KR20140054536A - Composition for prevention and treatment of skin diseases containing quercetagetin - Google Patents
Composition for prevention and treatment of skin diseases containing quercetagetin Download PDFInfo
- Publication number
- KR20140054536A KR20140054536A KR1020120120124A KR20120120124A KR20140054536A KR 20140054536 A KR20140054536 A KR 20140054536A KR 1020120120124 A KR1020120120124 A KR 1020120120124A KR 20120120124 A KR20120120124 A KR 20120120124A KR 20140054536 A KR20140054536 A KR 20140054536A
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- skin diseases
- composition
- quercetagetin
- prevention
- treatment
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Abstract
Description
본 발명은 피부질환 예방 및 치료용 조성물에 관한 것으로, 더욱 상세하게는 쿼세타제틴(quercetagetin)을 유효성분으로 함유하는 것을 특징으로 하는 피부질환 예방 및 치료용 약제 조성물 또는 피부질환 개선용 식품 조성물에 관한 것이다.
The present invention relates to a composition for preventing and treating skin diseases, and more particularly, to a pharmaceutical composition for preventing or treating skin diseases or a composition for improving skin diseases, which comprises quercetagetin as an active ingredient .
최근 들어 환경오염의 노출과 스트레스의 증가, 식생활의 변화 등 다양한 외부의 자극에 의하여 현대인에게 피부질환을 포함한 다양한 질환들이 급증하고 있다. 이러한 외부의 자극원으로는 직접적으로 섭취되거나 접촉함으로써 질환을 일으키는 것들도 있는 반면, 자외선과 같이 쉽게 인지할 수는 없지만 항상 노출되어 있고 피할 수 없는 자극원도 있다. In recent years, various diseases including skin diseases have been rapidly increasing in modern people due to various external stimuli such as exposure to environmental pollution, increase in stress, change in diet. Some of these external stimulus sources include those that are ingested or contacted directly to cause disease, while others, such as ultraviolet light, are not readily recognizable but are always exposed and inevitable.
태양 빛은 가시광선, 자외선, 적외선으로 구성되는데, 이 중 자외선은 체내에서 비타민 D를 합성하고, 살균작용과 같은 좋은 작용을 하는 반면, 환경오염으로 오존층이 파괴되어 쉽게 노출될 수 있는 강력한 자극원으로서 장시간 지속적으로 노출될 시 피부염증, 피부암과 같은 다양한 피부질환을 유도할 수 있다. 이러한 자외선은 그 파장에 따라 A, B, C로 구분되는데, 이중 UVC는 대부분 오존층에 의하여 차단되며, UVA(320~400 nm)와 UVB(280~320 nm)가 지구표면에 도달하여 피부질환을 초래할 수 있다(Matsumura, Y. and Ananthaswamy, H.N. Expert Rev Mol Med . 4:1-22, 2002; Afaq, F., Adhami, V.M. and Mukhtar, H. Mutat. Res . 571,153-73, 2005). 특히, UVB(290~320 nm)는 비교적 낮은 조사강도로 피부질환을 초래할 수 있기 때문에, 피부 질환연구에 주로 UVB 영역의 파장을 이용한다(Bode, A.M. and Dong, Z., SciSTKE . 2003; Matsumura, Y. and Ananthaswamy, H.N. Expert Rev Mol Med. 4:1-22, 2002). 하지만, 95% 이상의 UVA와 5% 미만의 UVB가 지구표면에 전달되기 때문에, 자외선 조사에 의한 피부질환의 정확한 연구를 위해서는 자연광과 유사한 비율의 UVA와 UVB를 동시에 조사할 수 있는 시스템 개발이 필요하다고 할 수 있다. The sunlight consists of visible light, ultraviolet rays, and infrared rays. Among them, ultraviolet rays synthesize vitamin D in the body and perform a good function such as sterilization. On the other hand, a strong stimulus source Such as skin irritation and skin cancer, can be induced when exposed for a long time. These ultraviolet rays are classified into A, B and C according to their wavelengths. Most UVC is blocked by the ozone layer, and UVA (320 to 400 nm) and UVB (280 to 320 nm) (Matsumura, Y. and Ananthaswamy, HNExpert Rev Mol Med .4:1-22, 2002; Afaq, F., Adhami, V.M. and Mukhtar, H.Mutat. Res .571, 153-73, 2005). In particular, since UVB (290 to 320 nm) can cause skin diseases at a relatively low irradiation intensity, wavelengths of the UVB region are mainly used for skin disease studies (Bode, A. M. and Dong, Z.,SciSTKE .2003; Matsumura, Y. and Ananthaswamy, H.N.Expert Rev Mol Med.4:1-22, 2002). However, since more than 95% of UVA and less than 5% of UVB are transmitted to the earth's surface, it is necessary to develop a system capable of simultaneously irradiating UVA and UVB at a similar rate to natural light in order to accurately study skin diseases caused by UV irradiation can do.
한편, 염증은 암, 심혈관 질환, 치매, 당뇨, 비만 등의 다양한 질환의 원인이 된다. 특히, 그 치료가 어려운 만성 및 퇴행성 질환 치료에 있어서 '염증반응의 조절을 통한 접근'이 새로운 패러다임으로 부각되고 있다(Aggarwal, et al.,Biochemical Pharmacology, 72:1605-1621, 2006, Coussens, et al.,Nature, 420:860-867, 2002, Hwang, et al.,Biochemical pharmacology, 54:87-96, 1997, Turini, et al.,Annual Review of Medicine, 53:35-57, 2002). AP-1(Activator protein-1, 이하 "AP-1"이라 칭함)과 NF-κB(Nuclear factor kappa-light-chain-enhancer of activated B cells, 이하 "NF-κB"라 칭함)는 이러한 염증반응을 조절하는 주요한 전사인자로 이들의 저해제를 이용하여, 피부염증 및 질환을 억제할 수 있음이 보고되고 있다. On the other hand, inflammation causes various diseases such as cancer, cardiovascular disease, dementia, diabetes and obesity. In particular, in the treatment of chronic and degenerative diseases in which the treatment is difficult, 'approach through controlled modulation of the inflammatory reaction' has emerged as a new paradigm (Aggarwal, et al., Biochemical Pharmacology, 72 : 1605-1621, 2006, Coussens, et al, Nature, 420:. 860-867 , 2002, Hwang, et al, Biochemical pharmacology, 54:. 87-96, 1997, Turini, et al, Annual Review of Medicine, 53:. 35-57, 2002). AP-1 (hereinafter referred to as "AP-1") and NF-κB (hereinafter referred to as "NF-κB" Has been reported to be able to inhibit skin inflammation and disease by using their inhibitors as a major transcription factor.
위와 같은 인자들을 조절해서 피부염증 및 피부암을 비롯한 각종 피부 질환을 예방ㆍ치료하려는 시도가 계속되고 있는 가운데, 최근에는 합성물에 비해 인체 안전성이 훨씬 높은 천연물을 이용하여 피부암을 예방하려는 연구가 많이 진행 중이다. 이미 식품에 함유된 각종 파이토케미컬들의 피부암 예방 효능에 대한 연구가 진행되어 있지만, 아직까지 쿼세타제틴(quercetagetin)에 대한 피부염증 및 피부암을 비롯한 피부 질환 예방용 또는 치료용 조성물에 대해서는 개시된 바 없다.
Recently, attempts have been made to prevent skin cancer by using natural substances, which are much more safe than synthetic substances, in an attempt to prevent or treat various skin diseases including skin inflammation and skin cancer by controlling the above factors . Studies on the skin cancer prevention efficacy of various phytochemicals already contained in foods have been conducted, but no compositions for preventing or treating skin diseases including skin inflammation and skin cancer for quercetagetin have been disclosed.
이에 본 발명은 쿼세타제틴(quercetagetin)을 유효성분으로 포함하는 것을 특징으로 하는 피부질환 예방 및 치료용 약제 조성물 또는 피부질환 개선용 식품 조성물을 제공하는데 그 목적이 있다.
Accordingly, it is an object of the present invention to provide a pharmaceutical composition for preventing or treating skin diseases or a composition for improving skin diseases, which comprises quercetagetin as an active ingredient.
상기의 목적을 달성하기 위해 본 발명은 하기의 화학식 1의 구조를 갖는 쿼세타제틴(quercetagetin)을 유효성분으로 포함하는 것을 특징으로 하는 피부질환 예방 및 치료용 약제 조성물을 제공한다.In order to achieve the above object, the present invention provides a pharmaceutical composition for preventing and treating skin diseases, which comprises quercetagetin having the structure of the following formula (1) as an active ingredient.
또한, 본 발명은 화학식 1의 구조를 갖는 쿼세타제틴(quercetagetin)을 유효성분으로 포함하는 것을 특징으로 하는 피부질환 개선용 식품 조성물을 제공한다.Also, the present invention provides a food composition for improving skin diseases, which comprises quercetagetin having the structure of Chemical Formula 1 as an active ingredient.
[화학식 1][Chemical Formula 1]
이하, 본 발명의 과제 해결 수단에 대해 상세히 설명하고자 한다. Hereinafter, the means for solving the problems of the present invention will be described in detail.
염증반응과 관련된 전사인자로 AP-1(Activator Protein-1, 이하 "AP-1"이라 함)과 NF-κB(Nuclear factor kappa-light-chain-enhancer of activated B cells, 이하 "NF-κB"라 함)가 있는데, 이들은 염증에 관련되는 여러 신호전달 체계에 의해 활성화되고, 염증 반응을 매개하는 것으로 알려져 있다. 한편, 자외선 조사와 같은 암을 유발하는 다양한 암 원인 물질은 신호전달 물질을 통해 암 개시 및 촉진과정을 유발한다. 다양한 신호전달 물질 중 MAPKs(Mitogen-activated protein kinase)는 세포의 성장, 분화, 세포사멸 등을 조절하여 암 개시 및 촉진과정을 유발하는데 중요한 역할을 한다고 보고되어 있으며(Bode, A.M. and Dong, Z., SciSTKE. 2003), JNK(c-Jun N-terminal kinase), PI3K(phosphoinositide 3-kinase)도 염증반응을 조절하는 중요한 신호전달 단백질로 알려져 있다.AP-1 (Activator Protein-1, hereinafter referred to as "AP-1") and NF-κB (hereinafter referred to as "NF-κB" ), Which are activated by various inflammatory signaling pathways and are known to mediate inflammatory responses. On the other hand, various cancer causing substances such as ultraviolet irradiation cause cancer initiation and promotion process through signal transduction materials. Among various signal transduction materials, mitogen-activated protein kinase (MAPKs) has been reported to play an important role in inducing cancer initiation and promoting processes by regulating cell growth, differentiation, and apoptosis (Bode, AM and Dong, Z. , SciSTKE. 2003), JNK (c-Jun N-terminal kinase) and PI3K (phosphoinositide 3-kinase) are known to be important signal transduction proteins that regulate the inflammatory response.
본 발명에서는 자연광과 유사한 비율의 자외선(UVA 30 kJ/m2 와 UVB 1.8 kJ/m2)을 개발하여 "S-UV"라고 칭하고, 세포주에 쿼세타제틴(quercetagetin)을 도포한 후, SUV를 처리한 결과, 세포주 모델에서 쿼세타제틴(quercetagetin)에 의해 JNK 및 PI3K 신호전달 단백질의 인산화가 억제되며, 쿼세타제틴(quercetagetin)은 각종 발암물질 및 암 유발 유전자 등으로 유도되는 암세포화를 억제하는 효능이 있으며, 피부염증의 지표인 AP-1, NF-κB의 활성을 억제하는 효능이 있음을 확인하였다. In the present invention, ultraviolet rays (
본 발명의 피부질환 예방 및 치료용 약제 조성물에 포함되는 쿼세타제틴(quercetagetin)의 함량은, 예방 및 치료제의 사용방법, 복용자의 상태, 질환의 종류 및 질환의 중증 정도에 따라 바람직하게 조절하는 것이 좋다. 본 발명의 조성물에서 쿼세타제틴(quercetagetin)의 함량은 0.000001~50중량% 일 수 있으나, 반드시 이에 한정되는 것은 아니다. 그러나, 그 함량이 0.000001중량% 미만일 경우에는 그 효과가 미비하고, 50중량%를 초과하는 경우에는 사용량 대비 효과 상승률이 낮아 비경제적일 수 있다.The content of quercetagetin contained in the pharmaceutical composition for prevention and treatment of skin diseases of the present invention is preferably adjusted depending on the use of the preventive and therapeutic agent, the condition of the recipient, the kind of the disease and the severity of the disease good. The content of quercetagetin in the composition of the present invention may be 0.000001 to 50% by weight, but is not limited thereto. However, when the content is less than 0.000001% by weight, the effect is insufficient. When the content is more than 50% by weight, the rate of increase in the effect relative to the usage amount is low, which may be uneconomical.
한편, 본 발명의 피부질환 예방 및 치료용 약제 조성물에 함유되는 쿼세타제틴(quercetagetin)의 농도는 바람직하게 10 μM∼1 mM인 것이 좋은데, 반드시 이에 한정되지는 아니한다.Meanwhile, the concentration of quercetagetin contained in the pharmaceutical composition for skin disease prevention and treatment of the present invention is preferably 10 μM to 1 mM, but is not limited thereto.
한편, 본 발명의 피부질환 예방 및 치료용 약제 조성물은 유효성분 이외에 약제학적으로 허용 가능한 담체, 희석제 또는 부형제를 더욱 포함할 수 있다. 사용가능한 담체, 부형제 또는 희석제로는, 락토즈, 덱스트로즈, 수크로즈, 솔비톨, 만니톨, 자이리톨, 에리스리톨, 말티톨, 전분, 아카시아 고무, 알지네이트, 젤라틴, 칼슘 포스페이트, 칼슘 실리케이트, 셀룰로즈, 메틸 셀룰로즈, 미정질 셀룰로즈, 폴리비닐피롤리돈, 물, 메틸하이드록시벤조에이트, 프로필하이드록시벤조에이트, 탈크, 마그네슘 스테아레이트 및 광물유가 있으며, 이들은 1종 이상 사용될 수 있다. 또한, 예방 및 치료제가 약제인 경우 충진제, 항응집제, 윤활제, 습윤제, 향료, 유화제 또는 방부제 등이 추가적으로 포함될 수 있다. Meanwhile, the pharmaceutical composition for preventing or treating skin diseases according to the present invention may further comprise a pharmaceutically acceptable carrier, diluent or excipient in addition to the active ingredient. Examples of usable carriers, excipients or diluents include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia rubber, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methylcellulose, Microcrystalline cellulose, polyvinylpyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil. These may be used singly or in combination. When the preventive and therapeutic agent is a pharmaceutical agent, a filler, an anticoagulant, a lubricant, a wetting agent, a flavoring agent, an emulsifying agent or an antiseptic agent may be additionally included.
한편, 본 발명의 피부질환 예방 및 치료용 약제 조성물의 제형은 사용방법에 따라 바람직한 형태일 수 있으며, 당업계에 공지된 방법을 채택하여 제형화 하는 것이 좋다. 구체적인 제형의 예로는 경고제(PLASTERS), 과립제(GRANULES), 로션제(LPTIONS), 리니멘트제(LINIMENTS), 리모나데제(LEMONADES), 방향수제(AROMATIC WATERS), 산제(POWDERS), 시럽제(SYRUPS), 안연고제(OPHTALMIC OINTMENTS), 액제(LIQUIDS AND SOLUTIONS), 에어로솔제(AEROSOLS), 엑스제(EXTRACTS), 엘릭실제(ELIXIRS), 연고제(OINTMENTS), 유동엑스제(FLUIDEXTRACTS), 유제(EMULSIONS), 현탁제(SUSPESIONS), 전제(DECOCTIONS), 침제(INFUSIONS), 점안제(OPHTHALMIC SOLUTIONS), 정제(TABLETS), 좌제(SUPPOSITIORIES), 주사제(INJECTIONS), 주정제(SPIRITS), 카타플라스마제(CATAPLSMA), 캅셀제(CAPSULES), 크림제(CREAMS), 트로키제(TROCHES), 틴크제(TINCTURES), 파스타제(PASTES), 환제(PILLS), 연질 및 경질 젤라틴 캅셀 중 선택되는 어느 하나일 수 있다. Meanwhile, the pharmaceutical composition for prevention and treatment of skin diseases according to the present invention may be in a form suitable for the method of use, and may be formulated by employing a method known in the art. Examples of specific formulations include PLASTERS, GRANULES, LPTIONS, LINIMENTS, LEMONADES, AROMATIC WATERS, POWDERS, Syrups, SYRUPS, OPHTALMIC OINTMENTS, LIQUIDS AND SOLUTIONS, AEROSOLS, EXTRACTS, ELIXIRS, OINTMENTS, FLUIDEXTRACTS, EMULSIONS, ), Suspensions, DECOCTIONS, INFUSIONS, OPHTHALMIC SOLUTIONS, TABLETS, SUPPOSITIORIES, INJECTIONS, SPIRITS, CATAPLSMA, ), Capsules (CAPSULES), creams (CREAMS), troches (TROCHES), TINCTURES, PASTES, PILLS, soft and hard gelatin capsules.
한편, 본 발명의 피부질환 예방 및 치료용 약제 조성물의 투여량은 투여방법, 복용자의 연령, 성별, 체중 및 질환의 중증도 등을 고려하여 결정하는 것이 좋다. 일예로, 본 발명의 피부질환 예방 및 치료용 약제 조성물은 유효성분을 기준으로 하였을 때 1일 0.1 내지 100 ㎎/㎏(체중)으로 1회 이상 투여가능하다. 그러나 상기의 투여량은 예시하기 위한 일 예에 불과하며, 복용자의 상태에 따라 의사의 처방에 의해 변화될 수 있다.Meanwhile, the dose of the pharmaceutical composition for preventing or treating skin diseases of the present invention is preferably determined in consideration of the administration method, the age, sex, weight and severity of the disease. For example, the pharmaceutical composition for skin disease prevention and treatment of the present invention may be administered at least once at a dose of 0.1 to 100 mg / kg (body weight) per day based on the active ingredient. However, the dosage is only an example and may be changed by a doctor's prescription depending on the condition of the recipient.
본 발명은 쿼세타제틴(quercetagetin)을 유효성분으로 함유하는 것을 특징으로 하는 피부질환 개선용 식품 조성물을 제공하는데, 쿼세타제틴(quercetagetin)은 바람직하게 피부질환 개선용 식품 조성물 대비 0.000001∼50중량% 포함되는 것이 좋다. 0.000001중량% 미만일 경우에는 그 효과가 미비하고, 50중량%를 초과하는 경우에는 사용량 대비 효과 증가가 미미하여 비경제적이다. The present invention provides a food composition for improving skin diseases, which comprises quercetagetin as an active ingredient, wherein quercetagetin is preferably used in an amount of 0.000001 to 50% by weight, It should be included. When the amount is less than 0.000001% by weight, the effect is insufficient. When the amount is more than 50% by weight, the increase in the effect on the usage amount is insignificant, which is uneconomical.
한편, 본 발명의 피부질환 개선용 식품 조성물은 바람직하게 육류, 곡류, 카페인 음료, 일반음료, 초콜렛, 빵류, 스넥류, 과자류, 피자, 젤리, 면류, 껌류, 아이스크림류, 알코올성 음료, 술, 비타민 복합제 및 그 밖의 건강보조식품류 중 선택되는 어느 하나인 것인 것이 좋으나, 반드시 이에 한정되는 것은 아니다. Meanwhile, the food composition for improving skin diseases according to the present invention preferably contains at least one selected from the group consisting of meat, cereal, caffeinated beverages, ordinary beverages, chocolates, breads, snacks, confectionery, pizza, jelly, noodles, gums, ice cream, And other health supplement foods. However, the present invention is not limited thereto.
한편, "유효성분으로 포함된다"는 의미는 본 발명의 쿼세타제틴(quercetagetin)으로부터 피부질환의 예방 및 억제 효능이라는 약리효과를 나타낼 수 있는 정도로 피부질환 예방 및 치료용 약제 조성물 또는 피부질환 개선용 식품 조성물에 쿼세타제틴(quercetagetin)이 첨가되는 것을 의미하고, 약물전달 및 안정화 등을 위하여 다양한 성분을 부성분으로 첨가하여 다양한 형태로 포뮬레이션(formulation)되는 것을 포함하는 의미이다.
On the other hand, the term "included as an active ingredient" means that the quercetagetin of the present invention has a drug effect for preventing and treating skin diseases, Means that quercetagetin is added to a food composition, and it is meant that various components are formulated into various forms by adding various ingredients for drug delivery and stabilization.
본 발명에 의하면 피부질환 예방 및 치료용 약제 조성물 또는 피부질환 개선용 식품 조성물에 유효성분으로 함유된 쿼세타제틴(quercetagetin)이 JNK-1, PI3K와 직접결합하여, 피부염증 및 피부암과 같은 피부질환의 발생을 감소시킨다. 뿐만 아니라, S-UV의 조사에 의해 증가한 AP-1, NF-κB의 활성을 억제하며, S-UV의 조사에 의해 증가한 c-jun, Akt, GSK3β의 인산화를 감소시키는 효과를 발휘한다.
According to the present invention, quercetagetin, which is an active ingredient, is directly bound to JNK-1 and PI3K in a pharmaceutical composition for preventing or treating skin diseases or a skin disease-improving food composition, . In addition, it inhibits the activity of AP-1 and NF-κB which are increased by irradiation with S-UV, and exhibits an effect of reducing the phosphorylation of c-jun, Akt and GSK3β increased by S-UV irradiation.
도 1은 쿼세타제틴(quercetagetin)에 의한 피부암발생 억제 효과를 나타낸 도이다.
도 2는 상기 군에서 발생한 종양의 개수를 분석한 도이다.
도 3은 상기 군에서 발생한 종양의 크기를 분석한 도이다.
도 4는 쿼세타제틴(quercetagetin)에 의한 JNK 신호전달체계의 억제 효과를 나타낸 도이다.
도 5는 쿼세타제틴(quercetagetin)에 의한 PI3K 신호전달체계의 억제 효과를 나타낸 도이다.
도 6은 쿼세타제틴(quercetagetin)에 의한 AP-1 활성의 억제 효과를 나타낸 도이다.
도 7은 쿼세타제틴(quercetagetin)에 의한 NF-κB 활성의 억제 효과를 나타낸 도이다.
도 8은 쿼세타제틴(quercetagetin)의 JNK-1의 활성을 억제하는 효과를 나타낸 도이다.
도 9는 쿼세타제틴(quercetagetin)의 JNK-1의 결합활성을 나타낸 도이다.
도 10은 쿼세타제틴(quercetagetin)이 ATP 경쟁적으로 JNK-1에 결합하는지의 여부를 나타낸 도이다.
도 11은 쿼세타제틴(quercetagetin)의 PI3K의 활성을 억제하는 효과를 나타낸 도이다.
도 12는 쿼세타제틴(quercetagetin)의 PI3K의 결합활성을 나타낸 도이다.
도 13은 쿼세타제틴(quercetagetin)이 ATP 경쟁적으로 PI3K에 결합하는지의 여부를 나타낸 도이다. 1 is a graph showing the effect of quercetagetin on skin cancer development.
FIG. 2 is an analysis of the number of tumors in the group. FIG.
FIG. 3 is an analysis of tumor size in the group.
FIG. 4 is a graph showing the inhibitory effect of the JNK signaling system by quercetagetin. FIG.
Figure 5 shows the inhibitory effect of the PI3K signaling system by quercetagetin.
6 is a graph showing the inhibitory effect of quercetagetin on AP-1 activity.
7 is a graph showing the inhibitory effect of quercetagetin on NF-kB activity.
FIG. 8 is a graph showing the effect of quercetagetin inhibiting the activity of JNK-1. FIG.
9 is a graph showing the binding activity of JNK-1 of quercetagetin.
Figure 10 shows whether quercetagetin competitively binds to JNK-1 ATP.
Fig. 11 shows the effect of quercetagetin inhibiting PI3K activity. Fig.
Fig. 12 shows binding activity of PI3K of quercetagetin. Fig.
Figure 13 shows whether quercetagetin binds competitively to PI3K ATP.
이하, 본 발명의 구성 및 작용에 대해 하기 실시예에서 더욱 상세히 설명하고자 한다. 다만, 본 발명의 권리범위가 하기 실시예에만 한정되는 것은 아니고, 그와 등가의 기술적 사상의 변형까지를 포함한다.
Hereinafter, the structure and action of the present invention will be described in more detail in the following examples. However, the scope of the present invention is not limited to the following embodiments, and includes modifications of equivalent technical ideas.
실험예Experimental Example 1: One: 쿼세타제틴(quercetagetin)의Of the quercetagetin S- S- UVUV 에 의해 증가한 피부암 발생 억제 효과Of skin cancer
SKH-1 쥐에 일주일에 3번 쿼세타제틴(quercetagetin)을 등에 도포하고, 1시간 후에 S-UV를 조사하였다. 상기와 같이 처리한 쥐를 28주간 키운 후 등에 생긴 종양의 개수와 크기를 분석하였다.SKH-1 rats were treated with quercetagetin 3 times a week on the back and irradiated with S-
분석결과, S-UV 조사에 의해 증가한 종양의 개수와 크기가 쿼세타제틴(quercetagetin)을 처리한 군에서는 현저하게 감소하는 것을 알 수 있었다(도 1, 도 2, 도 3).
As a result of the analysis, it was found that the number and size of tumors increased by S-UV irradiation were remarkably decreased in the group treated with quercetagetin (FIGS. 1, 2, and 3).
실험예Experimental Example 2: 2: 쿼세타제틴(quercetagetin)의Of the quercetagetin S- S- UVUV 에 의해 증가한 Increased by JNKJNK 및 And PI3KPI3K 신호전달체계 억제 Signaling system inhibition 효과effect
쥐 피부 상피세포인 JB6 P+ 세포를 5% 우태아 혈청(Fetal bovine serum: FBS)과 페니실린/스트렙토마이신 7.5 mg/L를 함유하는 MEM 배지에 2일간 배양 (5 % CO2, 37℃ Forma Scientific Co., Marjetta, OH, USA)한 후에 우태아 혈청을 첨가하지 않은 MEM 배지로 교환하고, 24시간 배양하였다. 이후, 쿼세타제틴(quercetagetin) 첨가 군과 무첨가 군으로 나누어 시료를 첨가한 다음 S-UV를 조사하고 배양기에서 배양하였다. 그 후 JB6 P+ 세포에서 단백질을 분리하여 웨스턴블랏팅을 이용하여 JNK, c-jun, Akt, GSK3β의 인산화 정도를 측정하였다. Rat skin epithelial cells, JB6 P + cells, were cultured in MEM medium containing 5% fetal bovine serum (FBS) and penicillin / streptomycin for 2 days (5% CO2, 37 ° C, form Scientific Co.). , Marjetta, OH, USA) and then exchanged with MEM medium without fetal bovine serum and cultured for 24 hours. Thereafter, the samples were divided into quercetagetin-added group and non-additive group, followed by irradiation with S-UV and culturing in an incubator. The protein was then isolated from JB6 P + cells and the degree of phosphorylation of JNK, c-jun, Akt and GSK3β was measured using Western blotting.
측정결과, S-UV 조사에 의해 증가한 c-jun, Akt, GSK3β의 인산화가 쿼세타제틴(quercetagetin)을 처리한 군에서는 현저하게 감소하는 것을 알 수 있었다(도 4, 도 5). 이에 본 발명은 쿼세타제틴(quercetagetin)이 염증반응을 조절하는 중요한 신호전달체계인 JNK, PI3K 신호전달체계를 저해함을 확인하였고, 쿼세타제틴(quercetagetin)의 항염증 효과를 확인할 수 있었다.
As a result of measurement, phosphorylation of c-jun, Akt and GSK3? Increased by S-UV irradiation was remarkably decreased in the group treated with quercetagetin (FIGS. 4 and 5). Accordingly, the present invention confirmed that quercetagetin inhibits the JNK and PI3K signal transduction systems, which are important signal transduction systems for inflammatory responses, and confirmed the anti-inflammatory effect of quercetagetin.
실험예Experimental Example 3: 3: 쿼세타제틴(quercetagetin)의Of the quercetagetin S- S- UVUV 에 의해 증가한 Increased by APAP -1, -One, NFNF -κB 전사인자 억제 효과-κB transcription factor inhibitory effect
AP-1 및 NF-κB가 결합하는 프로모터 부분에 루시퍼레이즈 효소를 코딩하는 유전자서열을 삽입시킨 JB6 P+ 세포를 이용하여 AP-1과 NF-κB의 활성을 측정하였다. 상기 세포를 5% 우태아 혈청(Fetal bovine serum: FBS)과 페니실린/스트렙토마이신 7.5 mg/L를 함유하는 MEM 배지에 2일간 배양(5 % CO2, 37℃ Forma Scientific Co., Marjetta, OH, USA)한 후에 우태아 혈청을 첨가하지 않은 MEM 배지로 교환하고, 24시간 배양하였다. 이후, 쿼세타제틴(quercetagetin) 첨가 군과 무첨가 군으로 나누어 시료를 첨가후에 S-UV를 조사하고 배양기에서 배양하였다. 그 후 상기 세포를 깨어서 발현된 루시퍼레이즈의 정도를 측정하는 방법으로 AP-1 및 NF-κB의 활성을 측정하였다. The activity of AP-1 and NF-κB was measured using JB6 P + cells in which the gene sequence encoding the luciferase enzyme was inserted into the promoter region to which AP-1 and NF-κB bind. The cells were cultured in MEM medium containing 5% fetal bovine serum (FBS) and penicillin / streptomycin for 2 days (5
측정결과, S-UV 조사에 의해 증가한 AP-1, NF-κB의 활성이 쿼세타제틴(quercetagetin)을 처리한 군에서는 현저하게 감소하는 것을 알 수 있었다(도 6, 도 7). 이에 본 발명은 쿼세타제틴(quercetagetin)이 염증반응과 관련된 AP-1, NF-κB 전사인자의 활성을 저해함을 확인함으로써 쿼세타제틴(quercetagetin)의 항염증 효과를 확인할 수 있었다.
As a result of the measurement, it was found that the activity of AP-1 and NF-κB increased by S-UV irradiation was remarkably decreased in the group treated with quercetagetin (FIGS. 6 and 7). Therefore, the present invention can confirm the anti-inflammatory effect of quercetagetin by confirming that quercetagetin inhibits the activity of AP-1 and NF-κB transcription factors related to the inflammatory reaction.
실험예Experimental Example 4: 4: 쿼세타제틴(quercetagetin)의Of the quercetagetin JNKJNK -1과의 결합을 통한 인산화 활성 저해 효과-1 < / RTI >
쿼세타제틴(quercetagetin)의 JNK-1의 활성억제 효과는 UPSTATE BIOTECHNOLOGY(Upstate Biotechnology, Inc., MA, USA, #14-327)에서 제공하는 방법을 이용하였다. 상기 방법은 쿼세타제틴(quercetagetin)이 JNK-1 인산화 활성을 억제할 경우에 기질에 인산기를 붙이는 능력이 감소하는 것을 방사성동위원소 32P로 표지된 ATP를 이용하여 검출하는 방법이다. 활성화된 JNK-1 단백질과 쿼세타제틴(quercetagetin)을 혼합하고, JNK-1의 기질과 방사성동위원소 32P로 표지된 ATP를 넣고 혼합한 후 JNK-1의 기질에 붙은 방사성동위원소 32P를 검출하는 방법으로 쿼세타제틴(quercetagetin)이 JNK-1 인산화 활성에 미치는 영향을 분석하였다. The inhibitory effect of quercetagetin on the activity of JNK-1 was determined by UPSTATE BIOTECHNOLOGY (Upstate Biotechnology, Inc., MA, USA, # 14-327). The method is a method for detection using a labeled to query theta jetin (quercetagetin) a reduced ability to attach a phosphate group to a substrate in the case to inhibit the phosphorylation of JNK-1 activity with a radioactive isotope 32 P ATP. The activated JNK-1 protein and quercetagetin were mixed, and the substrate of JNK-1 and the radioactive isotope 32 P-labeled ATP were mixed and mixed. The radioactive isotope 32 P attached to the substrate of JNK-1 The effect of quercetagetin on JNK-1 phosphorylation activity was analyzed.
분석결과, 쿼세타제틴(quercetagetin) 고농도 첨가 군에서 JNK-1의 활성이 완전히 억제되었고, 이 효과는 상업적으로 사용되고 있는 JNK-1의 저해제인 SP600215보다 우수한 억제 활성을 나타내었다(도 8). As a result, the activity of JNK-1 was completely inhibited in the quercetagetin-added group at a high concentration, and this effect was superior to that of SP600215, which is a commercial JNK-1 inhibitor (FIG. 8).
또한, JNK-1 단백질에 세파로스 4B(sepharose 4B)와 쿼세타제틴-세파로스 4B(quercetagetin-sepharose 4B)를 각각 첨가하여, 결합활성을 비교한 결과, 세파로스 4B(Sepharose 4B)는 JNK-1과 결합하지 않았지만, 쿼세타제틴-세파로스 4B(quercetagetin-sepharose 4B)는 JNK-1과 결합하는 것을 알 수 있었고(도 9), 쿼세타제틴(quercetagetin)과 JNK-1의 결합은 ATP와 경쟁적임을 확인할 수 있었다(도 10).
실험예Experimental Example 5: 5: 쿼세타제틴(quercetagetin)의Of the quercetagetin PI3KPI3K 와의 결합을 통한 인산화 활성 저해 효과Inhibition of phosphorylation activity by binding with
쿼세타제틴(quercetagetin)의 PI3K의 활성억제 효과는 UPSTATE BIOTECHNOLOGY(Upstate Biotechnology, Inc., MA, USA, #14-602)에서 제공하는 방법을 이용하여 분석하였다. 이 방법은 쿼세타제틴(quercetagetin)이 PI3K 인산화 활성을 억제할 경우에 기질에 인산기를 붙이는 능력이 감소하는 것을 방사성동위원소 32P로 표지된 ATP를 이용하여 검출하는 방법이다. 활성화된 PI3K 단백질과 쿼세타제틴(quercetagetin)을 혼합하고, PI3K의 기질과 방사성동위원소 32P로 표지된 ATP를 넣고 혼합한 후 PI3K의 기질에 붙은 방사성동위원소 32P를 검출하는 방법으로 쿼세타제틴(quercetagetin)이 PI3K 인산화 활성에 미치는 영향을 분석하였다. The inhibitory effect of quercetagetin on PI3K activity was analyzed using the method provided by UPSTATE BIOTECHNOLOGY (Upstate Biotechnology, Inc., MA, USA, # 14-602). This method is a method of detecting, using the query theta jetin (quercetagetin) a cover to the reduced ability to attach a phosphate group to a substrate in the case to inhibit PI3K activity by phosphorylation radioisotopes 32 P ATP. Activated PI3K protein query theta jetin (quercetagetin) a method of mixing, and into the substrate with a radioactive isotope of ATP labeled with 32 P in the PI3K were mixed detecting the radioisotope 32 P attached to the substrate for the PI3K to query theta The effect of quercetagetin on PI3K phosphorylation activity was analyzed.
분석결과, 쿼세타제틴(quercetagetin) 고농도 첨가 군에서 PI3K의 활성이 완전히 억제되었고, 이 효과는 상업적으로 사용되고 있는 PI3K의 저해제인 LY294002보다 우수한 억제 활성을 나타내었다(도 11). As a result, the activity of PI3K was completely inhibited in quercetagetin-added group at a high concentration, and this effect was superior to that of commercially available PI3K inhibitor LY294002 (FIG. 11).
또한, PI3K 단백질에 세파로스 4B(sepharose 4B)와 쿼세타제틴-세파로스 4B(quercetagetin-sepharose 4B)를 각각 첨가하여, 결합활성을 비교한 결과, 세파로스 4B(Sepharose 4B)는 PI3K와 결합하지 않았지만, 쿼세타제틴-세파로스 4B(quercetagetin-sepharose 4B)는 PI3K와 결합하는 것을 알 수 있었고(도 12), 쿼세타제틴(quercetagetin)과 PI3K의 결합은 ATP와 경쟁적임을 확인할 수 있었다(도 13).
Claims (10)
[화학식 1]
A pharmaceutical composition for the prevention and treatment of skin diseases, which comprises quasetazetine having a structure represented by the following formula (1) as an active ingredient.
[Chemical Formula 1]
상기 쿼세타제틴은,
전체 조성물 중 0.000001~50중량% 함유되는 것을 특징으로 하는 피부질환 예방 및 치료용 약제 조성물.
The method according to claim 1,
The quercetzetine,
A pharmaceutical composition for the prevention and treatment of skin diseases, which comprises 0.001 to 50% by weight of the total composition.
상기 쿼세타제틴은,
농도가 10 μM~1 mM인 것을 특징으로 하는 피부질환 예방 및 치료용 약제 조성물.
The method according to claim 1,
The quercetzetine,
Wherein the concentration is 10 [mu] M to 1 mM.
상기 피부질환은,
피부암인 것을 특징으로 하는 피부질환 예방 및 치료용 약제 조성물.
The method according to claim 1,
The skin diseases include,
A pharmaceutical composition for the prevention and treatment of skin diseases, characterized by being skin cancer.
상기 피부질환은,
피부염인 것을 특징으로 하는 피부질환 예방 및 치료용 약제 조성물.
The method according to claim 1,
The skin diseases include,
A pharmaceutical composition for the prevention and treatment of skin diseases, characterized by being a dermatitis.
상기 피부질환 예방 및 치료용 약제 조성물은,
경고제(PLASTERS), 과립제(GRANULES), 로션제(LPTIONS), 리니멘트제(LINIMENTS), 리모나데제(LEMONADES), 방향수제(AROMATIC WATERS), 산제(POWDERS), 시럽제(SYRUPS), 안연고제(OPHTALMIC OINTMENTS), 액제(LIQUIDS AND SOLUTIONS), 에어로솔제(AEROSOLS), 엑스제(EXTRACTS), 엘릭실제(ELIXIRS), 연고제(OINTMENTS), 유동엑스제(FLUIDEXTRACTS), 유제(EMULSIONS), 현탁제(SUSPESIONS), 전제(DECOCTIONS), 침제(INFUSIONS), 점안제(OPHTHALMIC SOLUTIONS), 정제(TABLETS), 좌제(SUPPOSITIORIES), 주사제(INJECTIONS), 주정제(SPIRITS), 카타플라스마제(CATAPLSMA), 캅셀제(CAPSULES), 크림제(CREAMS), 트로키제(TROCHES), 틴크제(TINCTURES), 파스타제(PASTES), 환제(PILLS), 연질 및 경질 젤라틴 캅셀 중 선택되는 어느 하나 이상의 제형인 것을 특징으로 하는 피부질환 예방 및 치료용 약제 조성물.
The method according to claim 1,
The pharmaceutical composition for preventing and treating skin diseases,
It is recommended to use PLASTERS, GRANULES, LPTIONS, LINIMENTS, LEMONADES, AROMATIC WATERS, POWDERS, SYRUPS, OPTICAL OINTMENTS, LIQUIDS AND SOLUTIONS, AEROSOLS, EXTRACTS, ELIXIRS, OINTMENTS, FLUIDEXTRACTS, EMULSIONS, SUSPESIONS, DECOCTIONS, INFUSIONS, OPHTHALMIC SOLUTIONS, TABLETS, SUPPOSITIORIES, INJECTIONS, SPIRITS, CATAPLSMA, CAPSULES, ), A cream (CREAMS), a TROCHES, a TINCTURES, a PASTES, a PILLS, a soft and a hard gelatin capsule. A pharmaceutical composition for prevention and treatment.
[화학식 1]
1. A food composition for improving skin conditions, comprising quercetzetine having a structure represented by the following formula (1) as an active ingredient.
[Chemical Formula 1]
상기 쿼세타제틴은,
전체 조성물 중 0.000001~50중량% 함유되는 것을 특징으로 하는 피부질환 개선용 식품 조성물.
8. The method of claim 7,
The quercetzetine,
Wherein the composition is contained in an amount of 0.000001 to 50% by weight based on the whole composition.
상기 쿼세타제틴은,
농도가 10 μM~1 mM인 것을 특징으로 하는 피부질환 개선용 식품 조성물.
8. The method of claim 7,
The quercetzetine,
Wherein the concentration is 10 μM to 1 mM.
상기 피부질환 예방용 식품 조성물은,
육류, 곡류, 카페인 음료, 일반음료, 초콜렛, 빵류, 스넥류, 과자류, 피자, 젤리, 면류, 껌류, 아이스크림류, 알코올성 음료, 술, 비타민 복합제 및 그 밖의 건강보조식품류 중 선택되는 어느 하나 이상인 것을 특징으로 하는 피부질환 억제용 식품 조성물.8. The method of claim 7,
In the food composition for preventing skin diseases,
And at least one selected from meat, cereal, caffeinated beverages, ordinary beverages, chocolate, bread, snacks, confectionery, pizza, jelly, noodles, gums, ice cream, alcoholic drinks, alcoholic drinks, vitamin complexes and other health supplement foods Wherein the composition is used as a food composition.
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| KR1020120120124A KR20140054536A (en) | 2012-10-29 | 2012-10-29 | Composition for prevention and treatment of skin diseases containing quercetagetin |
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| KR1020120120124A KR20140054536A (en) | 2012-10-29 | 2012-10-29 | Composition for prevention and treatment of skin diseases containing quercetagetin |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2021223682A1 (en) * | 2020-05-06 | 2021-11-11 | 晨光生物科技集团股份有限公司 | Quercetagetin-containing feed and use thereof |
| KR20220093605A (en) | 2020-12-28 | 2022-07-05 | 에이치디씨랩스 주식회사 | Facility Management System and Method for Providing Management Information of Multiple Facilities |
-
2012
- 2012-10-29 KR KR1020120120124A patent/KR20140054536A/en not_active Application Discontinuation
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2021223682A1 (en) * | 2020-05-06 | 2021-11-11 | 晨光生物科技集团股份有限公司 | Quercetagetin-containing feed and use thereof |
| KR20220093605A (en) | 2020-12-28 | 2022-07-05 | 에이치디씨랩스 주식회사 | Facility Management System and Method for Providing Management Information of Multiple Facilities |
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