WO2007142096A1 - Inhibiteur de synthase d'oxyde nitrique inductible, boisson/aliment, et aliment neutraceutique - Google Patents

Inhibiteur de synthase d'oxyde nitrique inductible, boisson/aliment, et aliment neutraceutique Download PDF

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Publication number
WO2007142096A1
WO2007142096A1 PCT/JP2007/060984 JP2007060984W WO2007142096A1 WO 2007142096 A1 WO2007142096 A1 WO 2007142096A1 JP 2007060984 W JP2007060984 W JP 2007060984W WO 2007142096 A1 WO2007142096 A1 WO 2007142096A1
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Prior art keywords
zinc
copper
food
added
olive fruit
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PCT/JP2007/060984
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English (en)
Japanese (ja)
Inventor
Shigeaki Ohno
Kazuhiro Ogami
Takako Nogami
Mari Kamegai
Yoshikiyo Ono
Akiko Yokota
Kazunaga Yazawa
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Organo Corporation
Eye Ambitious, Co., Ltd.
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Priority claimed from JP2006155274A external-priority patent/JP2006342161A/ja
Priority claimed from JP2006155273A external-priority patent/JP2006328072A/ja
Application filed by Organo Corporation, Eye Ambitious, Co., Ltd. filed Critical Organo Corporation
Publication of WO2007142096A1 publication Critical patent/WO2007142096A1/fr

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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)
    • A61K36/80—Scrophulariaceae (Figwort family)
    • 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
    • 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)
    • A61K36/63—Oleaceae (Olive family), e.g. jasmine, lilac or ash tree
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A—HUMAN NECESSITIES
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    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00—Drugs for disorders of the urinary system
    • A61P13/08—Drugs for disorders of the urinary system of the prostate
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00—Drugs for disorders of the urinary system
    • A61P13/12—Drugs for disorders of the urinary system of the kidneys
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
    • A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
    • A61P25/16—Anti-Parkinson drugs
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00—Drugs for disorders of the senses
    • A61P27/02—Ophthalmic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/08—Antiallergic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
    • C12N9/99—Enzyme inactivation by chemical treatment

Definitions

  • the present invention relates to an inhibitor of inducible nitric acid-nitrogen synthase containing bacopa monniera extract as an active ingredient, a food and drink and a dietary supplement that exhibits an inhibitory function of inducible nitric oxide synthase.
  • the present invention relates to an inhibitor of inducible nitric oxide synthase comprising olive fruit polyphenol as an active ingredient, a food and drink and a nutritional supplement that exhibits an inhibitory function of inducible nitric oxide synthase.
  • Nitric acid-nitrogen has a wide range of effects on living tissues. While it plays a role in biological defense such as blood pressure regulation and information transmission control, excessive synthesis can cause inflammation and carcinogenesis.
  • Nitric oxide is synthesized by a plurality of nitric oxide synthases in living tissues, and in particular, it is known that inducible nitric acid nitric acid synthase synthesizes a large amount of nitric acid nitric acid.
  • Bacopa monniera is a herb that grows naturally in the lowland wetlands of India, and has been regularly used in India as a remedy for aurveda. Contains many types of flavonoids and saponins
  • Olive is a plant native to the Mediterranean region, and its fruit is rich in eating experience. It contains many kinds of polyphenols and has strong anti-acid activity, so it has been said to maintain and promote health since ancient times.
  • polyphenols in fruit juice a wide range of antioxidant activity has been observed in all tissues of the body, including the activity of suppressing the oxidation of low-density lipoprotein in the blood.
  • the fact that people in the Mediterranean region prefer meat and greasy meals but low vascular disease such as arteriosclerosis has led to frequent consumption of polyphenols in olive juice.
  • it has been reported that it is effective in preventing diabetes, cancer, cranial nerve diseases such as Alzheimer's and Parkinson's disease, and skin roughness.
  • Patent Document 1 JP 2003-137776
  • Patent Document 2 Special Table 2005-506986
  • Patent Document 3 JP 2004-161664
  • Patent Document 4 JP-A-2005-213242
  • Patent Document 5 JP 2006-83149 A
  • Patent Document 6 JP-A-2005-35981
  • bacopa monniera extract an extract of bacopamo-ela
  • olive fruit polyphenol has an inhibitory effect on inducible nitric acid-nitrogen synthase
  • the present invention relates to the side effects of bismuth subgallate described in Patent Document 1, such as when ingested by a person with constipation, a patient who has undergone a colon fistula or a patient with a digestive tract diverticulum.
  • Inducible monoacid-nitrogen synthase inhibitor and inducible type 1 that are mild in action and less likely to cause vomiting, loss of appetite, gingivitis, and even severe cases.
  • the object is to provide a food or drink having a function of inhibiting nitric oxide synthase.
  • Bacopa monniera extract is a fruit-free polyphenol with an inhibitory action of inducible nitric oxide synthase.
  • bacopa monniera extract and olive fruit polyphenols are suitable for use in new applications (for example, prevention and control of inflammation and carcinogenesis). Based on this, the present invention has been completed.
  • An inhibitor of inducible nitric oxide synthase as an exemplary aspect of the present invention is characterized in that Bacopa moniera extract is an active ingredient.
  • Another exemplary aspect of the present invention is an inhibitor of inducible monoacid-nitrogen synthase comprising an olive fruit polyphenol as an active ingredient.
  • an inhibitor of inducible nitric acid-nitrogen synthase comprises Nocopa monniera extract and olive fruit polyphenol as active ingredients.
  • This inhibitor of inducible monoxide-nitrogen synthase may be one obtained by further adding at least one of copper and zinc.
  • a food and drink as another exemplary aspect of the present invention is characterized by adding a Bacopa monniera extract exhibiting an inhibitory function of inducible monoacid-nitrogen synthase.
  • the weight ratio of Nocopa monniera extract is preferably 20% or less based on the total weight of the food and drink.
  • a food and drink as still another exemplary aspect of the present invention is characterized by the addition of olive fruit polyphenol which exhibits an inhibitory function of inducible monoacid-nitrogen synthase.
  • the weight ratio of olive fruit polyphenol is 20% or less based on the total weight of the food and drink. More desirable! /
  • Still another exemplary aspect of the present invention is a food or drink product comprising a bacopa monniera extract and olive fruit polyphenol that exhibit an inhibitory function of inducible monoacid-nitrogen synthase. It is characterized by.
  • the total weight of Nocopa monniera extract and olive fruit polyphenol is more preferably 40% or less with respect to the total weight.
  • the food or drink may be obtained by further adding at least one of copper and zinc.
  • the weight ratio of the added copper and zinc should be 1: 1 or more and 1: 200 or less. If it is 1: 4 or more and 1: 100 or less More desirable 1: 4 or more and 1:50 or less are more desirable.
  • a dietary supplement as still another exemplary aspect of the present invention is characterized by comprising a Bacopa monniera extract that exhibits an inhibitory function of inducible monoacid-nitrogen synthase.
  • the weight ratio of Nocopa monniera extract is 5% or more and 98% or less with respect to the total weight.
  • a dietary supplement as still another exemplary aspect of the present invention is characterized by adding olive fruit polyphenol that exhibits an inhibitory function of inducible monoacid-nitrogen synthase.
  • the weight ratio of olive fruit polyphenol is desirably 5% or more and 98% or less based on the total weight.
  • a dietary supplement as still another exemplary aspect of the present invention comprises the addition of Nocopa monniera extract and olive fruit polyphenol that exerts the inhibitory function of inducible monoacid-nitrogen synthase. It is characterized by becoming.
  • the total weight of Nocopa monniera extract and olive fruit polyphenol is preferably 5% or more and 98% or less based on the total weight.
  • This dietary supplement may be obtained by further adding at least one of copper and zinc.
  • Copper is a component of various enzymes and acts as a catalyst for oxygen transport, electron transfer, redox, and the like. Insufficient copper is said to cause anemia, leukopenia and bone abnormalities, and excessive intake may cause liver damage. According to the Japanese dietary intake standard in 2005, the recommended amount is 0.3 to 0.8 (additional amount of pregnant women and lactating women 0.1, 0.6) mg / day (depending on age and sex), upper limit is lOmgZ days And the copper in the composition should not exceed lOmg / day! /, Which is preferred U.
  • Zinc is also a component of various enzymes and is involved in biological reactions such as gene expression and protein synthesis. Zinc deficiency is said to result in loss of appetite and taste disorders, and overdose may cause gastric disorders, dizziness, nausea in acute poisoning, anemia in the chronic, immune disorders, neurological symptoms, diarrhea, etc. is there. According to the Japanese dietary intake standard in 2005, the recommended amount is 2 to 10 (pregnant and lactating supplements 3) mgZ days (depending on age and sex), and the upper limit is 30 mg / day. Should not exceed 30 mg / day.
  • the weight ratio of copper to zinc is preferably in the range of 1: 1 to 1: 200, more preferably 1: 4 to 1: 100, more preferably 1 : 4 or more and 1:50 or less.
  • vitamin C vitamin E
  • vitamin A which has anti-acidic action
  • rutin zeaxanthin
  • ⁇ -lipoic acid ant
  • you may add cyanine, anthocyanin, wastaxanthin, yew leaf extract, 13 carotene, lycopene, or omega-3 fatty acids such as EPA and DHA.
  • Nutritional supplements here are all foods that are useful for maintaining and improving health.
  • Health functional foods specific health foods, nutritional functional foods
  • health supplements nutrition-enriched foods
  • nutritional adjustments Including food and supplements.
  • Additives such as excipients, binders, disintegrants, solubilizers
  • it can be made into dosage forms such as tablets, capsules, pills, powders, granules, syrups, and injections by known production techniques.
  • the weight ratio of Nocopa monniera extract is preferably 2% or more and 98% or less based on the total weight, although it depends on the dosage form. In particular, when it is used as a tablet or capsule, it is preferably 5% or more and 80% or less.
  • the weight ratio of olive fruit polyphenol is preferably 2% or more and 98% or less based on the total weight, although it depends on the dosage form. In particular, when it is used as a tablet or capsule, it is preferably 5% or more and 75% or less.
  • the foods and drinks that are added include Altono with less toxicity and side effects, prevention of Imah's disease and Parkinson's disease, reduction of symptoms, improvement of mental disorders such as anxiety, atopic dermatitis, sunburn, burns, etc.
  • Skin diseases allergic keratoconjunctivitis, ulceris, ciliitis, scleritis, inflammatory eye diseases such as photopathy, glomerulonephritis, pyelonephritis, prostatitis, bronchitis, pneumonia, gastroenteritis, rheumatoid arthritis It is useful for prevention and symptom relief of autoimmune diseases such as osteoporosis, colon cancer, Behcet's disease and collagen disease.
  • An inducible nitric oxide synthase inhibitor containing olive fruit polyphenol of the present invention as an active ingredient and an olive fruit polyphenol exhibiting an inhibitory function of inducible nitric oxide synthase are added.
  • Foods and drinks are vascular diseases such as arteriosclerosis and hypertension with minimal toxicity and side effects, skin diseases such as atopic dermatitis, sunburn, burns, allergic keratoconjunctivitis, ulceris, ciliitis, scleritis Inflammatory eye diseases such as age-related macular degeneration, diabetic retinopathy, cataracts caused by light damage, glomerulonephritis, pyelonephritis, prostatitis, tracheositis, pneumonia, gastroenteritis, rheumatoid arthritis, osteoporosis, colon cancer, It is useful for preventing diseases caused by ocular circulation such as Behcet's disease and collagen diseases such as autoimmune diseases, regulatory eye strain, regulatory convulsions
  • Bacopa monniera extract olive fruit polyphenol has a bitter taste, and when added to food or drink, it has the effect of deepening the taste of the food or drink and increasing the sense of quality.
  • the bacopa monniera extract should be a food or drink for inhibiting inducible nitric acid nitric acid synthase that has an appropriate bitter taste without impairing the flavor of the food or drink by keeping the amount of added force below a certain level. Can do.
  • the Bacopa monniera extract which is an active ingredient of the present invention, can be obtained by drying the whole plant of Bacopamo-ela and extracting the extract with ethanol. Specifically, dry whole grass is pulverized and extracted with ethanol at about 60 ° C to 70 ° C. Filter the extract to remove solids and dry to make Bacopa monniera extract. As a drying method, evaporation, spray drying, freeze drying, or the like can be used. The Bacopa monniera extract used here was extracted at 65 ° C for 15 minutes with 3 times the volume of ethanol in the ground whole dried Bacopamo-ela.
  • the olive fruit polyphenol which is an active ingredient of the present invention, is obtained by squeezing olive fruit with water to which a reducing agent is added in an amount equal to the weight of the fruit, and removing the oil content by squeezing the pulp.
  • the obtained aqueous layer can be obtained by drying by a method such as evaporation, spray drying or freeze drying.
  • the purpose of adding a reducing agent to the water in the fruit is to prevent the browning of the olive fruit polyphenol due to the acidity of the olive fruit polyphenol. Any reducing agent can be used as long as it fulfills its purpose, and vitamin C 'cysteine and citrate are suitable.
  • the olive fruit polyphenol preparation actually used for the test was added with water with a citrate concentration of 1% added to the olive fruit, squeezed, separated the aqueous layer, and then the aqueous layer was separated. It was obtained by freeze-drying.
  • This lyophilized olive fruit polyphenol can be used for food and drink applications.
  • a method such as spray drying can also be used.
  • Inhibitors of inducible nitric acid-nitrogen synthase containing Bacopa monniera extract olive oil polyphenol as an active ingredient according to the present invention have an anti-inflammatory action, for example, its immunomodulatory action, etc. It is useful as an immunomodulator.
  • Applicable diseases that can be prevented or alleviated include allergic keratoconjunctivitis, ulceris, ciliary inflammation, scleritis, keratitis due to light disorder, cataract, retinal diseases such as age-related macular degeneration, inflammatory eye Diseases, atopic dermatitis, hay fever, glomerulonephritis, pyelonephritis, prostatitis, bronchitis, pneumonia, gastroenteritis, rheumatoid arthritis, osteoporosis, colon cancer, Behcet's disease, collagen disease, etc. Examples include ophthalmic regulatory convulsions due to cancer and fatigue.
  • the inhibitor of inducible nitric oxide synthase containing bacopamo-ela extract according to the present invention as an active ingredient is applicable to prevention of eye strain or alleviation of symptoms.
  • Inhibitors of inducible nitric oxide synthase containing Bacopa monniera extract olive fruit polyphenol as an active ingredient according to the present invention include additives such as excipients, binders, disintegrants, and solubilizers.
  • additives such as excipients, binders, disintegrants, and solubilizers.
  • tablets, capsules, powders, granules, syrups by known formulation techniques
  • a dosage form such as an injection.
  • the food and drink according to the present invention is manufactured by adding Bacopa monniera extract or olive fruit polyphenol which exhibits an inhibitory function of inducible nitric oxide synthase to various foods and drinks.
  • examples of food and drink include soft drinks, confectionery, frozen confectionery, dairy products, alcoholic beverages, and meats.
  • Bacopamoniella extract and olive fruit polyphenol have some bitterness, so they are inherently bitter (such as chiyocholate and cocoa), tasteful food (such as western liquor), and stimulating.
  • Foods and beverages eg carbonated drinks
  • the appropriate intake of Bacopa monniera extract is 50 to 50 OOmgZ per adult for oral intake, preferably 200 to 1000mgZ days of effective ingestion range
  • the dose can be adjusted according to the condition of the person taking the food.
  • the appropriate intake of olive fruit polyphenol is 5 per adult for oral intake.
  • the force s is effective uptake range 100 ⁇ 1000mgZ ⁇ , depending on the state of those who ingested for the prevention or relief of symptoms of various diseases, in increased or decreased appropriately child transgression .
  • the content of Bacopa monniera extract olive fruit polyphenol as an effective component of the inhibitory function of inducible nitric oxide synthase in the food and drink according to the present invention is as follows.
  • the content can be specified so that the normal intake satisfies the above-mentioned appropriate intake or effective intake.
  • the bitterness becomes stronger and there is a higher possibility of adversely affecting the original taste of food and drink.
  • the amount of bacopa monniera echis and olive fruit polyphenol is added to the total weight of the food and drink. It is desirable to keep the weight ratio to 20% or less.
  • the DMSO-containing culture solution is a mixture of 1/10 volume of immobilized fetal bovine serum in RPMI-1640 medium supplemented with 2 mM glutamine, 100 U / ml penicillin, and 1 OO ml streptomycin.
  • inducible nitric oxide synthase was examined by Western plotting. It was. The group stimulated with LPS but not added bacopa monniera extract (hereinafter referred to as P group) and the control group not stimulated with LPS and also added no bacopa monniera extract (hereinafter referred to as Q group! / ⁇ ) .) was also provided. In either case, DMSO was added to a final concentration of 0.01%. After 24 hours of stimulation, TNF-alpha release into the medium and expression of inducible nitric oxide synthase were examined. The release of TNF-alpha is observed to increase especially when cells are stimulated. The TNF-alpha concentration was analyzed by ELISA, and the expression level of inducible monoacid-nitrogen synthase was analyzed by Western plotting.
  • FIG. 1 shows the detection result of TNF-alpha concentration.
  • the TNF-alpha concentration was significantly increased in the P group, and TNF-alpha was observed to be released by stimulation of cells by LPS.
  • the Bacopa monniera ex added group hereinafter referred to as “A group”
  • the TNF-alpha concentration decreased with the increase in the amount of bacopa monniera supplement, and the bacopa monniera extract increased in a concentration-dependent manner. —It was confirmed that the release of alpha into the medium was suppressed.
  • group A the amount of added Bacopa monniera exk 1 ⁇ gZml is group A1
  • the amount of bacopamoniella extract added 10 ⁇ gZ ml is group A2
  • the amount of bacopa monniera extract added The group of 100 ⁇ gZml was designated as A3 group.
  • FIG. 2 shows expression level marks 21-25 indicating the expression level of inducible nitric oxide synthase in each test group (Group A, Group P, Group Q).
  • FIG. 2 shows that the smaller the expression level mark, the more the inducible monoacid-nitrogen synthase is inhibited and the expression level becomes smaller.
  • the expression level mark 21 is the Q group as the control group
  • the expression level mark 22 is the P group
  • the expression level mark 23 is the A1 group as the bacopa monniera extract addition group
  • the expression level mark 24 is the bacopa monniera extract addition group
  • the A2 group and the expression level mark 25 correspond to the A3 group as the Bacopa monniera extract added group.
  • the expression level mark 25 corresponding to the A3 group is smaller than the expression level mark 22 corresponding to the P group, and the expression of inducible nitric acid-nitrogen synthase is suppressed in the Nocopa monniera extract. Function was recognized. From the above results, it was confirmed that the release of TNF-alpha was inhibited by the Nocopa monniera extract and the expression of inducible nitric acid-nitrogen synthase was inhibited.
  • Uveitis was induced by administering 200 g of LPS dissolved in 200 ⁇ l of sterilized distilled water subcutaneously in both hind footpads of 6-week old Lewis male rats (body weight 200-250 g). Thereafter, bacopa monniera exi was dissolved in 2 ml of PBS (containing 0.1% dimethyl sulfoxide) per kg of body weight of the rat and administered to the rat. The dose of Nocopa monniera extract was adjusted to 1 mg, 10 mg, and lOO mg, respectively, per kg body weight of the rat, and the tail vein was administered immediately after LPS administration, and this was administered (hereinafter referred to as B group). ).
  • the group administered with lmg bacopamoniella extract per kg body weight of rat B1 group, the group administered with 1 Omg bacopamoniella extract per kg body weight of rat B group, the rat body weight lkg Group B3 was the group that received lOOmg of Nocopamonella extract.
  • the control group (hereinafter referred to as R group) without LPS administration and the non-administration group (hereinafter referred to as S group) not administered with Bacopa monniera extract had 2 ml PBS (0.1% dimethyl) per kg body weight of rats. (Containing sulfoxide) was administered on the same time schedule as in Group B. The number of cases was 8 per group.
  • rat endotoxin LPS
  • lipopolysaccharide LPS
  • the number of inflammatory cells per ml of anterior aqueous humor is 48.1 ⁇ 11.9 X 10 5 in group B1, 3 2. 7 ⁇ 2. 1 X 10 5 in group B2, and 3.6 in group B3. ⁇ 0. 4 X 10 5 pieces.
  • the protein concentration was measured using a simple protein measurement kit manufactured by Pierce. Figure 4 shows the measurement results.
  • the protein concentration in the anterior aqueous humor increased by about 70-fold to 20.3 ⁇ 3.6 mg in the S group compared to 0.3 ⁇ 0.lmg per ml in the R group as a control group. did.
  • the administration group Group B
  • an inhibitory effect on the protein concentration in the anterior aqueous humor was observed, particularly in the B2 and B3 groups, in order to correspond to the increased dose.
  • the B2 group had a protein concentration of 15.7 ⁇ 3.4 mg per ml of anterior aqueous humor
  • the B3 group had a protein concentration of 8.2 ⁇ 1.4 mg per ml of anterior aqueous humor.
  • Example 1 show that Bacopa monniera extract suppresses the expression of inducible nitric oxide synthase induced by LPS stimulation at the cellular level and is specifically observed in stimulated cells. Has been shown to inhibit the release of TNF-alpha.
  • Example 2 show that the uveitis of rats induced by stimulation with Nocopa monniera extract LPS is markedly suppressed. Therefore, it was possible to propose a mechanism that Bacopa monniera extract suppresses the overexpression of inducible nitric oxide synthase and further suppresses the inflammatory response.
  • a healthy adult volunteer was administered 300 mg of Bacopa monniera extract per day, and a questionnaire regarding the constitution and physical condition and a questionnaire regarding mental condition and eye strain were conducted before the start of administration and after one month of administration.
  • a control group to which no Bacopa monniera extract was administered was also provided, and a questionnaire was conducted according to the same time schedule as the administration group. There were 55 patients in the treatment group and 23 in the control group.
  • the questionnaire regarding the constitution and physical condition is as follows. Easy to peel off, easy to remove hair, no hair stiffness, no lustrous hair, easy constipation, easy to diarrhea, easy to swell, cold, anemia, easy to dizzy or dizzy, tired Easy, poor sleep, light sleep, poor appetite, easy to get a fever, easy to catch a cold, low physical fitness , Low energy, easy to get frustrated, fun no matter what, motivated
  • the questionnaire on mental state and eye strain is: “Eye is tired!”, Eyes hurt, Eyes are blurred, Tears are easy to tear, Eyes are red, Things are flickering, Shoulders and hips Irritated, easily irritated, prone to heavy head, prone to headache, poor vision, narrow vision, feeling heavy eyelids, painful back of eyes, prone to hyperemia Drowsiness, dry eyes, blurred focus, waking up, yesterday's weather, unable to remember yesterday's dinner, no person's name, no concentration, reading books, irritability “I feel vague anxiety driven by“
  • bacopamo that exhibits the inhibitory function of the inducible monoacid-nitrogen synthase according to the present invention.
  • a method for producing a marble cookie as an example of a food or drink obtained by adding Niera extract will be described.
  • This marble cookie originally uses cocoa powder, which has a bitter taste, and even if the cocoa dough is made by adding bacopa monniera extract, the change in the taste of the cookie can be kept relatively low. If possible, it is convenient because it gives a deeper and more luxurious taste to the cookies.
  • Example 4 when the weight ratio of the bacopamoniella extract to the cocoa dough exceeds 0.6%, the bitterness of the bacopamoniella extract becomes too strong, and the flavor of the marble cookie becomes too strong. Damaged.
  • This raw chocolate is originally made from chocolate with a bitter taste, cocoa powder, and rum that has a strong taste, and even if bacopa monniera extract is added, the change in taste is kept relatively low. If you can, it is convenient because it gives you a deep and high-class feel to the flavor of fresh chocolate.
  • Example 5 when the weight ratio of the Bacopa monniera extract exceeds 0.6%, which is 0.6%, the bitter taste of the Bacopa monniera extract becomes too strong and the flavor of the raw chocolate is impaired.
  • RAW264. 7 cells which are derived from mouse macrophages, were adjusted so that the number of cells was 5 x 10 4 per well of a 24 well plate, while the final concentration of olive fruit polyphenol was l ⁇ u Culture solutions containing 1% dimethyl sulfoxide (DMSO) adjusted to gZml, lO ⁇ g / ml, and 100 gZml were added, respectively. Then, the RAW264.7 cells after addition of this culture medium are pre-treated in the presence of 37 ° C and 5% CO for 24 hours.
  • DMSO dimethyl sulfoxide
  • the DMSO-containing culture solution is a mixture of 1/10 volume of immobilized fetal bovine serum in RPMI-1640 medium supplemented with 2 mM glutamine, 100 U / ml besylin, and 100 ml streptomycin. .
  • T group a group stimulated with LPS but not added olive fruit polyphenol
  • U group a control group which is not stimulated with LPS nor added with olive fruit polyphenol.
  • DMSO was added to a final concentration of 0.01%.
  • TNF-alpha release into the medium and expression of inducible nitric oxide synthase were examined. TNF-alpha release is observed to increase specifically when cells are stimulated.
  • the TNF-alpha concentration was determined by ELISA, and the expression level of inducible nitric oxide synthase was determined by Western plotting.
  • FIG. 5 shows the detection result of the TNF-alpha concentration.
  • the TNF-alpha concentration was significantly increased in the T group, and TNF-alpha was observed to be released by stimulation of cells by LPS.
  • the olive fruit polyphenol addition group hereinafter referred to as group C
  • the TNF-alpha concentration decreased with the increase in the olive fruit polyphenol addition, and the olive fruit polyphenola concentration dependent TNF— It was confirmed that the release of alpha into the medium was suppressed.
  • the group with olive fruit polyphenol added 1 gZml, group C1, the group with olive fruit polyphenol added 10 ⁇ g Zml, group C2, and the addition of olive fruit polyphenol.
  • the group with an amount of 100 ⁇ g Zml was designated as C3 group.
  • FIG. 6 shows expression level marks 31 to 35 indicating the expression level of inducible nitric oxide synthase in each test group (group C, group T, group U).
  • FIG. 6 shows that the smaller the expression level mark, the more the inducible monoxide-nitrogen synthase is inhibited and the lower the expression level.
  • the expression mark 31 is the U group as a control group
  • the expression mark 32 is the T group
  • the expression mark 33 is the C1 group as the olive fruit polyphenol addition group
  • the expression mark 34 is the olive fruit polyphenol addition.
  • the C2 group as a group and the expression level mark 35 correspond to the C3 group as a group added with olive fruit polyphenol.
  • Uveitis was induced by administering 200 g of LPS dissolved in 200 ⁇ l of sterilized distilled water subcutaneously in both hind footpads of 6-week old Lewis male rats (body weight 200-250 g). Thereafter, olive fruit polyphenol was dissolved in 2 ml of PBS (containing 0.1% dimethyl sulfoxide) per kg of body weight of the rat and administered to the rat. Olive fruit polyphenols were adjusted to 1 mg, lOmg, and lOOmg, respectively, per lkg body weight of the rat. It was.
  • group D1 was administered lmg olive fruit polyphenol per kg body weight of rat D
  • group D2 was administered lOmg olive fruit polyphenol per kg body weight of rat
  • group L2 was rat body weight lkg
  • D3 group The group to which lOOmg of olive fruit polyphenol was administered was designated as D3 group.
  • the control group (hereinafter referred to as V group) not administered with L PS and the non-administered group (hereinafter referred to as W group) not administered with olive fruit polyphenol were treated with 2 ml PBS (0.1% dimethyl) per kg of body weight of rats. Sulphoxide-containing) was administered on the same time schedule as group D. The number of cases was 8 per group.
  • rat endotoxin LPS
  • lipopolysaccharide LPS
  • the protein concentration in the anterior aqueous humor increased by about 70-fold to 20.3 ⁇ 3.6 mg in the W group compared to 0.3 ⁇ 0.lmg per ml in the V group as a control group. did.
  • Group D an inhibitory effect on the protein concentration in the anterior aqueous humor was observed, particularly in the D2 and D3 groups, in order to correspond to the increased dose. That is, in the D2 group, the protein concentration was 10.6 ⁇ 3.4 mg per ml of anterior aqueous humor, and in the D3 group, the protein concentration was 5.8 ⁇ 1.4 mg per ml of anterior aqueous humor.
  • Example 6 suppressed the expression of inducible nitric oxide synthase induced by LPS stimulation at the olive fruit polyphenola cell level and were specifically observed in the stimulated cells. It has been shown to inhibit the release of TNF-alpha.
  • Example 7 show that rat uveitis induced by stimulation of olive fruit polyphenola LPS is markedly suppressed. Therefore, we could propose a mechanism that olive fruit polyphenol suppresses overexpression of inducible nitric oxide synthase and further suppresses the inflammatory response.
  • the effect of olive fruit polyphenol on blood vessel age was analyzed in human volunteers. Olive fruit polyphenols processed into tablets were administered to adult volunteers at a dose of 300 mg per person per day. Blood vessel age was measured before the start of administration and one month after the start of administration. On the other hand, a control group to which no olive fruit polyphenol was administered was also provided, and the blood vessel age was measured according to the same schedule as the administration group. 54 patients in the treatment group, 26 in the control group It was a name.
  • an acceleration pulse wave meter (BLOOD CIRCULATION CHECKER: manufactured by FUTU RE WAVE) was used. This device measures the state of peripheral blood circulation. The measurement results are from the younger vascular age: A +, A, A-, B +, B + X, B, BX, C +, C, B 1, B— X, C 1, C——, E + , E, D +, D, D—, E—, F, F—, G, G—. Each evaluation was statistically processed with a score from 20 to 0 from A to GZG-. Scoring power after 1 month of olive fruit polyphenols It was.
  • UV Illuminator TM20 manufactured by Funakoshi Co., Ltd. (planar light source equipped with 6 UV lamps with a wavelength of 302 nm, voltage of 100 V, and output of 8 W), UV irradiation is applied to the subject's arm to improve pigmentation due to sunburn. The effect was confirmed.
  • a black rubber sheet (not shown) having 12 holes continuously covered one arm of the subject and irradiated with UV for 3 minutes from a distance of 26 cm from the arm (control test). Prior to irradiation, all holes were concealed with adhesive tape to prevent UV irradiation of the skin under the holes. The adhesive tape with a single hole was removed at 15-second intervals to expose the skin, and the UV irradiation time was increased according to the order of the holes. The UV irradiation site of this arm corresponding to each hole position was also set as irradiation site lp to irradiation site 12p in order of the short direction of irradiation time.
  • the other arm of the same subject was irradiated with UV under the same conditions (effect confirmation test) to confirm the inflammatory reaction.
  • the UV irradiation part of the other arm corresponding to each hole position was also set as irradiation part lq to irradiation part 12q in order of the shortest irradiation time.
  • the force with a long irradiation time is 9 places, that is, the irradiated part 4c! Inflammatory reaction was observed at ⁇ 12q (see Fig. 10 (c)).
  • This marble cookie originally uses cocoa powder with a bitter taste, and even if olive fruit polyphenol is added to make cocoa dough, the change in cookie taste can be kept relatively low. It is convenient because it gives a deeper and more luxurious taste to the cookies.
  • Example 10 the weight ratio of olive fruit polyphenol to cocoa dough is 0.35%. When the strength exceeds 20%, the bitter taste of olive fruit polyphenol becomes too strong and the flavor of marble cookies is impaired. It is.
  • raw chocolate as another example of a food or drink obtained by adding olive fruit polyphenol which exhibits the inhibitory function of inducible nitric oxide synthase according to the present invention.
  • This raw chocolate originally uses chocolate chocolate with a bitter taste, cocoa powder with a strong taste, and a strong taste of rum. If you can, it is convenient because it gives you a deeper and more luxurious feel to the taste of raw chocolate.
  • Example 11 the weight ratio of olive fruit polyphenol is 0.35%. When the force exceeds 20%, the bitter taste of olive fruit polyphenol becomes too strong and the flavor of raw chocolate is impaired. .
  • a test drug was prepared by suspending Bacopa monniera extract, olive fruit polyphenol, copper dalconate, and zinc dalconate in 0.5 carboxymethylcellulose (CMC).
  • Oral administration was performed at 5 mlZkg for 24 hours, 3 hours, LPS administration, 1 hour, and 3 hours before LPS administration.
  • the LPS group (Y group) and the control group (X group) received 0.5% CMC at the same time schedule.
  • Anterior aqueous humor was collected 24 hours after LPS administration, and the protein concentration and the number of cells were measured.
  • Table 7 shows the experimental conditions. The experimental results are shown in FIGS.
  • the present invention it is possible to provide humans and animals with pharmaceuticals and foods and drinks for the purpose of inhibiting an inducible nitric oxide synthase containing olive fruit polyphenol as an active ingredient. If people take these medicines and foods, they can relieve eye irritation, improve peripheral blood vessels, and suppress pigmentation after sunburn.
  • FIG. 1 A diagram illustrating the results of Example 1 of the present invention, which shows release of TNF-alpha from LPS-stimulated cells in RAW264. 7 cells, which are cells derived from mouse macrophages. It is a figure showing that Bacopa monniera extract suppresses.
  • FIG. 2 is a diagram for explaining the results of Example 1 of the present invention, in which derivates of inducible nitrogen monoxide synthase in cells stimulated with LPS in RAW264. 7 cells, which are cells derived from mouse macrophages. It is a figure showing that Bacopa monniera extract suppresses expression.
  • FIG. 3 is a diagram for explaining the results of Example 2 of the present invention, in which 6-week-old Lewis male rats (body weight 200-250 g) were dissolved in 200 ⁇ l of sterile distilled water subcutaneously in both hind footpads. It is a figure showing that Bacopa monniera extract suppresses the infiltration of the inflammatory cell into anterior aqueous humor in the uveitis induced by administering 200 ⁇ g of LPS.
  • FIG. 4 is a diagram for explaining the results of Example 2 of the present invention, in which 6-week-old Lewis male rats (body weight 200-250 g) were dissolved in 200 ⁇ 1 of sterile distilled water under the skin of both hind limbs It is a figure showing that Bacopa monniera extract suppresses the increase in the protein concentration in anterior aqueous humor in the uveitis induced by administering 200 ⁇ g of LPS.
  • FIG. 5 is a diagram for explaining the results of Example 6 of the present invention, in which TNF-alpha from cells stimulated with LPS in RAW264.7 cells, which are cells derived from mouse macrophages. It is a figure showing that an olive fruit polyphenol suppresses discharge
  • FIG. 6 is a diagram illustrating the results of Example 6 of the present invention, in which derivates of inducible nitrogen monoxide synthase in cells stimulated with LPS in RAW 264.7 cells, which are cells derived from mouse macrophages. It is a figure showing that an olive fruit polyphenol suppresses an expression.
  • FIG. 7 is a diagram for explaining the results of Example 7 of the present invention, which was dissolved in 200 ⁇ 1 of sterile distilled water subcutaneously on both hind footpads of 6-week-old Lewis male rats (body weight 200-250 g). It is a figure showing that olive fruit polyphenol suppresses infiltration of inflammatory cells into anterior chamber water in uveitis induced by administration of 200 ⁇ g of LPS.
  • FIG. 8 is a diagram for explaining the results of Example 7 of the present invention, in which 6-week-old Lewis male rats (body weight 200-250 g) were dissolved in 200 ⁇ l of sterilized distilled water subcutaneously in both hind footpads. It is a figure showing that olive fruit polyphenol suppresses the increase in the protein concentration in anterior aqueous humor in the uveitis induced by administering 200 ⁇ g of LPS.
  • Example 8 of the present invention A diagram illustrating the results of Example 8 of the present invention, in which a plurality of administration groups administered with olive fruit polyphenol for one month were compared with a plurality of control groups not administered with olive fruit polyphenol. In comparison, it shows that a marked improvement in vascular age was observed.
  • FIG. 10 is a diagram for explaining the results of Example 9 of the present invention, and shows how pigmentation due to sunburn is significantly reduced when olive fruit polyphenol is administered for 1 month. .
  • FIG. 11 is a diagram for explaining the results of Example 11 of the present invention, showing changes in protein concentration in anterior aqueous humor when bacopa monniera extract, copper and zinc are orally administered.
  • FIG. 12 is a diagram for explaining the results of Example 11 of the present invention, and showing changes in the number of inflammatory cells in anterior aqueous humor when bacopa monniera extract, copper and zinc are orally administered.
  • FIG. 13 is a diagram for explaining the results of Example 11 of the present invention, and shows changes in protein concentration in anterior aqueous humor when orive fruit polyphenol, copper and zinc are orally administered.
  • Example 11 of the present invention A diagram for explaining the results of Example 11 of the present invention, in which olive fruit polyphenol It is a figure which shows the change of the number of inflammatory cells in an anterior aqueous humor at the time of administering orally, ru, copper and zinc.
  • FIG. 15 is a diagram for explaining the results of Example 11 of the present invention, in which the ratio of copper to zinc was 1:20, and the ratio of Nocopa monniera extract to olive fruit polyphenol was varied. It is a figure which shows the change of the protein concentration in an aqueous humor at the time of administering.
  • FIG. 16 is a diagram for explaining the results of Example 11 of the present invention, in which the ratio of copper to zinc was 1:20, and the ratio of Nocopa monniera extract to olive fruit polyphenol was changed to It is a figure which shows the change of the inflammatory cell number in the anterior aqueous humor at the time of administering.

Abstract

L'invention concerne un inhibiteur de synthase d'oxyde nitrique inductible qui produit peu d'effets secondaires négatifs et peut être assimilé aisément. L'invention concerne également une boisson ou un aliment produisant un effet inhibiteur sur une synthase d'oxyde nitrique inductible. L'inhibiteur contient un extrait de Bacopa monniera en tant que principe actif. L'inhibiteur peut contenir un polyphénol issu de l'olive en tant que principe actif.
PCT/JP2007/060984 2006-06-02 2007-05-30 Inhibiteur de synthase d'oxyde nitrique inductible, boisson/aliment, et aliment neutraceutique WO2007142096A1 (fr)

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JP2006155274A JP2006342161A (ja) 2006-06-02 2006-06-02 誘導型一酸化窒素合成酵素の阻害剤及び飲食品
JP2006155273A JP2006328072A (ja) 2006-06-02 2006-06-02 誘導型一酸化窒素合成酵素の阻害剤及び飲食品
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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN109395055A (zh) * 2019-01-07 2019-03-01 琪庆生物医药(上海)有限公司 一种具有修复关节软组织损伤作用的组合物及其制备方法
CN110475561A (zh) * 2017-03-23 2019-11-19 美纳里尼制药工业联合股份有限公司 具有抗氧化活性的保健性、饮食性和营养性组合物

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1999040897A1 (fr) * 1998-02-12 1999-08-19 Sederma S.A. Compositions a usage cosmetiques ou dermopharmaceutique contenant un extrait vegetal obtenu a partir de bacopa monnieri (l.)
JP2002262831A (ja) * 2001-03-12 2002-09-17 Kyosei Seiyaku Kk ホタテ貝外套膜を用いるミネラル強化素材
JP2003531860A (ja) * 2000-04-28 2003-10-28 ロレアル Ｎｏ合成酵素阻害剤としてのオリーブ種の植物抽出物とその使用
JP2006328072A (ja) * 2006-06-02 2006-12-07 Japan Organo Co Ltd 誘導型一酸化窒素合成酵素の阻害剤及び飲食品
JP2006342161A (ja) * 2006-06-02 2006-12-21 Japan Organo Co Ltd 誘導型一酸化窒素合成酵素の阻害剤及び飲食品

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1999040897A1 (fr) * 1998-02-12 1999-08-19 Sederma S.A. Compositions a usage cosmetiques ou dermopharmaceutique contenant un extrait vegetal obtenu a partir de bacopa monnieri (l.)
JP2003531860A (ja) * 2000-04-28 2003-10-28 ロレアル Ｎｏ合成酵素阻害剤としてのオリーブ種の植物抽出物とその使用
JP2002262831A (ja) * 2001-03-12 2002-09-17 Kyosei Seiyaku Kk ホタテ貝外套膜を用いるミネラル強化素材
JP2006328072A (ja) * 2006-06-02 2006-12-07 Japan Organo Co Ltd 誘導型一酸化窒素合成酵素の阻害剤及び飲食品
JP2006342161A (ja) * 2006-06-02 2006-12-21 Japan Organo Co Ltd 誘導型一酸化窒素合成酵素の阻害剤及び飲食品

Non-Patent Citations (9)

* Cited by examiner, † Cited by third party
Title
BITLER C.M. ET AL.: "Hydrolyzed olive vegetation water in mice has anti-inflammatory activity", JOURNAL OF NUTRITION, vol. 135, no. 6, 2005, pages 1475 - 1479, XP002449046 *
DATABASE BIOSIS [online] SHERMAN M.P. ET AL.: "Zinc and copper inhibit expression of inducible nitric oxide synthase in rat alveolar macrophages: A reason for the production of metal-binding proteins during endotoxemia?", XP003019796, Database accession no. (1997:238322) *
FUJITA H. ET AL.: "Olive Suiyosei Chushutsubutsu Hidrox no Kosanka Sayo to Sono Kaiseki", THE JOURNAL OF MEDICINE, vol. 53, no. 1, 2005, pages 99 - 108, XP003019795 *
IDEMURA Y. ET AL.: "Hito Haidomyaku Naihi Saibo no NO Gosei Koso Kassei ni Oyobosu Kinzoku Ion no Koka", RESPIRATION RESEARCH, vol. 18, no. 7, 1999, pages 755 - 759, XP003019798 *
PEDIATRIC RESEARCH, vol. 41, no. 4, PART 2, 1997, pages 307A *
RUSSO A. ET AL.: "Free radical scavenging capacity and protective effect of Bacopa monniera L. on DNA damage", PHYTOTHERAPY RESEARCH, vol. 17, no. 8, 2003, pages 870 - 875, XP003019793 *
RUSSO A. ET AL.: "Nitric oxide-related toxicity in cultured astrocytes: effect of Bacopa monniera", LIFE SCIENCES, vol. 73, no. 12, 2003, pages 1517 - 1526, XP003019792 *
TIAN L. ET AL.: "Metal-induced modulation of nitric oxide production in vitro by murine macrophages: lead, nickel, and cobalt utilize different mechanisms", TOXICOLOGY AND APPLIED PHARMACOLOGY, vol. 141, no. 2, 1996, pages 540 - 547, XP003019797 *
ZASLAVER M. ET AL.: "Natural Compounds Derived from Foods Modulate Nitric Oxide Production and Oxidative Status in Epithelial Lung Cells", J. AGRIC. FOOD CHEM., vol. 53, no. 26, 2005, pages 9934 - 9939, XP003019794 *

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN110475561A (zh) * 2017-03-23 2019-11-19 美纳里尼制药工业联合股份有限公司 具有抗氧化活性的保健性、饮食性和营养性组合物
CN109395055A (zh) * 2019-01-07 2019-03-01 琪庆生物医药(上海)有限公司 一种具有修复关节软组织损伤作用的组合物及其制备方法

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