JP2019026566A - INHIBITORS OF BENZO[a]PYRENE-INDUCED DNA DAMAGE - Google Patents

Abstract

To provide novel inhibitors of benzo[a]pyrene-induced DNA damage with superior inhibition effect and high safety, and compositions comprising the same.SOLUTION: The invention relates to an inhibitor of DNA damage induced by benzo[a]pyrene comprising an extract of Bacopa monniera or monieroside A that is contained in the extract as an effective ingredient, as well as compositions comprising the inhibitor of benzo[a]pyrene-induced DNA damage.SELECTED DRAWING: None

Description

  The present invention relates to an inhibitor of benzo [a] pyrene-induced DNA damage containing a treated product derived from an Otomezena plant, such as an extract, and a composition containing the same.

  Benzo [a] pyrene is produced when carbohydrates, proteins, fats, etc. are incompletely burned, and may be contained in smoked foods, automobile exhaust, coal tar, tobacco smoke, etc. Are known. In addition, when accumulated in the human body, it is categorized as a group 1 carcinogen by the International Agency for Research on Cancer (IARC) because it binds to genes and damages DNA to induce cell carcinogenesis. ing.

  Conventionally, various studies have been made from the viewpoint of suppressing the action expression of benzo [a] pyrene. For example, Patent Document 1 reports that S-adenosylmethionine (SAM) -dependent methyltransferase inhibits the action by specifically binding to benzo [a] pyrene and is effective in preventing and treating carcinogenesis. ing. As this SAM-dependent methyltransferase, extracts from microorganisms and animal organs can be used.

  Patent Document 2 discloses that the rosemary extract has an action of reducing DNA damage caused by various harmful substances contained in tobacco smoke such as benzo [a] pyrene. Patent Document 3 discloses that palm oil fruit extracts contain natural phenols such as cinnamic acid esters and benzoic acid esters, and are used to treat or prevent genomic DNA damage. .

  On the other hand, Bacopa monniera is a wet perennial widely distributed in Europe, North Africa, Asia and the Americas, including Japan, and has been used as a treatment for traditional medicine (Ayurveda) in India. One of herbs. So far, otomeazena has been confirmed to have brain function improving effects such as anxiety reduction, improvement of memory and cognitive ability, improvement of attention deficit hyperactivity disorder, prevention of Alzheimer's disease and the like (see, for example, Patent Documents 4 and 5).

JP 2006-045228 A JP2013-150619A JP-T-2006-509010 Japanese Patent Laid-Open No. 2008-074785 JP, 2006-196413, A

  However, it is not known that the extract of otomeazena has an action of inhibiting DNA damage caused by benzo [a] pyrene.

  The present invention relates to a novel inhibitor of benzo [a] pyrene-induced DNA damage and a composition containing the same, which have an excellent effect of inhibiting DNA damage by benzo [a] pyrene and are highly safe.

  As a result of intensive studies to achieve the above-mentioned object, the present inventors have discovered a previously unknown attribute of an action of inhibiting DNA damage caused by benzo [a] pyrene in an extract of otomezena, and the extract of otomezena is extracted based on the attribute. Has been found to be suitable for new uses (for example, prevention and / or treatment of cancer), and the present invention has been completed.

That is, the present invention relates to the following [1] to [7].
[1] An inhibitor of benzo [a] pyrene-induced DNA damage, comprising an extract of otomezena as an active ingredient.
[2] The inhibitor of the above-mentioned [1], comprising Monielelloside A.
[3] A composition comprising the inhibitor of benzo [a] pyrene-induced DNA damage according to [1] or [2].
[4] The composition according to [3] above, which is a pharmaceutical composition.
[5] The composition according to [3], wherein the composition is a food or drink composition.
[6] The composition according to [3], which is a cosmetic composition.
[7] The composition according to any one of [3] to [6], which is used for preventing and / or treating cancer.

The present invention also includes the following aspects.
[8] A method for preventing and / or treating cancer, comprising a step of administering the inhibitor of benzo [a] pyrene-induced DNA damage according to [1] or [2].
[9] Use of otomezena extract for the prevention and / or treatment of cancer.
[10] Use of an extract of otomeazena for producing a preventive and / or therapeutic agent for cancer.

  The inhibitor of benzo [a] pyrene-induced DNA damage of the present invention is excellent in the effect of inhibiting DNA damage caused by benzo [a] pyrene and has an excellent effect of high safety. Moreover, by the said effect | action, by extension, the canceration of a cell is suppressed and there exists an outstanding effect that it is excellent in the prevention and / or treatment of cancer.

  The inhibitor of benzo [a] pyrene-induced DNA damage of the present invention comprises an extract of otomezena as an active ingredient, and hereinafter, the extract of otomezena is described as the extract of otomezena or the extract of the present invention. There is also. In the present specification, benzo [a] pyrene-induced DNA damage is an action in which DNA damage is induced by benzo [a] pyrene, and the inhibitor of the present invention suppresses such action.

  The inhibitor of benzo [a] pyrene-induced DNA damage of the present invention inhibits DNA damage caused by benzo [a] pyrene, but it needs to act directly on benzo [a] pyrene to exhibit inhibition. There is no limitation as long as it directly or indirectly inhibits the DNA damaging action of benzo [a] pyrene. In this specification, as an action of inhibiting the DNA damaging action by benzo [a] pyrene, cell death in the presence of benzo [a] pyrene is reduced compared to the case where no sample is present. For example, it can be confirmed by the method described in Examples described later. The extract of the present invention is not particularly limited as long as it is reduced as compared with cell death in the presence of benzo [a] pyrene in the absence of the extract, but for example 3% or more, preferably 5% As described above, it is desirable to have an action of reducing by 7% or more, more preferably by 10% or more.

  The extract of the present invention is made from otomezena, but is not particularly limited as long as it is obtained by artificially treating the plant.For example, in addition to the extract (extract), an essential oil (for example, , Steam distillate, juice, press, solvent extract, supercritical fluid extract). These can be used alone or in combination of two or more. Otome Azena has been conventionally used as an edible herb, and thus it can be seen that the extract of the present invention is highly safe.

  Otome Zena used in the present invention is not particularly limited in production area, and may be obtained from any production area such as Europe, North Africa, Asia, and the Americas.

  About the site | part used, a rhizome, a leaf, a fruit, a seed, a flower, or the whole plant can be used, for example, and can also be used as processed goods, such as these cut material, crushed material, and dried material. .

  The extract used in the present invention can be obtained by extracting with the solvent using the above-described otomezena according to a known method and distilling off the solvent.

  Examples of the extraction solvent include lower alcohols (methanol, ethanol, propanol, isopropyl alcohol, n-butanol, isobutyl alcohol, etc.), polyhydric alcohols (ethylene glycol, propylene glycol, 1,3-butylene glycol, etc.), ketones (acetone). , Methyl ethyl ketone, etc.), ether (dioxane, methyl ethyl ether, diethyl ether, etc.), halogenated hydrocarbons (chloroform, dichloromethane, dichloroethane, etc.), polar solvents (dimethylformamide, dimethyl sulfoxide, etc.), ethyl acetate, toluene, n -Various organic solvents such as hexane and petroleum ether, or water can be used alone or in combination of two or more.

  The extraction temperature cannot be generally set depending on the solvent to be used, the part / form of the plant, etc., but from the viewpoint of extraction efficiency, the lower limit may be 4 ° C. and the upper limit may be 150 ° C. In the present invention, the upper limit value and the lower limit value can be appropriately set within the above-described temperature range, for example, 10 ° C., 15 ° C., 20 ° C., 30 ° C., 40 ° C., 60 ° C., 80 ° C., 100 ℃, 120 ℃, 140 ℃ etc. can be set as the upper limit value or the lower limit value. The extraction time can be appropriately set according to the amount of raw material used for extraction and the apparatus.

  In addition, for the extract obtained by extraction, one or more treatments selected from the group consisting of filtration, centrifugation, concentration, ultrafiltration, lyophilization, pulverization, and fractionation, You may carry out according to a well-known method. If necessary, the treatment can be performed under normal pressure or reduced pressure. One embodiment of the inhibitor of benzo [a] pyrene-induced DNA damage of the present invention includes the treated product.

  In the extract thus obtained, for example, the following formula:

Monieroside A represented by Since monieroside A has an action of directly or indirectly inhibiting DNA damage caused by benzo [a] pyrene, as one aspect of the present invention, benzo [a] pyrene-induced DNA damage comprising monieroside A as an active ingredient Can be provided.

  The content of monielloside A in the extract is not set unconditionally depending on the extraction conditions, and for example, 0.0001 to 100% by weight is exemplified. In this specification, the content means, for example, when the object is a liquid, the dryness of the target component expressed as a percentage of the total weight of the dried product obtained when the liquid is dried with an evaporator or the like. It is a product equivalent value and may be described as dry weight or simply content.

  In the present invention, it is possible to improve the content of monieroside A in the extract by combining treatments such as partition extraction, concentration, and chromatographic purification. For example, in the partition extraction, the extraction may be performed singly or in combination of two or more selected from ethyl acetate, n-butanol and water. Chromatographic purification may be repeated by appropriately combining the normal phase and the reverse phase. In addition, confirmation of monieroside A can be performed by, for example, NMR spectrum, optical rotation, or MS spectrum measurement.

  The shape of the extract of the present invention is not particularly limited, and may be any of powder, solid, and liquid. Moreover, the granular solid substance obtained by granulating the said extract by a well-known method can also be used as an extract of this invention. The granulation method is not particularly limited, but rolling granulation, stirring granulation, fluidized bed granulation, air flow granulation, extrusion granulation, compression molding granulation, pulverization granulation, spray granulation, spray granulation or spray granulation Examples are grains. In addition, as the liquid extract, in addition to the liquid itself obtained by the method for producing the extract, concentrates and dilutions thereof, the powdery extract is dissolved in a liquid such as water or alcohol. The liquid form is exemplified.

  In the present invention, the extract may be combined with monieroside A produced according to a known method. As monielloside A, in addition to the free form, pharmacologically acceptable salts, esters, ether compounds Can be included.

  Examples of the pharmacologically acceptable salt of monieroside A include alkali metal salts such as sodium salt and potassium salt, and alkaline earth metal salts such as magnesium salt and calcium salt.

  The esters of monieroside A are obtained by esterifying the phenolic hydroxyl group of monieroside A with carboxylic acid, sulfonic acid, or phosphonic acid. Esterification can be carried out, for example, by reacting monieroside A with an acid chloride of the above acid. Examples of the ester residue include alkylcarbonyl, alkylsulfonyl, alkylphosphoryl, and the like. As the alkyl group, for example, C1-C4 lower alkyl such as methyl, ethyl, propyl, and butyl is preferable.

  The ethers of monieroside A can be obtained, for example, by reacting monieroside A or a pharmacologically acceptable salt thereof with a halide (for example, alkyl halide). Here, as the alkyl group, for example, C1-C4 lower alkyl such as methyl, ethyl, propyl, and butyl is preferable.

  These salts, esters and ether compounds can be produced according to known methods.

  The inhibitor of benzo [a] pyrene-induced DNA damage of the present invention is not particularly limited as long as it contains an extract of otomezena as an active ingredient, and the content of otomezena extract in the inhibitor is, for example, 0.1 to 100 Weight percent is exemplified. Further, the content of monieroside A in the inhibitor is not particularly limited, and examples thereof include 0.01 to 100% by weight.

  Inhibitors of benzo [a] pyrene-induced DNA damage of the present invention ingest foods containing benzopyrene such as dysphagia, stomach pain, nausea, heartburn and indigestion by suppressing DNA damage caused by benzo [a] pyrene Symptoms and diseases based on symptom and disease such as cough, dyspnea, sputum, chest pain, etc. Symptoms and diseases based on ingestion of benzopyrene-containing exhaust gas or sidestream smoke of cigarettes; It can be suitably used as a preventive, ameliorating and / or therapeutic agent for symptoms and diseases caused by contact with sidestream smoke of tobacco. It can also be suitably used for the improvement or treatment of diseases caused by these symptoms and diseases such as bronchitis, lung cancer, skin cancer, esophageal cancer, gastric cancer, gastritis and gastric ulcer.

  The form of the benzo [a] pyrene-induced DNA damage inhibitor of the present invention is not particularly limited as long as the extract of the present invention can be applied to the surface of a living body or ingested into the body. Alternatively, it may be prepared in a form that can be used for raw materials such as pharmaceuticals, quasi drugs, foods and drinks, and cosmetics.

  The present invention also provides a composition containing an inhibitor of benzo [a] pyrene-induced DNA damage of the present invention. The form of the composition is not particularly limited as long as the extract of the present invention can be taken into cells. For example, the composition is suitably used as a pharmaceutical composition, a food / beverage composition, or a cosmetic composition. Is done.

  The pharmaceutical composition can be widely used as pharmaceuticals, quasi-drugs, etc., and the form as an external preparation composition from the viewpoint of exhibiting the effect and the form as an internal preparation composition from the viewpoint of being easily ingested Is done. Further, since the pharmaceutical composition of the present invention can suppress DNA damage caused by benzo [a] pyrene, it can be used for the treatment and prevention of bronchitis, lung cancer, skin cancer, esophageal cancer, gastric cancer, gastritis, gastric ulcer and the like. It can use suitably for a use.

  As long as the pharmaceutical composition of the present invention contains the benzo [a] pyrene-induced DNA damage inhibitor of the present invention, the carriers, bases, and / or additives generally used in the pharmaceutical field according to conventional methods. An agent and the like can be appropriately blended and prepared within a range that achieves the object of the present invention.

  Specifically, for example, tablets (including uncoated tablets, sugar-coated tablets, film-coated tablets, sublingual tablets, orally disintegrating tablets, buccal tablets, etc.), pills, powders, granules, capsules (soft capsules, microcapsules) ), Lozenges, syrups, solutions, emulsions, suspensions, controlled-release preparations (e.g., immediate-release preparations, sustained-release preparations, sustained-release microcapsules), aerosols, films (e.g. , Orally disintegrating film, oral mucosa adhesive film), injection (eg, subcutaneous injection, intravenous injection, intramuscular injection, intraperitoneal injection), instillation, transdermal preparation, ointment, lotion Oral or parenteral preparations such as suppositories, patches, suppositories (eg, anal suppositories, vaginal suppositories), pellets, nasal preparations, pulmonary preparations (inhalants), eye drops and the like. Carriers or additives that can be blended are not particularly limited, but various carriers such as water, physiological saline, other aqueous solvents, aqueous or oily bases; excipients, binders, pH adjusters, disintegrants, absorption Various additives such as an accelerator, a lubricant, a colorant, a corrigent, and a fragrance are included.

  Additives that can be mixed into tablets, capsules and the like include binders such as gelatin, corn starch, tragacanth, gum arabic, excipients such as crystalline cellulose, corn starch, gelatin, alginic acid and the like. Leavening agents, lubricants such as magnesium stearate, sweeteners such as sucrose, lactose or saccharin, flavorings such as peppermint, red oil and cherry. When the dispensing unit form is a capsule, a liquid carrier such as fats and oils can be further contained in the above type of material. Sterile compositions for injection can be prepared according to normal pharmaceutical practice (for example, dissolving or suspending the active ingredient in a solvent such as water for injection or natural vegetable oil, or lyophilizing it as an ergonomic solution) . As an aqueous solution for injection, for example, an isotonic solution containing physiological saline, glucose and other adjuvants (for example, D-sorbitol, D-mannitol, sodium chloride) and the like are used. For example, alcohols (eg, ethanol), polyalcohols (eg, propylene glycol, polyethylene glycol), nonionic surfactants (eg, polysorbate 80TM, HCO-50) and the like may be used in combination. As the oily liquid, for example, sesame oil, soybean oil and the like are used, and they may be used in combination with solubilizing agents such as benzyl benzoate and benzyl alcohol. Buffers (e.g. phosphate buffer, sodium acetate buffer), soothing agents (e.g. benzalkonium chloride, procaine hydrochloride), stabilizers (e.g. human serum albumin, polyethylene glycol), preservatives (e.g. For example, you may mix | blend with benzyl alcohol, a phenol), antioxidant, etc.

  Since the preparation thus obtained is safe and has low toxicity, for example, it is administered to humans and other mammals (for example, rats, mice, rabbits, sheep, pigs, cows, cats, dogs, monkeys) be able to.

  The content of the extract of otomezena varies depending on the dosage form, administration method, carrier and the like, but is usually 0.01 to 100% by weight, preferably 0.1 to 95% by weight in the pharmaceutical composition of the present invention.

  The dose varies depending on the subject of administration, symptoms, administration route, etc., but in the case of oral administration, for example, generally in a human body of about 60 kg body weight, about 0.01 to 1000 mg per day as the dry weight of the extract of otomeazena , Preferably about 0.1-100 mg, more preferably about 0.5-50 mg. The total daily dose may be a single dose or divided doses.

  In addition, the pharmaceutical composition of the present invention can be used additively or synergistically, for example, in combination with known therapeutic drugs for diseases such as bronchitis, lung cancer, skin cancer, esophageal cancer, gastric cancer, gastritis, and gastric ulcer. The improvement of the effect can be expected.

  Examples of the food and beverage composition include beverages and foods for suppressing DNA damage caused by benzo [a] pyrene, and are effective in, for example, cough, itching, pain, nausea, heartburn improvement, etc. It can be suitably used as a food or drink. The foods and drinks include functional foods, nutritional functional foods, foods for specified health use, foods for special purposes, foods for the elderly, foods for the sick, and health supplements (supplements). The form of the food or drink is not particularly limited.

  Specifically, for example, beverages such as tea beverages, soft drinks, carbonated beverages, nutritional beverages, fruit beverages, lactic acid beverages; noodles such as buckwheat, udon, Chinese noodles, instant noodles; strawberries, candy, gum, chocolate, snacks, Biscuits, jellies, jams, creams, baked confectioneries, breads and other confectionery and breads; fish and livestock processed foods such as kamaboko, ham and sausage; dairy products such as processed milk and fermented milk; salad oil, tempura oil, margarine, mayonnaise , Shortening, whipped cream, dressing and other fats and oils processed foods; sauces, sauces and other seasonings; curry, stew, rice cakes, rice cakes, miscellaneous dishes, etc .; frozen desserts such as ice cream, sorbet, shaved ice; tablets , Supplements such as granules, powders, and drinks. Note that these may be those prepared by adding the benzo [a] pyrene-induced DNA damage inhibitor of the present invention to a ready-made food at the time of preparation or after preparation, and the addition timing and addition method are not particularly limited. It is not something. Moreover, content of the otome Zena extract in food-drinks composition will not be specifically limited if it is in the range which exhibits the effect of this invention.

  Examples of the cosmetic composition include cosmetics for suppressing DNA damage caused by benzo [a] pyrene and can be suitably used as cosmetics for improving or preventing stains, wrinkles, moles, eczema and the like. Cosmetics include so-called medicinal cosmetics (quasi-drugs). Cosmetics include, for example, cleaning agents, shampoos, rinses, hair nicks, hair lotions, after shave lotions, body lotions, cosmetic lotions, cleansing creams, massage creams, emollient creams, aerosol products, deodorants, fragrances, deodorants or Examples include bath salts.

  If the cosmetic composition of the present invention contains the benzo [a] pyrene-induced DNA damage inhibitor of the present invention, the carriers, bases, and / or Additives and the like can be appropriately blended and prepared within a range that achieves the object of the present invention. Specifically, for example, surfactants, moisturizers, animal and plant derived fats and oils, silicones, higher alcohols, lower alcohols, extracts derived from animals and plants other than the extract of otome Zena, UV absorbers, anti-inflammatory agents, metal sequestering agents, vitamins Antioxidants, thickeners, preservatives, bactericides, pH adjusters, colorants, various fragrances and the like can be appropriately blended depending on the purpose. The content of the extract of otomezena in the cosmetic composition is not particularly limited as long as it is within the range in which the effect of the present invention is exhibited.

  The present invention also provides a food additive containing the inhibitor of benzo [a] pyrene-induced DNA damage of the present invention. The food additive of the present invention is suitable as an additive for foods and drinks that exerts an effect on cough, itching, pain, nausea, heartburn improvement and the like. The form of the food additive of the present invention is not particularly limited, and examples thereof include a liquid form, a paste form, a powder form, a flake form, and a granular form. The food additive of this invention can be manufactured according to the manufacturing method of a general food additive.

  Furthermore, the present invention can be implemented as a feed or a feed additive containing the inhibitor of benzo [a] pyrene-induced DNA damage of the present invention.

  The present invention also provides a method for preventing and / or treating cancer comprising the step of administering to a subject the inhibitor of benzo [a] pyrene-induced DNA damage of the present invention. Examples of cancer include lung cancer, skin cancer, esophageal cancer, and stomach cancer.

  Furthermore, since the extract of otomezena inhibits DNA damage caused by benzo [a] pyrene, and thus can prevent and / or treat cancer, the present invention provides an aspect of the present invention as an aspect of the present invention. Provided is the use of otomezena extract for the prevention and / or treatment, and the use of otomezena extract for the manufacture of a preventive and / or therapeutic agent for cancer.

  EXAMPLES Hereinafter, although an Example demonstrates this invention in detail, this invention is not limited to these.

Preparation Example 1 of Otome Azena Extract
<Extraction and purification operations>
Whole dried plants (2.0 kg) of Bacopa monniera were hot extracted (80 ° C.) with methanol. The obtained extract was filtered, methanol was added to the residue, and the same extraction operation was performed 3 times. The methanol extracts were combined, and the solvent was distilled off under reduced pressure to obtain a methanol extract (608.82 g, yield 30.4%).

  The methanol extract (608.82 g) was partitioned with ethyl acetate, n-butanol and water. As a result, an ethyl acetate fraction (31.8 g, yield 4.8%), an n-butanol fraction (57.94 g, yield 8.8%), and a water fraction (110.3 g, yield 16.8%) were obtained.

Next, the obtained ethyl acetate fraction was repeatedly separated and purified by normal phase silica gel, reverse phase ODS column chromatography and reverse phase HPLC, and as a result, powdered Monieroside A was obtained (yield). 0.016%). The compound was identified by ¹ H-NMR spectrum, ¹³ C-NMR spectrum, optical rotation and MS spectrum.

Example 1
Human fibroblast-derived HDF cells were cultured in 10% fetal bovine serum (FBS), 100 units / mL penicillin, 100 μg / mL streptomycin-containing MEM medium (Sigma) under conditions of 5% CO ₂ and 37 ° C. Next, 96-well microplates were seeded with HDF cells, and then benzo [a] pyrene (final concentration 50 μM) and test substances were added at the concentrations shown in Table 1 or Table 2, respectively. After culturing for 20 hours, the absorbance was measured by the MTT method (measurement wavelength: 570 nm, reference wavelength: 655 nm), and the relative cell viability (%) was calculated when the viability of the control group was taken as 100%. The results are shown in Tables 1 and 2. In addition, the control group is a group cultured without adding any of benzo [a] pyrene and the test substance, and each group shows an average of the results obtained a plurality of times.

  According to Tables 1 and 2, cell death occurs in the control group when exposed to benzo [a] pyrene. In both the group using the extract of otomezena as it is and the group using Monieroside A, cell death occurs. It was found to reduce. In addition, in the group using monieroside A, cell death was significantly reduced even at a very low concentration of 10 μM, and otomeazena extract or monielloside A sufficiently suppressed cell damage or cell death induced by benzo [a] pyrene. It turns out that you can.

  Although it is known that DNA is damaged by benzo [a] pyrene, the mechanism leading to canceration has not been fully elucidated. However, from the above results, it has been clarified that the extract of otomezena and monielloside A of the present invention has an action of strongly suppressing benzo [a] pyrene-induced DNA damage and suppressing cell damage or cell death. It is fully suggested that the extract of otomeazena or monielloside A of the present invention suppresses carcinogenesis related to benzo [a] pyrene.

  Hereinafter, a specific formulation of the composition containing the inhibitor of benzo [a] pyrene-induced DNA damage of the present invention will be exemplified. The numerical value at the right end of each formulation example means weight% of each component.

Formulation Example 1: Pharmaceutical composition (granular internal medicine)
Lactose 25.0
Cornstarch 55.0
Crystalline cellulose 9.0
Polyvinylpyrrolidone 1.0
Otome Azena Extract 10.0

Formulation Example 2: Food and beverage composition (drink agent)
Sugar 5.0
Citric acid 10.0
Phosphoric acid 5.0
Vitamins 3.0
Otome Azena Extract Extract 5.0
Fragrance 1.5
Water balance

Formulation Example 3: Cosmetic composition (lotion)
Otome Azena Extract Extract 5.0
Ethanol 8.0
Propylene glycol 12.0
Preservative appropriate amount Purified water balance

  The inhibitor of benzo [a] pyrene-induced DNA damage of the present invention inhibits DNA damage caused by benzo [a] pyrene, thus preventing and / or suppressing cell damage and cell death, Or it can use suitably as a therapeutic agent.

Claims (7)

  An inhibitor of benzo [a] pyrene-induced DNA damage, comprising an extract of otomezena as an active ingredient.   The inhibitor according to claim 1, which comprises monieroside A.   A composition comprising the benzo [a] pyrene-induced DNA damage inhibitor according to claim 1 or 2.   4. The composition according to claim 3, which is a pharmaceutical composition.   The composition of Claim 3 which is a food-drinks composition.   The composition according to claim 3, which is a cosmetic composition.   The composition according to any one of claims 3 to 6, which is used for preventing and / or treating cancer.