JP2004075640A - Agent for inhibiting differentiation of lipocyte - Google Patents

Agent for inhibiting differentiation of lipocyte Download PDF

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Publication number
JP2004075640A
JP2004075640A JP2002241369A JP2002241369A JP2004075640A JP 2004075640 A JP2004075640 A JP 2004075640A JP 2002241369 A JP2002241369 A JP 2002241369A JP 2002241369 A JP2002241369 A JP 2002241369A JP 2004075640 A JP2004075640 A JP 2004075640A
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agent
mushrooms
plants
obesity
plant
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JP2002241369A
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Japanese (ja)
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JP4363825B2 (en
Inventor
Akiko Asai
Nobuko Kajiwara
Daisuke Kamimura
Masaki Kita
Tomoko Tsuji
Kaoru Yamada
Koji Yamaguchi
上村 大輔
北 将樹
山口 宏二
山田 薫
梶原 伸子
浅井 章子
辻 智子
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Fancl Corp
株式会社ファンケル
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Abstract

An object of the present invention is to provide an effective and highly safe preadipocyte differentiation inhibitor, an antiobesity agent, an agent for improving cellulitis, and a food, a medicine and a cosmetic containing the same, which have no fear of side effects.
Kind Code: A1 An agent for inhibiting differentiation of preadipocytes, a fat accumulation inhibitor, an anti-obesity agent, and a food containing the same, comprising at least one selected from mushrooms such as agaricus and valerian, a plant or a plant group. Pharmaceuticals and cosmetics. Since the agent of the present invention strongly suppresses the differentiation of preadipocytes, it can contribute to the suppression and improvement of fat accumulation and obesity, and the prevention and treatment of cellulitis caused by local adipocyte hypertrophy. [Selection diagram] that is effective for

Description

[0001]
TECHNICAL FIELD OF THE INVENTION
The present invention relates to a preadipocyte differentiation inhibitor, and more particularly to a food, medicine or cosmetic which suppresses and prevents obesity by suppressing the number of mature adipocytes and preventing systemic and / or local accumulation of excessive fat. .
[0002]
[Prior art]
Conventionally, obesity due to abnormal fat deposition in body adipose tissue and various organs, or hyperlipidemia is considered to be closely involved in the development of various lifestyle-related diseases such as hypertension, arteriosclerosis, and diabetes. I have.
Obesity is also a major problem in the field of beauty because it causes the body to lose its shape and its appearance is significantly impaired. In the subcutaneous adipose tissue, local enlargement of fat cells causes swelling of the subcutaneous connective tissue, which causes unevenness of the skin surface, which is compared to orange peel, that is, cellulitis.
[0003]
Obesity is said to be caused by constitutional factors, dietary factors, mental factors, central factors, metabolic factors, lack of exercise, etc., resulting in calories ingested exceeding calories consumed and fat accumulation. ing. In obesity, the amount of fat, that is, triglyceride, accumulated in individual fat cells in a living body increases, and the cells are enlarged. In recent years, it has been clarified that the number of adipocytes increases even after adulthood, suppressing the differentiation of preadipocytes into mature adipocytes, reducing the number of mature adipocytes, and suppressing fat accumulation in mature adipocytes. By doing so, it is expected that the progress of obesity will be suppressed and obesity will be improved.
[0004]
There are not many foods, medicaments or cosmetics which suppress the increase in the number of fat cells and exhibit an anti-obesity effect. For example, those containing a preadipocyte differentiation-inhibiting peptide as an active ingredient (Patent Document 1) and activated whey (Patent Document 2). There is also an attempt to apply an ω-3 type highly unsaturated fatty acid as an active ingredient to an external preparation for skin (Patent Document 3). However, there is still no sufficient effect, and a novel inhibitor of preadipocyte differentiation has been desired.
[0005]
[Patent Document 1]
JP-A-6-293796 [Patent Document 2]
JP 2000-37738 A [Patent Document 3]
JP-A-11-130656
[Problems to be solved by the invention]
An object of the present invention is to provide an effective and highly safe preadipocyte differentiation inhibitor, an antiobesity agent, an agent for improving cellulitis, and a food, a medicine and a cosmetic containing the same, which have no fear of side effects. It is in.
[0007]
[Means for Solving the Problems]
The present inventors have found a strong activity of inhibiting preadipocyte differentiation in certain mushrooms and plants, and have completed the present invention.
That is, the present invention
1. Kawatake mushroom, Valeriana officinalis, Uwamasana, Paschaka, Paiko, Agrayaho, Gajutsu, Chamomile, Kumazasa, Guava leaf, Caffa lime, Juniper berry, Nutmeg, Basil, Mace, Lemongrass, Rosemary, Persimmon leaf, Gymnema sylvestre, Aoyama willow, Mushrooms consisting of lemon verbena, a preadipocyte differentiation inhibitor comprising at least one selected from the group of plant or plant parts,
2.1 mushrooms, plants or adipocyte fat accumulation inhibitor comprising at least one selected from plant parts,
3.1 an anti-obesity agent comprising at least one selected from the group consisting of mushrooms, plants or plant parts (excluding Kumazasa, guava leaves and Gymnema sylvestre);
4. Kumazasa, guava leaves or gymnema sylvester as a preadipocyte differentiation inhibitor, anti-obesity composition,
5.1 The cellulitis improving agent containing at least one selected from the group consisting of mushrooms, plants and plant parts according to 5.1.
6.1 Foods containing any of the agents or compositions of 1 to 5,
A medicament containing any of the agents or compositions of 7.1 to 5, and a cosmetic containing any of the agents or compositions of 8.1 to 5,
About.
[0008]
BEST MODE FOR CARRYING OUT THE INVENTION
The mushrooms used in the present invention may be Coriolus versicolor (L .: Fr.) Quel, and the plants may be Valeriana fauriei, Jawaranda copaia, Geranium geranium and Geranian geranium Chenopodium ambrosioides), Agurayaho (Berberis vulgaris), zedoary (Curcuma zeodaris), chamomile (matricaria chamomilla), Sasa (Sasa veitchii), guava leaves (Psidium guajava L.), Kaffa lime (Citrus hystrix), juniper berry (Juniperus commun is), nutmeg (Myristica fragrans), basil (Ocimum basilicum), mace (Myristica fragrans), lemongrass (Cymbopogon citrastus), rosemary (Rosmarinus officinalis), rosemary (Rosmarinus officinis) Cyclocarina paliurus and lemon verbena can be used, and may be those usually used as food or an extract extracted using a suitable solvent.
[0009]
Coriolus versicolor (L .: Fr.) Quel is a basidiomycete and a mushroom belonging to the family Sarcodonaceae, and is widely distributed from the subtropical to the subarctic. The complex polysaccharide isolated from the cultured mycelium of this fungus was found to have antitumor activity, and has been clinically applied.
Valeriana fauriei is a perennial dicotyledonous plant belonging to the family Oleoptera, distributed from Hokkaido to Kyushu, Sakhalin, Korea, and China. The root contains about 8% of essential oils, has a peculiar odor, and is used in Chinese medicine for mental instability and sedation of hysteria.
Uwasamana (Jacaranda copaia) is a tall tree of the dicotyledonous plant belonging to the family Pondaceae, and is distributed in Central America and northern South America. Details of its medicinal properties and pharmacology are unknown, but its leaves and bark contain alkaloids, catechins, steroids, phenols, saponins and tannins.
[0010]
Paschaka (Geranium dielsianum) is a dicotyledonous plant of the family Anthracaceae, and is distributed in Central and South America. Although the details of its medicinal properties and pharmacology are unknown, it is known privately to have a hypoglycemic effect and a pancreatic function-enhancing effect, and is used to assist in the treatment of diabetes.
Paiko (Chenopodium ambrosioides) is an annual plant of the dicotyledonous plant of the family Acagusaceae, and is also referred to as "Cariatasou". It is widely distributed in temperate regions of the world, and is also found in Japan. It is known for its powerful anthelmintic activity and is also used for digestive enhancement, gastritis and antiflatulence.
Agrayaho (Berberis vulgaris) is a deciduous shrub of dicotyledonous plants of the barberry family, and is also called as barberry. Distributed from Europe to Central Asia, the fruits were edible and cultivated. In Europe, it is used as a folk medicine for chronic indigestion, constipation, healthy stomach, kidney stones, etc.
[0011]
Gejutsu (Curcuma zeodaris) is a perennial monocotyledonous plant of the ginger family. It is widely cultivated in tropical and subtropical areas from India to Southeast Asia. It is used as a stomach and expectorant in Chinese medicine.
Chamomile (Matricaria chamomilla) is a dicotyledonous plant of the Asteraceae family, distributed from Europe to West Asia, and also cultivated for medicinal purposes. In Europe, it is used as tea and as a folk medicine for anti-inflammatory, carminative, stomach, sweating and mental instability.
Kumazasa is a monocotyledonous plant belonging to the Poaceae family and is a special product of Japan, which grows naturally and is often planted for ornamental use. The details of its medicinal properties and pharmacology are unknown, but the leaves are used as a folk medicine for stomachic, diabetes and hypertension.
[0012]
Guava leaves (Psidium guajava L.) are evergreen shrubs of dicotyledonous plants of the family Myrtaceae, and are also called bunjirou. Tropical America is distributed from the tropical zone of origin to the subtropical zone. The fruit is eaten raw and is mainly used as juice. There is a habit of using leaves as tea, and it has recently been shown to be effective for hypertension.
Kaffa lime (Citrus hystrix) is a shrub of dicotyledonous plants of the Rutaceae family, and is also called Swangi or Kaffir lime. Distributed in tropical Asia. The fruit is yellow-ripened, has a lot of juice, and has strong acidity and bitterness. Used as a condiment.
Juniper berry (Juniperus communis) is a tall tree of a gymnosperm of the cypress family, and is also referred to as a northern squirrel or scorpion. Gin is widely distributed in the Northern Hemisphere and contains its cones. It is known to promote digestion and excrete water, and is used for diseases of the urethra.
[0013]
Nutmeg and mace (Myristica fragrans) are the seeds of evergreen tree, a dicotyledonous plant of the family Diptaceae. Nutmeg is the one except for the temporary seed coat that surrounds the seeds, and mace is the net-like vermilion temporary seed coat. Suitable for a marine climate, it grows well on tropical islands and is currently producing in Indonesia, East Africa and the West Indies. Contains essential oil components such as myristicin, pinene, eugenol, and safrole, and is widely used as a spice. In Kampo, it is used for indigestion, abdominal pain, diarrhea, etc.
Basil (Ocimum basilicum) is a dicotyledonous plant of the Labiatae family, and is also called Mebuki. It is considered to be native to tropical Asia, but is currently grown worldwide. It contains essential oil components such as estradiol, eugenol, lineole, linalool, thymol, tannin, and basil camphor, and is widely used as spices and herbs. It is also used as a medicament for antitussive, antipyretic, carminative, palpitation, constipation and gonorrhea.
[0014]
Lemongrass (Cymbopogon citratus) is a monocotyledonous plant of the Poaceae family, and is also called lemon sow. It is a perennial plant native to the Indian subcontinent. It contains essential oils that emit a lemon-like aroma in the whole plant, and is grown in tropical and subtropical regions. In addition to using essential oil components such as citral as flavors, it is used as a spice and as a medicament for cold headache, stomach pain, joint pain, menstrual irregularities and anorexia.
Rosemary (Rosmarinus officinalis) is an evergreen small shrub of a dicotyledonous plant of the Labiatae family, and is also called mannenrow. Native to the Mediterranean region, rosemary oil is used as a fragrance and contains essential oils such as pinene, cineole, dragon brain, and camphor. Used in cooking as spices and herbs. Both essential oil components and whole herbs are widely used as medicinal products such as digestive aid, carminative, diuretic, antidepressant, intense, gynecological, sedative and anti-inflammatory.
[0015]
Persimmon leaf (Diospyros kaki) is a leaf of a deciduous tree of a dicotyledonous plant of the genus Oyster. It is distributed in the temperate zone of East Asia, and is currently grown as a cold-resistant persimmon fruit tree in tropical highlands and in temperate regions of Europe and the United States. Fruits are rich in sugars, pectins, carotenoids, and vitamin C and are made edible. The astringency is due to tannins, and the tannins are insolubilized by various methods and are astringently removed. The leaves contain vitamin C, such as kaempferol glycoside and quercetin glycoside, and are used as folk medicine for hypertension.
Gymnema sylvestris is a dicotyledonous plant belonging to the family Potato, and is an evergreen vine that grows in shrub forests and is distributed in southern China, Taiwan, Vietnam, India, and other tropical regions. The leaves contain a triterpene glycoside called gymnemic acid, which is known to have a sugar absorption inhibitory effect, a blood sugar increase inhibitory effect, and an anti-cariogenic effect. The alcohol extract of Gymnema leaves suppresses the increase in blood sugar caused by growth hormone or corticosteroids. In China, it is used for mastitis, trauma, and swelling.
[0016]
Qingcheng willow (Cyclocarya paliurus) is a tree of the dicotyledonous plant of the walnut family, Guangdong Province, Guangxi Zhuang Autonomous Region, Guizhou Province, Hunan Province, Hubei Province, Sichuan Province, Fujian Province, Jiangxi Province, Zhejiang Province, It grows in Anhui Province. Although the details of the pharmacology and pharmacology are unknown, it is used as a folk medicine in recent years for suppressing an increase in blood sugar level.
Lemon verbena (Lippia citriodora) is a dicotyledonous plant of the family Spruce and is an evergreen shrub distributed from the tropics to the subtropics. It is distributed in Peru, Chile and parts of Brazil in South America and is grown and used as a substitute for tea and to flavor foods. It contains essential oil components such as limonene, dipentene, cineol, citral, and methylheptenone, and is said to have a stomachic effect and is used as a digestive medicine. It is also said to have antispasmodic and tonic effects.
[0017]
As the plant, all parts such as above-ground parts such as leaves, stems, buds, flowers, woody parts, bark parts (bark) and underground parts such as roots and tubers, seeds, fruits and resins can be used.
Mushrooms, plants or their parts are dried products that have dried themselves, their crushed products, squeezed juice obtained by squeezing and extracting themselves, water or alcohol, ether, crude extracts with organic solvents such as acetone, And an extract fraction obtained by partitioning the crude extract and purifying it stepwise by various chromatographies such as column chromatography and the like. These may be used alone or in combination of two or more.
For example, an extract obtained by adding 3 L of a 99.5% ethanol extract to 1 kg of a dried plant of Valeriana fauliei and immersing at room temperature overnight may be used as it is, or may be subjected to various types of chromatography. And purified ones may be used.
[0018]
It has not been known at all that these specific mushrooms, plants, and dried or extracted plant parts have the activity of inhibiting the differentiation of preadipocytes, and new findings obtained by the present invention. It is.
The dried product or extract of the mushroom, plant, or plant part of the present invention has an excellent activity of suppressing preadipocyte differentiation, and contains a fat accumulation inhibitor, an antiobesity agent, a cellulitis improving agent, and the like. It can be used as food, medicine and cosmetics.
Manufacture mushrooms, plants, and dried or extracted plant parts as preadipocyte differentiation inhibitors, fat accumulation inhibitors, antiobesity agents, cellulitis improving agents, and foods, medicaments and cosmetics containing them be able to.
[0019]
The method of application as a medicament can be either oral administration or parenteral administration. Upon administration, the active ingredient can be mixed with a solid or liquid nontoxic pharmaceutical carrier suitable for administration methods such as oral administration, rectal administration and injection, and administered in the form of a conventional pharmaceutical preparation. Such preparations include, for example, solid preparations such as tablets, granules, powders and capsules, liquid preparations such as solutions, suspensions and emulsions, and lyophilized preparations. It can be prepared by conventional means. Examples of the above pharmaceutical non-toxic carrier include, for example, glucose, lactose, sucrose, starch, mannitol, dextrin, fatty acid glyceride, polyethylene glycol, hydroxyethyl starch, ethylene glycol, polyoxyethylene sorbitan fatty acid ester, amino acid, gelatin, Examples include albumin, water, and physiological saline. Further, if necessary, conventional additives such as a stabilizer, a wetting agent, an emulsifier, a binder, and a tonicity agent can be appropriately added.
[0020]
As food, it is eaten as it is or as a health food or food material useful for treatment and prevention of cellulitis or obesity by adding various nutrients or by including it in food or drink. For example, after adding the above-mentioned appropriate auxiliaries, using conventional means, edible forms, such as granules, granules, tablets, capsules, pastes, etc., may be edible, Various foods, for example, ham, processed meat foods such as sausage, kamaboko, processed marine products such as chikuwa, bread, confectionery, butter, powdered milk, fermented dairy products, or used in addition to water, juice, milk, It may be used by adding to a beverage such as a soft drink.
[0021]
The effective dose is appropriately selected and determined depending on the patient's age, body weight, symptoms, degree of the patient, administration route, administration schedule, formulation, strength of the inhibitory activity of the material, and the like. In general, about 0.001 to 1000 mg / kg body weight per day, and in the case of a hot water extract of guamana (Jacaranda copaia), it is about 1 to 300 mg / kg body weight per day. Is also good.
[0022]
Further, when used as a cosmetic or a cosmetic material, for example, a dried product or extract of Coriolus versicolor (L .: Fr.) Quel is added to wheat germ oil or olive oil to inhibit preadipocyte differentiation. The composition can be used as a cosmetic material. The amount added is not particularly limited, but as an example, is 0.1% by mass or more and 60% by mass or less, preferably 0.5% by mass or more and 50% by mass with respect to the weight of wheat germ oil or olive oil. % Or less is appropriate.
In addition, a cosmetic having a preadipocyte differentiation action can be produced by directly using it as a cosmetic component.
[0023]
The cosmetic is not particularly limited, but from the functional aspect, for example, a face or body emulsion, a cosmetic solution, a cream, a lotion, an essence, a pack, a sheet, and the like are preferable.
Such a cosmetic can be manufactured according to a conventional method. The amount of addition in the cosmetic is not particularly limited, but as an example, about 0.01% by mass to 20% by mass of the total weight of the cosmetic is appropriate.
Since the plant of the present invention is a natural product, its toxicity is low. For example, even if a hot water extract of rosemary (Rosmarinus officinalis) is orally administered to rats over a long period of 100 mg / kg for 100 days every day, No deaths were observed and no change in body weight was observed.
[0024]
【Example】
Hereinafter, the present invention will be described in detail with reference to examples, but the present invention is not limited thereto.
[0025]
[Pharmacological test]
Preparation of Sample 1: Approximately 1200 (Coriolus versicolor) (Coriolus versicolor) were pulverized by a mixer and immersed in 5 L of 80% ethanol-water for 3 days. The filtrate obtained by filtration under reduced pressure was concentrated by an evaporator to obtain 16.6 g of a crude extract as a brown oil. This crude extract was partitioned between 400 mL of water and 400 mL of ethyl acetate. The obtained aqueous layer was further partitioned twice with 400 mL of ethyl acetate, and all the ethyl acetate layers were collected and concentrated by an evaporator to obtain 1.21 g of ethyl acetate-soluble matter as a brown oil. This was used as a sample for measuring fat accumulation.
[0026]
Preparation of Sample 2: Plants Valerian (Valeriana fauriei), Uwamasamana (Jacaranda copaia), Pasuchaka (Geranium dielsianum), Paiko (Chenopodium ambrosioides), Agurayaho (Berberis vulgaris), zedoary (Curcuma zeodaris), chamomile (Matricaria chamomilla), Sasa veitchii ( Sasa veitchii, guava leaves (Psidium guajava L.), kaffir lime (Citrus hystrix), juniper berries (Juniperus communis), nutmeg (Myristica fragrans), basil (Ocium umium) ristica fragrans, lemongrass (Cymbopogon citratus), rosemary (Rosmarinus officinalis), persimmon leaves (Diospyros kaki), gymne sylvestris (Gymnemar sylvestris, Gymnemar sylvestris) After adding 300 ml of 80% ethanol-water to each 100 g and immersing for 3 days, the filtrate was freeze-dried to obtain each of the ethanol-extracted and dried products 520, 780, 10560, 820, 4040, 1260, 1160, 520, 1200, 1620, 7500, 5000, 1240, 17600, 2160, 6440, 2920, 4840, 900, 180 It was obtained mg. This was used as a sample for measuring fat accumulation.
[0027]
[Measurement of preadipocyte fat accumulation rate]
In two 24-well microplates, mouse preadipocytes (3T3-L1) are present in 1 mL of culture medium (DMEM containing 10% fetal calf serum (glucose concentration 4500 mg / mL)) at 5% CO 2 until they reach confluence. The cells were cultured at 37 ° C for 7 days. In the same manner for both sheets, the medium was removed by suction, and 1 μM dexamethasone, 10 μg / mL insulin and 0.5 mM 3-isobutyl-1-methylxanthine were added to a differentiation-inducing medium (DMEM containing 10% fetal bovine serum (glucose concentration 4500 mg / mL)). (Dissolved medium) was replaced with 1.5 mL, and then 7.5 μL of a methanol solution of the sample was added. At this time, wells which were not replaced with the differentiation induction medium and wells to which only methanol was added instead of the sample solution were prepared as controls. The cells were cultured at 37 ° C. for 6 days in the presence of 5% CO 2 , one of which was used for measuring fat mass, and the other was used for measuring viability.
[0028]
For one piece of fat mass measurement, 100 μL of 2% Triton-X100 was added to each well, left standing for 30 minutes, then applied a sealing tape (manufactured by Asahi Techno Glass) and sonicated for 1 minute on an ultrasonic cleaner. Was. 20 μL of each well content was collected in a 96-well microplate, 100 μL of a triglyceride G-Test Wako (manufactured by Wako Pure Chemical Industries, Ltd.) coloring reagent was added thereto, and the mixture was cultured at 37 ° C. for 30 minutes, followed by absorbance (550 nm) with a plate reader. Was measured. The ratio of the absorbance of the sample-added group to the absorbance of the sample-free group was determined as a percentage, and was defined as a fat accumulation rate. Table 1 shows the fat accumulation rates of the obtained samples. It can be seen that the lower the fat accumulation rate, the more the adipocyte differentiation is suppressed.
[0029]
[Safety test]
To one well for measuring the survival rate, 20 μL of a cell counting kit (manufactured by Dojindo Laboratories) was added to each well, and after culturing at 37 ° C. for 4 hours, the absorbance (450 nm) was measured with a plate reader. The ratio of the absorbance of the sample-added group to the absorbance of the sample-free group was determined as a percentage, and was defined as the cell viability. Table 1 shows the cell viability of each sample obtained. It can be seen that any mushroom, plant or plant part has no problem with safety.
[0030]
[Table 1]
[0031]
Formulation Example 1
[Manufacture of tablets]
Using the ethanol extract of lemon verbena (Lippia citridorora) obtained in the sample preparation for the pharmacological test, tablets having the following composition were produced according to a conventional method.
[0032]
Formulation Example 2
[Manufacture of juice]
Using the ethanol extract of chamomile (Matricaria chamomilla) obtained in the sample preparation for the pharmacological test, juice having the following composition was produced according to a conventional method.
[0033]
Formulation Example 3
[Manufacture of face cream]
Using an ethanol extract of Juniperus communis obtained in [Sample preparation] of the pharmacological test, a face cream having the following composition was produced according to a conventional method.
[0034]
【The invention's effect】
The mushrooms, plants, and plant parts of the present invention strongly contribute to the suppression and improvement of fat accumulation and obesity because they strongly suppress the differentiation of preadipocytes, and the honeycomb resulting from local fat cell hypertrophy. It is effective in preventing and treating inflammation.

Claims (8)

  1. Kawatake mushroom, Valeriana officinalis, Uwamasana, Paschaca, Paiko, Agrayaho, Gajutsu, Chamomile, Kumazasa, Guava leaf, Caffa lime, Juniper berry, Nutmeg, Basil, Mace, Lemongrass, Rosemary, Persimmon leaf, Gymnema sylvestre, Blue liquorice, An agent for inhibiting differentiation of preadipocytes comprising at least one selected from mushrooms, plants or plant parts consisting of lemon verbena.
  2. An adipocyte fat accumulation inhibitor comprising at least one selected from the group consisting of the mushrooms, plants and plant parts according to claim 1.
  3. An anti-obesity agent comprising at least one member selected from the group of mushrooms, plants or plant parts (excluding Kumazasa, guava leaves and Gymnema sylvestre) according to claim 1.
  4. An anti-obesity composition comprising Kumazasa, guava leaf or gymnema sylvestre as a preadipocyte differentiation inhibitor.
  5. A cellulitis improving agent comprising at least one selected from the group consisting of mushrooms, plants and plant parts according to claim 1.
  6. A food containing the agent or the composition according to claim 1.
  7. A medicament comprising the agent or composition according to claim 1.
  8. A cosmetic comprising the agent or the composition according to claim 1.
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