WO2019009525A1 - Pharmaceutical composition for prevention or treatment of fibrosis containing platycodi radix extract as effective ingredient - Google Patents

Pharmaceutical composition for prevention or treatment of fibrosis containing platycodi radix extract as effective ingredient Download PDF

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WO2019009525A1
WO2019009525A1 PCT/KR2018/006418 KR2018006418W WO2019009525A1 WO 2019009525 A1 WO2019009525 A1 WO 2019009525A1 KR 2018006418 W KR2018006418 W KR 2018006418W WO 2019009525 A1 WO2019009525 A1 WO 2019009525A1
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fibrosis
extract
group
present
preventing
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PCT/KR2018/006418
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French (fr)
Korean (ko)
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최명숙
김예진
권은영
류리
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경북대학교 산학협력단
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/34—Campanulaceae (Bellflower family)
    • A61K36/346—Platycodon
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/105—Plant extracts, their artificial duplicates or their derivatives
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2200/00—Function of food ingredients
    • A23V2200/30—Foods, ingredients or supplements having a functional effect on health

Definitions

  • the present invention relates to a pharmaceutical composition for preventing or treating fibrosis comprising Ganoderma lucidum extract as an active ingredient.
  • Fibrosis is an abnormal accumulation of the collagen matrix due to injury or inflammation that changes the structure and function of various tissues. Regardless of the location of fibrosis, most of the etiology of fibrosis involves excessive accumulation of collagen matrices replacing normal tissue. Progressive fibrosis in the kidney, liver, fat, lung, heart, bone or marrow, and skin is a major cause of death or pain.
  • adipocytes increase the synthesis and secretion of extracellular matrix by macrophage mobilization and invasion, thereby accelerating fibrosis.
  • MMPs matrix metalloproteinases
  • lumican lumican
  • TGF ⁇ transforming growth factor beta
  • TGF [beta] stimulate the production of various extracellular matrix proteins and promote tissue fibrosis by inhibiting degradation (see Korean Patent No. KR 10-1497935).
  • Platycodon grandiflorum also known as bellflower
  • Platycodon grandiflorum is a medicinal herb that is made by removing the roots or juniper of the bellflower, and is said to have a slight smell, taste, and quality.
  • Gyungyung acts on the lungs to treat symptoms that have many seawater and sputum and uncomfortable breathing, and it has the effect of stopping the cough and removing the feces. It is also used when the urine is not visible and there is systemic edema and urine volume is low. Therefore, it is prescribed for sore throat, cold cough, sputum, nasal congestion, asthma, bronchial inflammation, pleurisy, headache, chills and tonsillitis.
  • the pharmacological action was reported to be the action of gadam, the cholesterol lowering action, However, the effect of treatment of fibrosis of Gil-gyeung has not been revealed to date.
  • the inventors of the present invention conducted a study to develop a novel therapeutic agent for fibrosis, and as a result, the present inventors completed the present invention by confirming that Gakyung Extract has an excellent effect of inhibiting the accumulation of connective tissue in adipose tissue.
  • the present invention aims to provide a pharmaceutical composition for preventing or treating fibrosis comprising Ganoderma lucidum extract as an active ingredient.
  • the present invention also relates to a health functional food for preventing or ameliorating fibrosis comprising Ganoderma lucidum extract as an active ingredient.
  • the fibrosis includes adipocytopenia.
  • the present invention provides a method for producing a ginseng extract comprising Ganoderma lucidum extract as an active ingredient.
  • a pharmaceutical composition for preventing or treating fibrosis is provided.
  • the present invention provides a health functional food for preventing or ameliorating fibrosis, comprising Ganoderma lucidum extract as an active ingredient.
  • the extract is selected from the group consisting of water, C 1 to C 4 lower alcohols, n-hexane, ethyl acetate, acetone, butyl acetate, 1,3-butylene glycol, methylene chloride, Or may be extracted with a solvent selected from the group consisting of.
  • the extract of Ganoderma lucidum is selected from the group consisting of matrix metalloproteinases (MMPs), Cd44 (CD antigen 44), Lum (lumican), TGF (transforming growth factor?) And cathepsin It is possible to inhibit expression above the species.
  • MMPs matrix metalloproteinases
  • Cd44 CD antigen 44
  • Lum lumican
  • TGF transforming growth factor
  • the present invention also provides a method of preventing or treating fibrosis, comprising administering the composition to a subject.
  • the present invention provides the use of the composition for preventing or treating fibrosis.
  • the fibrosis may be adipocytopenia.
  • the extract of Ganoderma lucidum according to the present invention has an excellent effect of inhibiting the accumulation of connective tissue and inhibiting macrophage infiltration in adipose tissue and thus can be usefully used for prevention or treatment of adipocytopenia.
  • FIG. 1 is a graph showing degree of fibrosis in adipose tissues of normal group, fibrosis-induced group, and Gakyung extract-treated group (experimental group).
  • FIG. 2 is a graph showing the degree of transcript expression of collagen, which is the most abundant component in fibrosis-related ECM of adipose tissue.
  • FIG. 3 is a graph showing the results of analysis of inflammation-induced inflammation-induced cytokines and chemokine transcripts in adipose tissue.
  • FIG. 4 shows the results of analysis of Cd44 (CD antigen 44), Lum (lumican), MMPs (matrix metalloproteinases) and TGF ⁇ (transforming growth factor ⁇ ) transcripts, which are factors regulating fibrosis-related ECM expression in adipose tissue .
  • FIG. 5 is a graph showing the results of analysis of transcript expression of a protein hydrolyzable lysosome, cathepsin, involved in the remodeling of fibrosis-related ECM of adipose tissue.
  • the present inventors completed the present invention on the basis of observing the inhibitory effect of Ganoderma lucidum extract on lipid fibrosis as a result of mixing Ganoderma lucidum extract with a high fat diet in dietary obesity-induced mouse model.
  • the present invention relates to a composition containing Ganoderma lucidum extract as an active ingredient.
  • a pharmaceutical composition for preventing or treating fibrosis is provided.
  • &quot means any action that inhibits obesity or delays onset by administration of a pharmaceutical composition according to the present invention.
  • " treatment " as used in the present invention means all the actions for improving or alleviating symptoms of obesity by administration of the pharmaceutical composition according to the present invention.
  • compositions of the present invention may further comprise suitable carriers, excipients and diluents conventionally used in the manufacture of pharmaceutical compositions.
  • it can be formulated in the form of powders, granules, tablets, capsules, suspensions, emulsions, oral preparations such as syrups and aerosols, external preparations, suppositories and sterilized injection solutions according to a conventional method.
  • suitable formulations known in the art are preferably those disclosed in Remington's Pharmaceutical Science, 18th Ed, Mack Publishing Company, Easton PA.
  • carriers, excipients and diluents which may be included include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia rubber, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methylcellulose, Polyvinylpyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate, and mineral oil.
  • Solid formulations for oral administration include tablets, pills, powders, granules, capsules and the like, which may contain at least one excipient such as starch, calcium carbonate, sucrose, lactose, Gelatin and the like. In addition to simple excipients, lubricants such as magnesium stearate and talc are also used.
  • Liquid preparations for oral administration include suspensions, solutions, emulsions, syrups and the like.
  • excipients such as wetting agents, sweeteners, fragrances, preservatives and the like may be included in addition to water and liquid paraffin, which are simple diluents commonly used. have.
  • Formulations for parenteral administration include sterilized aqueous solutions, non-aqueous solutions, suspensions, emulsions, freeze-dried preparations, and suppositories.
  • the suspending agent include propylene glycol, polyethylene glycol, vegetable oil such as olive oil, injectable ester such as ethyl oleate, and the like.
  • suppository bases include withexol, macrogol, tween 61, cacao butter, laurin, glycerogelatin and the like.
  • the present invention also provides a method of preventing or treating fibrosis, comprising administering the pharmaceutical composition to a subject.
  • Administration " in the present invention means providing the subject invention with a composition of the invention in any suitable manner.
  • &quot refers to a subject in need of treatment of a disease, and more specifically refers to a mammal such as a human or non-human primate, mouse, dog, cat, horse, do.
  • the preferred dosage of the pharmaceutical composition of the present invention varies depending on the condition and the weight of the patient, the degree of disease, the drug form, the administration route and the period, and can be appropriately selected by those skilled in the art.
  • the daily dose of Ganoderma lucidum extract in the composition of the present invention is 1 mg to 5000 mg / kg per day, which may be administered once a day or divided into several times. Accordingly, the dosage is not limited in any way to the scope of the present invention.
  • composition of the present invention may be administered to a subject in various routes. All modes of administration may be expected, for example, by oral, rectal or intravenous, intramuscular, subcutaneous, intra-uterine dural or intracerebral injection.
  • composition of the present invention may contain one or more known active ingredients having an effect of preventing or treating fibrosis in combination with Ganoderma lucidum extract.
  • composition of the present invention can be used alone or in combination with methods using surgery, radiation therapy, hormone therapy, chemotherapy and biological response modifiers for the prevention or treatment of fibrosis.
  • the present invention also provides a health functional food for preventing or ameliorating fibrosis, comprising Ganoderma lucidum extract as an active ingredient.
  • the health functional food refers to a food having a biological control function such as prevention and improvement of disease, bio-defense, immunity, recovery after disease, suppression of aging, and is harmless to human body when taken over a long period of time.
  • the composition of the present invention When the composition of the present invention is used as a food additive, the composition can be added as it is or can be used together with other food or food ingredients, and can be suitably used according to a conventional method.
  • the amount of the active ingredient to be mixed can be suitably determined according to the intended use (prevention, health or therapeutic treatment).
  • the composition of the present invention is added in an amount of not more than 15% by weight, preferably not more than 10% by weight based on the raw material, in the production of food or beverage.
  • the amount may be less than the above range, and since there is no problem in terms of safety, the active ingredient may be used in an amount exceeding the above range.
  • the kind of the food There is no particular limitation on the kind of the food.
  • the foods to which the above substances can be added include dairy products including meat, sausage, bread, chocolate, candy, snacks, confectionery, pizza, ramen noodles, gums, ice cream, various soups, drinks, tea, Alcoholic beverages, and vitamin complexes, all of which include health foods in a conventional sense.
  • composition of the present invention When the composition of the present invention is used in beverages, various flavors or natural carbohydrates such as ordinary beverages may be included as an additional ingredient.
  • natural carbohydrates include monosaccharides such as glucose and fructose, disaccharides such as maltose and sucrose, and natural sweeteners such as dextrin and cyclodextrin, and synthetic sweeteners such as saccharine and aspartame.
  • the ratio of the natural carbohydrate is generally about 0.01 to 10 g, preferably about 0.01 to 0.1 g per 100 ml of the composition of the present invention.
  • composition of the present invention may further contain various nutrients, vitamins, electrolytes, flavors, colorants, pectic acid and salts thereof, alginic acid and salts thereof, organic acids, protective colloid thickeners, pH adjusters, stabilizers, preservatives, glycerin, A carbonating agent used in a carbonated beverage, and the like.
  • composition of the present invention may comprise flesh for the production of natural fruit juices, fruit juice drinks and vegetable drinks. These components may be used independently or in combination. Although the ratio of such additives is not critical, it is generally selected in the range of 0.01 to 0.1 parts by weight per 100 parts by weight of the composition of the present invention.
  • the extract of Ganoderma lucidum of the present invention can be extracted according to a conventional method known in the art for extracting an active ingredient from a natural product, that is, using a conventional solvent under the conditions of ordinary temperature and pressure.
  • the extract of Ganoderma lucidum is selected from the group consisting of water, an alcohol having 1 to 4 carbon atoms, n-hexane, ethyl acetate, acetone, butyl acetate, 1,3-butylene glycol, methylene chloride, Can be extracted using one or more selected solvents, preferably ethanol, and more preferably 70% ethanol.
  • the method for extracting the extract from Ganoderma lucidum can be extracted by various methods such as hot water extraction, cold extraction, reflux extraction, ultrasonic extraction and the like, but is not limited thereto.
  • the extract thus prepared may be filtered, concentrated or dried to remove the solvent, and may be subjected to both filtration, concentration and drying.
  • the filtration can be performed using a filter paper or a vacuum filter
  • the concentration can be carried out using a vacuum concentrator
  • the lyophilization can be carried out, but the present invention is not limited thereto.
  • the extract extracted with the solvent may be further subjected to fractionation with a solvent selected from the group consisting of butanol, n-hexane, methylene chloride, acetone, ethyl acetate, ethyl ether, chloroform, water, .
  • the fractionation temperature may be 4 ⁇ to 120 ⁇ , but is not limited thereto.
  • the male C57BL / 6J mice were classified into the group of the normal type, fibrosis induction group, and the Gakyung extract group, and were cultured for 12 weeks.
  • the changes of the fibrosis-related transcript markers of adipose tissue were measured,
  • the expression levels of MMPs (matrix metalloproteinases), Cd44 (CD antigen 44), Lum (lumican), TGF ⁇ (transforming growth factor ⁇ ) and cathepsin were significantly increased (CD antigen 44), Lum (lumican), transforming growth factor ⁇ (TGF ⁇ ) and cathepsin (TGF ⁇ ), which are similar to those of the normal diet, cathepsin) was found to be increased, thereby confirming that the extract of Ganoderma lucidum had an effect of inhibiting adipocyte fibrosis (see Examples 3 to 6).
  • the fibrosis is a disease in which abnormal formation, accumulation and deposition of extracellular matrix occurs.
  • the fibrosis is a fibrosis, fibrosis, renal fibrosis, pulmonary fibrosis, dermal fibrosis, cardiac fibrosis, , Peritoneal fibrosis, and the like, and is preferably, but not limited to, adipocytosis.
  • Gakyung was purchased from Omni Hub Company. After grinding to facilitate extraction, 30 L of 70% ethanol was added per 3 kg of Gyunggi and extracted at 50 °C for 6 hours. The extract was concentrated under reduced pressure at 50 °C and freeze - dried. The yield of Gyungyang extract was calculated as 13.3%.
  • normal diet 10
  • 60% kcal fat fibrosis induction group
  • HFD 12 weeks High-fat diets are known to cause fibrosis by inducing the
  • the collected blood was treated with heparin and centrifuged at 1,000 ⁇ g for 15 min at 4 ° C. Plasma was collected and stored at -70 ° C. until analysis.
  • the rats were rinsed several times with PBS (phosphate buffered saline) solution, and the surface moisture was removed and the weight was measured.
  • the sample was quenched in liquid nitrogen and stored at -70 ° C until analysis.
  • Some of the adipose tissue was also fixed in 10% formaldehyde solution for microscopic analysis.
  • MRNA-sequencing was performed to extract the genes (Differentially Expressed Genes, DEGs) for the evaluation of the control effect of fatty tissue fibrosis according to the gilbang extract administration.
  • the obtained DEGs were fold change more than 2 times Or less), p-value less than 0.05 was cut off, and the extracted DEGs were presented as the normal group and the experimental group as compared to the fibrosis-inducing group.
  • Masson's Trichrome staining of collagen and muscle fibers was performed, and then observed with an optical microscope at a magnification of 400 times.
  • connective tissue (CT) is stained with blue light and nuclei are stained with dark red.
  • CT stained blue is composed of cells, fibers, extracellular matrix (ECM) and body fluids and is used as an indicator of fibrosis.
  • the fibrotic induction group had a large accumulation of CT in the adipocytes, and the experimental group ingested the extract of Gil Gyeonggye showed that the degree of fibrosis was greatly suppressed.
  • ECM collagen was significantly increased in the fibrotic induction group compared to the normal group, whereas collagen transcripts were decreased in the Gakyung extract group as well as the normal group.
  • the statistical significance between the fibrosis-induced group and the normal group was * p ⁇ 0.05, ** p ⁇ 0.01, *** p ⁇ 0.001, ≪ 0.01 and # p ⁇ 0.001.
  • Example 4 Expression of inflammatory cytokines and chemokine transcripts related to fibrosis in adipose tissue
  • the extract of Ganoderma lucidum exhibits an excellent effect for inhibiting the expression of inflammatory cytokines and chemokine transcripts, which are increased by fibrosis.
  • Cd44 CD antigen 44
  • Lum lumican
  • MMPs matrix metalloproteinases
  • TGF [beta] transforming growth factor [beta]
  • Example 6 Analysis of transcript expression of cathepsin involved in remodeling of ECM associated with fibrosis of adipose tissue
  • the extract of Gakkyeong of the present invention has an excellent effect of inhibiting accumulation of connective tissue and inhibiting macrophage infiltration in adipose tissue, and thus it is expected to be usefully used for prevention or treatment of adipocytic fibrosis.

Abstract

The preset invention relates to a pharmaceutical composition for prevention or treatment of steatofibrosis containing a platycodi radix extract as an effective ingredient. The platycodi radix extract according to the present invention has excellent effects of inhibiting accumulation of connective tissue in adipose tissue and inhibiting infiltration of macrophages such that the extract can be effectively used for the prevention or treatment of steatofibrosis.

Description

길경추출물을 유효성분으로 포함하는 섬유증의 예방 또는 치료용 약학적 조성물 A pharmaceutical composition for the prevention or treatment of fibrosis comprising Gakyung extract as an active ingredient
본 발명은 길경추출물을 유효성분으로 포함하는 섬유증의 예방 또는 치료용 약학적 조성물 등에 관한 것이다.The present invention relates to a pharmaceutical composition for preventing or treating fibrosis comprising Ganoderma lucidum extract as an active ingredient.
조직은 세포 외 매트릭스에 결합되어 있고, 혈관 네트워크에 의해 둘러싸여 있는 잘 정돈된 세포 군집을 포함한다. 섬유화 또는 섬유증(Fibrosis)은 다양한 조직의 구조 및 기능을 변화시키는 손상(injury) 또는 염증에 따른 콜라겐 매트릭스의 비정상적인 축적이다. 섬유증의 발생 위치에 무관하게, 섬유증의 대부분의 병인학은 정상 조직을 대체하는 콜라겐 매트릭스의 과도한 축적을 포함한다. 신장, 간, 지방, 폐, 심장, 뼈 또는 골수, 그리고 피부에서의 진행성 섬유화는 사망 또는 고통의 주요한 요인이다.The tissue is bound to an extracellular matrix and includes well organized cell clusters surrounded by a vascular network. Fibrosis is an abnormal accumulation of the collagen matrix due to injury or inflammation that changes the structure and function of various tissues. Regardless of the location of fibrosis, most of the etiology of fibrosis involves excessive accumulation of collagen matrices replacing normal tissue. Progressive fibrosis in the kidney, liver, fat, lung, heart, bone or marrow, and skin is a major cause of death or pain.
고지방 식이 등에 의해 염증유발 케모카인 및 사이토카인이 분비될 경우, 지방 조직에서는 교원질 (collagen)과 같은 과도한 세포외 기질 (extracellular matrix)의 합성이 유도되어 지방세포 사이에 섬유성 물질 (fibrotic material)의 축적을 야기할 뿐만 아니라, 간 조직의 간성상세포를 활성화시켜 지방 조직과 마찬가지로 세포 외 기질이 생성된다. 이때 생성된 세포외 기질은 디세강 (space of Disse) 주위로 흘러들어가 침착되면서 간섬유증을 유발하며, 이 과정이 지속되면 간경변증으로 진행된다 (Henegar, 2008; Mutch, 2009; Bataller, 2005). 또한 지방세포는 대식세포의 동원과 침윤에 의해 세포 외 기질의 합성과 분비를 증가시키며, 이로인해 섬유증이 가속화된다. MMPs(matrix metalloproteinases)는 세포 외 기질의 리모델링을 가능하게 하여 세포 외 기질 발현을 조절하며, MMPs와 함께 lumican (Lum)은 상피세포의 간질세포로의 변이(epithelialmesenchymal transition)를 유도하여 섬유화 상태를 악화시킨다 (Rada, 1993). 사이토카인 중 TGF β(transforming growth factor beta)는 조직의 보수에 중요한 역할을 수행하는 다기능 인자의 일종으로, 대식세포와 같은 침윤세포에 의해서 생산되거나 분비되며, 거의 모든 조직에서 발견된다. 일반적으로 TGF β의 분비와 활성 증가는 다양한 세포 외 기질 단백질의 생성을 자극하고, 분해를 저해함으로써 조직 섬유증을 촉진한다(한국등록특허 KR 10-1497935 참조).Induction of inflammation by high-fat diets When secreted by chemokines and cytokines, synthesis of extracellular matrix, such as collagen, is induced in adipose tissue, resulting in accumulation of fibrotic material between adipocytes As well as activating hepatic stellate cells in the liver tissue and producing extracellular matrix as well as adipose tissue. In this case, the extracellular matrix formed around the space of the disse deposits and causes the hepatic fibrosis. When this process is continued, cirrhosis progresses (Henegar, 2008; Mutch, 2009; Bataller, 2005). In addition, adipocytes increase the synthesis and secretion of extracellular matrix by macrophage mobilization and invasion, thereby accelerating fibrosis. MMPs (matrix metalloproteinases) enable remodeling of extracellular matrix and regulate extracellular matrix expression, and lumican (Lum) together with MMPs induce epithelial mesenchymal transition to the epidermal cells to deteriorate the fibrotic state (Rada, 1993). TGFβ (transforming growth factor beta) in cytokines is a multifunctional factor that plays an important role in the repair of tissues. It is produced or secreted by infiltrating cells such as macrophages, and is found in almost all tissues. In general, secretion and activation of TGF [beta] stimulate the production of various extracellular matrix proteins and promote tissue fibrosis by inhibiting degradation (see Korean Patent No. KR 10-1497935).
한편, 도라지로 잘 알려져 있는 길경(Platycodon grandiflorum)은 길경근으로도 불리며 초롱꽃과의 도라지의 뿌리 또는 주피를 제거하여 만든 약재로서, 냄새가 약간 있고 맛은 쓰고 매우며 성질은 평하다고 알려져 있다. 길경은 폐에 작용하여 해수와 가래가 많고 호흡이 불편한 증상을 치료하며 기침을 멈추고 담을 없애는 효과가 있다. 또한, 소변을 잘 보지 못하여 전신부종이 있고 소변양이 적을 때도 사용한다. 따라서 인후통, 감기로 인한 기침, 가래, 코막힘, 천식, 기관지염증, 흉막염, 두통, 오한, 편도선염 등에 처방되어 사용한다. 약리작용으로는 거담작용, 콜레스테롤 강하작용, 및 개선균 억제작용 등이 보고되었다. 그러나, 현재까지 길경의 섬유증 치료 효과에 대해서는 밝혀진 바가 없다.Platycodon grandiflorum, also known as bellflower, is a medicinal herb that is made by removing the roots or juniper of the bellflower, and is said to have a slight smell, taste, and quality. Gyungyung acts on the lungs to treat symptoms that have many seawater and sputum and uncomfortable breathing, and it has the effect of stopping the cough and removing the feces. It is also used when the urine is not visible and there is systemic edema and urine volume is low. Therefore, it is prescribed for sore throat, cold cough, sputum, nasal congestion, asthma, bronchial inflammation, pleurisy, headache, chills and tonsillitis. The pharmacological action was reported to be the action of gadam, the cholesterol lowering action, However, the effect of treatment of fibrosis of Gil-gyeung has not been revealed to date.
이에 본 발명자들은 새로운 섬유증 치료 약물을 개발하기 위해 연구를 수행한 결과, 길경추출물이 지방 조직에서 결합 조직의 축적을 억제하는 우수한 효과를 가지고 있음을 확인함으로써, 본 발명을 완성하였다.Therefore, the inventors of the present invention conducted a study to develop a novel therapeutic agent for fibrosis, and as a result, the present inventors completed the present invention by confirming that Gakyung Extract has an excellent effect of inhibiting the accumulation of connective tissue in adipose tissue.
본 발명은 길경추출물을 유효성분으로 포함하는 섬유증의 예방 또는 치료용 약학적 조성물을 제공하는 것을 목적으로 한다.The present invention aims to provide a pharmaceutical composition for preventing or treating fibrosis comprising Ganoderma lucidum extract as an active ingredient.
또한, 본 발명은 길경추출물을 유효성분으로 포함하는 섬유증의 예방 또는 개선용 건강기능식품에 관한 것이다.The present invention also relates to a health functional food for preventing or ameliorating fibrosis comprising Ganoderma lucidum extract as an active ingredient.
본 발명에서 상기 섬유증은 지방 섬유증을 포함한다.In the present invention, the fibrosis includes adipocytopenia.
그러나 본 발명이 이루고자 하는 기술적 과제는 이상에서 언급한 과제에 제한되지 않으며, 언급되지 않은 또 다른 과제들은 아래의 기재로부터 본 발명이 속하는 기술 분야의 통상의 지식을 가진 자에게 명확하게 이해될 수 있을 것이다.However, the technical problem to be solved by the present invention is not limited to the above-mentioned problems and other problems not mentioned can be clearly understood by those skilled in the art from the following description will be.
상기 목적을 달성하기 위하여, 본 발명은 길경추출물을 유효성분으로 포함하는. 섬유증의 예방 또는 치료용 약학적 조성물을 제공한다.In order to accomplish the above object, the present invention provides a method for producing a ginseng extract comprising Ganoderma lucidum extract as an active ingredient. A pharmaceutical composition for preventing or treating fibrosis is provided.
또한, 본 발명은 길경추출물을 유효성분으로 포함하는, 섬유증의 예방 또는 개선용 건강기능식품을 제공한다.In addition, the present invention provides a health functional food for preventing or ameliorating fibrosis, comprising Ganoderma lucidum extract as an active ingredient.
본 발명의 일 구현예로, 상기 길경추출물은 물, C₁내지 C₄의 저급알코올, n-헥산, 에틸아세테이트, 아세톤, 부틸아세테이트, 1,3-부틸렌 글리콜, 메틸렌클로라이드, 및 이들의 혼합용매로 이루어진 군에서 선택된 용매로 추출된 것일 수 있다.In one embodiment of the present invention, the extract is selected from the group consisting of water, C 1 to C 4 lower alcohols, n-hexane, ethyl acetate, acetone, butyl acetate, 1,3-butylene glycol, methylene chloride, Or may be extracted with a solvent selected from the group consisting of.
본 발명의 다른 구현예로, 상기 길경추출물은 MMPs(matrix metalloproteinases), Cd44 (CD antigen 44), Lum(lumican), TGF β(transforming growth factor β) 및 카텝신(cathepsin)으로 이루어진 군에서 선택된 1종 이상의 발현을 억제시킬 수 있다.In another embodiment of the present invention, the extract of Ganoderma lucidum is selected from the group consisting of matrix metalloproteinases (MMPs), Cd44 (CD antigen 44), Lum (lumican), TGF (transforming growth factor?) And cathepsin It is possible to inhibit expression above the species.
또한, 본 발명은 상기 조성물을 개체에 투여하는 단계를 포함하는, 섬유증의 예방 또는 치료 방법을 제공한다.The present invention also provides a method of preventing or treating fibrosis, comprising administering the composition to a subject.
또한, 본 발명은 상기 조성물의 섬유증 예방 또는 치료 용도를 제공한다.In addition, the present invention provides the use of the composition for preventing or treating fibrosis.
본 발명의 일 구현예로, 상기 섬유증은 지방 섬유증일 수 있다.In one embodiment of the present invention, the fibrosis may be adipocytopenia.
본 발명에 따른 길경추출물은 지방 조직에서 결합 조직의 축적을 억제하고 대식세포의 침윤을 억제하는 우수한 효과를 가지고 있어, 지방 섬유증의 예방 또는 치료에 유용하게 이용될 수 있다.The extract of Ganoderma lucidum according to the present invention has an excellent effect of inhibiting the accumulation of connective tissue and inhibiting macrophage infiltration in adipose tissue and thus can be usefully used for prevention or treatment of adipocytopenia.
도 1은 정상군, 섬유증 유도군 및 길경추출물 투여군(실험군)의 지방 조직에서의 섬유화 정도를 나타낸 도이다.FIG. 1 is a graph showing degree of fibrosis in adipose tissues of normal group, fibrosis-induced group, and Gakyung extract-treated group (experimental group).
도 2는 지방 조직의 섬유화 관련 ECM에서 가장 풍부하게 존재하는 성분인 콜라겐들의 전사체 발현정도를 나타낸 도이다.FIG. 2 is a graph showing the degree of transcript expression of collagen, which is the most abundant component in fibrosis-related ECM of adipose tissue.
도 3은 지방 조직의 섬유화 관련 염증 유도성 사이토카인 및 케모카인 전사체 발현을 분석한 결과를 나타낸 도이다.FIG. 3 is a graph showing the results of analysis of inflammation-induced inflammation-induced cytokines and chemokine transcripts in adipose tissue.
도 4는 지방조직의 섬유화 관련 ECM 발현을 조절하는 인자인 Cd44(CD antigen 44), Lum(lumican), MMPs(matrix metalloproteinases) 및 TGF β(transforming growth factor β) 전사체 발현을 분석한 결과를 나타낸 도이다.FIG. 4 shows the results of analysis of Cd44 (CD antigen 44), Lum (lumican), MMPs (matrix metalloproteinases) and TGFβ (transforming growth factor β) transcripts, which are factors regulating fibrosis-related ECM expression in adipose tissue .
도 5는 지방조직의 섬유화 관련 ECM의 리모델링에 관여하는 단백질 가수분해성 리소좀 효소(lysosome)인 카텝신의 전사체 발현을 분석한 결과를 나타낸 도이다.FIG. 5 is a graph showing the results of analysis of transcript expression of a protein hydrolyzable lysosome, cathepsin, involved in the remodeling of fibrosis-related ECM of adipose tissue.
본 발명자들은 식이성 비만 유도 마우스 모델에서 길경추출물을 고지방식이에 혼합하여 급여시키며 관찰한 결과, 길경추출물의 지방 섬유증에 대한 억제 효과를 관찰함으로써 이에 기초하여 본 발명을 완성하였다.The present inventors completed the present invention on the basis of observing the inhibitory effect of Ganoderma lucidum extract on lipid fibrosis as a result of mixing Ganoderma lucidum extract with a high fat diet in dietary obesity-induced mouse model.
이에, 본 발명은 길경추출물을 유효성분으로 포함하는. 섬유증의 예방 또는 치료용 약학적 조성물을 제공한다.Accordingly, the present invention relates to a composition containing Ganoderma lucidum extract as an active ingredient. A pharmaceutical composition for preventing or treating fibrosis is provided.
본 발명에서 사용되는 용어, “예방”이란 본 발명에 따른 약학적 조성물의 투여에 의해 비만을 억제시키거나 발병을 지연시키는 모든 행위를 의미한다.As used herein, the term " prophylactic " means any action that inhibits obesity or delays onset by administration of a pharmaceutical composition according to the present invention.
본 발명에서 사용되는 용어, “치료”란 본 발명에 따른 약학적 조성물의 투여에 의해 비만에 대한 증세가 호전되거나 이롭게 변경되는 모든 행위를 의미한다.The term " treatment " as used in the present invention means all the actions for improving or alleviating symptoms of obesity by administration of the pharmaceutical composition according to the present invention.
본 발명의 약학적 조성물은 약학적 조성물의 제조에 통상적으로 사용하는 적절한 담체, 부형제 및 희석제를 더 포함할 수 있다. 또한 통상의 방법에 따라 산제, 과립제, 정제, 캡슐제, 현탁액, 에멀젼, 시럽, 에어로졸 등의 경구형 제형, 외용제, 좌제 및 멸균 주사용액의 형태로 제형화하여 사용될 수 있다. 당해 기술 분야에 알려진 적합한 제제는 문헌 (Remington's Pharmaceutical Science, 18th Ed, Mack Publishing Company, Easton PA)에 개시되어 있는 것을 사용하는 것이 바람직하다. 포함될 수 있는 담체, 부형제 및 희석제로는 락토오스, 덱스트로오스, 수크로오스, 소르비톨, 만니톨, 자일리톨, 에리트리톨, 말티톨, 전분, 아카시아 고무, 알지네이트, 젤라틴, 칼슘 포스페이트, 칼슘 실리케이트, 셀룰로오스, 메틸 셀룰로오스, 미정질 셀룰로오스, 폴리비닐 피롤리돈, 물, 메틸히드록시 벤조에이트, 프로필히드록시 벤조에이트, 탈크, 마그네슘 스테아레이트 및 광물유 등이 있다. 경구투여를 위한 고형제제에는 정제, 환제, 산제, 과립제, 캡슐제 등이 포함되며, 이러한 고형제제는 상기 조성물에 적어도 하나 이상의 부형제 예를 들면, 전분, 칼슘카보네이트 (calcium carbonate), 수크로오스, 락토오스, 젤라틴 등을 섞어 조제된다. 또한 단순한 부형제 이외에 마그네슘 스테아레이트, 탈크 같은 윤활제들도 사용된다. 경구투여를 위한 액상 제제로는 현탁제, 내용액제, 유제, 시럽제 등이 해당되는데 흔히 사용되는 단순 희석제인 물, 리퀴드 파라핀 이외에 여러 가지 부형제, 예를 들면 습윤제, 감미제, 방향제, 보존제 등이 포함될 수 있다. 비경구 투여를 위한 제제에는 멸균된 수용액, 비수성용제, 현탁제, 유제, 동결건조 제제, 좌제가 포함된다. 비수성용제, 현탁제로는 프로필렌글리콜, 폴리에틸렌글리콜, 올리브 오일과 같은 식물성 기름, 에틸올레이트와 같은 주사 가능한 에스테르 등이 사용될 수 있다. 좌제의 기제로는 위텝솔, 마크로골, 트윈 61, 카카오지, 라우린지, 글리세로제라틴 등이 사용될 수 있다.The pharmaceutical compositions of the present invention may further comprise suitable carriers, excipients and diluents conventionally used in the manufacture of pharmaceutical compositions. In addition, it can be formulated in the form of powders, granules, tablets, capsules, suspensions, emulsions, oral preparations such as syrups and aerosols, external preparations, suppositories and sterilized injection solutions according to a conventional method. Suitable formulations known in the art are preferably those disclosed in Remington's Pharmaceutical Science, 18th Ed, Mack Publishing Company, Easton PA. Examples of carriers, excipients and diluents which may be included include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia rubber, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methylcellulose, Polyvinylpyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate, and mineral oil. Solid formulations for oral administration include tablets, pills, powders, granules, capsules and the like, which may contain at least one excipient such as starch, calcium carbonate, sucrose, lactose, Gelatin and the like. In addition to simple excipients, lubricants such as magnesium stearate and talc are also used. Liquid preparations for oral administration include suspensions, solutions, emulsions, syrups and the like. Various excipients such as wetting agents, sweeteners, fragrances, preservatives and the like may be included in addition to water and liquid paraffin, which are simple diluents commonly used. have. Formulations for parenteral administration include sterilized aqueous solutions, non-aqueous solutions, suspensions, emulsions, freeze-dried preparations, and suppositories. Examples of the suspending agent include propylene glycol, polyethylene glycol, vegetable oil such as olive oil, injectable ester such as ethyl oleate, and the like. Examples of suppository bases include withexol, macrogol, tween 61, cacao butter, laurin, glycerogelatin and the like.
또한, 본 발명은 상기 약학적 조성물을 개체에 투여하는 단계를 포함하는 섬유증의 예방 또는 치료 방법을 제공한다.The present invention also provides a method of preventing or treating fibrosis, comprising administering the pharmaceutical composition to a subject.
본 발명에서 “투여”는 임의의 적절한 방법으로 개체에게 소정의 본 발명의 조성물을 제공하는 것을 의미한다.&Quot; Administration " in the present invention means providing the subject invention with a composition of the invention in any suitable manner.
본 발명에서 “개체”란 질병의 치료를 필요로 하는 대상을 의미하고, 보다 구체적으로는, 인간 또는 비-인간인 영장류, 생쥐(mouse), 개, 고양이, 말, 및 소 등의 포유류를 의미한다. The term " individual " as used herein refers to a subject in need of treatment of a disease, and more specifically refers to a mammal such as a human or non-human primate, mouse, dog, cat, horse, do.
본 발명의 약학적 조성물의 바람직한 투여량은 환자의 상태 및 체중, 질병의 정도, 약물형태, 투여경로 및 기간에 따라 다르며, 당업자에 의해 적절하게 선택될 수 있다. 그러나 바람직한 효과를 위해서, 본 발명의 조성물 내 길경추출물의 일일 투여량은 1일 1 mg 내지 5000 mg/kg이며, 하루에 한번 투여할 수도 있고, 수 회 나누어 투여할 수도 있다. 따라서 상기 투여량은 어떠한 면으로든 본 발명의 범위를 한정하는 것은 아니다.The preferred dosage of the pharmaceutical composition of the present invention varies depending on the condition and the weight of the patient, the degree of disease, the drug form, the administration route and the period, and can be appropriately selected by those skilled in the art. However, for the desired effect, the daily dose of Ganoderma lucidum extract in the composition of the present invention is 1 mg to 5000 mg / kg per day, which may be administered once a day or divided into several times. Accordingly, the dosage is not limited in any way to the scope of the present invention.
본 발명의 약학적 조성물은 개체에게 다양한 경로로 투여될 수 있다. 투여의 모든 방식은 예상될 수 있는데, 예를 들면, 경구, 직장 또는 정맥, 근육, 피하, 자궁 내 경막 또는 뇌혈관 내 주사에 의해 투여될 수 있다.The pharmaceutical composition of the present invention may be administered to a subject in various routes. All modes of administration may be expected, for example, by oral, rectal or intravenous, intramuscular, subcutaneous, intra-uterine dural or intracerebral injection.
본 발명의 조성물은 길경추출물과 함께 섬유증의 예방 또는 치료 효과를 갖는 공지의 유효성분을 1종 이상 더 함유할 수 있다.The composition of the present invention may contain one or more known active ingredients having an effect of preventing or treating fibrosis in combination with Ganoderma lucidum extract.
본 발명의 조성물은 섬유증의 예방 또는 치료를 위하여 단독으로, 또는 수술, 방사선 치료, 호르몬 치료, 화학치료 및 생물학적 반응 조절제를 사용하는 방법들과 병용하여 사용할 수 있다.The composition of the present invention can be used alone or in combination with methods using surgery, radiation therapy, hormone therapy, chemotherapy and biological response modifiers for the prevention or treatment of fibrosis.
또한, 본 발명은 길경추출물을 유효성분으로 포함하는, 섬유증 예방 또는 개선용 건강기능식품을 제공한다.The present invention also provides a health functional food for preventing or ameliorating fibrosis, comprising Ganoderma lucidum extract as an active ingredient.
본 발명에서 건강기능식품이란 질병의 예방 및 개선, 생체방어, 면역, 병후의 회복, 노화 억제 등 생체조절기능을 가지는 식품을 말하는 것으로, 장기적으로 복용하였을 때 인체에 무해하여야 한다.In the present invention, the health functional food refers to a food having a biological control function such as prevention and improvement of disease, bio-defense, immunity, recovery after disease, suppression of aging, and is harmless to human body when taken over a long period of time.
본 발명의 조성물을 식품 첨가물로 사용할 경우, 상기 조성물을 그대로 첨가하거나 다른 식품 또는 식품 성분과 함께 사용될 수 있고, 통상적인 방법에 따라 적절하게 사용될 수 있다. 유효성분의 혼합양은 사용 목적 (예방, 건강 또는 치료적 처치)에 따라 적합하게 결정될 수 있다. 일반적으로, 식품 또는 음료의 제조 시에 본 발명의 조성물은 원료에 대하여 15 중량 % 이하, 바람직하게는 10 중량 % 이하의 양으로 첨가된다. 그러나, 건강 및 위생을 목적으로 하거나 또는 건강 조절을 목적으로 하는 장기간의 섭취의 경우에는 상기 범위 이하일 수 있으며, 안전성 면에서 아무런 문제가 없기 때문에 유효성분은 상기 범위 이상의 양으로도 사용될 수 있다.When the composition of the present invention is used as a food additive, the composition can be added as it is or can be used together with other food or food ingredients, and can be suitably used according to a conventional method. The amount of the active ingredient to be mixed can be suitably determined according to the intended use (prevention, health or therapeutic treatment). In general, the composition of the present invention is added in an amount of not more than 15% by weight, preferably not more than 10% by weight based on the raw material, in the production of food or beverage. However, in the case of long-term intake for the purpose of health and hygiene or for the purpose of controlling health, the amount may be less than the above range, and since there is no problem in terms of safety, the active ingredient may be used in an amount exceeding the above range.
상기 식품의 종류에는 특별한 제한은 없다. 상기 물질을 첨가할 수 있는 식품의 예로는 육류, 소시지, 빵, 초콜릿, 캔디류, 스낵류, 과자류, 피자, 라면, 기타 면류, 껌류, 아이스크림류를 포함한 낙농제품, 각종 수프, 음료수, 차, 드링크제, 알코올 음료 및 비타민 복합제 등이 있으며, 통상적인 의미에서의 건강식품을 모두 포함한다.There is no particular limitation on the kind of the food. Examples of the foods to which the above substances can be added include dairy products including meat, sausage, bread, chocolate, candy, snacks, confectionery, pizza, ramen noodles, gums, ice cream, various soups, drinks, tea, Alcoholic beverages, and vitamin complexes, all of which include health foods in a conventional sense.
본 발명의 조성물을 음료에 이용할 경우, 통상의 음료와 같이 여러 가지 향미제 또는 천연 탄수화물 등을 추가 성분으로서 포함할 수 있다. 상술한 천연 탄수화물은 포도당, 과당과 같은 모노사카라이드, 말토스, 수크로오스와 같은 디사카라이드, 및 덱스트린, 사이클로덱스트린과 같은 천연 감미제나, 사카린, 아스파르탐과 같은 합성감미제 등을 사용할 수 있다. 상기 천연 탄수화물의 비율은 본 발명의 조성물 100 ml 당 일반적으로 약 0.01 내지 10 g, 바람직하게는 약 0.01 내지 0.1 g 이다.When the composition of the present invention is used in beverages, various flavors or natural carbohydrates such as ordinary beverages may be included as an additional ingredient. Such natural carbohydrates include monosaccharides such as glucose and fructose, disaccharides such as maltose and sucrose, and natural sweeteners such as dextrin and cyclodextrin, and synthetic sweeteners such as saccharine and aspartame. The ratio of the natural carbohydrate is generally about 0.01 to 10 g, preferably about 0.01 to 0.1 g per 100 ml of the composition of the present invention.
상기 외에 본 발명의 조성물은 여러 가지 영양제, 비타민, 전해질, 풍미제, 착색제, 펙트산 및 그의 염, 알긴산 및 그의 염, 유기산, 보호성 콜로이드 증점제, pH 조절제, 안정화제, 방부제, 글리세린, 알코올, 탄산 음료에 사용되는 탄산화제 등을 포함할 수 있다. 그 밖에 본 발명의 조성물은 천연 과일주스, 과일주스 음료 및 야채음료의 제조를 위한 과육을 포함할 수 있다. 이러한 성분은 독립적으로 또는 조합하여 사용할 수 있다. 이러한 첨가제의 비율은 크게 중요하진 않지만 본 발명의 조성물 100 중량부 당 0.01 내지 0.1 중량부의 범위에서 선택되는 것이 일반적이다.In addition to the above, the composition of the present invention may further contain various nutrients, vitamins, electrolytes, flavors, colorants, pectic acid and salts thereof, alginic acid and salts thereof, organic acids, protective colloid thickeners, pH adjusters, stabilizers, preservatives, glycerin, A carbonating agent used in a carbonated beverage, and the like. In addition, the composition of the present invention may comprise flesh for the production of natural fruit juices, fruit juice drinks and vegetable drinks. These components may be used independently or in combination. Although the ratio of such additives is not critical, it is generally selected in the range of 0.01 to 0.1 parts by weight per 100 parts by weight of the composition of the present invention.
본 발명의 길경추출물은 천연물로부터 유효성분을 추출하는 당업계에 공지된 통상적인 방법에 따라, 즉, 통상적인 온도, 압력의 조건 하에서 통상적인 용매를 사용하여 추출할 수 있다. 예컨대, 본 발명에서 길경추출물은 물, 탄소 수 1 내지 4의 알코올, n-헥산, 에틸아세테이트, 아세톤, 부틸아세테이트, 1,3-부틸렌 글리콜, 메틸렌클로라이드, 및 이들의 혼합 용매로 이루어진 군으로부터 선택된 1종 이상의 용매를 사용하여 추출할 수 있고, 바람직하게는 에탄올을 사용하여 추출할 수 있으며, 더욱 바람직하게는 70% 에탄올을 사용하여 추출할 수 있다. 또한, 길경으로부터 추출물을 추출하는 방법은 열수 추출, 냉침 추출, 환류 추출, 초음파 추출 등의 다양한 방법을 통하여 추출할 수 있지만, 이것으로 제한되는 것은 아니다.The extract of Ganoderma lucidum of the present invention can be extracted according to a conventional method known in the art for extracting an active ingredient from a natural product, that is, using a conventional solvent under the conditions of ordinary temperature and pressure. For example, in the present invention, the extract of Ganoderma lucidum is selected from the group consisting of water, an alcohol having 1 to 4 carbon atoms, n-hexane, ethyl acetate, acetone, butyl acetate, 1,3-butylene glycol, methylene chloride, Can be extracted using one or more selected solvents, preferably ethanol, and more preferably 70% ethanol. In addition, the method for extracting the extract from Ganoderma lucidum can be extracted by various methods such as hot water extraction, cold extraction, reflux extraction, ultrasonic extraction and the like, but is not limited thereto.
상기 제조된 추출물은 이후 여과하거나 농축 또는 건조과정을 수행하여 용매를 제거할 수 있으며, 여과, 농축 및 건조를 모두 수행할 수 있다. 예컨대, 여과는 여과지를 이용하거나 감압여과기를 이용할 수 있으며, 농축은 감압 농축기, 건조는 동결건조법 등을 수행할 수 있으나, 이것으로 제한되는 것은 아니다.The extract thus prepared may be filtered, concentrated or dried to remove the solvent, and may be subjected to both filtration, concentration and drying. For example, the filtration can be performed using a filter paper or a vacuum filter, the concentration can be carried out using a vacuum concentrator, and the lyophilization can be carried out, but the present invention is not limited thereto.
또한, 상기 용매로 추출한 추출물은 이후 부탄올, n-헥산, 메틸렌클로라이드, 아세톤, 에틸아세테이트, 에틸에테르, 클로로포름, 물, 및 이들의 혼합물로 이루어진 군으로부터 선택된 용매로 분획과정을 추가로 실시할 수도 있다. 상기 분획 시 온도는 4℃ 내지 120℃일 수 있으나, 이에 제한되지는 않는다.Further, the extract extracted with the solvent may be further subjected to fractionation with a solvent selected from the group consisting of butanol, n-hexane, methylene chloride, acetone, ethyl acetate, ethyl ether, chloroform, water, . The fractionation temperature may be 4 캜 to 120 캜, but is not limited thereto.
본 발명의 일실시예에서는, 수컷 C57BL/6J 마우스를 정상식이군, 섬유증 유도군, 및 길경추출물 급여군으로 분류하여 12주 동안 사육하며 지방 조직의 섬유증 관련 전사체 마커들의 변화를 측정한 결과 섬유증 유도군은 정상식이군에 비하여 지방 조직 섬유화와 관련된 MMPs(matrix metalloproteinases), Cd44 (CD antigen 44), Lum(lumican), TGF β(transforming growth factor β) 및 카텝신(cathepsin)의 발현량이 유의적으로 증가하는데 반해 길경추출물 급여군의 경우에는 정상식이군과 유사한 수준으로 지방 조직 섬유화와 관련된 MMPs(matrix metalloproteinases), Cd44 (CD antigen 44), Lum(lumican), TGF β(transforming growth factor β) 및 카텝신(cathepsin)의 발현량이 증가하는 것을 관찰함으로써 길경추출물에 지방 섬유증 억제 효과가 있음을 확인하였다(실시예 3 내지 실시예 6 참조).In one embodiment of the present invention, the male C57BL / 6J mice were classified into the group of the normal type, fibrosis induction group, and the Gakyung extract group, and were cultured for 12 weeks. The changes of the fibrosis-related transcript markers of adipose tissue were measured, The expression levels of MMPs (matrix metalloproteinases), Cd44 (CD antigen 44), Lum (lumican), TGFβ (transforming growth factor β) and cathepsin were significantly increased (CD antigen 44), Lum (lumican), transforming growth factor β (TGFβ) and cathepsin (TGFβ), which are similar to those of the normal diet, cathepsin) was found to be increased, thereby confirming that the extract of Ganoderma lucidum had an effect of inhibiting adipocyte fibrosis (see Examples 3 to 6).
본 발명에서 상기 섬유증 (fibrosis)은 세포 외 기질의 비정상적 생성, 축적 및 침착이 일어나는 질환으로, 간 섬유증, 지방 섬유증, 신장 섬유증, 폐 섬유증, 피부 섬유증, 심장 섬유증, 관절 섬유증, 신경 섬유증, 근 섬유증, 복막 섬유증 등을 포함하며, 바람직하게는, 지방 섬유증이나 이에 제한되지 않는다.In the present invention, the fibrosis is a disease in which abnormal formation, accumulation and deposition of extracellular matrix occurs. The fibrosis is a fibrosis, fibrosis, renal fibrosis, pulmonary fibrosis, dermal fibrosis, cardiac fibrosis, , Peritoneal fibrosis, and the like, and is preferably, but not limited to, adipocytosis.
이하, 본 발명의 이해를 돕기 위하여 바람직한 실시예를 제시한다. 그러나 하기의 실시예는 본 발명을 보다 쉽게 이해하기 위하여 제공되는 것일 뿐, 하기 실시예에 의해 본 발명의 내용이 한정되는 것은 아니다.Hereinafter, preferred embodiments of the present invention will be described in order to facilitate understanding of the present invention. However, the following examples are provided only for the purpose of easier understanding of the present invention, and the present invention is not limited by the following examples.
[실시예][Example]
실시예 1. 실험의 준비Example 1. Preparation of experiment
1-1. 길경추출물의 준비1-1. Preparation of Gakyung extract
길경은 옴니허브회사에서 구입하여 사용하였고, 추출이 용이하도록 분쇄한 후 길경 3 ㎏ 당 70% 에탄올(ethanol) 30L를 가하여 50℃에서 6시간 동안 추출하였으며, 추출횟수는 1회로 하였다. 추출액은 50℃에서 감압농축한 후 동결건조시켜 사용하였으며, 길경추출물의 수율은 13.3%로 산출되었다.Gakyung was purchased from Omni Hub Company. After grinding to facilitate extraction, 30 L of 70% ethanol was added per 3 kg of Gyunggi and extracted at 50 ℃ for 6 hours. The extract was concentrated under reduced pressure at 50 ℃ and freeze - dried. The yield of Gyungyang extract was calculated as 13.3%.
1-2. 섬유증 동물 모델 디자인1-2. Fibrosis Animal Model Design
4주령의 수컷 C57BL/6J 마우스를 실험에 사용하였으며, 1주일간의 적응 기간을 거친 후, 난괴법 (randomized complete block design)에 의해 정상식이를 급여한 군 (정상군; n=10), 고지방식이 (60% kcal fat)를 보충한 군 (섬유증 유도군; n=10) 및 HFD에 상기 실시예 1-1에서 준비한 길경추출물을 투여한 군 (실험군; 5%, n=10) 으로 나누어 총 12주간 실험하였다. 고지방 식이는 지방 세포 사이, 섬유질, 세포 외 기질과 체액으로 구성된 결합 조직 (connective tissue)의 축적을 유도함으로써 섬유화를 야기하는 것으로 알려져있다. 식이와 식수는 자유롭게 섭취하도록 하였고 (ad libitum) 실험 종료 후, 12시간 절식한 후 마취제(이소프란) 흡입을 통해 가벼운 마취를 시킨 후, 복부 하대 정맥 (inferior vena cava)으로부터 공복 혈액을 채취하였다. 채취된 혈액은 헤파린으로 처리한 후, 1,000×g, 4℃에서 15 분간 원심 분리한 후 혈장을 수집하였고 시료 분석 시까지 -70℃에서 보관하였다. 실험동물의 지방 조직을 분리한 후, PBS (phosphate buffered saline) 용액에 수차례 헹군 후 표면의 수분을 제거하여 무게를 측정하였고, 액체질소에 급냉시켜 시료 분석 시까지 -70℃에서 보관하였다. 또한 지방 조직 일부는 현미경 분석을 위해 10 % 포름알데히드 용액에 고정시켰다.Four-week-old male C57BL / 6J mice were used for the experiment. After a week of adaptation period, normal diet (n = 10), normal diet (randomized complete block design) (5%, n = 10) in the group supplemented with (60% kcal fat) (fibrosis induction group; n = 10) and HFD 12 weeks. High-fat diets are known to cause fibrosis by inducing the accumulation of connective tissue composed of adipocytes, fibrous, extracellular matrix and body fluids. Diet and drinking water were ad libitum. After the end of the experiment, they were fasted for 12 hours and then anesthetized by inhalation of anesthetic (isofran), and then fasting blood was collected from the inferior vena cava. The collected blood was treated with heparin and centrifuged at 1,000 × g for 15 min at 4 ° C. Plasma was collected and stored at -70 ° C. until analysis. After removing the adipose tissue, the rats were rinsed several times with PBS (phosphate buffered saline) solution, and the surface moisture was removed and the weight was measured. The sample was quenched in liquid nitrogen and stored at -70 ° C until analysis. Some of the adipose tissue was also fixed in 10% formaldehyde solution for microscopic analysis.
1-3. 지방 조직의 섬유화 관련 전사체 발현 분석 방법1-3. Analysis of fibrosis-associated transcript expression in adipose tissue
길경추출물 급여에 따른 지방조직 섬유화 제어 효능 평가를 위해 유의한 유전자(Differentially Expressed Genes, DEGs)를 추출하기 위하여 mRNA-sequencing (mRNA-seq) 분석을 진행하였으며, 획득한 DEGs는 fold change 2배 이상 (또는 이하), p-value 0.05 이하를 cut off 하여 추출하였고, 상기 추출된 DEGs는 섬유증 유도군 대비 정상군과 실험군으로 제시하였다.MRNA-sequencing was performed to extract the genes (Differentially Expressed Genes, DEGs) for the evaluation of the control effect of fatty tissue fibrosis according to the gilbang extract administration. The obtained DEGs were fold change more than 2 times Or less), p-value less than 0.05 was cut off, and the extracted DEGs were presented as the normal group and the experimental group as compared to the fibrosis-inducing group.
실시예 2. 지방 조직의 섬유화 분석Example 2. Analysis of fibrosis of adipose tissue
조직의 형태학적 관찰을 위해, 콜라겐과 근섬유를 염색하는 Masson‘s Trichrome 염색을 수행한 후, 광학현미경으로 400배 배율에서 관찰하였다. Masson's trichrome 염색법에서 결합조직 (connective tissue, CT)은 푸른빛, 핵은 검붉은색으로 염색된다. 파란색으로 염색되는 CT는 세포, 섬유질 (fibers), 세포 외 기질 (extracellular matrix, ECM)과 체액으로 구성되며 섬유화의 지표로 사용된다.For morphological observation of the tissues, Masson's Trichrome staining of collagen and muscle fibers was performed, and then observed with an optical microscope at a magnification of 400 times. In Masson's trichrome staining, connective tissue (CT) is stained with blue light and nuclei are stained with dark red. CT stained blue is composed of cells, fibers, extracellular matrix (ECM) and body fluids and is used as an indicator of fibrosis.
그 결과, 도 1에 나타난 바와 같이, 섬유증 유도군은 지방 세포 사이에 CT가 많이 축적되어 있었으며, 길경추출물을 섭취한 실험군은 이러한 섬유화 정도가 크게 억제되어 있음을 확인하였다.As a result, as shown in FIG. 1, the fibrotic induction group had a large accumulation of CT in the adipocytes, and the experimental group ingested the extract of Gil Gyeonggye showed that the degree of fibrosis was greatly suppressed.
실시예 3. 지방 조직의 섬유화 관련 콜라겐의 전사체 발현 분석Example 3. Transcriptional Expression Analysis of Fibrosis-Associated Collagen in Adipose Tissue
섬유증 유도 마우스 모델에서 길경추출물 섭취가 지방 조직의 섬유화에 미치는 영향을 알아보기 위해, 상기 실시예 1-3의 전사체 발현 분석 방법을 이용하여 ECM 콜라겐 전사체의 발현을 분석하였다. In order to examine the effect of Ganoderma extract on the fibrosis of adipose tissue in the fibrosis-induced mouse model, using the transcript expression assay method of Example 1-3 Expression of ECM collagen transcripts was analyzed.
그 결과, 도 2에 나타난 바와 같이, 섬유증 유도군의 경우 정상군에 비해 ECM 콜라겐이 유의적으로 증가한 것에 반해 길경추출물 급여군의 경우 정상군과 유사하게 콜라겐 전사체들의 발현이 감소됨을 확인하였다. As a result, as shown in FIG. 2, ECM collagen was significantly increased in the fibrotic induction group compared to the normal group, whereas collagen transcripts were decreased in the Gakyung extract group as well as the normal group.
상기로부터, 길경추출물이 섬유증 유도시에 증가하는 ECM 콜라겐들 발현을 정상화 시키는 효과가 있음을 확인하였다.From the above, it was confirmed that the extract of Ganoderma lucidum normalizes the expression of ECM collagen which is increased upon induction of fibrosis.
이하 실시예에서 섬유증 유도군 및 정상군 간의 통계적 유의성은 *p<0.05, **p<0.01, ***p<0.001이고, 섬유증 유도군 및 실험군 간의 통계적 유의성은 #p<0.05, ##p<0.01, #p<0.001 이다. In the following examples, the statistical significance between the fibrosis-induced group and the normal group was * p <0.05, ** p <0.01, *** p <0.001, &Lt; 0.01 and # p < 0.001.
실시예 4. 지방 조직의 섬유화 관련 염증 유도성 사이토카인 및 케모카인 전사체 발현 분석Example 4. Expression of inflammatory cytokines and chemokine transcripts related to fibrosis in adipose tissue
길경추출물 섭취에 의한 지방 조직 섬유화 관련 염증 유도성 사이토카인 및 케모카인 전사체 발현을 상기 실시예 1-3의 전사체 발현 분석 방법을 이용하여 분석하였다.Expression of inflammatory cytokines and chemokine transcripts related to adipose tissue fibrosis by Gakyungguk extract was assayed by the transcript expression assay method of Example 1-3 Respectively.
그 결과, 도 3에 나타난 바와 같이, 섬유증 유도군에 비해 길경추출물 급여군에서 Ccl2-4, Ccl6-9, Ccl22가 유의적으로 감소되었고, 이는 정상군과 유사한 수준으로 나타났다.As a result, as shown in Fig. 3, Ccl2-4, Ccl6-9, and Ccl22 were significantly decreased in the Gilsonia extract-fed group compared to the fibrosis-induced group, which was similar to that of the normal group.
상기로부터, 길경추출물이 섬유증으로 인해 증가되는 염증 유도성 사이토카인 및 케모카인 전사체 발현 억제에 탁월한 효능이 있음을 확인하였다. From the above, it was confirmed that the extract of Ganoderma lucidum exhibits an excellent effect for inhibiting the expression of inflammatory cytokines and chemokine transcripts, which are increased by fibrosis.
실시예 5. 지방 조직의 섬유화 관련 ECM 발현을 조절하는 인자들의 전사체 발현 분석Example 5 Transcript Expression Analysis of Factors Regulating Fibrosis-Associated ECM Expression in Adipose Tissue
지방 조직 섬유화와 관련된 ECM의 발현을 조절하는 인자인 Cd44 (CD antigen 44), Lum (lumican), MMPs (matrix metalloproteinases) 및 TGF β (transforming growth factor β) 유전자의 발현을 상기 실시예 1-3의 전사체 발현 분석 방법을 이용하여 분석하였다.Expression of Cd44 (CD antigen 44), Lum (lumican), MMPs (matrix metalloproteinases) and TGF [beta] (transforming growth factor [beta]) genes, which are factors regulating the expression of ECM associated with adipose tissue fibrosis, Using transcript expression analysis methods Respectively.
그 결과, 도 4에 나타난 바와 같이, 길경추출물을 섭취한 실험군은 섬유증 유도군에 비해 지방 조직에서 Cd44, Lum, Mmp2-3, Mmp9, Mmp12-14, Mmp19 및 Tgfb1 유전자의 발현이 감소되었다.As a result, as shown in FIG. 4, the expression of Cd44, Lum, Mmp2-3, Mmp9, Mmp12-14, Mmp19 and Tgfb1 genes was decreased in the adipose tissue-induced adipose tissues compared with the fibrotic induction group.
상기로부터, 길경추출물은 염증 유도성 사이토카인 및 케모카인 발현뿐만 아니라 ECM의 발현을 조절하는 인자들의 전사체 발현도 정상군 수준으로 현저하게 감소시키는 것을 확인하였다.From the above, it was confirmed that the extract of Ganoderma lucidum significantly reduced the expression of inflammatory cytokines and chemokines, as well as the transcript expression of the factors regulating the expression of ECM, to the normal group level.
실시예 6. 지방 조직의 섬유화 관련 ECM의 리모델링에 관여하는 카텝신의 전사체 발현 분석Example 6. Analysis of transcript expression of cathepsin involved in remodeling of ECM associated with fibrosis of adipose tissue
길경추출물이 지방 조직에서 섬유화 관련 전사체 발현에 미치는 영향을 확인하기 위하여, ECM의 리모델링에 관여하는 단백질 가수분해성 리소좀 효소 (lysosome)인 카텝신 전사체 발현을 상기 실시예 1-3의 전사체 발현 분석 방법을 이용하여 분석하였다.In order to examine the effect of Gakyung extract on the expression of fibrosis-related transcripts in adipose tissue, expression of cathepsin transcript, a protein hydrolyzable lysosome, involved in remodeling of ECM, Using analytical methods Respectively.
그 결과, 도 5에 나타난 바와 같이, 섬유증 유도군의 지방 조직에서 카텝신의 발현이 정상군에 비해 유의적으로 증가하였고, 길경추출물의 급여로 이들 발현이 정상군 수준으로 회복되는 것을 확인하였다.As a result, as shown in FIG. 5, the expression of cathepsin in the adipose tissues of the fibrosis-induced group was significantly increased compared with that of the normal group, and the expression of these genes was restored to the normal level by the administration of Gakyung extract.
상기로부터, 길경추출물이 섬유증이 유도된 지방 조직에서 카텝신의 전사체 발현을 효과적으로 억제함으로써, 우수한 지방 조직 섬유화 치료 효과를 가지고 있음을 확인하였다.From the above, it was confirmed that the extract of Ganoderma lucidum effectively inhibited the transcript expression of cathepsin in adipose tissue-induced adipose tissue-derived adipose tissue-derived adipose tissue.
상기 진술한 본 발명의 설명은 예시를 위한 것이며, 본 발명이 속하는 기술 분야의 통상의 지식을 가진 자는 본 발명의 기술적 사상이나 필수적인 특징을 변경하지 않고서 다른 구체적인 형태로 쉽게 변형이 가능하다는 것을 이해할 수 있을 것이다. 그러므로 이상에서 기술한 실시예들은 모든 면에서 예시적인 것이며 한정적이 아닌 것으로 이해해야만 한다.It will be apparent to those skilled in the art that various modifications and variations can be made in the present invention without departing from the spirit or scope of the invention. There will be. It is therefore to be understood that the above-described embodiments are illustrative in all aspects and not restrictive.
본 발명의 길경추출물은 지방 조직에서 결합 조직의 축적을 억제하고 대식세포의 침윤을 억제하는 우수한 효과를 가지고 있어, 지방 섬유증의 예방 또는 치료에 유용하게 이용될 수 있을 것으로 기대된다.The extract of Gakkyeong of the present invention has an excellent effect of inhibiting accumulation of connective tissue and inhibiting macrophage infiltration in adipose tissue, and thus it is expected to be usefully used for prevention or treatment of adipocytic fibrosis.

Claims (10)

  1. 길경추출물을 유효성분으로 포함하는. 섬유증의 예방 또는 치료용 약학적 조성물.Containing Gakyung extract as an active ingredient. A pharmaceutical composition for preventing or treating fibrosis.
  2. 제1항에 있어서,The method according to claim 1,
    상기 섬유증은 지방 섬유증인 것을 특징으로 하는, 섬유증의 예방 또는 치료용 약학적 조성물.A pharmaceutical composition for preventing or treating fibrosis, wherein the fibrosis is adipocytic fibrosis.
  3. 제1항에 있어서,The method according to claim 1,
    상기 길경추출물은 물, C₁내지 C₄의 저급알코올, n-헥산, 에틸아세테이트, 아세톤, 부틸아세테이트, 1,3-부틸렌 글리콜, 메틸렌클로라이드, 및 이들의 혼합용매로 이루어진 군에서 선택된 용매로 추출된 것을 특징으로 하는, 섬유증의 예방 또는 치료용 약학적 조성물.The extract is extracted with a solvent selected from the group consisting of water, C 1 to C 4 lower alcohol, n-hexane, ethyl acetate, acetone, butyl acetate, 1,3-butylene glycol, methylene chloride, &Lt; / RTI &gt; or a pharmaceutically acceptable salt thereof.
  4. 제1항에 있어서,The method according to claim 1,
    상기 길경추출물은 MMPs(matrix metalloproteinases), Cd44 (CD antigen 44), Lum(lumican), TGF β(transforming growth factor β) 및 카텝신(cathepsin)으로 이루어진 군에서 선택된 1종 이상의 발현을 억제하는 것을 특징으로 하는, 섬유증의 예방 또는 치료용 약학적 조성물.The ginseng extract is characterized by inhibiting the expression of at least one selected from the group consisting of MMPs (matrix metalloproteinases), Cd44 (CD antigen 44), Lum (lumican), TGF (transforming growth factor?) And cathepsin Or a pharmaceutically acceptable salt thereof, for the prophylaxis or treatment of fibrosis.
  5. 제1항의 길경추출물을 유효성분으로 포함하는 조성물을 개체에 투여하는 단계를 포함하는, 섬유증의 예방 또는 치료 방법.A method for preventing or treating fibrosis, comprising administering to a subject a composition comprising the extract of Ganoderma lucidum of claim 1 as an active ingredient.
  6. 제1항의 길경추출물을 유효성분으로 포함하는 조성물의, 섬유증의 예방 또는 치료 용도.Use of the composition of claim 1 as an active ingredient for preventing or treating fibrosis.
  7. 길경추출물을 유효성분으로 포함하는, 섬유증의 예방 또는 개선용 건강기능식품.A health functional food for prevention or improvement of fibrosis, comprising Gakyung extract as an active ingredient.
  8. 제7항에 있어서,8. The method of claim 7,
    상기 섬유증은 지방 섬유증인 것을 특징으로 하는, 섬유증의 예방 또는 개선용 건강기능식품.Wherein said fibrosis is adipocytic fibrosis.
  9. 제7항에 있어서,8. The method of claim 7,
    상기 길경추출물은 물, C₁내지 C₄의 저급알코올, n-헥산, 에틸아세테이트, 아세톤, 부틸아세테이트, 1,3-부틸렌 글리콜, 메틸렌클로라이드, 및 이들의 혼합용매로 이루어진 군에서 선택된 용매로 추출된 것을 특징으로 하는, 섬유증의 예방 또는 개선용 건강기능식품.The extract is extracted with a solvent selected from the group consisting of water, C 1 to C 4 lower alcohol, n-hexane, ethyl acetate, acetone, butyl acetate, 1,3-butylene glycol, methylene chloride, &Lt; / RTI &gt; or a pharmaceutically acceptable salt thereof, for the prevention or amelioration of fibrosis.
  10. 제7항에 있어서,8. The method of claim 7,
    상기 길경추출물은 MMPs(matrix metalloproteinases), Cd44 (CD antigen 44), Lum(lumican), TGF β(transforming growth factor β) 및 카텝신(cathepsin)으로 이루어진 군에서 선택된 1종 이상의 발현을 억제하는 것을 특징으로 하는, 섬유증의 예방 또는 개선용 건강기능식품.The ginseng extract is characterized by inhibiting the expression of at least one selected from the group consisting of MMPs (matrix metalloproteinases), Cd44 (CD antigen 44), Lum (lumican), TGF (transforming growth factor?) And cathepsin , A functional food for preventing or improving fibrosis.
PCT/KR2018/006418 2017-07-04 2018-06-05 Pharmaceutical composition for prevention or treatment of fibrosis containing platycodi radix extract as effective ingredient WO2019009525A1 (en)

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Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR20040028020A (en) * 2002-09-28 2004-04-03 주식회사 장생도라지 Drug comprising old platycodon extracts for prevention and treatment of hepatic fibrosis
CN104306896A (en) * 2014-11-06 2015-01-28 王建萍 Traditional Chinese medicine for treating myocardial fibrosis
KR20160101535A (en) * 2015-02-17 2016-08-25 충남대학교산학협력단 Composition for the anti-angiogenesis containing platycodon grandiflorum saponin and platyconic acid a isolated therefrom as an effective ingredient
WO2016153262A2 (en) * 2015-03-26 2016-09-29 B&C Biopharm Co., Ltd. Pharmaceutical composition comprising the extract of platycodon grandiflorum enhanced effective saponin contents for treatment of rheumatoid arthritis

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR20040028020A (en) * 2002-09-28 2004-04-03 주식회사 장생도라지 Drug comprising old platycodon extracts for prevention and treatment of hepatic fibrosis
CN104306896A (en) * 2014-11-06 2015-01-28 王建萍 Traditional Chinese medicine for treating myocardial fibrosis
KR20160101535A (en) * 2015-02-17 2016-08-25 충남대학교산학협력단 Composition for the anti-angiogenesis containing platycodon grandiflorum saponin and platyconic acid a isolated therefrom as an effective ingredient
WO2016153262A2 (en) * 2015-03-26 2016-09-29 B&C Biopharm Co., Ltd. Pharmaceutical composition comprising the extract of platycodon grandiflorum enhanced effective saponin contents for treatment of rheumatoid arthritis

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
LEE , KYUNG JIN ET AL.: "Suppressive Effects of Platycodon Grandiflorum on the Progress of Carbon Tetrachlonde-Induced Hepatic Fibrosis", ARCHIVES OF PHARMACAL RESEARCH, vol. 27, no. 12, December 2004 (2004-12-01), pages 1238 - 1244, XP053007037 *
LIM, J-H ET AL.: "Protective Effect of the Roots Extract of Platycodon Grandiflorum on Bile Duct Ligation-induced Hepatic Fibrosis in Rats", HUMAN & EXPERIMENTAL TOXICOLOGY, vol. 32, no. 11, 19 February 2013 (2013-02-19), pages 1197 - 1205, XP008169573 *

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