KR20180114267A - Pharmaceutical composition for preventing or treating Parkinson's disease comprising Juniperus chinensis extract or Juniperus chinensis-derived compound - Google Patents
Pharmaceutical composition for preventing or treating Parkinson's disease comprising Juniperus chinensis extract or Juniperus chinensis-derived compound Download PDFInfo
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- KR20180114267A KR20180114267A KR1020170045239A KR20170045239A KR20180114267A KR 20180114267 A KR20180114267 A KR 20180114267A KR 1020170045239 A KR1020170045239 A KR 1020170045239A KR 20170045239 A KR20170045239 A KR 20170045239A KR 20180114267 A KR20180114267 A KR 20180114267A
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Abstract
Description
본 발명은 향나무 추출물 또는 향나무 유래 화합물을 포함하는 파킨슨 병 예방 또는 치료용 약학 조성물에 관한 것으로서, 보다 구체적으로는, 향나무 추출물 또는 향나무로부터 분리될 수 있는 위드롤(widdrol) 또는 세드롤(cedrol)을 유효성분으로 포함하는 파킨슨 병 예방 또는 치료용 약학 조성물 또는 건강기능식품에 관한 것이다.The present invention relates to a pharmaceutical composition for preventing or treating Parkinson's disease, which comprises a fragrant extract or a fescue-derived compound. More specifically, the present invention relates to a pharmaceutical composition for preventing or treating Parkinson's disease, comprising a widdrol extract or a cedrol, The present invention relates to a pharmaceutical composition or a health functional food for preventing or treating Parkinson's disease.
파킨슨 병은 흑질 치밀부(substantia nigra pars compacta, SNc)에서 도파민작동성 뉴런의 신경퇴화가 특징으로써, 이는 선조체(striatum)에서 점차 도파민의 고갈을 일으킨다. 파킨슨 병의 특징은 기저핵 순환의 균형을 망가뜨리고 운동뉴런의 제 기능을 못하게 하여, 경직(rigidity), 진전(tremor), 운동불능(akinesia)를 일으킨다. 50대 이상의 인구의 1~5 %가 두 번째로 가장 흔하게 겪는 신경퇴화 질병이다. Parkinson 's disease is characterized by neurodegeneration of dopaminergic neurons in the substantia nigra pars compacta (SNc), which causes gradual depletion of dopamine in the striatum. Parkinson's features break down the balance of the basal ganglia and disrupt the functioning of motor neurons, causing rigidity, tremor, and akinesia. 1-5% of the population over 50 is the second most common neurodegenerative disease.
파킨슨 병의 궁극적인 원인은 아직 밝혀지지 않은 상황이나 정상인의 중뇌의 흑질(substantia nigra) 부위의 신경세포에서 만들어지는 뇌의 신경전달 물질인 도파민(dopamine)의 결핍으로 인해 여러 증상들이 나타나는 것으로 알려져있다.The ultimate cause of Parkinson's disease is unknown, but it is known that many symptoms occur due to dopamine deficiency, which is a neurotransmitter in the brain of neurons in the substantia nigra of the normal brain .
뇌의 흑질에 분포하는 신경세포에서 생성된 도파민은 선조체(corpus striatum)를 포함하는 뇌의 기저핵(basal ganglia)과 연결된다. 기저핵은 뇌의 운동피질 및 기타 여러 부위와 복잡하게 연결되어 있어 인체의 운동을 부드럽고 조화롭게 그리고 정확하게 수행할 수 있도록 해주는 매우 중요한 부위이다. 이러한 도파민성 신경의 손상에 의하여 결과적으로 기저핵 도파민성 신경 말단에서 유리되는 도파민의 결핍이 파킨슨 병에서 나타나는 운동성 장애의 주요 원인이다.Dopamine produced in neurons distributed in the black matter of the brain is connected to the basal ganglia of the brain, including the corpus striatum. The basal ganglia is a complex part of the motor cortex and many other parts of the brain, making it a very important part of the body that enables smooth, harmonious and accurate exercise. The consequence of this dopaminergic neuronal injury is the deficiency of dopamine, which is consequently liberated from the basal ganglionic dopaminergic nerve endings, which is a major cause of motor impairment in Parkinson's disease.
파킨슨 병의 원인, 즉, 무엇 때문에 흑질의 신경세포가 파괴되는가에 대하여 아직 정확한 해답이 없으나, 이를 규명하기 위하여 활발한 연구가 진행되고 있다. 바이러스성 뇌염 등 감염설, 면역기전이 관계된다는 면역설, 선천적으로 그 기질을 타고난다는 유전설, 유리기가 생성되어 신경세포를 파괴한다는 설, 신경독성 물질의 중독설, 그리고 도파민의 생성 및 대사과정에 문제가 있다는 설 등이 있으나 아직 파킨슨 병 전체를 설명하기에는 부족한 점이 많다.There is no definite answer to the cause of Parkinson's disease, namely, what causes black nerve cells to be destroyed, but active research is under way to identify them. Infectious diseases such as viral encephalitis, paradoxical paradox that immune mechanism is involved, genetics that inherits its temperament, hypothesis that free radicals are generated and destroy nerve cells, toxic substance addiction, and the production and metabolism of dopamine But there is still a lack of explanation for Parkinson's disease.
상기 파킨슨 병의 유발 물질로써, 6-히드록시도파민(6-hydroxydopamine, 6-OHDA)과 L-글루탐산(L-glutamic acid)가 알려져 있다.6-hydroxydopamine (6-OHDA) and L-glutamic acid are known as the inducers of Parkinson's disease.
상기 6-OHDA는 신경독소로서, 도파민과 화학적 구조가 유사하여 도파민 수송체(DAT)에 의해 흡수되며, 자유 라디칼(free radical)을 만들어내므로 도파민 신경세포를 손상시켜 신경세포 사멸을 일으키는 것으로 알려져 있다(Nat Rev Neurosci, 2001, 2(5), 325-334).The 6-OHDA is a neurotoxin that is similar in chemical structure to dopamine and is absorbed by dopamine transporter (DAT) and produces free radicals, thus damaging dopaminergic neurons and causing neuronal cell death (Nat Rev Neurosci, 2001, 2 (5), 325-334).
상기 L-글루탐산은 정상 농도에서 생리학적으로 중요한 역할을 하지만 과량 분비되면 흥분 독성을 유발하는 아미노산으로 작용하여, 흥분성 신경 전달물질에 의한 흥분 독성을 일으켜 신경세포의 손상 또는 사멸을 유발한다. 그 결과 기억력 감퇴, 인지기능 저하뿐 아니라, 알츠하이머병, 파킨슨 병 등 다양한 신경퇴행성 질환을 야기한다 (Samuel et al., Localization of N-methyl-D-aspartate receptors in the rat striatum: effects of specific lesions on the [3H] 3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid binding. J Neurochem 1990; 54: 1926-1933; Weihmuller et al., Elevated NMDA receptors in Parkinsonian striatum. Neuroreport 1992;3: 997-980).Although L-glutamic acid plays a physiologically important role at normal concentration, excessive secretion of L-glutamic acid acts as an amino acid which causes excitotoxicity, and causes excitotoxicity by excitatory neurotransmitter, resulting in damage or death of nerve cells. As a result, it causes a variety of neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease as well as memory decline and cognitive decline (Samuel et al., Localization of N-methyl-D-aspartate receptors in the rat striatum: effects of specific lesions on Elevated NMDA receptors in Parkinsonian striatum, Neuroreport 1992; 3: 2-carboxypiperazin-4-yl) propyl-1-phosphonic acid binding, J. Neurochem 1990; 54: 1926-1933, Weihmuller et al. 997-980).
상기 흥분성 신경전달물질 또는 신경독소 등에 의한 신경세포손상은 중추신경계 내 신경세포의 과도한 세포사멸에 의해 나타나며, 따라서 신경세포의 세포사멸을 저해시키는 것은 기억력 감퇴, 인지기능 저하, 나아가서 신경퇴행성 질환으로부터 신경세포를 보호하는데 많은 도움이 될 것이다. The neuronal cell damage caused by the excitatory neurotransmitter or neurotoxin is caused by excessive cell death of the neuron in the central nervous system. Thus, inhibition of neuronal cell apoptosis is caused by memory loss, cognitive dysfunction, It will be very helpful in protecting the cells.
특히 최근에 신경세포 사멸 및 퇴행성 신경질환으로부터 보호하기 위하여 신경전달물질 수용체에 대한 길항제, GABA 효능제, 세포내 칼슘감소제, 유리 라디칼 제거제, 글루타메이트 유리 억제제 등 다양한 약물의 개발이 시도되고 있으나, 대부분이 위험요소와 부작용을 가지고 있어, 각종 천연자원으로부터 보다 안전하고 신경세포 보호효과가 뛰어난 치료제의 개발이 요구된다.In recent years, various drugs such as antagonists for neurotransmitter receptors, GABA agonists, intracellular calcium reducers, free radical scavengers and glutamate free inhibitors have been attempted to protect against neuronal apoptosis and neurodegenerative diseases, These risks and side effects have led to the development of therapeutic agents that are safer and more effective in protecting nerve cells from various natural sources.
이러한 배경하에서, 본 발명자들은 향나무 추출물 또는 향나무 유래 화합물을 이용하여 파킨슨 병을 예방 또는 치료할 수 있는 약학 조성물을 개발하기 위한 예의 노력한 결과, 향나무 추출물 또는 그로부터 분리한 화합물인 위드롤 또는 세드롤이 신경세포에 대하여 보호효과를 가지는 것을 확인함으로써 본 발명을 완성하였다.Under these circumstances, the present inventors have made intensive efforts to develop a pharmaceutical composition capable of preventing or treating Parkinson's disease by using a fragrant extract or a fescue-derived compound. As a result, it has been found that a fragrant extract or a compound separated therefrom, The present invention has been completed.
본 발명의 하나의 목적은, 향나무 추출물 또는 그로부터 분리한 화합물을 유효성분으로 포함하는, 파킨슨 병 예방 또는 치료용 약학 조성물을 제공하는 것이다.It is an object of the present invention to provide a pharmaceutical composition for preventing or treating Parkinson's disease, which comprises a fragrant extract or a compound isolated therefrom as an active ingredient.
또한, 본 발명의 다른 목적은, 향나무 추출물 또는 그로부터 분리한 화합물을 유효성분으로 포함하는 약학 조성물을 인간을 제외한 개체에 투여하는 단계를 포함하는, 파킨슨 병 예방 또는 치료 방법을 제공하는 것이다.Another object of the present invention is to provide a method for preventing or treating Parkinson's disease comprising the step of administering to a subject other than a human, a pharmaceutical composition containing a fragrant extract or a compound isolated therefrom as an active ingredient.
나아가 향나무 추출물 또는 그로부터 분리한 화합물을 유효성분으로 포함하는 파킨슨 병 예방 또는 개선용 건강기능식품을 제공하고,Furthermore, the present invention provides a health functional food for preventing or ameliorating Parkinson's disease, which comprises a juniper extract or a compound isolated therefrom as an active ingredient,
향나무 추출물 또는 그로부터 분리한 화합물을 유효성분으로 포함하는 파킨슨 병 예방 또는 개선용 의약외품 조성물을 제공하는 것이다.Which comprises as an active ingredient a herb extract or a compound isolated therefrom.
이를 구체적으로 설명하면 다음과 같다. 한편, 본 발명에서 개시된 각각의 설명 및 실시형태는 각각의 다른 설명 및 실시 형태에도 적용될 수 있다. 즉, 본 발명에서 개시된 다양한 요소들의 모든 조합이 본 발명의 범주에 속한다. 또한, 하기 기술된 구체적인 서술에 의하여 본 발명의 범주가 제한된다고 볼 수 없다.This will be described in detail as follows. On the other hand, each description and embodiment disclosed in the present invention can be applied to each other description and embodiment. That is, all combinations of various elements disclosed in the present invention fall within the scope of the present invention. Further, the scope of the present invention is not limited by the detailed description described below.
본 발명의 하나의 양태로서, 본 발명은 향나무 추출물 또는 그로부터 분리한 화합물을 유효성분으로 포함하는, 파킨슨 병 예방 또는 치료용 약학 조성물을 제공한다.As one embodiment of the present invention, the present invention provides a pharmaceutical composition for preventing or treating Parkinson's disease, comprising a fragrant extract or a compound isolated therefrom as an active ingredient.
본 발명에서 용어, "향나무(Juniperus chinensis)"란 천연, 잡종 또는 변종 향나무의 모든 기관, 예를 들어, 뿌리, 가지, 줄기, 잎, 꽃을 모두 포함하여 의미할 수 있다. 상기 향나무는 측백나무과 (Cypressaceae)에 속하는 교목으로 관상용, 약용으로 쓰이고 관상수 및 조각재, 가구재, 향료를 제조하며 민간에서는 잎과 열매를 이뇨, 통경약으로 쓴다 (김태정, 한국의 자원식물, 1 권, pp64, 1996, 서울대학교 출판부, 서울).In the present invention, the term " juniperus chinensis "may mean all organs of natural, hybrid, or variegated juniper, including, for example, roots, branches, stems, leaves and flowers. The juniper is a tree belonging to the Cypressaceae, (Kim Tae-jung, Resource Plants of Korea, Vol. 1, pp. 64, 1996, Seoul National University Press, Seoul, Korea), which is used for medicinal purposes and produces tubular water, sculpture, furniture and perfume.
상기 향나무 추출물은 물, 에탄올, 메탄올 또는 이들의 혼합물을 용매로 사용하여 추출할 수 있으나, 이에 제한되는 것은 아니다.The juniper extract can be extracted using water, ethanol, methanol or a mixture thereof, but is not limited thereto.
본 발명에서 사용된 용어 '향나무 유래 화합물','향나무 추출물로부터 분리한 화합물' 또는'그로부터 분리한 화합물'은 향나무 추출물로부터 분리한 화합물을 의미한다. As used herein, the term "fragrance-derived compound", "compound isolated from the fragrance extract" or "compound separated therefrom" means a compound isolated from the fragrance extract.
구체적으로, 상기 화합물은 위드롤(widdrol) 또는 세드롤(cedrol)일 수 있다. C15H26O의 일반식을 갖는 상기 위드롤 및 세드롤은 향나무에서 분리될 수 있으며, 파킨슨 병 예방 또는 치료 효과를 나타내는 것에 대해서는 알려진 바가 전혀 없다.Specifically, the compound may be a widdrol or a cedrol. The above-mentioned Weed roll and the Sed roll having the general formula of C 15 H 26 O can be separated from the fragrant wood, and there is no known effect of preventing or treating Parkinson's disease.
[화학식 1][Chemical Formula 1]
본 발명에서 용어, "위드롤(widdrol)"은 상기 화학식 1의 화합물로서 세스퀴테르펜계(Sesquiterpene) 화합물을 의미한다. 그 일반식은 C15H26O로 표시되며, 명칭은 (7S,9aS)-4,4,7,9a-tetramethyl-1,2,3,6,8,9-hexahydrobenzo[7] annulen-7-ol로 표시되고 있다.The term " widdrol "in the present invention means a sesquiterpene compound as the compound of the above formula (1). The general formula is represented by C 15 H 26 O and is named (7S, 9aS) -4,4,7,9a-tetramethyl-1,2,3,6,8,9-hexahydrobenzo [7] annulen- ol.
[화학식 2](2)
본 발명에서 용어, "세드롤(cedrol)"은 상기 화학식 2의 화합물로서 세스퀴테르펜계(Sesquiterpene) 화합물을 의미한다. 그 일반식은 C15H26O로 표시되며, 명칭은 (1S,2R,5S,7R,8R)-2,6,6,8-tetramethyltricyclo[5.3.1.01, 5]undecan-8-ol로 표시되고 있다.In the present invention, the term "cedrol" means a sesquiterpene compound as the compound of the above formula (2). The general formula is represented by C 15 H 26 O, the name is displayed in (1S, 2R, 5S, 7R , 8R) -2,6,6,8-tetramethyltricyclo [5.3.1.0 1, 5] undecan-8-ol .
본 발명의 상기 위드롤 또는 세드롤은 천연물질, 구체적으로는 식물로부터 분리할 수 있다. 천연, 잡종, 변종 식물의 다양한 기관, 뿌리, 줄기, 잎, 꽃뿐만 아니라 식물 조직 배양물을 추출하여 분리 가능하다. 또한, 당 분야의 공지된 방법으로 화학적 합성이 가능하나, 판매되는 것을 구입하여 사용할 수 있다.The weed roll or the shed roll of the present invention can be separated from a natural substance, specifically a plant. It can be extracted by extracting various organ, root, stem, leaf, flower as well as plant tissue culture of natural, hybrid, and variant plants. In addition, chemical synthesis is possible by a known method in the art, but those sold can be purchased and used.
구체적으로, 본 발명의 상기 위드롤 또는 세드롤은 향나무로부터 분리된 것일 수 있다. Specifically, the weed roll or the shed roll of the present invention may be separated from the juniper.
식물로부터 위드롤 또는 세드롤을 수득하는 방법은 공지의 다양한 추출방법에 의할 수 있다. 예를 들어, 식물을 분쇄한 뒤 저급 알코올 용매, 예를 들어, 메탄올, 에탄올 등으로 추출한 다음, 이를 증류수에 현탁시켜 비극성 유기 용매, 예를 들어, 노말헥산, 에테르, 디클로로메탄, 클로로포름, 에틸아세테이트 또는 이들의 혼합 용매로 비극성용매 가용층을 추출, 분리하여 수득할 수 있다. 얻은 비극성 유기 용매 분획으로부터 화학식 1의 위드롤을 수득할 수 있다. 추출물을 1회 이상의 크로마토그래피를 수행함으로써 더욱 정제할 수 있고, 이때 칼럼의 종류와 전개 용매는 다양하게 조절될 수 있다.A method of obtaining a weed roll or a seed roll from a plant can be carried out by various known extraction methods. For example, the plant may be pulverized and then extracted with a lower alcohol solvent such as methanol or ethanol and then suspended in distilled water, followed by washing with a nonpolar organic solvent such as normal hexane, ether, dichloromethane, chloroform, ethyl acetate Or a mixed solvent thereof, and extracting and separating the non-polar solvent soluble layer. From the obtained non-polar organic solvent fraction, a weed roll of formula (1) can be obtained. The extract can be further purified by performing one or more chromatographs, wherein the type of column and the developing solvent can be varied.
본 발명의 일 실시예에서는 분말로 파쇄한 향나무(J. chinensis)에 에탄올을 가하여 에탄올 추출물을 얻었다. 또한 분말로 파쇄한 향나무에 메탄올을 가하여 메탄올 추출물을 얻었으며, 상기 메탄올 추출물을 물층과 디클로로메탄층으로 분획한 후, 상기 디클로로메탄층으로부터 실리카겔 컬럼 크로마토그래피로 위드롤 및 세드롤을 분리하였다 (도 1).In one embodiment of the present invention, ethanol was added to a juniper ( J. chinensis ) crushed into powder to obtain an ethanol extract. Further, methanol was added to the fragrant juniper which was crushed with the powder to obtain a methanol extract. The methanol extract was fractionated into a water layer and a dichloromethane layer, and a weed roll and a sedo roll were separated from the dichloromethane layer by silica gel column chromatography One).
본 발명에서 사용된 용어 '파킨슨 병'은 뇌의 흑질(substantia nigra)에 분포하는 도파민의 신경세포가 점차 소실되어 발생하며 안정떨림, 경직, 운동완만 및 자세 불안정성이 특징적으로 나타나는 신경계의 만성 진행성 퇴행성 질환을 의미한다.As used herein, the term " Parkinson's disease " refers to a disease characterized by progressive loss of dopaminergic neurons in the substantia nigra of the brain, chronic progressive degeneration of the nervous system characterized by stable tremor, stiffness, ≪ / RTI >
본 발명에서 사용되는 용어 '예방'은 상기 위드롤 또는 세드롤을 유효성분으로 포함하는 조성물의 투여로 질환을 억제 또는 지연시키는 모든 행위를 의미한다. As used herein, the term " prevention " means any action that inhibits or delays disease by the administration of a composition comprising the above-mentioned Weed roll or a Sedo roll as an active ingredient.
본 발명에서 사용되는 용어 '치료'는, 상기 위드롤 또는 세드롤을 유효성분으로 포함하는 조성물의 투여로 질환의 증세가 호전되거나 이롭게 변경되는 모든 행위를 의미한다.The term " treatment " used in the present invention means all the actions that improve or ameliorate symptoms of a disease by administration of a composition containing the above-mentioned Weed roll or a Sedo roll as an active ingredient.
본 발명에서 파킨슨 병의 치료는 신경세포 보호, 신경세포의 수 증가에 의한 것일 수 있다.In the present invention, the treatment of Parkinson's disease may be due to nerve cell protection, increase in the number of nerve cells.
상기 신경세포는 주요 신경전달물질이 도파민인 신경세포를 의미할 수 있고, 중뇌의 복측피개영역(ventral tegmental area, VTA), 흑질 치밀부(substantia nigra pars compacta), 시상하부 궁상핵(arcuate nucleus of the hypothalamus) 또는 선조체(striatum)에 위치할 수 있다.The neurons may be nerve cells whose main neurotransmitter is dopamine, and include ventral tegmental area (VTA), substantia nigra pars compacta, arcuate nucleus of the midbrain the hypothalamus, or the striatum.
구체적인 일 실시예에서, 6-OHDA를 처리한 신경세포에 향나무 추출물, 위드롤 또는 세드롤을 처리한 후, 위드롤 또는 세드롤이 6-OHDA로 유도된 신경세포의 사멸을 회복시킴을 확인하였다 (도 5 및 6).In a specific example, it was confirmed that after treatment of 6-OHDA-treated nerve cells with a bamboo extract, a Weed roll or a Sedo roll, the Weed roll or Sedo roll restored the death of 6-OHDA-induced neuronal cells (Figures 5 and 6).
본 발명의 또 다른 양태로서, 본 발명은 향나무 추출물 또는 그로부터 분리한 화합물을 유효성분으로 포함하는 약학 조성물을 인간을 제외한 개체에 투여하는 단계를 포함하는, 파킨슨 병 예방 또는 치료 방법을 제공한다.In another aspect of the present invention, the present invention provides a method for preventing or treating Parkinson's disease, comprising administering to a subject other than a human, a pharmaceutical composition comprising a fragrant extract or a compound isolated therefrom as an active ingredient.
상기 향나무 추출물, 그로부터 분리한 화합물, 파킨슨 병은 상기 설명한 바와 같다.The above-mentioned fragrance extract, compounds isolated therefrom, and Parkinson's disease are as described above.
본 발명에서 용어, "개체"는 본 발명의 파킨슨 병을 보유하거나 또는 발병한, 인간을 포함한 모든 동물을 의미하며, 인간을 제외한 개체일 수 있다. 본 발명의 약학 조성물을 개체에 투여함으로 파킨슨병의 예방 및 치료 효과를 얻을 수 있다. In the present invention, the term "individual" means all animals, including humans, who have or develop Parkinson's disease of the present invention, and may be individuals other than humans. By administering the pharmaceutical composition of the present invention to an individual, the preventive and therapeutic effect of Parkinson's disease can be obtained.
상기 본 발명의 약학 조성물은 약학적으로 유효한 양으로 투여한다.The pharmaceutical composition of the present invention is administered in a pharmaceutically effective amount.
본 발명에서 용어, "투여"는 어떠한 적절한 방법으로 대상에게 본 발명의 약학 조성물을 도입하는 것을 말하며, 투여 경로는 목적 조직에 도달할 수 있는 한 경구 또는 비경구의 다양한 경로를 통하여 투여될 수 있다. The term "administering" as used herein refers to introducing a pharmaceutical composition of the present invention to a subject by any suitable method, and the administration route can be administered through various routes of oral or parenteral administration as long as it can reach the target tissue.
상기 약학 조성물은 목적 또는 필요에 따라 당업계에서 사용되는 통상적인 방법, 투여 경로, 투여량에 따라 적절하게 개체에 투여될 수 있다. 투여 경로의 예로는 경구, 비경구, 피하, 복강 내, 폐 내, 및 비강 내로 투여될 수 있으며, 비경구 주입에는 근육 내, 정맥 내, 동맥 내, 복강 내 또는 피하투여가 포함된다. 또한 당업계에 공지된 방법에 따라 적절한 투여량 및 투여 횟수가 선택될 수 있으며, 실제로 투여되는 본 발명의 약학 조성물의 양 및 투여 횟수는 치료하고자 하는 증상의 종류, 투여 경로, 성별, 건강 상태, 식이, 개체의 연령 및 체중, 및 질환의 중증도와 같은 다양한 인자에 의해 적절하게 결정될 수 있다.The pharmaceutical composition may be appropriately administered to an individual according to the purpose or necessity, depending on the conventional methods, routes of administration and dosage used in the art. Examples of routes of administration include oral, parenteral, subcutaneous, intraperitoneal, intrapulmonary, and intranasal routes, and parenteral injection includes intramuscular, intravenous, intraarterial, intraperitoneal, or subcutaneous administration. The amount and the frequency of administration of the pharmaceutical composition of the present invention to be actually administered can be appropriately selected according to the type of the symptom to be treated, route of administration, sex, health condition, Diet, age and weight of the individual, and the severity of the disease.
본 발명에서의 용어 "약학적으로 유효한 양"은 의학적 용도에 적용 가능한 합리적인 수혜/위험 비율로 혈관 투과성 증가를 억제 또는 완화하기에 충분한 양을 의미하며, 유효 용량 수준은 개체 종류 및 중증도, 연령, 성별, 약물의 활성, 약물에 대한 민감도, 투여 시간, 투여 경로 및 배출 비율, 치료기간, 동시 사용되는 약물을 포함한 요소 및 기타 의학 분야에 잘 알려진 요소에 따라 결정될 수 있다. 본 발명의 조성물은 개별 치료제로 투여하거나 다른 치료제와 병용하여 투여될 수 있고 종래의 치료제와는 순차적 또는 동시에 투여될 수 있다. 그리고 단일 또는 다중 투여될 수 있다. 상기 요소를 모두 고려하여 부작용 없이 최소한의 양으로 최대 효과를 얻을 수 있는 양을 투여하는 것이 중요하며, 당업자에 의해 용이하게 결정될 수 있다.The term "pharmaceutically effective amount " as used herein means an amount sufficient to inhibit or alleviate an increase in vascular permeability at a reasonable benefit / risk ratio applicable to medical use, and effective dosage levels will vary depending on the species and severity, Sex, the activity of the drug, the sensitivity to the drug, the time of administration, the route of administration and the rate of excretion, the duration of the treatment, factors including co-administered drugs, and other factors well known in the medical arts. The composition of the present invention may be administered as an individual therapeutic agent or in combination with other therapeutic agents, and may be administered sequentially or simultaneously with conventional therapeutic agents. And can be administered singly or multiply. It is important to take into account all of the above factors and to administer the amount in which the maximum effect can be obtained in a minimal amount without adverse effect, and can be easily determined by those skilled in the art.
본 발명의 또 다른 양태로서, 본 발명은 향나무 추출물 또는 그로부터 분리한 화합물을 유효성분으로 포함하는 파킨슨 병 예방 또는 개선용 건강기능식품을 제공한다.As another embodiment of the present invention, the present invention provides a health functional food for preventing or ameliorating Parkinson's disease comprising a fragrant extract or a compound isolated therefrom as an active ingredient.
상기 향나무 추출물, 그로부터 분리한 화합물, 파킨슨 병은 상기 설명한 바와 같다.The above-mentioned fragrance extract, compounds isolated therefrom, and Parkinson's disease are as described above.
본 발명에서 사용된 용어, '건강기능식품'이라 함은 건강기능식품에 관한 법률 제6727호에 따른 인체에 유용한 기능성을 가진 원료나 성분을 사용하여 제조 및 가공한 식품을 의미하며, '기능성'이라 함은 인체의 구조 및 기능에 대하여 영양소를 조절하거나 생리학적 작용 등과 같은 보건 용도에 유용한 효과를 얻을 목적으로 섭취하는 것을 의미한다.The term " health functional food " used in the present invention means a food prepared and processed using raw materials or ingredients having useful functions in accordance with the Health Functional Food No. 6727, Means that the structure and function of the human body are ingested for the purpose of obtaining nutritional control effects or physiological effects and health effects.
상기 건강기능식품은 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, 알코올, 탄산음료에 사용되는 탄산화제 등을 함유할 수 있다.The health functional food may contain flavoring agents such as various nutrients, vitamins, minerals (electrolytes), synthetic flavors and natural flavors, coloring agents and thickening agents (cheese, chocolate etc.), pectic acid and its salts, alginic acid and its salts, Organic acids, protective colloid thickeners, pH adjusting agents, stabilizers, preservatives, glycerin, alcohols, carbonating agents used in carbonated drinks, and the like.
그 밖에 천연 과일쥬스 및 과일쥬스 음료 및 야채 음료의 제조를 위한 과육을 함유할 수 있다. 이러한 성분은 독립적으로 또는 조합하여 사용할 수 있다. 또한, 건강기능식품은 육류, 소세지, 빵, 쵸코렛, 캔디류, 과자류, 피자, 라면, 껌류, 아이스크림류, 스프, 음료수, 차, 기능수, 드링크제, 알콜 음료 및 비타민 복합제 중 어느 하나의 형태일 수 있다.In addition, it may contain natural fruit juice and pulp for the production of fruit juice drinks and vegetable drinks. These components may be used independently or in combination. The health functional food may be in the form of any one of meat, sausage, bread, chocolate, candy, confectionery, pizza, ramen, gum, ice cream, soup, beverage, tea, functional water, have.
또한, 상기 건강기능식품은 식품첨가물을 추가로 포함할 수 있으며, '식품첨가물'로서의 적합 여부는 다른 규정이 없는 한 식품의약품안전처에 승인된 식품첨가물공전의 총칙 및 일반시험법 등에 따라 해당 품목에 관한 규격 및 기준에 의하여 판정한다.In addition, the health functional foods may further include food additives, and the suitability as a 'food additive' may be determined by the Food and Drug Administration in accordance with the general rules of the Food Additives Ordinance approved by the Food and Drug Administration, Of the present invention.
상기 '식품첨가물공전'에 수재된 품목으로 예를 들어, 케톤류, 글리신, 구연산칼륨, 니코틴산, 계피산 등의 화학적 합성품, 감색소, 감초추출물, 결정셀룰로오스, 구아검 등의 천연첨가물, L-글루타민산 나트륨제제, 면류첨가 알칼리제, 보존료 제제, 타르색소제제 등의 혼합 제제류들을 들 수 있다.Examples of the above-mentioned 'food additives' include natural compounds such as ketones, glycine, potassium citrate, nicotinic acid, cinnamic acid and the like, sensory coloring matter, licorice extract, crystalline cellulose and guar gum, sodium L- A mixed preparation such as a preparation, a noodle-added alkali agent, a preservative preparation, a tar coloring agent, and the like.
구체적으로, 본 발명의 향나무 추출물은 6.25 ㎍/ml 이상, 세드롤과 위드롤의 경우는 50 ㎍/ml 이상부터 SH-SY5Y 세포의 생존을 저해한다는 것을 통하여, 독성이 관찰되지 않은 농도(0 내지 3 ㎍/ml)의 향나무 추출물, 위드롤 또는 세드롤을 사용 시 세포 독성이 없는 것을 관찰함으로써 건강기능식품으로 사용 할 수 있다는 것을 확인하였다.Specifically, the present invention provides a method for inhibiting the survival of SH-SY5Y cells at a concentration of not less than 6.25 占 퐂 / ml, more than 50 占 퐂 / ml in the case of a sheath and a weed roll, 3 ㎍ / ml) of juniper extract, weed roll or shed roll was used as a health functional food.
본 발명의 또 다른 양태로서, 본 발명은 향나무 추출물 또는 그로부터 분리한 화합물을 유효성분으로 포함하는 파킨슨 병 예방 또는 개선용 의약외품 조성물을 제공한다.According to another aspect of the present invention, there is provided a quasi-drug composition for preventing or ameliorating Parkinson's disease comprising a fragrant extract or a compound isolated therefrom as an active ingredient.
상기 향나무 추출물, 그로부터 분리한 화합물, 파킨슨 병은 상기 설명한 바와 같다.The above-mentioned fragrance extract, compounds isolated therefrom, and Parkinson's disease are as described above.
본 발명에서 용어, "의약외품"은 사람이나 동물의 질병을 치료, 경감, 처치 또는 예방할 목적으로 사용되는 섬유, 고무제품 또는 이와 유사한 것, 인체에 대한 작용이 약하거나 인체에 직접 작용하지 아니하며, 기구 또는 기계가 아닌 것과 이와 유사한 것, 감염형 예방을 위하여 살균, 살충 및 이와 유사한 용도로 사용되는 제제 중 하나에 해당하는 물품으로서, 사람이나 동물의 질병을 진단, 치료, 경감, 처치 또는 예방할 목적으로 사용하는 물품 중 기구, 기계 또는 장치가 아닌 것 및 사람이나 동물의 구조와 기능에 약리학적 영향을 줄 목적으로 사용하는 물품 중 기구, 기계 또는 장치가 아닌 것을 제외한 물품을 의미한다.The term "quasi-drug" in the present invention means a fiber, a rubber product or the like used for the purpose of treating, alleviating, treating or preventing a disease of a human or an animal, Or products similar to those that are not machinery, preparations used for sterilization, insecticides and similar uses for the prevention of infectious diseases, for the purpose of diagnosing, treating, alleviating, treating, or preventing diseases of human beings or animals Means goods, machinery, or apparatus other than the apparatus, machinery or equipment of the commodity being used and used for the purpose of giving pharmacological effects to the structure and function of humans or animals.
본 발명의 조성물을 의약외품 첨가물로 사용할 경우, 상기 조성물을 그대로 첨가하거나 다른 의약외품 또는 의약외품 성분과 함께 사용할 수 있고, 통상적인 방법에 따라 적절하게 사용할 수 있다. 유효성분의 혼합량은 사용 목적에 따라 적합하게 결정될 수 있다.When the composition of the present invention is used as a quasi-drug additive, the composition may be added as it is or may be used together with other quasi-drugs or quasi-drugs, and may be appropriately used according to a conventional method. The amount of the active ingredient to be mixed can be appropriately determined depending on the purpose of use.
본 발명의 의약외품 조성물은 이에 제한되지는 않으나, 바람직하게는 소독청결제, 샤워폼, 가그린, 물티슈, 세제비누, 핸드워시, 가습기 충진제, 마스크, 연고제 또는 필터충진제일 수 있다.The quasi-drug composition of the present invention may be, but is not limited to, disinfectant cleaner, shower foam, gagrin, wet tissue, detergent soap, hand wash, humidifier filler, mask, ointment or filter filler.
구체적으로, 상기 기술한 바와 마찬가지로 독성이 관찰되지 않은 농도(0 내지 3 ㎍/ml)의 향나무 추출물, 위드롤 또는 세드롤을 사용 시 세포 독성이 없는 것을 관찰함으로써 의약외품으로 사용 할 수 있다는 것을 확인하였다 (도 3 및 4).Specifically, it was confirmed that the fragrance extract of the juniper, the weed roll or the shed roll having no toxicity observed (0 to 3 ㎍ / ml) as described above can be used as a quasi-drug by observing that there is no cytotoxicity (Figs. 3 and 4).
본 발명의 향나무 추출물 또는 그로부터 분리한 화합물 위드롤 또는 세드롤을 유효성분으로 포함하는 조성물은, 신경세포 보호 효과 및 신경세포에서 세포사멸 억제효과를 나타냄을 확인하였는바, 이는 파킨슨 병 예방 또는 치료용 약학물로 유용하게 사용 될 수 있다.It was confirmed that the composition comprising the extract of jukebox of the present invention or the compound of the present invention as the active ingredient of the weed roll or the seed roll exhibited the protective effect of the neuron and the effect of inhibiting apoptosis in the neuron, It can be usefully used as a pharmaceutical.
도 1은, 향나무에서 향나무 추출물 또는 향나무 유래 화합물을 추출 또는 분리하는 과정을 나타낸 모식도이다.
도 2는, 향나무 추출물, 세드롤 및 위드롤의 SH-SY5Y 세포의 생존에 미치는 영향을 나타낸 것이다.
도 3은, 향나무 추출물, 세드롤 및 위드롤의 L-글루탐산이 처리된 SH-SY5Y세포에서 신경세포 보호 효과를 나타낸 것이다.
도 4는, 향나무 추출물, 세드롤 및 위드롤의 6-OHDA가 처리된 SH-SY5Y세포에서 신경세포 보호 효과를 나타낸 것이다.
도 5는, 향나무 추출물, 세드롤 및 위드롤의 L-글루탐산이 처리된 SH-SY5Y세포에서 세포자멸사(apoptosis) 억제 효과를 나타낸 것이다.
도 6는, 향나무 추출물, 세드롤 및 위드롤의 6-OHDA가 처리된 SH-SY5Y세포에서 세포자멸사(apoptosis) 억제 효과를 나타낸 것이다.1 is a schematic view showing a process of extracting or isolating a fragrant wood extract or a fescue-derived compound from a fragrant wood.
Fig. 2 shows the effect of the extract of the juniper, the sedo roll and the weed roll on the survival of SH-SY5Y cells.
Fig. 3 shows the protective effect of neural cells in SH-SY5Y cells treated with L-glutamic acid of juniper extract, shred roll and weed roll.
Fig. 4 shows the protective effect of nerve cells on SH-SY5Y cells treated with 6-OHDA of juniper extract, sedo roll and weed roll.
Fig. 5 shows the effect of inhibiting apoptosis in SH-SY5Y cells treated with L-glutamic acid of juniper extract, sedo roll and weed roll.
6 shows the effect of inhibiting apoptosis in SH-SY5Y cells treated with 6-OHDA of juniper extract, sedo roll and weed roll.
이하 본 발명을 실시예를 통하여 보다 상세하게 설명한다. 그러나 이들 실시예는 본 발명을 예시적으로 설명하기 위한 것으로 본 발명의 범위가 이들 실시예에 한정되는 것은 아니다.Hereinafter, the present invention will be described in more detail with reference to examples. However, these examples are for illustrative purposes only, and the scope of the present invention is not limited to these examples.
실시예Example 1: 재료 및 방법 1: Materials and Methods
1-1.1-1. 향나무 추출물 제조 및 향나무 유래 화합물 Manufacture of juniper extracts and compounds derived from fescue 세드롤(cedrol)과Cedrol and 위드롤(widdrol)의Of widdrol 분리 detach
향나무 에탄올 추출물(향나무 추출물)을 제조하기 위하여 3 Kg의 향나무 분말에 5배의 에탄올을 가하여, 75에서 3회 반복하여 추출하였다. 추출한 시료는 여과 후 농축한 다음 동결건조하였다. 그 결과 에탄올 추출물 181 g을 수득하였다 (수율 6.03%).In order to prepare the ethanol extract of juniper (juniper), 3 Kg of juniper powder was added 5 times of ethanol and extracted 75 times three times. The extracted samples were filtered, concentrated, and lyophilized. As a result, 181 g of an ethanol extract was obtained (yield: 6.03%).
또한 향나무 유래 화합물인 세드롤(cedrol)과 위드롤(widdrol)의 분리를 위하여 향나무 메탄올 추출물을 물(H2O) 층과 디클로로메탄(dichloromethane, CH2Cl2) 층으로 분획하였다. 그 결과 디클로로메탄(CH2Cl2)층 분획물 399.36 g과 물층 분획물 313.8 g을 수득하였다. For the separation of cedrol and widdrol, the fragrant compounds, manganese methanol extract was fractionated into a water (H 2 O) layer and a dichloromethane (CH 2 Cl 2 ) layer. As a result, dichloromethane (CH 2 Cl 2) to give the fraction layer 399.36 g and an aqueous layer fraction 313.8 g.
상기 분획물에서 디클로로메탄층 분획물로 실리카겔 컬럼 크로마토그래피(Silicagel Column Chromatography)를 수행하였다. 그 결과 단일 화합물인 세드롤(cedrol) 123.8 g과 위드롤(widdrol) 15.88 g을 분리하였다(도 1). 향나무 추출물 및 위드롤, 세드롤은 각각 디메틸설폭시드(DMSO)에 녹여 사용하였다.Silicagel Column Chromatography was performed on the fractions with dichloromethane layer fractions. As a result, 123.8 g of a single compound cedrol and 15.88 g of a widdrol were separated (Fig. 1). Leaf extract, Weed roll, and Set roll were dissolved in dimethyl sulfoxide (DMSO).
1-2.1-2. 신경세포주의Nerve cell line 배양 culture
사람 신경모세포종 SH-SY5Y 세포는 American Type Culture Collection (ATCC, USA)로부터 구입하여 사용하였으며, 10% fetal bovine serum (FBS) 및 페니실린/스트렙토마이신이 포함된 돌베코수정이글배지(DMEM)를 사용하여 37℃, 5% CO2 조건하에서 배양하였다. Human neuroblastoma SH-SY5Y cells were purchased from the American Type Culture Collection (ATCC, USA) and used in Dulbecco's modified Eagle's medium (DMEM) containing 10% fetal bovine serum (FBS) and penicillin / streptomycin And cultured at 37 ° C and 5% CO 2 .
1-3.1-3. 추출물 및 화합물의 전처리 및 신경세포 독성 유발Pretreatment of extracts and compounds and induction of neuronal cytotoxicity
SH-SY5Y 세포(5×104 cells/well) 를 96-well plate에 분주하여 부착시킨 다음, 다양한 농도(0 내지 3 ㎍/ml)의 향나무 추출물, 위드롤 또는 세드롤을 24시간 전처리하였다. 이 후 신경세포 독성을 유발하기 위하여 L-글루탐산 (monosodium salt hydrate, 75 mM) 또는 6-히드록시도파민 (6-hydroxydopamine, 6-OHDA) (100 μM)를 첨가하여 37℃에서 48시간 배양하였다.SH-SY5Y cells (5 × 10 4 cells / well) were plated on 96-well plates and then pretreated with various concentrations (0 to 3 μg / ml) of juniper extracts, weed rolls or seed rolls for 24 hours. L-glutamic acid (75 mM) or 6-hydroxydopamine (6-OHDA) (100 μM) was added to induce neuronal cytotoxicity and the cells were cultured at 37 ° C for 48 hours.
실시예Example 2. 향나무 추출물 및 향나무 유래 화합물의 신경세포에 대한 독성 2. Toxicity to nerve cells of juniper extracts and oak-derived compounds
향나무 추출물 및 향나무 유래 화합물의 신경세포보호 효능을 관찰하기 앞서, 향나무 추출물, 위드롤 또는 세드롤의 신경세포에 대한 직접적 독성 유무 확인을 위하여 WST assay를 이용하여 SH-SY5Y 세포의 생존도를 측정하였다. Prior to observing neuronal cell protection efficacy of juniper extracts and fenugreek-derived compounds, the survival rate of SH-SY5Y cells was measured using a WST assay to confirm the direct toxicity of the extracts, weed rolls, .
먼저, SH-SY5Y 세포(5×104 cells/well) 를 96-well plate에 분주하여 부착시킨 다음, 0 내지 50 ㎍/ml의 향나무 추출물, 위드롤 또는 세드롤을 48시간 처리하였다. 배양이 끝난 SH-SY5Y 세포의 배양액을 제거하고 WST 시약(Daeillab, Korea)이 포함된 배지를 분주한 후 37℃에서 1시간 동안 배양시켰다. 이 후 microplate reader (Molecular Devices, USA)를 사용하여 450 nm에서 흡광도를 측정하였다. 측정값은 3회 반복 실험을 하여 평균값으로 나타내었다.First, SH-SY5Y cells (5 × 10 4 cells / well) were dispensed on a 96-well plate and then treated with 0 to 50 μg / ml of juniper extract, weed roll or sheild roll for 48 hours. After the culture of the cultured SH-SY5Y cells was removed, the culture medium containing the WST reagent (Daeillab, Korea) was dispensed and cultured at 37 ° C for 1 hour. The absorbance at 450 nm was measured using a microplate reader (Molecular Devices, USA). The measured values were expressed as a mean value by repeating the experiment three times.
그 결과, 도 2와 같이 향나무 추출물의 경우는 6.25 ㎍/ml 이상, 세드롤과 위드롤의 경우는 50 ㎍/ml 이상부터 SH-SY5Y 세포의 생존을 저해하였다.As a result, as shown in Fig. 2, the survival rate of SH-SY5Y cells was inhibited from 6.25 ㎍ / ml in the case of the jellybean extract and from 50 ㎍ / ml in the case of the sedo roll and the weed roll.
따라서 이하에서 독성이 관찰되지 않은 농도(0 내지 3 ㎍/ml)의 향나무 추출물, 위드롤 또는 세드롤을 사용하여 신경세포보호 효능, 구체적으로 파킨슨 병에 대한 예방 및 치료 효과를 확인하였다.Therefore, the preventive and therapeutic effect on nerve cell protection efficacy, specifically Parkinson's disease, was confirmed by using a fragrance extract, a weed roll or a sheild roll of a concentration (0 to 3 ㎍ / ml) at which no toxicity was observed below.
실시예Example 3. 향나무 추출물 및 향나무 유래 화합물의 3. Leaf extract and oak-derived compounds 파킨슨 병Parkinson's disease 치료 효과 확인 Check the effectiveness of treatment
3-1. 향나무 추출물 및 향나무 유래 화합물에 의한 신경세포보호 효능 3-1. Neuroprotective efficacy of juniper extract and herbaceous compounds
향나무 추출물, 위드롤 또는 세드롤의 L-글루탐산 또는 6-OHDA에 의해 유발된 독성에 대한 SH-SY5Y 세포보호 효능 확인을 위하여 WST assay를 이용하여 SH-SY5Y 세포의 생존도를 측정하였다.The survival rate of SH-SY5Y cells was measured using the WST assay for confirming SH-SY5Y cytoprotective effect against toxicity induced by L-glutamic acid or 6-OHDA of juniper extract,
먼저 다양한 농도(0 내지 3 ㎍/ml)의 향나무 추출물, 위드롤, 세드롤 및 양성대조군(ascorbic acid, 75 mM)을 24시간 전처리 한 다음, L-글루탐산(75 mM) 를 48시간 처리하여 신경독성을 유발시켰다. 이후, 추출물 및 화합물에 의해 신경세포 생존율이 증가되는 지 관찰하였다. We first pretreated for 24 hours with various concentrations (0 to 3 ㎍ / ml) of juniper extract, weed roll, sedo roll and positive control (ascorbic acid, 75 mM) and then treated with L-glutamic acid (75 mM) Toxic. Then, we observed whether the survival rate of neurons was increased by extracts and compounds.
그 결과, DMSO 처리에 비해 0.5 ㎍/ml의 향나무 추출물, 위드롤 또는 세드롤을 전처리 한 경우, 세포 생존율이 각각 14.72%, 13.60%, 16.61% 증가하여 양성대조군으로 사용한 ascorbic acid보다 더 높은 증가율을 보였다(도 3). As a result, cell viability was increased by 14.72%, 13.60%, and 16.61%, respectively, compared with DMSO treatment, and the cell viability was increased more than ascorbic acid used as a positive control when 0.5 ㎍ / (Fig. 3).
또한, 다양한 농도(0 내지 3 ㎍/ml)의 향나무 추출물, 위드롤, 세드롤을 24시간 전처리 한 다음, 6-OHDA(100 μM)를 48시간 처리하여 신경세포 보호 효능을 관찰하였다. We also examined the effects of various concentrations (0 to 3 μg / ml) of juniper extract, weed roll, and shed rolls for 24 hours and then treated with 6-OHDA (100 μM) for 48 hours.
그 결과, DMSO 처리에 비해 0.5 ㎍/ml의 향나무 추출물 처리의 경우 SH-SY5Y 세포 생존율이 11.42% 증가하였으며, 0.1 ㎍/ml의 세드롤과 위드롤 전처리에 의해 SH-SY5Y 세포 생존율이 각각 17.46%, 20.20% 증가하였다(도 4).As a result, the survival rate of SH-SY5Y cells was increased by 11.42% when 0.5 ㎍ / ml of juniper extract was treated with DMSO, and the survival rate of SH-SY5Y cells was 17.46% by 0.1 ㎍ / , And increased by 20.20% (Fig. 4).
상기 결과로부터 향나무 추출물, 위드롤 또는 세드롤이 L-글루탐산 또는 6-OHDA에 의해 유발되는 신경세포 독성으로부터 세포생존율을 증가시켜, 신경세포를 보호하고, 파킨슨 병에 대한 치료 효과를 보유함을 확인하였다.From the above results, it was confirmed that the fragrant extract, the weed roll or the sedo roll increased cell survival rate from the neuronal cytotoxicity induced by L-glutamic acid or 6-OHDA to protect neurons and have a therapeutic effect on Parkinson's disease Respectively.
3-2. 향나무 추출물 및 향나무 유래 화합물에 의한 신경세포 3-2. Nerve cells by the extracts 세포자멸Apoptosis 사(apoptosis)의 저해Inhibition of apoptosis
향나무 추출물, 위드롤 또는 세드롤에 의한 신경세포 보호 효능의 기전을 확인하기 위하여 향나무 추출물, 위드롤 또는 세드롤이 L-글루탐산 또는 6-OHDA에 의해 유발되는 신경세포의 세포자멸사를 저해하는지 확인하였다.To confirm the mechanism of nerve cell protection effect by fragrant extracts, weed rolls or shed rolls, we examined whether the fragrance extract, the weed roll or the sedo roll inhibited the apoptosis of neurons induced by L-glutamic acid or 6-OHDA .
SH-SY5Y 세포의 세포자멸사를 측정하기 위하여, Muse™ Annexin V & Dead Cell Kit를 사용하였다. SH-SY5Y 세포를 2×105 cells/well로 24-well plate에 분주한 다음 향나무 추출물, 위드롤 또는 세드롤을 전처리하고 L-글루탐산 또는 6-OHDA를 처리하여 독성을 유도하였다. 이후 배양이 끝난 세포를 회수하고 Muse™ Annexin V & Dead Cell reagent (100 μl)를 첨가하여 실온에서 빛을 차단하여 20분간 염색시킨 다음, 염색된 세포들은 Muse™ Cell Analyzer (Merck Millipore, Germany)를 사용하여 분석하였다.To determine the apoptosis of SH-SY5Y cells, the Muse ™ Annexin V & Dead Cell Kit was used. SH-SY5Y cells were plated at 2 × 10 5 cells / well in a 24-well plate, and the toxin was induced by pretreating the extracts of chestnut tree, the weed roll or the seed roll, and treating with L-glutamic acid or 6-OHDA. After incubation, cells were harvested and stained with Muse ™ Annexin V and Dead Cell reagent (100 μl) at room temperature for 20 minutes. The cells were then stained with Muse ™ Cell Analyzer (Merck Millipore, Germany) Respectively.
먼저, SH-SY5Y 세포에 DMSO를 전처리 한 다음 L-글루탐산을 처리한 경우, Live 세포(Annexin V-/7-AAD- 세포)의 비율이 감소하는 반면, apoptotic 세포(Annexin V+ 세포) 비율이 크게 증가하였으며, 이로부터 L-글루탐산에 의해 SH-SY5Y 세포의 독성이 유발되어 세포자멸사가 일어나는 것을 알 수 있었다(도 5). First, when SH-SY5Y cells were pretreated with DMSO and treated with L-glutamic acid, the proportion of Live cells (Annexin V - / 7 - AAD - cells) decreased while the ratio of apoptotic cells (Annexin V + cells) And it was found that SH-SY5Y cells were induced by L-glutamic acid to induce apoptosis (FIG. 5).
반면 추출물과 화합물을 전처리한 결과, L-글루탐산에 의한 신경세포의 apoptotic 세포는 DMSO 전처리 시 28.3%에서 향나무 추출물 (0.1 ㎍/ml), 세드롤(0.5 ㎍/ml), 위드롤(0.1 ㎍/ml) 전처리시 각각 20.7%, 21.55%, 20.8%로 감소하였으며, live 세포는 DMSO 전처리에 비해 증가하는 것을 확인하였다(도 5). On the other hand, as a result of pretreatment of extracts and compounds, apoptotic cells of L - glutamic acid - induced apoptotic cells were detected in 28.3% of DMSO pretreatment by the addition of scent extract (0.1 ㎍ / ml), siderol (0.5 ㎍ / ml) pretreatment were 20.7%, 21.55% and 20.8%, respectively, and that the live cells were increased compared with the DMSO pretreatment (FIG. 5).
또한, SH-SY5Y 세포에 DMSO를 전처리 한 다음 6-OHDA를 처리한 경우, Live 세포(Annexin V-/7-AAD- 세포)의 비율이 감소하는 반면, apoptotic 세포(Annexin V+ 세포) 비율이 크게 증가하였으며, 이로부터 6-OHDA에 의해 SH-SY5Y 세포의 독성이 유발되어 세포자멸사가 일어나는 것을 알 수 있었다(도 6).In addition, when SH-SY5Y cells were pretreated with DMSO and then treated with 6-OHDA, the proportion of live cells (Annexin V - / 7 - AAD - cells) decreased while apoptotic cells (Annexin V + cells) 6-OHDA induced SH-SY5Y cell toxicity and apoptosis (FIG. 6).
반면 추출물과 화합물을 전처리한 결과, 6-OHDA에 의한 신경세포의 apoptotic 세포는 DMSO 전처리 시 24.7%에서 향나무 추출물 (0.1 ㎍/ml), 세드롤(0.5 ㎍/ml), 위드롤(0.1 ㎍/ml) 전처리시 각각 15.11%, 10.19%, 11.77%로 감소하였으며, live 세포는 DMSO 전처리에 비해 증가하는 것을 확인하였다(도 6).On the other hand, pretreatment of extracts and compounds showed that apoptotic cells of 6-OHDA induced apoptotic cells in 24.7% of DMSO pretreatment with the extract of juniper (0.1 ㎍ / ml), shed (0.5 ㎍ / ml) ml) pretreatment were 15.11%, 10.19%, and 11.77%, respectively, and that the live cells were increased compared with the DMSO pretreatment (FIG. 6).
이러한 결과로부터 향나무 추출물, 위드롤 또는 세드롤에 의한 신경세포 보호 효능 및 파킨슨 병의 치료 효능은 L-글루탐산 또는 6-OHDA에 의해 유발되는 신경세포의 세포자멸사를 저해함으로써 나타나는 것을 알 수 있었다.From these results, it was found that the effect of protecting the nerve cell by the scent extract, the weed roll or the shed roll, and the therapeutic effect of Parkinson's disease are caused by inhibiting the apoptosis of neurons induced by L-glutamic acid or 6-OHDA.
이상의 설명으로부터, 본 발명이 속하는 기술분야의 당업자는 본 발명이 그 기술적 사상이나 필수적 특징을 변경하지 않고서 다른 구체적인 형태로 실시될 수 있다는 것을 이해할 수 있을 것이다. 이와 관련하여, 이상에서 기술한 실시예들은 모든 면에서 예시적인 것이며 한정적인 것이 아닌 것으로 이해해야만 한다. 본 발명의 범위는 상기 상세한 설명보다는 후술하는 특허 청구범위의 의미 및 범위 그리고 그 등가 개념으로부터 도출되는 모든 변경 또는 변형된 형태가 본 발명의 범위에 포함되는 것으로 해석되어야 한다.From the above description, it will be understood by those skilled in the art that the present invention may be embodied in other specific forms without departing from the spirit or essential characteristics thereof. In this regard, it should be understood that the embodiments described above are illustrative in all aspects and not restrictive. The scope of the present invention should be construed as being included in the scope of the present invention without departing from the scope of the present invention as defined by the appended claims.
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