KR101770035B1 - Composition comprising Morifolium extract asan effective component for preventing and treatingarthritis - Google Patents
Composition comprising Morifolium extract asan effective component for preventing and treatingarthritis Download PDFInfo
- Publication number
- KR101770035B1 KR101770035B1 KR1020150145021A KR20150145021A KR101770035B1 KR 101770035 B1 KR101770035 B1 KR 101770035B1 KR 1020150145021 A KR1020150145021 A KR 1020150145021A KR 20150145021 A KR20150145021 A KR 20150145021A KR 101770035 B1 KR101770035 B1 KR 101770035B1
- Authority
- KR
- South Korea
- Prior art keywords
- extract
- composition
- preventing
- present
- arthritis
- Prior art date
Links
- 239000000284 extract Substances 0.000 title claims abstract description 114
- 239000000203 mixture Substances 0.000 title claims abstract description 48
- 108010002352 Interleukin-1 Proteins 0.000 claims abstract description 45
- 206010003246 arthritis Diseases 0.000 claims abstract description 36
- 230000000699 topical effect Effects 0.000 claims abstract description 16
- 239000004480 active ingredient Substances 0.000 claims abstract description 14
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 14
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 14
- 201000008482 osteoarthritis Diseases 0.000 claims description 11
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 10
- 244000199866 Lactobacillus casei Species 0.000 claims description 8
- 235000013958 Lactobacillus casei Nutrition 0.000 claims description 8
- 229940017800 lactobacillus casei Drugs 0.000 claims description 8
- 238000000034 method Methods 0.000 claims description 7
- 235000013305 food Nutrition 0.000 claims description 5
- 239000012046 mixed solvent Substances 0.000 claims description 5
- 125000004432 carbon atom Chemical group C* 0.000 claims description 3
- 239000002904 solvent Substances 0.000 claims description 3
- 241000193830 Bacillus <bacterium> Species 0.000 claims description 2
- 240000004922 Vigna radiata Species 0.000 claims description 2
- 235000010721 Vigna radiata var radiata Nutrition 0.000 claims description 2
- 235000011469 Vigna radiata var sublobata Nutrition 0.000 claims description 2
- 229940069765 bean extract Drugs 0.000 claims description 2
- 239000000453 juniperus communis l. leaf oil Substances 0.000 claims 1
- 229940109850 royal jelly Drugs 0.000 claims 1
- 230000000694 effects Effects 0.000 abstract description 26
- 102000002274 Matrix Metalloproteinases Human genes 0.000 abstract description 22
- 108010000684 Matrix Metalloproteinases Proteins 0.000 abstract description 22
- 102000043136 MAP kinase family Human genes 0.000 abstract description 16
- 108091054455 MAP kinase family Proteins 0.000 abstract description 16
- 102000003945 NF-kappa B Human genes 0.000 abstract description 16
- 108010057466 NF-kappa B Proteins 0.000 abstract description 16
- 102100029438 Nitric oxide synthase, inducible Human genes 0.000 abstract description 15
- 101710089543 Nitric oxide synthase, inducible Proteins 0.000 abstract description 15
- 102100038280 Prostaglandin G/H synthase 2 Human genes 0.000 abstract description 14
- 108050003267 Prostaglandin G/H synthase 2 Proteins 0.000 abstract description 14
- 230000005764 inhibitory process Effects 0.000 abstract description 7
- 239000000758 substrate Substances 0.000 abstract description 4
- 230000028709 inflammatory response Effects 0.000 abstract description 3
- 102000000589 Interleukin-1 Human genes 0.000 description 39
- 210000004027 cell Anatomy 0.000 description 35
- MWUXSHHQAYIFBG-UHFFFAOYSA-N Nitric oxide Chemical compound O=[N] MWUXSHHQAYIFBG-UHFFFAOYSA-N 0.000 description 34
- 201000010099 disease Diseases 0.000 description 32
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 32
- 240000000249 Morus alba Species 0.000 description 19
- 235000008708 Morus alba Nutrition 0.000 description 18
- 210000001612 chondrocyte Anatomy 0.000 description 17
- 208000027866 inflammatory disease Diseases 0.000 description 15
- 238000004519 manufacturing process Methods 0.000 description 15
- XEYBRNLFEZDVAW-ARSRFYASSA-N dinoprostone Chemical compound CCCCC[C@H](O)\C=C\[C@H]1[C@H](O)CC(=O)[C@@H]1C\C=C/CCCC(O)=O XEYBRNLFEZDVAW-ARSRFYASSA-N 0.000 description 14
- 230000002401 inhibitory effect Effects 0.000 description 14
- 108090000623 proteins and genes Proteins 0.000 description 14
- 235000013376 functional food Nutrition 0.000 description 13
- 229960002986 dinoprostone Drugs 0.000 description 12
- 239000003814 drug Substances 0.000 description 12
- 208000030159 metabolic disease Diseases 0.000 description 12
- XEYBRNLFEZDVAW-UHFFFAOYSA-N prostaglandin E2 Natural products CCCCCC(O)C=CC1C(O)CC(=O)C1CC=CCCCC(O)=O XEYBRNLFEZDVAW-UHFFFAOYSA-N 0.000 description 12
- 238000011282 treatment Methods 0.000 description 12
- 230000036541 health Effects 0.000 description 11
- 102100027995 Collagenase 3 Human genes 0.000 description 10
- 108050005238 Collagenase 3 Proteins 0.000 description 10
- 229940079593 drug Drugs 0.000 description 10
- 239000000796 flavoring agent Substances 0.000 description 10
- 235000019634 flavors Nutrition 0.000 description 10
- 102000004169 proteins and genes Human genes 0.000 description 10
- 102000000380 Matrix Metalloproteinase 1 Human genes 0.000 description 9
- 108010016113 Matrix Metalloproteinase 1 Proteins 0.000 description 9
- 208000001132 Osteoporosis Diseases 0.000 description 8
- 210000000845 cartilage Anatomy 0.000 description 8
- 230000015556 catabolic process Effects 0.000 description 8
- 238000006731 degradation reaction Methods 0.000 description 8
- 102000002574 p38 Mitogen-Activated Protein Kinases Human genes 0.000 description 8
- 108010068338 p38 Mitogen-Activated Protein Kinases Proteins 0.000 description 8
- 239000000047 product Substances 0.000 description 8
- 241000186016 Bifidobacterium bifidum Species 0.000 description 7
- 238000002360 preparation method Methods 0.000 description 7
- 230000002829 reductive effect Effects 0.000 description 7
- 239000012228 culture supernatant Substances 0.000 description 6
- 238000000605 extraction Methods 0.000 description 6
- 238000000855 fermentation Methods 0.000 description 6
- 230000004151 fermentation Effects 0.000 description 6
- 238000009472 formulation Methods 0.000 description 6
- 230000001404 mediated effect Effects 0.000 description 6
- 239000008194 pharmaceutical composition Substances 0.000 description 6
- 230000002441 reversible effect Effects 0.000 description 6
- 230000019491 signal transduction Effects 0.000 description 6
- 230000000638 stimulation Effects 0.000 description 6
- 230000004083 survival effect Effects 0.000 description 6
- VKUYLANQOAKALN-UHFFFAOYSA-N 2-[benzyl-(4-methoxyphenyl)sulfonylamino]-n-hydroxy-4-methylpentanamide Chemical compound C1=CC(OC)=CC=C1S(=O)(=O)N(C(CC(C)C)C(=O)NO)CC1=CC=CC=C1 VKUYLANQOAKALN-UHFFFAOYSA-N 0.000 description 5
- 102100026802 72 kDa type IV collagenase Human genes 0.000 description 5
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 5
- 238000002965 ELISA Methods 0.000 description 5
- 206010061218 Inflammation Diseases 0.000 description 5
- 102000003777 Interleukin-1 beta Human genes 0.000 description 5
- 108090000193 Interleukin-1 beta Proteins 0.000 description 5
- 108010055717 JNK Mitogen-Activated Protein Kinases Proteins 0.000 description 5
- 240000001046 Lactobacillus acidophilus Species 0.000 description 5
- 235000013956 Lactobacillus acidophilus Nutrition 0.000 description 5
- 241000218588 Lactobacillus rhamnosus Species 0.000 description 5
- 241001465754 Metazoa Species 0.000 description 5
- 108010052419 NF-KappaB Inhibitor alpha Proteins 0.000 description 5
- 102100039337 NF-kappa-B inhibitor alpha Human genes 0.000 description 5
- 102100030416 Stromelysin-1 Human genes 0.000 description 5
- 101710108790 Stromelysin-1 Proteins 0.000 description 5
- 230000004913 activation Effects 0.000 description 5
- 229940002008 bifidobacterium bifidum Drugs 0.000 description 5
- 239000003153 chemical reaction reagent Substances 0.000 description 5
- 208000016097 disease of metabolism Diseases 0.000 description 5
- 238000002474 experimental method Methods 0.000 description 5
- 230000002757 inflammatory effect Effects 0.000 description 5
- 230000004054 inflammatory process Effects 0.000 description 5
- 239000000546 pharmaceutical excipient Substances 0.000 description 5
- 238000001262 western blot Methods 0.000 description 5
- 101710151806 72 kDa type IV collagenase Proteins 0.000 description 4
- 241000186012 Bifidobacterium breve Species 0.000 description 4
- 102000004127 Cytokines Human genes 0.000 description 4
- 108090000695 Cytokines Proteins 0.000 description 4
- 102000019145 JUN kinase activity proteins Human genes 0.000 description 4
- 241000721662 Juniperus Species 0.000 description 4
- 206010057190 Respiratory tract infections Diseases 0.000 description 4
- 210000003321 cartilage cell Anatomy 0.000 description 4
- 230000001419 dependent effect Effects 0.000 description 4
- 239000000839 emulsion Substances 0.000 description 4
- 229940039695 lactobacillus acidophilus Drugs 0.000 description 4
- YBYRMVIVWMBXKQ-UHFFFAOYSA-N phenylmethanesulfonyl fluoride Chemical compound FS(=O)(=O)CC1=CC=CC=C1 YBYRMVIVWMBXKQ-UHFFFAOYSA-N 0.000 description 4
- 239000000843 powder Substances 0.000 description 4
- 108020003175 receptors Proteins 0.000 description 4
- -1 small molecule compound Chemical class 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- 239000000725 suspension Substances 0.000 description 4
- 239000006188 syrup Substances 0.000 description 4
- 235000020357 syrup Nutrition 0.000 description 4
- 231100000419 toxicity Toxicity 0.000 description 4
- 230000001988 toxicity Effects 0.000 description 4
- 241000186000 Bifidobacterium Species 0.000 description 3
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 3
- 102000029816 Collagenase Human genes 0.000 description 3
- 108060005980 Collagenase Proteins 0.000 description 3
- 102000007665 Extracellular Signal-Regulated MAP Kinases Human genes 0.000 description 3
- 108010007457 Extracellular Signal-Regulated MAP Kinases Proteins 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 201000001263 Psoriatic Arthritis Diseases 0.000 description 3
- 208000036824 Psoriatic arthropathy Diseases 0.000 description 3
- 102000005747 Transcription Factor RelA Human genes 0.000 description 3
- 108010031154 Transcription Factor RelA Proteins 0.000 description 3
- 230000009471 action Effects 0.000 description 3
- 208000006673 asthma Diseases 0.000 description 3
- 238000004113 cell culture Methods 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- 229960002424 collagenase Drugs 0.000 description 3
- 231100000135 cytotoxicity Toxicity 0.000 description 3
- 230000003013 cytotoxicity Effects 0.000 description 3
- 230000003247 decreasing effect Effects 0.000 description 3
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 3
- 238000011156 evaluation Methods 0.000 description 3
- 239000000945 filler Substances 0.000 description 3
- 102000006602 glyceraldehyde-3-phosphate dehydrogenase Human genes 0.000 description 3
- 108020004445 glyceraldehyde-3-phosphate dehydrogenase Proteins 0.000 description 3
- 210000004209 hair Anatomy 0.000 description 3
- 201000006417 multiple sclerosis Diseases 0.000 description 3
- 230000037361 pathway Effects 0.000 description 3
- 239000002953 phosphate buffered saline Substances 0.000 description 3
- 230000026731 phosphorylation Effects 0.000 description 3
- 238000006366 phosphorylation reaction Methods 0.000 description 3
- 230000002265 prevention Effects 0.000 description 3
- 235000013343 vitamin Nutrition 0.000 description 3
- 239000011782 vitamin Substances 0.000 description 3
- 229930003231 vitamin Natural products 0.000 description 3
- 229940088594 vitamin Drugs 0.000 description 3
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 2
- 201000001320 Atherosclerosis Diseases 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 244000063299 Bacillus subtilis Species 0.000 description 2
- 235000014469 Bacillus subtilis Nutrition 0.000 description 2
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- 244000025254 Cannabis sativa Species 0.000 description 2
- 206010012438 Dermatitis atopic Diseases 0.000 description 2
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 2
- 238000008157 ELISA kit Methods 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- 201000005569 Gout Diseases 0.000 description 2
- 102100034343 Integrase Human genes 0.000 description 2
- 241000186660 Lactobacillus Species 0.000 description 2
- 241001468191 Lactobacillus kefiri Species 0.000 description 2
- 240000006024 Lactobacillus plantarum Species 0.000 description 2
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 2
- 231100000002 MTT assay Toxicity 0.000 description 2
- 238000000134 MTT assay Methods 0.000 description 2
- 241000713869 Moloney murine leukemia virus Species 0.000 description 2
- 206010030113 Oedema Diseases 0.000 description 2
- 208000002193 Pain Diseases 0.000 description 2
- 201000004681 Psoriasis Diseases 0.000 description 2
- 108010092799 RNA-directed DNA polymerase Proteins 0.000 description 2
- 238000010240 RT-PCR analysis Methods 0.000 description 2
- 208000021386 Sjogren Syndrome Diseases 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 2
- 206010043255 Tendonitis Diseases 0.000 description 2
- 244000299461 Theobroma cacao Species 0.000 description 2
- 102100035100 Transcription factor p65 Human genes 0.000 description 2
- 238000002835 absorbance Methods 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- YZXBAPSDXZZRGB-DOFZRALJSA-N arachidonic acid Chemical compound CCCCC\C=C/C\C=C/C\C=C/C\C=C/CCCC(O)=O YZXBAPSDXZZRGB-DOFZRALJSA-N 0.000 description 2
- 201000008937 atopic dermatitis Diseases 0.000 description 2
- 235000013361 beverage Nutrition 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 229940098773 bovine serum albumin Drugs 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 150000001720 carbohydrates Chemical class 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 235000009508 confectionery Nutrition 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- 210000000805 cytoplasm Anatomy 0.000 description 2
- 230000007423 decrease Effects 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- 239000012153 distilled water Substances 0.000 description 2
- VHJLVAABSRFDPM-QWWZWVQMSA-N dithiothreitol Chemical compound SC[C@@H](O)[C@H](O)CS VHJLVAABSRFDPM-QWWZWVQMSA-N 0.000 description 2
- 239000003937 drug carrier Substances 0.000 description 2
- 235000013399 edible fruits Nutrition 0.000 description 2
- 238000001378 electrochemiluminescence detection Methods 0.000 description 2
- 229940088598 enzyme Drugs 0.000 description 2
- ZMMJGEGLRURXTF-UHFFFAOYSA-N ethidium bromide Chemical compound [Br-].C12=CC(N)=CC=C2C2=CC=C(N)C=C2[N+](CC)=C1C1=CC=CC=C1 ZMMJGEGLRURXTF-UHFFFAOYSA-N 0.000 description 2
- 235000015203 fruit juice Nutrition 0.000 description 2
- 239000008187 granular material Substances 0.000 description 2
- 239000004519 grease Substances 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 238000011534 incubation Methods 0.000 description 2
- 230000006698 induction Effects 0.000 description 2
- 230000001939 inductive effect Effects 0.000 description 2
- 239000003112 inhibitor Substances 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 239000002609 medium Substances 0.000 description 2
- 239000012528 membrane Substances 0.000 description 2
- 244000005700 microbiome Species 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 208000010125 myocardial infarction Diseases 0.000 description 2
- 239000012457 nonaqueous media Substances 0.000 description 2
- 235000012149 noodles Nutrition 0.000 description 2
- 230000004942 nuclear accumulation Effects 0.000 description 2
- 230000005937 nuclear translocation Effects 0.000 description 2
- 235000019629 palatability Nutrition 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- 239000006187 pill Substances 0.000 description 2
- 230000034190 positive regulation of NF-kappaB transcription factor activity Effects 0.000 description 2
- 230000003449 preventive effect Effects 0.000 description 2
- BOLDJAUMGUJJKM-LSDHHAIUSA-N renifolin D Natural products CC(=C)[C@@H]1Cc2c(O)c(O)ccc2[C@H]1CC(=O)c3ccc(O)cc3O BOLDJAUMGUJJKM-LSDHHAIUSA-N 0.000 description 2
- 238000003757 reverse transcription PCR Methods 0.000 description 2
- 150000003839 salts Chemical class 0.000 description 2
- 230000001953 sensory effect Effects 0.000 description 2
- UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 2
- 239000000829 suppository Substances 0.000 description 2
- 201000000596 systemic lupus erythematosus Diseases 0.000 description 2
- 239000003826 tablet Substances 0.000 description 2
- 229940124597 therapeutic agent Drugs 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 231100000331 toxic Toxicity 0.000 description 2
- 230000002588 toxic effect Effects 0.000 description 2
- 230000002103 transcriptional effect Effects 0.000 description 2
- 210000003462 vein Anatomy 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- KIUKXJAPPMFGSW-DNGZLQJQSA-N (2S,3S,4S,5R,6R)-6-[(2S,3R,4R,5S,6R)-3-Acetamido-2-[(2S,3S,4R,5R,6R)-6-[(2R,3R,4R,5S,6R)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2-carboxylic acid Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 KIUKXJAPPMFGSW-DNGZLQJQSA-N 0.000 description 1
- MSWZFWKMSRAUBD-IVMDWMLBSA-N 2-amino-2-deoxy-D-glucopyranose Chemical compound N[C@H]1C(O)O[C@H](CO)[C@@H](O)[C@@H]1O MSWZFWKMSRAUBD-IVMDWMLBSA-N 0.000 description 1
- AZKSAVLVSZKNRD-UHFFFAOYSA-M 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide Chemical compound [Br-].S1C(C)=C(C)N=C1[N+]1=NC(C=2C=CC=CC=2)=NN1C1=CC=CC=C1 AZKSAVLVSZKNRD-UHFFFAOYSA-M 0.000 description 1
- FWBHETKCLVMNFS-UHFFFAOYSA-N 4',6-Diamino-2-phenylindol Chemical compound C1=CC(C(=N)N)=CC=C1C1=CC2=CC=C(C(N)=N)C=C2N1 FWBHETKCLVMNFS-UHFFFAOYSA-N 0.000 description 1
- 208000030090 Acute Disease Diseases 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 206010002556 Ankylosing Spondylitis Diseases 0.000 description 1
- 206010003645 Atopy Diseases 0.000 description 1
- 241000193738 Bacillus anthracis Species 0.000 description 1
- 241000193388 Bacillus thuringiensis Species 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 108010062877 Bacteriocins Proteins 0.000 description 1
- 241000186018 Bifidobacterium adolescentis Species 0.000 description 1
- 241001608472 Bifidobacterium longum Species 0.000 description 1
- 241000186015 Bifidobacterium longum subsp. infantis Species 0.000 description 1
- 241000186148 Bifidobacterium pseudolongum Species 0.000 description 1
- 208000006386 Bone Resorption Diseases 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 102000019034 Chemokines Human genes 0.000 description 1
- 108010012236 Chemokines Proteins 0.000 description 1
- 229920002567 Chondroitin Polymers 0.000 description 1
- 208000017667 Chronic Disease Diseases 0.000 description 1
- 102000008186 Collagen Human genes 0.000 description 1
- 108010035532 Collagen Proteins 0.000 description 1
- 208000035473 Communicable disease Diseases 0.000 description 1
- 108020004635 Complementary DNA Proteins 0.000 description 1
- 206010010741 Conjunctivitis Diseases 0.000 description 1
- 208000011231 Crohn disease Diseases 0.000 description 1
- 201000004624 Dermatitis Diseases 0.000 description 1
- LVGKNOAMLMIIKO-UHFFFAOYSA-N Elaidinsaeure-aethylester Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC LVGKNOAMLMIIKO-UHFFFAOYSA-N 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 241000194032 Enterococcus faecalis Species 0.000 description 1
- 241000194031 Enterococcus faecium Species 0.000 description 1
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 1
- 108010037362 Extracellular Matrix Proteins Proteins 0.000 description 1
- 102000010834 Extracellular Matrix Proteins Human genes 0.000 description 1
- 208000001640 Fibromyalgia Diseases 0.000 description 1
- 239000004606 Fillers/Extenders Substances 0.000 description 1
- 208000007882 Gastritis Diseases 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 206010018634 Gouty Arthritis Diseases 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- 208000004575 Infectious Arthritis Diseases 0.000 description 1
- 206010023230 Joint stiffness Diseases 0.000 description 1
- 240000001929 Lactobacillus brevis Species 0.000 description 1
- 235000013957 Lactobacillus brevis Nutrition 0.000 description 1
- 241000186679 Lactobacillus buchneri Species 0.000 description 1
- 241000186673 Lactobacillus delbrueckii Species 0.000 description 1
- 241000186840 Lactobacillus fermentum Species 0.000 description 1
- 241000186606 Lactobacillus gasseri Species 0.000 description 1
- 240000002605 Lactobacillus helveticus Species 0.000 description 1
- 235000013967 Lactobacillus helveticus Nutrition 0.000 description 1
- 241000186605 Lactobacillus paracasei Species 0.000 description 1
- 235000013965 Lactobacillus plantarum Nutrition 0.000 description 1
- 241000186604 Lactobacillus reuteri Species 0.000 description 1
- 241000186869 Lactobacillus salivarius Species 0.000 description 1
- 241000186610 Lactobacillus sp. Species 0.000 description 1
- 241000194038 Lactococcus plantarum Species 0.000 description 1
- 241000194037 Lactococcus raffinolactis Species 0.000 description 1
- 241000192129 Leuconostoc lactis Species 0.000 description 1
- 241000192130 Leuconostoc mesenteroides Species 0.000 description 1
- 108010016165 Matrix Metalloproteinase 2 Proteins 0.000 description 1
- 102000000422 Matrix Metalloproteinase 3 Human genes 0.000 description 1
- 241000218231 Moraceae Species 0.000 description 1
- 244000293610 Morus bombycis Species 0.000 description 1
- 235000006721 Morus bombycis Nutrition 0.000 description 1
- IOVCWXUNBOPUCH-UHFFFAOYSA-M Nitrite anion Chemical compound [O-]N=O IOVCWXUNBOPUCH-UHFFFAOYSA-M 0.000 description 1
- 239000000020 Nitrocellulose Substances 0.000 description 1
- IOVCWXUNBOPUCH-UHFFFAOYSA-N Nitrous acid Chemical compound ON=O IOVCWXUNBOPUCH-UHFFFAOYSA-N 0.000 description 1
- 102100023050 Nuclear factor NF-kappa-B p105 subunit Human genes 0.000 description 1
- 240000007594 Oryza sativa Species 0.000 description 1
- 235000007164 Oryza sativa Nutrition 0.000 description 1
- 208000008558 Osteophyte Diseases 0.000 description 1
- 206010033078 Otitis media Diseases 0.000 description 1
- 229930040373 Paraformaldehyde Natural products 0.000 description 1
- 102000003982 Parathyroid hormone Human genes 0.000 description 1
- 108090000445 Parathyroid hormone Proteins 0.000 description 1
- 229920002230 Pectic acid Polymers 0.000 description 1
- 229930182555 Penicillin Natural products 0.000 description 1
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 238000002123 RNA extraction Methods 0.000 description 1
- 241000218206 Ranunculus Species 0.000 description 1
- 241000220222 Rosaceae Species 0.000 description 1
- 201000002661 Spondylitis Diseases 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 241000194017 Streptococcus Species 0.000 description 1
- 244000057717 Streptococcus lactis Species 0.000 description 1
- 235000014897 Streptococcus lactis Nutrition 0.000 description 1
- 241000194020 Streptococcus thermophilus Species 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- 208000000491 Tendinopathy Diseases 0.000 description 1
- 235000005764 Theobroma cacao ssp. cacao Nutrition 0.000 description 1
- 235000005767 Theobroma cacao ssp. sphaerocarpum Nutrition 0.000 description 1
- LUKBXSAWLPMMSZ-OWOJBTEDSA-N Trans-resveratrol Chemical compound C1=CC(O)=CC=C1\C=C\C1=CC(O)=CC(O)=C1 LUKBXSAWLPMMSZ-OWOJBTEDSA-N 0.000 description 1
- 239000013504 Triton X-100 Substances 0.000 description 1
- 229920004890 Triton X-100 Polymers 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 239000011543 agarose gel Substances 0.000 description 1
- 235000013334 alcoholic beverage Nutrition 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 239000000783 alginic acid Substances 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 229960001126 alginic acid Drugs 0.000 description 1
- 150000004781 alginic acids Chemical class 0.000 description 1
- 208000026935 allergic disease Diseases 0.000 description 1
- 230000007815 allergy Effects 0.000 description 1
- 230000003321 amplification Effects 0.000 description 1
- 239000003125 aqueous solvent Substances 0.000 description 1
- 229940114079 arachidonic acid Drugs 0.000 description 1
- 235000021342 arachidonic acid Nutrition 0.000 description 1
- 230000002917 arthritic effect Effects 0.000 description 1
- 210000001188 articular cartilage Anatomy 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
- 229940065181 bacillus anthracis Drugs 0.000 description 1
- 229940097012 bacillus thuringiensis Drugs 0.000 description 1
- 210000002469 basement membrane Anatomy 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- MSWZFWKMSRAUBD-UHFFFAOYSA-N beta-D-galactosamine Natural products NC1C(O)OC(CO)C(O)C1O MSWZFWKMSRAUBD-UHFFFAOYSA-N 0.000 description 1
- 229940004120 bifidobacterium infantis Drugs 0.000 description 1
- 229940009291 bifidobacterium longum Drugs 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 210000000988 bone and bone Anatomy 0.000 description 1
- 230000024279 bone resorption Effects 0.000 description 1
- 235000008429 bread Nutrition 0.000 description 1
- 235000001046 cacaotero Nutrition 0.000 description 1
- 229910000019 calcium carbonate Inorganic materials 0.000 description 1
- 235000014633 carbohydrates Nutrition 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 235000014171 carbonated beverage Nutrition 0.000 description 1
- 230000008355 cartilage degradation Effects 0.000 description 1
- 230000003848 cartilage regeneration Effects 0.000 description 1
- 230000003833 cell viability Effects 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 235000019219 chocolate Nutrition 0.000 description 1
- DLGJWSVWTWEWBJ-HGGSSLSASA-N chondroitin Chemical compound CC(O)=N[C@@H]1[C@H](O)O[C@H](CO)[C@H](O)[C@@H]1OC1[C@H](O)[C@H](O)C=C(C(O)=O)O1 DLGJWSVWTWEWBJ-HGGSSLSASA-N 0.000 description 1
- 208000037976 chronic inflammation Diseases 0.000 description 1
- 208000037893 chronic inflammatory disorder Diseases 0.000 description 1
- 206010009887 colitis Diseases 0.000 description 1
- 229920001436 collagen Polymers 0.000 description 1
- 239000000084 colloidal system Substances 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 239000002299 complementary DNA Substances 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 235000008504 concentrate Nutrition 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 210000002808 connective tissue Anatomy 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 210000004748 cultured cell Anatomy 0.000 description 1
- 238000012258 culturing Methods 0.000 description 1
- 230000001086 cytosolic effect Effects 0.000 description 1
- 235000013365 dairy product Nutrition 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 230000001934 delay Effects 0.000 description 1
- 239000000645 desinfectant Substances 0.000 description 1
- 239000003599 detergent Substances 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 230000002900 effect on cell Effects 0.000 description 1
- 239000003792 electrolyte Substances 0.000 description 1
- 238000001962 electrophoresis Methods 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 229940032049 enterococcus faecalis Drugs 0.000 description 1
- 210000002919 epithelial cell Anatomy 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 239000000469 ethanolic extract Substances 0.000 description 1
- 229960005542 ethidium bromide Drugs 0.000 description 1
- LVGKNOAMLMIIKO-QXMHVHEDSA-N ethyl oleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC LVGKNOAMLMIIKO-QXMHVHEDSA-N 0.000 description 1
- 229940093471 ethyl oleate Drugs 0.000 description 1
- 201000010934 exostosis Diseases 0.000 description 1
- 210000002744 extracellular matrix Anatomy 0.000 description 1
- 201000005577 familial hyperlipidemia Diseases 0.000 description 1
- 239000012091 fetal bovine serum Substances 0.000 description 1
- 239000000835 fiber Substances 0.000 description 1
- 210000002950 fibroblast Anatomy 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- MHMNJMPURVTYEJ-UHFFFAOYSA-N fluorescein-5-isothiocyanate Chemical compound O1C(=O)C2=CC(N=C=S)=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 MHMNJMPURVTYEJ-UHFFFAOYSA-N 0.000 description 1
- 239000006260 foam Substances 0.000 description 1
- 239000005417 food ingredient Substances 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 239000003205 fragrance Substances 0.000 description 1
- 235000011389 fruit/vegetable juice Nutrition 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 229960002442 glucosamine Drugs 0.000 description 1
- 210000000224 granular leucocyte Anatomy 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 208000019622 heart disease Diseases 0.000 description 1
- 208000014617 hemorrhoid Diseases 0.000 description 1
- 239000003906 humectant Substances 0.000 description 1
- 229920002674 hyaluronan Polymers 0.000 description 1
- 229960003160 hyaluronic acid Drugs 0.000 description 1
- 235000015243 ice cream Nutrition 0.000 description 1
- 238000010191 image analysis Methods 0.000 description 1
- 210000000987 immune system Anatomy 0.000 description 1
- 238000003119 immunoblot Methods 0.000 description 1
- 238000010166 immunofluorescence Methods 0.000 description 1
- 238000003125 immunofluorescent labeling Methods 0.000 description 1
- 230000002163 immunogen Effects 0.000 description 1
- 229940027941 immunoglobulin g Drugs 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 239000002917 insecticide Substances 0.000 description 1
- 239000002198 insoluble material Substances 0.000 description 1
- 102000014909 interleukin-1 receptor activity proteins Human genes 0.000 description 1
- 108040006732 interleukin-1 receptor activity proteins Proteins 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 208000018937 joint inflammation Diseases 0.000 description 1
- 210000005067 joint tissue Anatomy 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 229940039696 lactobacillus Drugs 0.000 description 1
- 229940012969 lactobacillus fermentum Drugs 0.000 description 1
- 229940054346 lactobacillus helveticus Drugs 0.000 description 1
- 229940072205 lactobacillus plantarum Drugs 0.000 description 1
- 229940001882 lactobacillus reuteri Drugs 0.000 description 1
- VMPHSYLJUKZBJJ-UHFFFAOYSA-N lauric acid triglyceride Natural products CCCCCCCCCCCC(=O)OCC(OC(=O)CCCCCCCCCCC)COC(=O)CCCCCCCCCCC VMPHSYLJUKZBJJ-UHFFFAOYSA-N 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 229940057995 liquid paraffin Drugs 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 206010025135 lupus erythematosus Diseases 0.000 description 1
- 239000012139 lysis buffer Substances 0.000 description 1
- 229960003511 macrogol Drugs 0.000 description 1
- 210000002540 macrophage Anatomy 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 235000013622 meat product Nutrition 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 210000004379 membrane Anatomy 0.000 description 1
- 108020004999 messenger RNA Proteins 0.000 description 1
- 230000000813 microbial effect Effects 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- VMGAPWLDMVPYIA-HIDZBRGKSA-N n'-amino-n-iminomethanimidamide Chemical compound N\N=C\N=N VMGAPWLDMVPYIA-HIDZBRGKSA-N 0.000 description 1
- 239000005445 natural material Substances 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 229920001220 nitrocellulos Polymers 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 231100000989 no adverse effect Toxicity 0.000 description 1
- 238000003199 nucleic acid amplification method Methods 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 235000019198 oils Nutrition 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 235000008390 olive oil Nutrition 0.000 description 1
- 239000004006 olive oil Substances 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 210000002997 osteoclast Anatomy 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- 229940094443 oxytocics prostaglandins Drugs 0.000 description 1
- 239000003002 pH adjusting agent Substances 0.000 description 1
- 229920002866 paraformaldehyde Polymers 0.000 description 1
- 239000000199 parathyroid hormone Substances 0.000 description 1
- 229960001319 parathyroid hormone Drugs 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- LCLHHZYHLXDRQG-ZNKJPWOQSA-N pectic acid Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)O[C@H](C(O)=O)[C@@H]1OC1[C@H](O)[C@@H](O)[C@@H](OC2[C@@H]([C@@H](O)[C@@H](O)[C@H](O2)C(O)=O)O)[C@@H](C(O)=O)O1 LCLHHZYHLXDRQG-ZNKJPWOQSA-N 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- 239000008196 pharmacological composition Substances 0.000 description 1
- 235000013550 pizza Nutrition 0.000 description 1
- 239000000419 plant extract Substances 0.000 description 1
- 239000002798 polar solvent Substances 0.000 description 1
- 229920002401 polyacrylamide Polymers 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 239000010318 polygalacturonic acid Substances 0.000 description 1
- 229920000136 polysorbate Polymers 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 230000000770 proinflammatory effect Effects 0.000 description 1
- 150000003180 prostaglandins Chemical class 0.000 description 1
- 239000011814 protection agent Substances 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 238000002731 protein assay Methods 0.000 description 1
- 238000000751 protein extraction Methods 0.000 description 1
- 239000012264 purified product Substances 0.000 description 1
- 230000000246 remedial effect Effects 0.000 description 1
- 206010039083 rhinitis Diseases 0.000 description 1
- 235000009566 rice Nutrition 0.000 description 1
- 235000013580 sausages Nutrition 0.000 description 1
- 201000001223 septic arthritis Diseases 0.000 description 1
- 230000011664 signaling Effects 0.000 description 1
- 235000020183 skimmed milk Nutrition 0.000 description 1
- 235000011888 snacks Nutrition 0.000 description 1
- 239000000344 soap Substances 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 239000011550 stock solution Substances 0.000 description 1
- 229960005322 streptomycin Drugs 0.000 description 1
- 108091007196 stromelysin Proteins 0.000 description 1
- 210000005065 subchondral bone plate Anatomy 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 239000002511 suppository base Substances 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 230000008685 targeting Effects 0.000 description 1
- 201000004415 tendinitis Diseases 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 239000003053 toxin Substances 0.000 description 1
- 231100000765 toxin Toxicity 0.000 description 1
- 241000701447 unidentified baculovirus Species 0.000 description 1
- 230000003827 upregulation Effects 0.000 description 1
- 210000001215 vagina Anatomy 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 235000013311 vegetables Nutrition 0.000 description 1
- 230000035899 viability Effects 0.000 description 1
- 150000003722 vitamin derivatives Chemical class 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 239000012224 working solution Substances 0.000 description 1
- 230000037303 wrinkles Effects 0.000 description 1
Images
Classifications
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
- A23L33/105—Plant extracts, their artificial duplicates or their derivatives
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- 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
- A23L29/00—Foods or foodstuffs containing additives; Preparation or treatment thereof
- A23L29/065—Microorganisms
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2200/00—Function of food ingredients
- A23V2200/30—Foods, ingredients or supplements having a functional effect on health
- A23V2200/306—Foods, ingredients or supplements having a functional effect on health having an effect on bone mass, e.g. osteoporosis prevention
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2300/00—Processes
- A23V2300/14—Extraction
-
- A23Y2220/03—
-
- A23Y2220/17—
-
- A23Y2220/73—
-
- A23Y2300/25—
-
- A23Y2300/29—
Landscapes
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Health & Medical Sciences (AREA)
- Nutrition Science (AREA)
- Chemical & Material Sciences (AREA)
- Food Science & Technology (AREA)
- Polymers & Plastics (AREA)
- Mycology (AREA)
- Botany (AREA)
- Microbiology (AREA)
- Medicines Containing Plant Substances (AREA)
- Coloring Foods And Improving Nutritive Qualities (AREA)
- Cosmetics (AREA)
Abstract
The present invention relates to a composition for preventing or ameliorating arthritis caused by IL-1? The composition for preventing or ameliorating arthritis caused by IL-1? According to the present invention may comprise a topical extract as an active ingredient.
Inhibition of MAPK family and NF-κB activity inhibits iNOS, NO, COX-2 and PGE 2 by IL-1β-containing compositions for preventing or improving arthritis, And MMP expression to protect the substrate and inhibit the inflammatory response.
Description
The present invention relates to a composition for preventing or ameliorating arthritis caused by IL-1? More particularly, the present invention relates to a composition for the prevention or amelioration of arthritis caused by IL-1 beta, which can be used for various fields such as functional foods for preventing or improving arthritis, which contains it as an active ingredient.
IL-1β (hereinafter referred to as "IL-1β") is known as a kind of cytokine that promotes inflammatory responses through various studies (Punzi L. et al., Crit Rev Clin Lab Sci. , 2002, 39 (1): 63-88). Factor nuclear factor-kappa B (NF-κB) induced by IL-1β regulates a variety of inflammatory factors, including heterodimers composed of p65 and p50 subunits, inactivated NF-κB, (IκB-α) is phosphorylated by stimulation of pro-inflammatory cytokines, chemokines, enzymes, etc. in the cytoplasm in association with inhibitor κB-alpha, α is degraded and NF-κB migrates into the nucleus and binds to the promoter of the target gene to secrete a cytokine by inflammation [Jeong et al., 2010].
According to recent reports, it has been shown that a family of mitogen-activated protein kinases (hereinafter referred to as 'MAPK'), extracellular signal regulated kinase, (P38 MAP kinases) and c-Jun N-terminal kinase (hereinafter referred to as "JNK") were induced by cartilage degradation and MMP It is known to play an important role in cytokine regulation [Thalhamer et al., 2008]. Was found to be the level of MAPK phosphorylation in arthritic cartilage model higher than in normal cartilage, by which through the MAPK than signaling pathways NO, increased
Thus, the relationship between the IL-1β-induced signaling pathway and inflammatory and metabolic diseases is already known. Inflammatory diseases are collectively referred to as inflammatory diseases. The inflammatory diseases include acute and chronic inflammatory diseases. Specifically, the inflammatory diseases include edema, dermatitis, allergy, atopy, asthma, conjunctivitis, rhinitis, otitis media, , Sjogren's syndrome (sjogren's syndrome), gastritis, Crohn's disease, colitis, hemorrhoids, gout, sinus spondylitis, lupus, fibromyalgia, psoriatic arthritis, osteoarthritis, rheumatoid arthritis, shoulder periitis, tendinitis, syndrome and multiple sclerosis.
On the other hand, the joint tissue in the human body is a place where two moving bones meet, and has a smooth cartilage structure for absorbing the impact from the joint. Arthritis is characterized by articular cartilage, decreased osteophyte formation, and subchondral bone hardening, which is a chronic disease in which joint inflammation is caused by edema and pain, and joint stiffness. The most common arthritis is osteoarthritis (degenerative arthritis), rheumatoid arthritis, gouty arthritis, ankylosing spondylitis, infectious arthritis, and arthritis. Small arthritis, achilles tendonitis, and the like. Recent treatments for arthritis include hyaluronic acid, glucosamine, and chondroitin, which are drugs and cartilage regeneration / protection agents that inhibit TNF to control pain and prevent complications.
Metabolic disease refers to diseases caused by imbalance such as carbohydrates, lipids, proteins, vitamins, minerals and water, and includes osteoporosis, diabetes, hypertension, hyperlipemia and heart disease. In this process, an imbalance occurs and osteoporosis occurs. At this time, it is known that IL-1β is involved in osteoclast differentiation and can be a therapeutic target in osteoporosis (A Nemetz, Gut 2001; 49: 644-649).
In order to treat IL-1β-mediated diseases, studies on the inhibition of the IL-1β-induced signal transduction system have been actively conducted, and the use of anti-IL-1R antibodies that are receptors of IL-1β 10-1317045). However, in the case of an anti-IL-1R antibody, it may be an immunogenic when used as a therapeutic agent, since it may have an epitope which is a part that can be recognized as an exogenous protein when introduced into an individual. In order to solve the above problems, many studies have been conducted to develop a therapeutic agent for IL-1β-mediated diseases using a small molecule compound that is not a protein not recognized by the immune system.
Although the pharmacological composition has been developed as a natural material, most of the products have been commercialized using the extract, and thus the exact mechanism of pharmacological action has not been clarified. However, since it is easy to take as an oral preparation and has little toxicity and side effects, .
Under these circumstances, the present inventors have made efforts to find a natural product targeting a pathway that is activated by IL-1 beta. As a result, it has been confirmed that the extract of Lycopersiconum effectively inhibits IL-1β-induced signal transduction system, Thereby completing the invention of a composition for preventing or ameliorating diseases caused by IL-1? Contained as an active ingredient.
It is an object of the present invention to provide a composition for preventing or ameliorating arthritis caused by IL-1 beta, which is capable of inhibiting inflammatory reaction and substrate degradation in an inflammatory or metabolic disease model by IL-1 beta.
Another object of the present invention is to provide a composition for preventing or ameliorating arthritis caused by IL-1 beta, which can be used in various fields such as a health functional food composition capable of preventing or improving arthritis.
In order to achieve the above object, a composition for preventing or improving arthritis caused by IL-1β according to an embodiment of the present invention comprises a topical extract as an active ingredient.
The topical extract may be extracted with a solvent selected from the group consisting of water, an alcohol having 1 to 6 carbon atoms, and a mixed solvent thereof.
The arthritis may be osteoarthritis or rheumatoid arthritis.
In the composition for preventing or ameliorating arthritis caused by IL-1β, the upper leaves may be selected from the group consisting of Lactobacillus casei, Lactobacillus rhamnosus, Bifidobacterium bifidum bifidus, Bifidobacterium breve bifidobacterium, and Lactobacillus acidophilus may be inoculated and inoculated in the fermented broth.
.
The composition for preventing or ameliorating arthritis caused by IL-1 [beta] may further comprise a juniper hot water extract.
The composition for preventing or ameliorating arthritis caused by IL-1 [beta] may further comprise Bacillus anthracis extract.
The quasi-drug composition for preventing or ameliorating arthritis caused by IL-1? By IL-1? According to another embodiment of the present invention may include a composition for preventing or ameliorating arthritis caused by IL-1?.
The food composition for preventing or ameliorating arthritis caused by IL-1? By IL-1? According to another embodiment of the present invention may include a composition for preventing or ameliorating arthritis caused by IL-1?.
Hereinafter, the present invention will be described in more detail.
The composition for preventing or ameliorating diseases caused by IL-1 [beta] according to an embodiment of the present invention comprises a topical extract as an active ingredient.
The top leaf of the present invention is a leaf of Morus alba Linne or Morus bombycis Koidzumi (Moraceae Moraceae). It is also called a winter 桑葉. Leaves egg-shaped or broad egg-shaped, 3- to 5-parted, 8 to 15 cm long, 7 to 13 cm wide. The top surface is yellowish green or light yellowish brown. The tip of the leaf is pointed, the bottom part is heart-shaped, and the edge of the leaf is fixed. On the underside there is a vein, and the vein is a net, with hair on it. The vagina is fragile and light. There is almost no smell, and the taste is good.
The term 'IL-1β-mediated disease' means a disease in which IL-1β binds to a receptor of IL-1β, induces the activity of MAPK and NF-κB, and expresses a target gene thereof. The disease caused by IL-1 [beta] is not limited thereto, but may be an inflammatory disease or a metabolic disease. The inflammatory diseases are collectively referred to as osteoarthritis, rheumatoid arthritis, psoriatic arthritis, atopic dermatitis, psoriasis, asthma, systemic lupus erythematosus, and multiple sclerosis , Preferably osteoarthritis or rheumatoid arthritis. The metabolic diseases are collectively referred to as diseases caused by metabolic disorders in vivo, and they may be selected from the group consisting of osteoporosis, atherosclerosis and myocardial infarction, preferably osteoporosis.
The term 'IL-1β-mediated disease' means a disease in which IL-1β binds to a receptor of IL-1β, induces the activity of MAPK and NF-κB, and expresses a target gene thereof. The disease caused by IL-1 [beta] is not limited thereto, but may be an inflammatory disease or a metabolic disease. The inflammatory diseases are collectively referred to as osteoarthritis, rheumatoid arthritis, psoriatic arthritis, atopic dermatitis, psoriasis, asthma, systemic lupus erythematosus, and multiple sclerosis , Preferably osteoarthritis or rheumatoid arthritis. The metabolic diseases are collectively referred to as diseases caused by metabolic disorders in vivo, and they may be selected from the group consisting of osteoporosis, atherosclerosis and myocardial infarction, preferably osteoporosis.
IL-1β binds to IL-1R, a receptor for IL-1β, and then regulates substrate degradation-related MMP and inflammation-related iNOS, COX-2 via downstream MAPK and NF-κB. The topical extract of the present invention has an activity of inhibiting the expression of MAPK family p38 and JNK in signal transduction by IL-1β and inhibits the degradation of IκB-α as an inhibitor of degradation of IκB-α Lt; RTI ID = 0.0 > NF-kB < / RTI > activity (Figures 7 and 8).
In one embodiment of the present invention, the topical extract of the present invention inhibits the expression of PGE 2 (prostaglandin E 2 ) synthesized from NO (nitric oxide), COX-2 and arachidonic acid, which are increased by inflammation-inducing iNOS and iNOS , And inhibited the inflammatory reaction. From these results, it was found that the extract of the present invention of the present invention can effectively prevent or treat osteoarthritis and rheumatoid arthritis, which are typical inflammatory diseases, and can be effectively used for the treatment of diseases caused by IL-1β such as inflammatory diseases Respectively.
In one embodiment of the present invention, it was confirmed that the leaf extract of the present invention effectively inhibited the activity of MMP which degrades the extracellular matrix of the connective tissue and the main component of the basement membrane. MMP is known to be a collagenase secreted by fibroblasts, polymorphonuclear leukocytes, epithelial cells and macrophages, and parathyroid hormone and intracellular toxin, prostaglandins, in association with bone resorption, increase the synthesis of MMP. The topical extract of the present invention protects cartilage by inhibiting collagenase by decreasing the expression of MMP, which is a target gene of MAPK family and MAPK, particularly MMP-1, MMP-3 and MMP-13, . From these results, it was confirmed that the leaf extracts of the present invention can effectively prevent or treat osteoarthritis, rheumatoid arthritis and osteoporosis, which are typical metabolic diseases, which are typical inflammatory diseases, and it is possible to prevent or treat diseases caused by IL-1β such as inflammatory diseases or metabolic diseases It may be effective for treatment.
In the present invention, " prevention " means any action that inhibits or delays disease caused by IL-1? By administration of the composition, and " treatment " Or to change or improve the symptoms of the disease.
In the present invention, the upper leaf extract may be extracted with a solvent selected from the group consisting of water, an alcohol having 1 to 6 carbon atoms, and a mixed solvent thereof. The term 'upper leaf extract' means an extract obtained by extracting upper leaves. The upper leaf extract is prepared by dissolving the upper leaf lobes in a polar solvent such as an alcohol of carbon number (C 1 ) to (C 6 ) such as water, ethanol, methanol or the like or a mixed solvent having a mixing ratio of alcohol and water of 1: 0.1 to 1:10 And may be eluted with a mixed solvent having a mixing ratio of ethanol and water of preferably 1: 3 to 5. At this time, the extraction temperature may be an extract extracted at 10 to 100 캜, preferably at room temperature, and for an extraction period of 12 to 4 days, preferably 24 hours. The filtered extract may be a result obtained by concentration under reduced pressure with a vacuum rotary concentrator. However, as long as it is a mulberry extract that can exhibit the therapeutic effect of the IL-1β according to the present invention, A concentrate, a dried product obtained by drying the extract, or a controlled preparation or a purified product thereof.
The top leaf has superior inhibitory effect on IL-1? Compared to stem, root, and fruit of mulberry. Therefore, it may be preferable to use an ethanol extract for the upper leaves.
Preferably, the ethanol may be 12 to 22 wt%. The extract according to the above range may be most advantageous for obtaining the active ingredient.
The upper leaf extract may be one extracted using a fermented upper leaf. When the fermented leaves are used, they are advantageous in that they can be used stably at a relatively high concentration because of low cytotoxicity.
Examples of the microorganism used for the fermentation include Lactobacillus salivarius, Lactobacillus acidophilus, Lactobacillus brevis, Lactobacillus rhamnosus, Lactobacillus plantarum Lactobacillus plantus, Lactobacillus plantarum, Lactobacillus helveticus, Lactobacillus fermentum, Lactobacillus paracasei, Lactobacillus casei, Lactobacillus delbrueckii, Such as Lactobacillus reuteri, Lactobacillus buchneri, Lactobacillus gasseri, Lactobacillus johonsonii, Lactobacillus kefir, and the like, lactic acid bacteria such as lactobacillus kefir, Lactococcus lactis, Lactococcus plantarum, Lactococcus raffinolactis, Enterococcus faecalis, Enterococcus faecium, Streptococcus thermophilus, Streptococcus spp. Bifidobacterium bifidum, Bifidobacterium bifidum, Bifidobacterium bifidum, and Bifidobacterium bifidum, such as Leuconostoc lactis, Leuconostoc mesenteroides and the like, Bifidobacterium species such as Bifidobacterium breve, Bifidobacterium infantis, Bifidobacterium longum, Bifidobacterium pseudolongum, Bifidobacterium themophilum, Bifidobacteria such as Bifidobacterium adolescentis, and the like, Lactobacillus casei, Lactobacillus rhamnosus, Bifidobacterium bifidum bifidobacterium, Bifidobacterium breve bifidobacterium, and Lactobacillus species such as Lactobacillus casei, Lactobacillus rhamnosus, And Lactobacillus acidophilus. ≪ Desc /
The pharmaceutical compositions of the present invention may comprise a pharmaceutically acceptable carrier. Compositions comprising a pharmaceutically acceptable carrier can be of various oral or parenteral formulations. In the case of formulation, it can be prepared using diluents or excipients such as fillers, extenders, binders, humectants, disintegrants, surfactants and the like which are usually used. Solid formulations for oral administration may include tablet pills, powders, granules, capsules and the like, which may contain one or more excipients such as starch, calcium carbonate, sucrose or lactose lactose, gelatin, and the like. In addition to simple excipients, lubricants such as magnesium stearate, talc, and the like may also be used. Liquid preparations for oral administration include suspensions, solutions, emulsions, syrups and the like. Various excipients such as wetting agents, sweeteners, fragrances, preservatives and the like may be included in addition to water and liquid paraffin, which are simple diluents commonly used. have. Formulations for parenteral administration may include sterile aqueous solutions, non-aqueous solutions, suspensions, emulsions, freeze-dried preparations, and suppositories. Examples of the non-aqueous solvent and the suspending agent include propylene glycol, polyethylene glycol, vegetable oil such as olive oil, and injectable ester such as ethyl oleate. Examples of the suppository base include witepsol, macrogol, tween 61, cacao paper, laurin, glycerogelatin and the like. In addition, the pharmaceutical composition of the present invention may be formulated into tablets, pills, powders, granules, capsules, suspensions, solutions, emulsions, syrups, sterilized aqueous solutions, non-aqueous solutions, suspensions, emulsions, lyophilized preparations and suppositories And can have any one of the formulations selected.
The topical extract of the present invention has been used for edible and medicinal purposes from the past, and there is no particular limitation on the dosage of the topical extract of the present invention. The amount of the extract of the topical extract of the present invention, , The severity of the disease, and the like. In general, the leaf extract is preferably administered in an amount of about 10 to 1000 mg per kg of body weight, and more preferably about 50 to 500 mg per kg of body weight. The pharmaceutical composition comprising the extract of the present invention as an active ingredient is prepared in consideration of an effective dose range, and the unit dosage formulations thus formulated are classified according to the judgment of an expert who monitors or observes the administration of the drug, , Or may be administered several times at regular intervals.
The present invention also provides a quasi-drug composition for preventing or ameliorating a disease caused by IL-1 [beta] comprising an extract of a topical extract as an active ingredient. The production and composition of the above leaf extract are as described above. More specifically, the plant extracts of the present invention can be added to quasi-drug compositions for the purpose of preventing or treating diseases caused by IL-1 ?.
In the present specification, the term 'Bok Jo-hui grass' is a deciduous shrub belonging to the buttercup butterfly. The leaf is a three-folded leaf composed of three small leaves. The small leaf is wide egg-shaped, and two of the three are next to each other. The leaves grow larger as they go up to the top, with sharp ends and coarse teeth, with slightly reddish ridged sawtooth on the edge, but are often divided into three shallowly.
In the case of using the above-mentioned Bacillus subtilis paste, it is effective for washing and improving skin wrinkles. However, it is necessary to remove the toxicity through the fermentation process because the bacteriocin has its own toxicity.
Preferably, the baculovirus full extract may be a full-fermented bacillus subtilis extract prepared by a fermentation extraction method. Since the bacillus grass is weakly toxic, it is necessary to remove the toxicity through the fermentation process.
In the present invention, the full fermentation extract of Bacillus thuringiensis is prepared by adding 1 to 3 parts of saccharide of skin and 0.05 to 0.25 part of suntan oil to 100 parts of rice sole, and adding 0.5 to 2.0 parts of skin microbial solution The whole pulverized product can be obtained by immersing the pulverized product in a volume of 10 to 30 parts by volume and then fermenting at room temperature for 3 to 15 days in a room temperature atmosphere.
The microorganism may be selected from the group consisting of Lactobacillus casei, Lactobacillus rhamnosus, Bifidobacterium bifidum bifidobacterium, Bifidobacterium breve bifidobacterium, and Lactobacillus sp. Lactobacillus acidophilus, and Bacillus acidophilus.
The juniper tree to be used in the present invention is also referred to as 杜松 (杜松), and belongs to the lateral buds. Leaves are narrow and narrow linear needle leaves, each of which rotates in three, with a length of 12 ~ 20mm, a pointed end, and a narrow white groove at the center of the surface.
Preferably, the juniper can be fermented in the same manner as the bovine juice paste. When fermenting the juniper, the effect of removing the inherent strong aroma of the upper leaves is high and the flavor can be enhanced.
As used in the present invention, 'kangsak' is a perennial plant belonging to the rose family. The height is about 30 to 100 centimeters. The stem grows from the coarse rootstock and has hairs throughout. Leaves are alternate phyllotaxis, 5 ~ 7 small leaves. In June ~ August, a yellow flower blooms in total sprout, and the fruit has thorny hairs and sticks to other things.
In the present invention, the term 'quasi-drug' means a fiber, a rubber product or the like used for the purpose of treating, alleviating, treating or preventing a disease of a human or an animal, a weak action against the human body, Used for the purpose of diagnosing, curing, alleviating, treating or preventing diseases of human or animal, which are not machinery, similar products, products for sterilization, insecticide and similar uses for the prevention of infectious diseases. Machinery, or apparatus, and that is not an apparatus, machine or apparatus of an article used for the purpose of causing pharmacological effects on the structure or function of a person or animal.
When the topical extract of the present invention is used as a quasi-drug additive, the topical extract may be directly added or used in combination with other quasi-drugs or quasi-drugs, and may be suitably used according to a conventional method. The amount of the active ingredient to be mixed can be appropriately determined depending on the purpose of use.
The quasi-drug composition of the present invention may be, but is not limited to, disinfectant cleaner, shower foam, gagrin, wet tissue, detergent soap, hand wash, humidifier filler, mask, ointment or filter filler.
The present invention also provides a health functional food composition for preventing or ameliorating a disease caused by IL-1? Comprising an upper leaf extract as an active ingredient. The production and composition of the above leaf extract are as described above. More specifically, the topical extract of the present invention may be added to a health functional food composition for the purpose of preventing or treating diseases caused by IL-1 ?.
When the leaf extract of the present invention is used as an additive for health functional food, the leaf extract can be used as it is or can be used in combination with other health functional food or health functional food ingredient and can be suitably used according to a conventional method. The amount of the active ingredient to be mixed can be appropriately determined depending on the purpose of use.
There is no particular limitation on the kind of the health functional food of the present invention. Examples of the health functional food to which the above extraction mixture can be added include meat products, sausages, breads, chocolates, candies, snacks, confectionery, pizza, ramen noodles, other noodles, gums, dairy products including ice cream, , A drink, an alcoholic beverage, and a vitamin complex, and may include foods used as food for animals, which may include all health functional foods in the conventional sense. In addition to the above, the health functional food composition of the present invention may contain various nutrients, vitamins, electrolytes, flavors, colorants, pectic acid and salts thereof, alginic acid and salts thereof, organic acids, protective colloid thickening agents, pH adjusting agents, stabilizers, , Alcohols, carbonating agents used in carbonated drinks, and the like. It may also contain flesh for the production of natural fruit juices, fruit juice drinks and vegetable drinks.
The present invention also provides a method for treating a disease caused by IL-1 [beta], comprising the step of administering the composition to a subject suspected of having a disease caused by IL-1 [beta] other than human.
In the present invention, the suspected individual of IL-1β refers to all animals which have developed or are capable of developing an inflammatory disease or metabolic disease, and the pharmaceutical composition comprising the extract of the present invention may be administered to a subject suspected of having a disease caused by IL- , The individual can be treated efficiently. The diseases caused by IL-1 [beta] are as described above.
In the present invention, 'administering' means introducing the pharmaceutical composition of the present invention into a subject suspected of having a disease caused by IL-1β by any appropriate method. The administration route may be any pathway of oral or parenteral routes ≪ / RTI >
The method of treatment of the present invention may include administering a pharmaceutical effective amount of a pharmaceutical composition comprising the leaf extract as an active ingredient. The appropriate total daily dose may be determined by the treatment within the scope of appropriate medical judgment, and may be administered once or several times. For purposes of the present invention, however, the specific therapeutically effective amount for a particular patient will depend upon the nature and extent of the reaction to be achieved, the particular composition, including whether or not other agents are used, the age, weight, Sex and diet of the patient, the time of administration, the route of administration and the rate of administration of the composition, the duration of the treatment, the drugs used or concurrently used with the specific composition, and similar factors well known in the medical arts.
When iNOS, NO, COX-2, PGE 2 and / or the like are inhibited by inhibiting the activity of the MAPK family and NF-κB by a composition for preventing or ameliorating diseases caused by IL-1β comprising the topical extract of the present invention as an active ingredient, MMP expression can be inhibited to protect the substrate and inhibit the inflammatory response. In particular, the disease caused by IL-1 [beta] may be arthritis caused by IL-1 [beta], and may exert an excellent preventive or remedial effect against arthritis.
Accordingly, the present invention can be applied to various fields such as health functional foods that can prevent and improve arthritis by using a composition for preventing or ameliorating diseases caused by IL-1 [beta].
BRIEF DESCRIPTION OF THE DRAWINGS FIG. 1 is a graph of the effect of SW leaf extract according to an embodiment of the present invention on the survival of SW1353 chondrocytes. FIG.
FIG. 2 is a graph illustrating the effect of the leaf-on-the-fly extract according to an embodiment of the present invention on the survival of SW1353 chondrocytes.
FIG. 3 is a graph showing the effect of inhibiting IL-1β induced production of MMP-1 and MMP-13 in SW1353 chondrocytes according to an embodiment of the present invention.
FIG. 4 is a graph showing the effect of inhibiting IL-1β induced expression of MMP-1 and MMP-13 in SW1353 chondrocytes according to an embodiment of the present invention.
5 is a graph showing the effect of inhibiting the production of IL-1? -Induced nitric oxide and PGE2 in SW1353 chondrocytes according to an embodiment of the present invention.
FIG. 7 shows IL-1? -Induced iNOS and COX-2 expression in SW1353 chondrocytes according to an embodiment of the present invention.
FIG. 8 shows the effect of inhibiting the IL-1β-induced activation of p38 MAPK in SW1353 chondrocytes according to an embodiment of the present invention.
Hereinafter, embodiments of the present invention will be described in detail so that those skilled in the art can easily carry out the present invention. The present invention may, however, be embodied in many different forms and should not be construed as limited to the embodiments set forth herein.
[ Manufacturing example : The top Preparation of extract]
One. Top Ready.
Mori folium, a leaf of M. alba L, was obtained from Bio-Fort Kori Sasa (Pusan, Korea) and from Korea University, Korea (Busan, Korea). Professor Hong. The dried leaves were cut into small pieces, made into fine powder, and then heated in distilled water (50 g / 500 ml) for 3 hours. The extract was filtered twice through Wattman No. 3 filter paper to remove insoluble matter, and the filtrate was lyophilized and then pulverized into fine powder.
The leaf extract was dissolved in distilled water to a concentration of 100 mg / ml, and the stock solution was diluted in the medium to the desired concentration before use.
In addition, Lactobacillus casei was inoculated with the upper leaves which had been fermented for 5 days, and the extract was extracted in the same manner as the above leaf extract to prepare the fermented leaf extract.
2. Cell culture
SW1353 chondrocytes were purchased from the American Type Culture Collection (Manassas, VA, USA).
The cells contained 5% CO2 and humidified at 37 [deg.] C in the presence or absence of leaflets, containing 10% v / v fetal bovine serum, 100 units / ml penicillin and 100 mg / ml streptomycin (Gibco-BRL, Grand Island, NY, USA).
[Test Methods]
One. MTT assay
Cell viability was assayed (MMT) using 3- (4,5-dimethylthiazol-2-yl) -2,5-diphenyltetrazolium bromide. Briefly, SW1353 cells were seeded in 6 well plates at a density of 2 * 10 < 5 > cells per well. After 24 hours of incubation, the cells were individually treated with various concentrations of leaf extracts or with 40 ng / ml of IL-l [beta] (R & D Systems Inc., Minneapolis, MN, USA), or the cells were treated with IL- Treated with different concentrations of leaf extracts for 1 hour.
After 24 hours, the medium was removed and MMT working solution (0.5 mg / ml, Sigma-Aldrich Chemical Co., St. Louis, Mo., USA) was added to the culture plates and incubated for 2 hours at 37 [ Respectively.
The culture supernatant was then removed from the wells and dimethylsulfoxide (DMSO, Sigma-Aldrich Chemical Co.) was added to dissolve the formazan crystals.
After shaking, the absorbance of each well was measured at a wavelength of 540 nm with a microplate reader (Dynatech Laboratories, Chantilly VA, USA) and the results were expressed as cell activity with respect to 100% viable and untreated control.
2. Enzyme-linked immunosorbent assay (ELISA)
The inhibitory effect of Mulberry extract on the production of MMPs (MMP-1, MMP-2, MMP-3 and MMP-13) and PGE2 was measured using a commercial ELISA kit (R & D Systems Inc.).
Briefly, cells were pretreated with IL-1β (40 ng / ml), respectively, or with various concentrations of leaf extracts for 1 hour before IL-1β treatment.
After 24 hours, the concentrations of MMPs and PGE2 in the culture medium were measured using selective ELISA kits according to the manufacturer's instructions.
3. RNA isolation and Reverse transcription Polymerase chain reaction (RT- PCR ) analysis.
Total RNA from the cultured cells was isolated using TRIzol reagent (Invitrogen Life Technologies, Carlsbad, Calif., USA) according to the manufacturer's instructions.
cDNA was synthesized with 1 μg of total RNA using AccuPower® RT PreMix (Bioneer, Daejeon, Korea) containing MMLV (moloney murine leukemia virus) reverse transcriptase. CDNAs generated by reverse transcriptase were amplified by PCR using primers purchased from Bioneer [Table 1].
After amplification, the PCR reaction was electrophoresed on 1% agarose gel and visualized using ethidium bromide (EtBr, Sigma-Aldrich Chemical Co.) staining.
In a parallel experiment, glyceraldehyde-3-phosphate dehydrogenase (GAPDH) was used as an internal control.
4. Protein extraction and Western blot Western blot analysis
For extraction of total protein, cells were harvested and lysed in lysis buffer [25 mM Tris-Cl (pH 7.5), 250 mM NaCl, 5 mM ethylenediaminetetraacetic acid (EDTA), 1% Nonidet- 40, 1 mM phenylmethylsulfonyl fluoride (PMSF) and 5 mM dithiothreitol (DTT)].
In parallel experiments, nuclear and cytoplasmic proteins were prepared using nuclear extraction reagents (Pierce, Rockford, IL, USA) according to the manufacturer's instructions.
The insoluble material was discarded by centrifugation at 13,000 x g for 20 minutes at 4 ° C.
Protein concentrations were determined using a BioRad protein assay kit (BioRad Laboratories, Hercules, Calif., USA) according to the manufacturer's instructions.
For Western blot analysis, the protein was separated by electrophoresis in a corresponding amount of sodium dodecyl sulfate (SDS) -polyacrylamide gel, and transferred to a nitrocellulose membrane (Schleicher and Schuell, Keene, NH, USA).
After blocking with 5% skimmed milk, the membranes were incubated with the protein specific antibody for 1 hour and then incubated with the appropriate enzyme-conjugated secondary antibody (ELSA) (Amersham Corp., Arlington Heights, IL, USA) And visualized using an enhanced chemiluminescence (ECL) solution (Amersham Corp.) according to the manufacturer's instructions.
Primary antibodies were purchased from Santa Cruz Biotechnology, Inc. (Santa Cruz, CA, USA) and Abcam (Cambridge, UK).
5. Nitrogen oxide Measurement of generation
The concentration of nitric oxide in the culture supernatant was determined by measuring the stable oxidation product of nitric oxide, nitrite, using a Griess reagent (Sigma-Aldrich Chemical Co.).
Cell culture conditions were the same as those used for ELISA. After culturing for 24 hours with IL-1 [beta] and / or mulberry extract, 100 [mu] l of each culture supernatant was mixed at the same volume of the grease reagent for 10 minutes at room temperature.
The absorbance was then measured at 540 nm with a microplate reader and the production of nitrous acid was determined by the NaNO 2 standard curve.
6. Fluorescent antibody method ( Immunofluorescence staining)
To detect the potential of NF-κB p65, SW1353 cells were grown in glass coverslips in 6-well plates for 24 hours.
Cells were pretreated with leaf extract (800 μg / ml) for 1 hour before stimulation with IL-1β (40 ng / ml).
After 30 min of incubation, the cells were washed twice with phosphate-buffered saline (PBS), fixed with 3.7% paraformaldehyde, treated with 0.2% Triton X-100, and incubated with 2% bovine serum albumin (bovine serum albumin).
The cells were incubated sequentially with anti-NF-κB p65 antibody and fluorescein isothiocyanate-conjugated Don Chiani-Rabbit immunoglobulin G (IgG, Jackson ImmunoResearch Laboratories, Inc., West Grove, Pa. Respectively.
After washing with PBS, the nuclei were stained with 4'6-diamidino-2-phenylindole (DAPI, Sigma-Aldrich Chemical Co.) and fluorescence was visualized using a fluorescence microscope (Carl Zeiss, Jena, Germany) Respectively.
7. Preparation of complex extract
The extracts A and B of Lactobacillus casei were fermented.
The hot water extract (Extract C), the hydrothermal extract (Extract D), the water extract (Extract E), and the hot water extract of mung bean Extract F) was prepared.
The extracts were then mixed according to the following Table 1 to prepare Examples.
(Unit: parts by weight)
[Test result]
1. The survival of SW1353 cartilage cells The top Effect of extract
To evaluate whether the leaf extract had toxic effects on SW1353 cells, cells were treated with various concentrations of leaf extracts for 24 hours.
In the MTT assay, the concentration of mulberry leaf extract did not cause cytotoxicity in SW1353 cells up to 800 g / ml.
On the other hand, the survival rate was remarkably decreased (about 70%, Fig. 1A) at 1000 μg / ml of the leaf extract.
In the subsequent experiments, treatment with IL-1? -Induced SW1353 cells at a concentration of 800 μg / ml or lower also had no adverse effect on cell viability (FIG. 1B).
On the other hand, it was confirmed that the cell survival rate was remarkably excellent when the fermented leaf extract was used, and the survival rate could be maintained at a relatively high level even at 1000 μg / ml (FIG. 2) There is an advantage that it can be provided without side effects.
Therefore, the concentration of leaf extract was applied to the remaining experiment within 800 ㎍ / ml.
2. In SW1353 cartilage cells MMP -1 and MMP - IL of 13 - 1β Suppress induction production
The above leaflet extract inhibits IL-1β induced production of MMP-1 and MMP-13 in SW1353 chondrocytes.
Various MMPs are involved in both physiological collagen conversion in cartilage and matrix degradation in cartilage arthritis. Therefore, in order to investigate the inhibitory effect of Mulberry leaf extract on the production of IL-1? -Induced MMPs, SW1353 cells were stimulated with IL-1β (40 ng / ml) for 24 hours in the presence or absence of leaf extract, Was detected in the culture supernatant using ELISA.
Increased release of MMPs (MMP-1, MMP-2, MMP-3 and MMP-13) was detected in the culture supernatant after stimulation with IL-1β (FIG. 3).
However, pretreatment of SW1353 cells with leaf extract resulted in a concentration-dependent decrease in the production of IL-1β stimulating collagenase, for example, MMP-1 and MMP-13. However, MMP-2 (gelatinase A) or MMP-3 (stromelysin) was comparable to levels found in untreated cells.
3. In SW1353 cartilage cells MMP -1 and MMP -13 < / RTI > 1β Suppress inducible expression
The above leaf extract inhibits IL-1β induced expression of MMP-1 and MMP-13 in SW1353 chondrocytes.
In order to evaluate the effect of mulberry leaf extract on IL-1β induced expression of MMPs in SW1353 cells, the cells were treated with IL-1β alone or at different concentrations of mulberry extract for 24 hours.
RT-PCR and immunoblot image analysis showed that the level of all MMPs was significantly increased in SW1353 cells treated with IL-1β alone compared to levels detected in untreated cells (FIG. 4).
In the SW1353 cartilage cells, IL- 1β Judo Nitrogen oxide And Of PGE2 Production inhibition
The above leaflet extract inhibits the production of IL-1? -Induced nitric oxide and PGE2 in SW1353 chondrocytes.
Since inflammatory mediators, such as nitric oxide and PGE2, are well known to play an important role in the progression of cartilage destruction in arthritis, the concentration of nitric oxide and PGE2 in IL-1β stimulated SW1353 cells The effect was measured.
To confirm the effect of the leaf extract on the concentration of nitric oxide and PGE2 produced by SW1353 cells, the treated cell culture supernatants were collected and each treated with a grease reagent and an ELISA.
Treatment of SW1353 cells with IL-1? Alone significantly increased the concentrations of nitric oxide and PGE2 as compared to the control (FIGS. 5A and B).
However, mulberry leaf extract significantly reduces the release of nitric oxide and PGE2 from IL-1? -Suced SW1353 cells in a concentration dependent manner in the range of 200 to 800 μg / ml.
5. In SW1353 chondrocytes, IL- 1β Judo iNOS and COX-2 expression
The above leaflet extract decreases IL-1? -Induced iNOS and COX-2 expression in SW1353 chondrocytes.
Next, RT-PCR and western blot analysis were performed to determine whether inhibition of nitric oxide and PGE2 production by mulberry extracts in IL-1β stimulated SW1353 cells associated with reduced concentrations of iNOS and COX-2 expression .
The results indicate that IL-1β-induced increase in iNOS and COX-2 mRNA levels is inversely related to mulberry leaf extract in a concentration-dependent manner (Figure 6A)
In parallel experiments, elevated protein concentrations of iNOS and COX-2 were reduced due to stimulation by IL-1 [beta] (Fig. 6B)
These results indicate that iNOS and COX-2 reduced expression at the transcriptional level contributes to the inhibitory effect of IL-1β-induced oxidative nitrogen and PGE2 on the mulberry leaf extract.
6. In SW1353 chondrocytes, IL- 1β Judo NF - KB Block nuclear potential
The leaf extract inhibits nuclear translocation of IL-1β-induced NF-κB in SW1353 chondrocytes.
Many studies indicate that IL-1β-induced NF-κB activation is involved in the upregulation of MMPs, iNOS and COX-2 transcriptional activity.
Therefore, whether or not the inhibitory effect of mulberry leaf extract on IL-1β induced activation of MMPs, iNOS and COX-2 mediated through the inhibition of NF-κB signaling was determined by measuring the nuclear potential of NF-κB.
Treatment of IL-1? Improved nuclear accumulation of NF-κB protein within 30 minutes and involved degradation of IκB-α in the cytoplasm (FIG. 7A).
However, leaf extract and pretreatment reduced the nuclear accumulation of IL-1β-induced NF-κB and the degradation of IκB-α compared to cells treated with IL-1β alone.
Immunofluorescence images also showed that the nuclear potential of NF-κB P65 was strongly induced after stimulation with IL-1β and cells, and that the shift in nuclear NF-κB P65 was completely eliminated after the mulberry extract and cell pretreatment. 7B)
These results indicate that the extracts of Mulberry leaf can inhibit IL-1β-induced NF-κB activation in SW1353 cells through inhibition of IκB degradation and nuclear translocation of NF-κB.
7. In SW1353 chondrocytes, p38 Of MAPK IL- 1β Suppress induction activation
The leaf extract inhibits IL-1β-induced activation of p38 MAPK in SW1353 chondrocytes.
Since it is well known that the MAPKs pathway is highly involved in the expression of IL-1β-induced MMPs and inflammatory mediators, we investigated whether the inhibitory effects of the mulberry leaf extract were mediated by MAPKs signaling cascades in their expression.
Western blot analysis confirmed that IL-1? Treatment improves the phosphorylation of JNK, p38 MAPK and ERK in the experimental system without affecting total protein concentration (Fig. 8A).
Therefore, we evaluated the effect of Mulberry leaf extract on IL-1? -Induced phosphorylation of MAPKs in SW1353 cells.
The results showed that IL-1β stimulation activity of p38 MAPK was greatly reduced near the control level in a concentration-dependent manner by the leaf extract and pretreatment, but there was no such effect on the activity of JNK and ERK (FIG. 8B) .
The results suggest that the inhibition of IL-1β-induced p38 MAPK activation by leaf extracts may play a role in the observed cartilage protection potential of IL-1β-stimulated SW1353 cells.
8. Compound extract Sensuality evaluation
The above complex extracts T1 to T10 were prepared as a beverage, and a sensory evaluation was performed on 20 adult male and female. The sensory evaluation was evaluated by an index of 1 to 10 according to taste and flavor based on flavor and taste, and classified by an average index. The results are shown in Table 2. (The higher the number is, the higher the palatability will be)
(Unit: index)
Referring to Table 2 above, the leaf extract has a tasty flavor and does not have a palatable flavor. The fermentation shows that the cytotoxicity is reduced but the flavor is not increased.
In addition, the flavor of the fermented upper leaves was not removed by fermented syrup extract alone, and almost no fermented syrup extract was used.
In addition, it was confirmed that the flavor of beverage was high and the taste was high when the extract was used.
Accordingly, the combined extract can provide a preventive or ameliorative effect of arthritis caused by IL-1β including a leaf extract, and can be provided as a food or a functional food having high palatability and easy to be supplied.
While the present invention has been particularly shown and described with reference to exemplary embodiments thereof, it is to be understood that the invention is not limited to the disclosed exemplary embodiments, Of the right.
Claims (8)
Bacillus grandiflorum extract;
Juniper extract;
Extract of royal jelly
Containing mung bean extract
A composition for preventing or ameliorating arthritis caused by IL-1 ?.
Wherein the topical extract is extracted with a solvent selected from the group consisting of water, an alcohol having 1 to 6 carbon atoms and a mixed solvent thereof,
A composition for preventing or ameliorating arthritis caused by IL-1 ?.
Wherein the arthritis is osteoarthritis or rheumatoid arthritis
A composition for preventing or ameliorating arthritis caused by IL-1 ?.
Food composition.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| KR1020150145021A KR101770035B1 (en) | 2015-10-17 | 2015-10-17 | Composition comprising Morifolium extract asan effective component for preventing and treatingarthritis |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| KR1020150145021A KR101770035B1 (en) | 2015-10-17 | 2015-10-17 | Composition comprising Morifolium extract asan effective component for preventing and treatingarthritis |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| KR20170045462A KR20170045462A (en) | 2017-04-27 |
| KR101770035B1 true KR101770035B1 (en) | 2017-08-22 |
Family
ID=58702671
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR1020150145021A KR101770035B1 (en) | 2015-10-17 | 2015-10-17 | Composition comprising Morifolium extract asan effective component for preventing and treatingarthritis |
Country Status (1)
| Country | Link |
|---|---|
| KR (1) | KR101770035B1 (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20190048794A (en) | 2017-10-31 | 2019-05-09 | 동의대학교 산학협력단 | Comppsition comprising mori folium extracts for preventing, treating muscular dystrophy |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR102055264B1 (en) * | 2017-05-08 | 2019-12-12 | 동의대학교 산학협력단 | MORI FOLIUM Extracts effective component for preventing and treating arthritis And Manufacturing Method of thereof |
| KR101942429B1 (en) * | 2017-10-31 | 2019-01-25 | 동의대학교 산학협력단 | Composition comprising Morifolium extract component effective for preventing and treatingarthritis |
| KR101856435B1 (en) * | 2018-02-05 | 2018-06-20 | 동의대학교 산학협력단 | Composition for tissue repair treatment comprising hyaluronic acid and the method for preparing the same |
| KR102157138B1 (en) * | 2019-02-07 | 2020-09-17 | 김성수 | Composition for preventing and treating arthritis comprising extract of juniperus rigida |
-
2015
- 2015-10-17 KR KR1020150145021A patent/KR101770035B1/en active IP Right Grant
Non-Patent Citations (3)
| Title |
|---|
| 병조희풀(네이버 지식백과, http://terms.naver.com/print.nhn?docId=1995304&cid=46686&categoryId=46694)(출처: 야고도감, 솔뫼(송상곤), 2010년 07월 05일, ㈜넥서스)* |
| 서형호 외 1 명, ‘상심자추출물 등 복합물의 퇴행성관절염 억제효과’, 한국약용작물학회지 제22권제4호, 262-269쪽, 2014년 8월.* |
| 암에 좋은 산야초] 관절염·통풍에 효험이 뛰어난 노간주나무(월간암 2009년 3월호, http://www.cancerline.co.kr/html/3442.html)(최종 수정일: 2009.07.02.)* |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20190048794A (en) | 2017-10-31 | 2019-05-09 | 동의대학교 산학협력단 | Comppsition comprising mori folium extracts for preventing, treating muscular dystrophy |
Also Published As
| Publication number | Publication date |
|---|---|
| KR20170045462A (en) | 2017-04-27 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| KR101770035B1 (en) | Composition comprising Morifolium extract asan effective component for preventing and treatingarthritis | |
| KR20040018375A (en) | Lipoteichoic acid from lactic acid bacteria and its use to modulate immune responses mediated by gram-negative bacteria, potential pathogenic gram-positive bacteria | |
| KR101997060B1 (en) | Composition for prevention or treatment of muscular disorder, or improvement of muscular functions comprising fermented deer antler | |
| KR20190133639A (en) | Lactobacillus Crispatus KBL693 and Use Thereof | |
| KR101770036B1 (en) | Composition comprising Schizandrae Fructus extract asan effective component for preventing and treatingarthritis | |
| KR20180129945A (en) | Bifidobacteria to increase the fat body weight | |
| KR101577792B1 (en) | A pharmaceutical composition for preventing or treating IL-6-mediated disease, comprising extract or fraction of Portulaca oleracea L. | |
| KR102263698B1 (en) | A mixture of Lactobacillus plantarum LRCC5195 and isomaltooligosaccharide having ameliorating or improving atopic dermatitis | |
| US10286021B2 (en) | Composition for prevention or treatment of arthritis, containing Sargassum serratifolium extract as active ingredient | |
| KR101402926B1 (en) | Pharmaceutical composition and functional food for prevention or treatment of bone disease comprising the lactic acid bacteria ferment of hwangryunhaedoktang | |
| JP2024050702A (en) | Composition for preventing or treating obesity or obesity-induced metabolic syndrome, comprising Enterococcus faecalis as an active ingredient | |
| KR101799251B1 (en) | Agent for reducing risk of developing cancer | |
| KR102346078B1 (en) | Fermented Cirsium japonicum var. maackii production method and anti-inflammatory composition prepared by the method | |
| JP6261688B2 (en) | QOL improvement or persistence agent | |
| KR101941183B1 (en) | Maximowiczia Chinensis Extracts effective component for preventing and treating arthritis And Manufacturing Method of thereof | |
| KR102143081B1 (en) | Composition comprising carpomitra costata(stackhouse) batters extract for preventing or treating osteoarthritis | |
| KR101795115B1 (en) | Anti-tuberculosis composition for treating or preventing tuberculosis comprising gamma-Linolenic acid | |
| JP2022516116A (en) | Kimchi for the prevention or treatment of Helicobacter pylori-related diseases | |
| KR102467815B1 (en) | A composition for inhibiting senescence comprising Akkermansia muciniphila or culture of the same | |
| KR102158134B1 (en) | Antibacterial composition comprising an extract of schisandra chinesis | |
| CN114949202A (en) | Probiotic and protein composition and application thereof in resisting helicobacter pylori | |
| KR101765988B1 (en) | Anti-tuberculosis composition for treating or preventing tuberculosis comprising Melia azedarach L. extracts and fractions thereof | |
| KR20150092045A (en) | A composition for treating or preventing tuberculosis comprising Artesunate | |
| KR20200000956A (en) | Compositions for Treatment or Prevention of Intestinal Diseases Comprising Propionibacterium freudenreichii, it culture broth or heat killed Propionibacterium freudenreichii as an active ingredient | |
| TWI725464B (en) | The reduced fat probiotic strain, composition thereof and use thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A201 | Request for examination | ||
| E902 | Notification of reason for refusal | ||
| E701 | Decision to grant or registration of patent right |