pyruvate, 5 mM malate in isolation buffer] and 1
미토콘드리아 막 전위 (MMP) 측정 결과에서는 PM2.5노출군 (71.82%)이 정상대조군 대비 (100.00%) 감소된 결과를 나타냈고, 감태 물 추출물 식이군 (WEE 50; 72.29%, WEE 100; 84.74%, WEE 200; 83.47%)은 매우 효과적으로 MMP를 개선시키는 것으로 나타났다 (도 7b).In the mitochondrial membrane potential (MMP) measurement results, the PM 2.5 exposure group (71.82%) decreased (100.00%) compared to the normal control group, and the Ecklonia water extract diet group (
8.4 초미세먼지에 노출된 뇌 조직에서의 미토콘드리아 기능평가 (미토콘드리아 내 ATP 함량 측정)8.4 Evaluation of mitochondrial function in brain tissue exposed to ultrafine dust (measurement of ATP content in mitochondria)
미토콘드리아 내 ATP 함량은 분리된 미토콘드리아에 1% TCA 용액을 첨가하여 얼음 위에서 방치한 후, 25 mM sodium acetate buffer (pH 7.4)를 첨가한다. 상층액은 ATP level은 ENLITEN®ATPassaysystemkit(Promega,Madison,WI,USA)를 사용하여 luminometer (Promega)에서 측정하였다.For the ATP content in the mitochondria, a 1% TCA solution was added to the separated mitochondria, left on ice, and then 25 mM sodium acetate buffer (pH 7.4) was added. The ATP level of the supernatant was measured on a luminometer (Promega) using ENLITEN ® ATPassaysystemkit (Promega, Madison, WI, USA).
미토콘드리아 ATP 함량 측정 결과는 PM2.5노출군 (1.86 pmole/mg of protein, 약 44.48 % 감소)에서 정상대조군 (3.35 pmole/mg of protein) 대비 현저히 감소된 함량을 나타냈다. 특히, 감태 물 추출물 식이는 (WEE 200; 5.36 pmole/mg of protein) 뇌 조직에서의 미토콘드리아 기능개선을 통하여 효과적으로 ATP 함량을 증가시키는 것으로 나타났다 (도 7c).The result of measuring mitochondrial ATP content was significantly reduced in the PM 2.5 exposure group (1.86 pmole/mg of protein, about 44.48% reduction) compared to the normal control (3.35 pmole/mg of protein). In particular, the diet of Ecklonia cava water extract (
8.5 초미세먼지에 노출된 뇌 조직에서의 미토콘드리아 기능평가 (웨스턴블랏법을 활용한 단백질 발현측정)8.5 Evaluation of mitochondrial function in brain tissue exposed to ultrafine dust (protein expression measurement using Western blot method)
뇌 조직에서의 단백질 발현은 1% protease inhibitor cocktails (Thermo Fisher Scientific, Rockford, IL, USA)이 함유되어 있는 ProtinExTMAnimalcell/tissue(GeneAllBiotechnology,Seoul,Korea)로 균질화 시켰다. 균질액은 원심분리 (13,000xg, 12분, 4°C) 시킨 후, 상층액은 Bradford 시약 (Bio-rad)을 사용하여 동량의 단백질이 되도록 맞추었다. 이 후, Laemelli buffer (5X)를 첨가하여 95°C에서 5분간 반응시켜, sodium dodecyl sulfate polyacrylamide gel (SDS-PAGE)을 통하여 분리하다. 분리된 단백질은 polyvinylidene difluoride membrane (Millipore, Billerica, MA, USA)으로 transfer시켜 5% 탈지유를 사용하여 blocking 하였다. Blocking 시킨 membrane은 4°C에서 1:1000로 희석한 1차 항체 (Santa Cruz Biotechnology, Santa Cruz, CA, USA)와 함께 반응시켰다. Overnight 후, membrane을 1:5000로 희석한 2차 항체와 함께 실온에서 2시간 동안 반응시켰고, ProNA™ ECL Ottimo (TransLab, Daejeon, Korea)를 첨가하여 ChemiDoc (Korea Biomics, Seoul, Korea)를 통해 검출하였다. Protein expression in brain tissue was homogenized with ProtinEx TM Animalcell/tissue (GeneAll Biotechnology, Seoul, Korea) containing 1% protease inhibitor cocktails (Thermo Fisher Scientific, Rockford, IL, USA). The homogenate was centrifuged (13,000xg, 12 minutes, 4°C), and the supernatant was adjusted to obtain the same amount of protein using Bradford reagent (Bio-rad). After that, Laemelli buffer (5X) was added and reacted at 95°C for 5 minutes, followed by separation through sodium dodecyl sulfate polyacrylamide gel (SDS-PAGE). The separated protein was transferred to a polyvinylidene difluoride membrane (Millipore, Billerica, MA, USA) and blocked using 5% skim milk. The blocked membrane was reacted with the primary antibody (Santa Cruz Biotechnology, Santa Cruz, CA, USA) diluted 1:1000 at 4°C. After overnight, the membrane was reacted for 2 hours at room temperature with a secondary antibody diluted 1:5000, and ProNA™ ECL Ottimo (TransLab, Daejeon, Korea) was added and detected through ChemiDoc (Korea Biomics, Seoul, Korea). I did.
뇌 조직에서의 초미세먼지 노출로 인한 초미세먼지 유도성 미토콘드리아 관련 apoptosis 단백질의 변화를 확인하였고, 폐 조직의 결과와 유사한 패턴을 나타냈다. 감태 물 추출물 식이군 (WEE 200)은 초미세먼지 유도성 미토콘드리아 관련 apoptosis 단백질(p-AMPKα, p-Akt, Bcl-2, mitochondrial cytochrome C, and cleaved caspase-3)들을 효과적으로 조절하는 것으로 나타났고, 초미세먼지 유도성 미토콘드리아 기능저하를 개선시킴으로써 뇌 조직을 효과적으로 보호하는 것으로 나타났다 (도 7d 및 도 7e).Changes in ultrafine dust-inducing mitochondrial-related apoptosis proteins due to exposure to ultrafine dust in brain tissue were confirmed, and a pattern similar to that of lung tissue was shown. Ecklonia cava water extract diet group (WEE 200) was shown to effectively regulate ultrafine dust-inducing mitochondrial-related apoptosis proteins (p -AMPKα, p -Akt, Bcl-2, mitochondrial cytochrome C, and cleaved caspase-3). It has been shown to effectively protect brain tissue by improving ultrafine dust-induced mitochondrial hypofunction (FIGS. 7D and 7E ).
[실시예 9] 뇌 조직에서의 인지기능 저하와 관련된 단백질의 변화 측정[Example 9] Measurement of protein changes related to cognitive decline in brain tissue
초미세먼지에 노출된 마우스의 뇌 조직에서의 인지기능 저하와 관련된 단백질의 변화를 측정하였고, 그 결과는 도 8과 같다. 뇌 조직내 산화적 스트레스의 발생은 JNK의 인산화 (p-JNK)를 유발함으로써 Aβ을 분해하는 효소인 IDE의 발현은 감소시켜 Aβ 생성과 축적을 유도하는 것으로 알려져 있다. 이러한 경로에서 초미세먼지는 Aβ을 직접적으로 영향을 주지는 않았으나, amyloid precursor protein (APP)의 발현시키는 것으로 나타났다 (도 8a 및 도 8b). 또한, p-JNK는 tau 인산화를 유도함으로써, 세포 내부의 neurofibrillary tangles (NFTs)의 생성을 유도하고 이는 신경세포의 기능 저하 및 세포의 사멸을 유도함으로써 인지기능 저하를 유도하게 된다. 초미세먼지 노출에 의하여 APP의 발현 및 tau 생성의 증가는 인지기능 저하에 영향을 주었을 것으로 판단되며, 감태 물 추출물 식이군 (WEE 200)은 Aβ 생성 및 tau 과인산화 signaling pathway에서의 단백질을 효과적으로 조절하는 것으로 확인되었다. 또한, brain-derived neurotrophic factor (BDNF)은 중추신경계에서 신경세포의 분화/생존에 관여할 뿐만 아니라 synapse plasticity에 영향을 미치는 중요한 단백질로 보고되고 있는데, 초미세먼지는 이러한 BDNF의 저하를 유도하는 것으로 나타났다. 반면 감태 물 추출물 식이군 (WEE 200)은 BDNF를 상당한 수준으로 회복시켜 주는 것으로 나타났다.Changes in proteins related to cognitive decline in brain tissues of mice exposed to ultrafine dust were measured, and the results are shown in FIG. 8. Oxidative stress in brain tissue is known to induce phosphorylation of JNK (p- JNK), thereby reducing the expression of IDE, an enzyme that degrades Aβ, leading to Aβ production and accumulation. In this pathway, ultrafine dust did not directly affect Aβ, but was found to express amyloid precursor protein (APP) (FIGS. 8A and 8B ). In addition, by inducing tau phosphorylation, p- JNK induces the generation of neurofibrillary tangles (NFTs) inside the cell, which induces a decrease in neuronal function and cell death, thereby inducing cognitive decline. It is thought that the increase in APP expression and tau production by exposure to ultrafine dust may have an effect on cognitive decline, and the Ecklonia cava extract diet group (WEE 200) effectively regulates proteins in the Aβ production and tau hyperphosphorylation signaling pathways. It was confirmed to be. In addition, brain-derived neurotrophic factor (BDNF) is reported to be an important protein not only involved in the differentiation/survival of neurons in the central nervous system, but also affecting synapse plasticity. appear. On the other hand, Ecklonia cava water extract diet group (WEE 200) was found to recover BDNF to a significant level.
[실시예 10] 초미세먼지 유도성 염증반응에 대한 조직보호 효과 (뇌 조직에서의 항염증 효과를 알아보기 위한 사이토카인 분석)[Example 10] Tissue protective effect on ultrafine dust-induced inflammatory reaction (cytokine analysis to determine anti-inflammatory effect in brain tissue)
뇌 조직 내 cytokine (IL-6, TNF-α, IFN-γ, and IL-10) 함량은 mouse magnetic luminex assays kit (LXSAMSM-4)를 사용하였으며, MAGPIXⓡ instrument (Luminex Corporation, Austin, TX, USA) 분석장비와 xMAP technology and xPONENT 4.2 software를 활용하여 분석하였다.The content of cytokine (IL-6, TNF-α, IFN-γ, and IL-10) in brain tissue was measured using a mouse magnetic luminex assays kit (LXSAMSM-4), and MAGPIX ⓡ instrument (Luminex Corporation, Austin, TX, USA). ) Analysis was performed using analysis equipment and xMAP technology and xPONENT 4.2 software.
뇌 조직에서의 초미세먼지 유도성 염증발생 경로는 TLR-4의 발현은 nuclear factor (NF)-κB 경로의 활성화를 유도하고, 이는 다시 NF-κB 경로 활성화 및 inflammasome의 형성을 유도하여 염증성 cytokine (IL-1β, IL-6 및 IFN-γ)들의 방출을 유도함으로써 뇌조직의 기능저하를 나타낼 수 있는 결과를 나타냈다 (도 9a, 도 9b 및 도 9c). 반면, 감태 물 추출물 식이군 (WEE 200)은 초미세먼지 유도성 염증반응에 대하여 효과적으로 NF-κB 경로의 활성 및 Inflammasome의 형성 억제를 통하여, 염증성 cytokine (IL-1β, IL-6 및 IFN-γ)들을 효과적으로 억제하는 것으로 나타났다.In brain tissue, the expression of TLR-4 induces the activation of the nuclear factor (NF)-κB pathway, which in turn induces the activation of the NF-κB pathway and the formation of inflammasomes, resulting in inflammatory cytokines ( IL-1β, IL-6 and IFN-γ) by inducing the release of) showed a result that can indicate the deterioration of the function of the brain tissue (Fig. 9a, Fig. 9b and Fig. 9c). On the other hand, Ecklonia cava water extract diet group (WEE 200) effectively inhibits the NF-κB pathway and the formation of inflammasome against ultrafine dust-induced inflammatory reactions, and inflammatory cytokines (IL-1β, IL-6 and IFN-γ ) Have been shown to effectively inhibit.
[실시예 11] Cholinergic system 활성 측정[Example 11] Cholinergic system activity measurement
11.1 Acetylcholinesterase (AChE) 활성 측정11.1 Acetylcholinesterase (AChE) activity measurement
마우스의 뇌를 적출하여 뇌 조직 무게의 10배에 해당하는 PBS를 넣고 bullet blander (Next Advance Inc., Averill Park USA)로 균질화하여 원심분리 하였으며 (14,000xg, 30분, 4°C), 그 상등액을 실험에 사용하였다. AChE 활성은 상등액 5 μL와 50 mM sodium phosphate buffer 65 μL를 혼합하고 37°C에서 15분간 pre-incuba-tion 한 뒤, 혼합물에 Ellman's reaction mixture 70 μL를 첨가하여 405 nm에서 10분 동안 2분 간격으로 흡광도를 측정하였다. 마우스 뇌 조직의 AChE 활성은 정상대조군을 100 %로 하여 비교한 % 활성으로 나타내었다.The brain of the mouse was excised, added PBS equivalent to 10 times the weight of the brain tissue, homogenized with a bullet blander (Next Advance Inc., Averill Park USA) and centrifuged (14,000xg, 30 minutes, 4°C), and the supernatant Was used in the experiment. AChE activity was obtained by mixing 5 μL of the supernatant and 65 μL of 50 mM sodium phosphate buffer, pre-incuba-tioning for 15 minutes at 37°C, and then adding 70 μL of Ellman's reaction mixture to the mixture at 405 nm for 10 minutes at 2 minute intervals. The absorbance was measured as. The AChE activity of the mouse brain tissue was expressed as% activity compared with the normal control group as 100%.
11.2 Acetylcholine (ACh) 함량 측정11.2 Acetylcholine (ACh) content measurement
ACh 함량은 alkaline hydroxylamine reagent [3.5 N sodium hydroxide, 2 M hydroxylamine in HCl]를 첨가하고 1분 동안 상온에서 반응시킨 후, 0.5 N HCl (pH 1.2)과 0.37 M FeCl3in0.1NHCl을 첨가하고 540 nm 파장에서 흡광도를 측정하였다.For ACh content, alkaline hydroxylamine reagent [3.5 N sodium hydroxide, 2 M hydroxylamine in HCl] was added and reacted at room temperature for 1 minute, then 0.5 N HCl (pH 1.2) and 0.37 M FeCl 3 in0.1 NHCl were added and 540 nm. The absorbance was measured at wavelength.
11.3 콜린성 시스템 (cholinergic system) 평가11.3 Cholinergic system evaluation
뇌 조직에서의 콜린성 시스템을 평가한 결과는 초미세먼지 노출 (120.51%)에 의하여 정상대조군 (100.00%) 대비 AChE의 활성이 증가된 결과를 나타내었다 (도 10a). 또한, ChAT and AChR-α3 발현 (도 10b 및 도 10c)의 감소는 최종적으로 ACh 함량 (정상 대조군; 5.39 nmole/mg of protein, PM2.5노출군; 4.07 nmole/mg of protein)을 감소시키는 것으로 나타났다 (도 10d). 이러한 결과는 초미세먼지 노출에 의하여 뇌 조직에서 콜린성 시스템의 기능저하가 유도되었으며, 인지기능 저하에 영향을 미쳤을 것으로 판단된다. 반면, 초미세먼지 유도성 콜린성 시스템 장애는 감태 물 추출물 식이에 의하여 AChE 활성 억제 (WEE 200; 96.43%), ChAT and AChR-α3 발현 증가를 통하여 최종적으로 ACh 함량 (WEE 200; 5.67 nmole/mg of protein)을 증가시켜 콜린성 시스템의 기능을 효과적으로 회복시킬 수 있는 것으로 판단된다.The result of evaluating the cholinergic system in the brain tissue showed the result of increasing the activity of AChE compared to the normal control group (100.00%) by exposure to ultrafine dust (120.51%) (FIG. 10A). In addition, it was found that the decrease in ChAT and AChR-α3 expression (FIGS. 10b and 10c) ultimately reduced ACh content (normal control; 5.39 nmole/mg of protein, PM 2.5 exposure group; 4.07 nmole/mg of protein). (Fig. 10d). These results suggest that the reduction of cholinergic system function in the brain tissue was induced by the exposure to ultrafine dust, and it is thought that the reduction of cognitive function was influenced. On the other hand, ultrafine dust-induced cholinergic system disorders were ultimately affected by inhibition of AChE activity (
[실시예 12] 감태 추출물의 주요생리활성 물질 분석[Example 12] Analysis of major physiologically active substances of Ecklonia cava extract
12.1 총 polysaccharide 함량 측정12.1 Determination of total polysaccharide content
감태 물 추출물에 함유되어 있는 총 polysaccharide 함량은 페놀-황산 (Phenol-sulfuric acid)법을 변형하여 측정하였다. 추출물에 5% phenol 용액, 진한 황산을 넣어 20분간 실온에 방치한 후 470 nm에서 흡광도를 측정하였다. 표준물질 glucose 이용하여 표준곡선을 작성하고, 이에 대입하고 계산하여 나타냈다.The total polysaccharide content contained in the Ecklonia cava water extract was measured by modifying the phenol-sulfuric acid method. A 5% phenol solution and concentrated sulfuric acid were added to the extract and left at room temperature for 20 minutes, and the absorbance was measured at 470 nm. A standard curve was prepared using the standard substance glucose, substituted for it, and calculated.
감태 물 추출물의 총 polysaccharide 함량과 구성성분 (sulfate 및 구성당)을 측정한 결과는 하기 표 1과 같다. 총 polysaccharide 함량은 34.26%으로 나타났다.The results of measuring the total polysaccharide content and constituents (sulfate and constituent sugar) of Ecklonia cava water extract are shown in Table 1 below. The total polysaccharide content was found to be 34.26%.
FucoseFucose
RhamnoseRhamnose
GalactoseGalactose
GlucoseGlucose
XyloseXylose
OthersOthers
12.2 평균 분자량 (Molecular weight; Mw) 측정 12.2 Molecular weight (Mw) measurement
감태 물 추출물의 평균 분자량은 gel permeation chromatography (HLC-8320, Tosoh Bioscience, Stuttgart, Germany)를 이용하여 측정하였다. 시료는 증류수에 용해시켜 0.45 μm Nylon filter (Millipore Co., Bedford, MA, USA)로 여과하였다. Tskgel guard PWxl, 2 x TSKgel GMPWxl, TSKgel G2500PWxl (7.8 x 300 mm, Tosoh Bioscience, Stuttgart, Germany)가 결합된 column을 사용하여 0.1 M NaNO3를 이동상으로 하여 1 mL/min으로 RI-detector로 분석하였다.The average molecular weight of the Ecklonia cava water extract was measured using gel permeation chromatography (HLC-8320, Tosoh Bioscience, Stuttgart, Germany). The sample was dissolved in distilled water and filtered through a 0.45 μm Nylon filter (Millipore Co., Bedford, MA, USA). Tskgel guard PWxl, 2 x TSKgel GMPWxl, TSKgel G2500PWxl (7.8 x 300 mm, Tosoh Bioscience, Stuttgart, Germany) was analyzed by RI-detector at 1 mL/min using 0.1 M NaNO 3 as a mobile phase using a combined column. .
감태 물 추출물의 총 polysaccharide 함량과 구성성분 (sulfate 및 구성당)을 측정한 결과는 상기 표 1과 같다. 평균 분자량은 160.13 kDa로 나타났다.The results of measuring the total polysaccharide content and constituents (sulfate and constituent sugar) of the Ecklonia cava water extract are shown in Table 1 above. The average molecular weight was found to be 160.13 kDa.
12.3 Sulfate 함량 측정12.3 Sulfate content measurement
시험용액 0.2 mL에 4% TCA용액 3.8 mL 및 BaCl2-gelatin시약 1 mL를 첨가하여 교반하고 20분간 방치한 후 360nm에서 흡광도를 측정하였다. 표준 검량선은 K2SO4로 작성하여 황산기 함량을 정량하였다.To 0.2 mL of the test solution, 3.8 mL of 4% TCA solution and 1 mL of BaCl 2 -gelatin reagent were added, stirred, and allowed to stand for 20 minutes, and the absorbance was measured at 360 nm. The standard calibration curve was prepared as K 2 SO 4 and the sulfuric acid group content was quantified.
감태 물 추출물의 총 polysaccharide 함량과 구성성분 (sulfate 및 구성당)을 측정한 결과는 상기 표 1과 같다. Sulfate 함량은 17.03%로 나타났다.The results of measuring the total polysaccharide content and constituents (sulfate and constituent sugar) of the Ecklonia cava water extract are shown in Table 1 above. The sulfate content was found to be 17.03%.
12.4 구성당 분석12.4 Analysis per composition
감태 물 추출물에 함유되어 있는 구성당 분석은 HPAEC-PAD system (Dionex, Sunnyvale, CA, USA)를 이용하여 측정하였다. 시료는 Trifluoroacetic acid로 가수분해한 후, 동결건조하고 증류수에 용해시켜 0.45 μm membrane filter (Millipore Co., Bedford, MA, USA)로 여과하였다. CarboPacTM PA1 column (0.4 X 25 cm, Dionex, Sunnyvale, CA, USA)을 사용하여 18 mM NaOH/200 mM NaOH를 이동상으로 하여 1 mL/min으로 RI detector로 분석하였다. 구성당의 동정·확인은 당류 표준품 (Fucose, Rhamnose, Galactose, Glucose, Xylose)의 머무름시간 (retention time, Rt)과 비교·검증하여 나타내었다.Constituent sugar analysis contained in the Ecklonia cava water extract was measured using the HPAEC-PAD system (Dionex, Sunnyvale, CA, USA). The sample was hydrolyzed with Trifluoroacetic acid, lyophilized, dissolved in distilled water, and filtered through a 0.45 μm membrane filter (Millipore Co., Bedford, MA, USA). Using a CarboPacTM PA1 column (0.4 X 25 cm, Dionex, Sunnyvale, CA, USA), 18 mM NaOH/200 mM NaOH was used as a mobile phase and analyzed with an RI detector at 1 mL/min. The identification and confirmation of constituent sugars were shown by comparing and verifying the retention time (Rt) of saccharide standards (Fucose, Rhamnose, Galactose, Glucose, Xylose).
감태 물 추출물의 총 polysaccharide 함량과 구성성분 (sulfate 및 구성당)을 측정한 결과는 상기 표 1과 같다. 상대적인 구성당의 비율은 xylose (48.97%) > rhamnose (16.03%) > fructose (9.76%) > glucose (6.65%) > galactose (6.53%) 순으로 나타났다.The results of measuring the total polysaccharide content and constituents (sulfate and constituent sugar) of the Ecklonia cava water extract are shown in Table 1 above. The relative ratio of constituent sugars was in the order of xylose (48.97%)> rhamnose (16.03%)> fructose (9.76%)> glucose (6.65%)> galactose (6.53%).
12.5 페놀성 화합물 분석12.5 Phenolic Compound Analysis
감태 추출물의 주요 생리활성 물질을 동정하기 위해 UPLC IMS-QTOF/MS (Vion, Waters, Milford, MA, USA)를 이용하여 분석하였으며. 시료는 메탄올에 용해한 후 0.2 μm filter를 이용하여 여과하였다. 컬럼은 C18 column (100x2.1 mm, 3.5 μm, Agilent, Santa Clara, CA, USA)을 사용하였으며, 이동상 용매로는 0.1% formic acid가 혼합된 3차 증류수 (A)와 acetonitrile (B)을 사용하였고, B 용매의 비율 조건은 다음과 같다: 0.1-25% 0-2분, 25-50% 2-8분으로 총 8분간 분석하였다. Electrospray ionization (ESI)의 negative ion 모드를 사용하여 다음 조건으로 수행되었다: 시료 온도, 100°C; desolvation line 온도. 400°C; 램프 충돌 에너지. 10-30 v; 모세관 전압, 2.5 kV. 검출된 페놀 화합물은 50-1500 m/z 범위 내에서 분석되었다.In order to identify the main physiologically active substances of Ecklonia cava extract, it was analyzed using UPLC IMS-QTOF/MS (Vion, Waters, Milford, MA, USA). The sample was dissolved in methanol and filtered using a 0.2 μm filter. C18 column (100x2.1 mm, 3.5 μm, Agilent, Santa Clara, CA, USA) was used as the column, and tertiary distilled water (A) and acetonitrile (B) mixed with 0.1% formic acid were used as the mobile phase solvent. And, the conditions of the ratio of the solvent B were as follows: 0.1-25% 0-2 minutes, 25-50% 2-8 minutes were analyzed for a total of 8 minutes. Electrospray ionization (ESI) was performed under the following conditions using the negative ion mode: sample temperature, 100°C; desolvation line temperature. 400°C; Lamp collision energy. 10-30 v; Capillary voltage, 2.5 kV. The detected phenolic compounds were analyzed within the range of 50-1500 m/z.
감태 추출물의 주요한 생리활성물질로 페놀성 화합물을 분석한 결과는 도 8과 표 2와 같다. 감태 물 추출물의 주요 페놀성 화합물들은 phloroglucinol을 기본구조로 하는 phlorotannin 계열들의 물질 (Tetraphloroetiol isomer, Eckol, 2′-phloroeckol, 6′6′-bieckol, dieckol, phlorofuroeckol A, 2,7″-phloroglucinol 6,6′-bieckol, 974-A)들이 검출되었다. 그 중, Peak 1 (2.60 min); tetraphloroetiol isomer (phloroglucinol tetramer; m/z 497.11278; 327, 265, 231, 139) 과 Peak 4 (3.25 min); 2′-phloroeckol (m/z 495.09875; 477, 387, 263, 244, 231, 229, 201)이 가장 높은 함량을 가지는 것으로 분석되었다.The results of analyzing the phenolic compound as the main physiologically active substance of the Ecklonia cava extract are shown in FIGS. The main phenolic compounds of Ecklonia cava water extract are substances of the phlorotannin family (Tetraphloroetiol isomer, Eckol, 2′-phloroeckol, 6′6′-bieckol, dieckol, phlorofuroeckol A, 2,7″-
[M-H] [M-H]
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[실시예 13] 통계처리[Example 13] Statistical processing
모든 실험은 반복 실행 후, mean±SD로 나타냈다. 실험 결과의 통계적 유의성은 SAS software (version 9.1, SAS Institute Inc., Cary, NC, USA)를 이용하여 평균값에 대한 유의성 검증은 one-way analysis of variance (ANOVA)에 의하여 계산되었으며, 각 그룹 간의 유의성은 Duncan의 다중범위검정법 (Duncan’s new multiple-range test)으로 유의차를 5% 수준 (p<0.05)에서 검증하였다.All experiments were expressed as mean±SD after repeated runs. The statistical significance of the experimental results was calculated by one-way analysis of variance (ANOVA) using SAS software (version 9.1, SAS Institute Inc., Cary, NC, USA). Was verified at the 5% level (p <0.05) with Duncan's new multiple-range test.
이제까지 본 발명에 대하여 그 바람직한 실시 예들을 중심으로 살펴보았다.So far, the present invention has been looked at around its preferred embodiments.
본 발명이 속하는 기술 분야에서 통상의 지식을 가진 자는 본 발명이 본 발명의 본질적인 특성에서 벗어나지 않는 범위에서 변형된 형태로 구현될 수 있음을 이해할 수 있을 것이다. 그러므로 개시된 실시 예들은 한정적인 관점이 아니라 설명적인 관점에서 고려되어야 한다. 본 발명의 범위는 전술한 설명이 아니라 특허청구 범위에 나타나 있으며, 그와 동등한 범위 내에 있는 모든 차이점은 본 발명에 포함된 것으로 해석되어야 할 것이다.Those of ordinary skill in the art to which the present invention pertains will be able to understand that the present invention may be implemented in a modified form without departing from the essential characteristics of the present invention. Therefore, the disclosed embodiments should be considered from a descriptive point of view rather than a limiting point of view. The scope of the present invention is shown in the claims rather than the above description, and all differences within the scope equivalent thereto should be construed as being included in the present invention.
Claims (17)
상기 추출물은 물 또는 유기용매 추출법으로 추출되는 것을 특징으로 하는, 미세먼지로 인한 뇌질환 예방 및 개선용 건강기능성식품 조성물.The method of claim 1,
The extract is a health functional food composition for preventing and improving brain diseases due to fine dust, characterized in that the extract is extracted by water or organic solvent extraction method.
상기 유기용매 추출법은 50 내지 80% 에탄올을 이용한 것을 특징으로 하는, 미세먼지로 인한 뇌질환 예방 및 개선용 건강기능성식품 조성물.The method of claim 2,
The organic solvent extraction method is a health functional food composition for preventing and improving brain diseases due to fine dust, characterized in that using 50 to 80% ethanol.
상기 뇌질환은 뇌 신경 질환인 것을 특징으로 하며, 상기 뇌 신경 질환은 뇌졸중, 알츠하이머 병, 치매 및 파킨슨병 중 어느 하나인 것인, 미세먼지로 인한 뇌질환 예방 및 개선용 건강기능성식품 조성물.The method of claim 1,
The brain disease is characterized in that the brain neurological disease, the brain neurological disease is any one of stroke, Alzheimer's disease, dementia and Parkinson's disease, health functional food composition for preventing and improving brain diseases caused by fine dust.
상기 조성물은 뇌 조직 내 ABTS 라디칼 소거 활성 또는 DPPH 라디칼 소거 활성이 증가된 것을 특징으로 하는, 미세먼지로 인한 뇌질환 예방 및 개선용 건강기능성식품 조성물.The method of claim 1,
The composition is characterized in that the ABTS radical scavenging activity or DPPH radical scavenging activity in the brain tissue is increased, the health functional food composition for preventing and improving brain diseases caused by fine dust.
상기 조성물은 뇌 조직 내 지방질과산화물인 말론디알데히드 (Malondialdehyde, MDA)의 생성을 억제하는 효과를 가지는 것인, 미세먼지로 인한 뇌질환 예방 및 개선용 건강기능성식품 조성물.The method of claim 1,
The composition is a health functional food composition for preventing and improving brain diseases due to fine dust, which has an effect of inhibiting the production of malondialdehyde (MDA), which is a fat peroxide in brain tissue.
상기 조성물은 뇌 조직 내 활성산소 (reactive oxygen species, ROS)의 생성을 억제시키는 효과를 가지는 것인, 미세먼지로 인한 뇌질환 예방 및 개선용 건강기능성식품 조성물.The method of claim 1,
The composition is a health functional food composition for preventing and improving brain diseases due to fine dust, which has an effect of inhibiting the production of reactive oxygen species (ROS) in brain tissue.
상기 조성물은 뇌 조직 내 세포사멸을 억제시키는 효과를 가지는 것인, 미세먼지로 인한 뇌질환 예방 및 개선용 건강기능성식품 조성물.The method of claim 1,
The composition is a health functional food composition for preventing and improving brain diseases due to fine dust, which has an effect of inhibiting apoptosis in brain tissue.
상기 조성물은 뇌 조직 내 염증반응에 대한 조직보호 효과를 가지는 것인, 미세먼지로 인한 뇌질환 예방 및 개선용 건강기능성식품 조성물.The method of claim 1,
The composition is a health functional food composition for preventing and improving brain diseases due to fine dust, which has a tissue protective effect against inflammatory reactions in brain tissue.
상기 조성물은 미세먼지로 인한 공간인지력 저하를 개선시키는 것을 특징으로 하는, 미세먼지로 인한 뇌질환 예방 및 개선용 건강기능성식품 조성물.The method of claim 1,
The composition is a health functional food composition for preventing and improving brain diseases due to fine dust, characterized in that to improve the reduction of spatial perception due to fine dust.
상기 조성물은 미세먼지로 인해 저하된 단기 학습 및 단기 기억력을 개선시키는 것을 특징으로 하는, 미세먼지로 인한 뇌질환 예방 및 개선용 건강기능성식품 조성물.The method of claim 1,
The composition is a health functional food composition for preventing and improving brain diseases due to fine dust, characterized in that to improve short-term learning and short-term memory degraded due to fine dust.
상기 조성물은 미세먼지로 인해 저하된 장기 학습 및 장기 기억력을 개선시키는 것을 특징으로 하는, 미세먼지로 인한 뇌질환 예방 및 개선용 건강기능성식품 조성물.The method of claim 1,
The composition is a health functional food composition for preventing and improving brain diseases due to fine dust, characterized in that to improve long-term learning and long-term memory deteriorated due to fine dust.
상기 조성물은 미세먼지로 인해 뇌 조직에서의 인지기능 저하를 개선시키는 것을 특징으로 하는, 미세먼지로 인한 뇌질환 예방 및 개선용 건강기능성식품 조성물.The method of claim 1,
The composition is a health functional food composition for preventing and improving brain diseases due to fine dust, characterized in that to improve the cognitive function decline in the brain tissue due to fine dust.
상기 조성물은 미세먼지로 인한 뇌 조직에서 콜린성 시스템의 기능저하를 개선시키는 것을 특징으로 하는, 미세먼지로 인한 뇌질환 예방 및 개선용 건강기능성식품 조성물.The method of claim 1,
The composition is a health functional food composition for preventing and improving brain diseases due to fine dust, characterized in that to improve the deterioration of the function of the cholinergic system in the brain tissue due to fine dust.
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