KR101614205B1 - Pharmaceutical composition comprising extract of Eucommiae coretex for prevention or treatment of muscle wasting disease - Google Patents
Pharmaceutical composition comprising extract of Eucommiae coretex for prevention or treatment of muscle wasting disease Download PDFInfo
- Publication number
- KR101614205B1 KR101614205B1 KR1020140054193A KR20140054193A KR101614205B1 KR 101614205 B1 KR101614205 B1 KR 101614205B1 KR 1020140054193 A KR1020140054193 A KR 1020140054193A KR 20140054193 A KR20140054193 A KR 20140054193A KR 101614205 B1 KR101614205 B1 KR 101614205B1
- Authority
- KR
- South Korea
- Prior art keywords
- expression
- extract
- present
- muscle
- pharmaceutical composition
- Prior art date
Links
- 239000000284 extract Substances 0.000 title claims abstract description 42
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 title abstract description 31
- 201000000585 muscular atrophy Diseases 0.000 title abstract description 27
- 206010028289 Muscle atrophy Diseases 0.000 title abstract description 24
- 239000008194 pharmaceutical composition Substances 0.000 title abstract description 22
- 230000002265 prevention Effects 0.000 title 1
- 239000000203 mixture Substances 0.000 claims abstract description 17
- 210000003205 muscle Anatomy 0.000 claims description 21
- 230000004069 differentiation Effects 0.000 claims description 18
- 239000004480 active ingredient Substances 0.000 claims description 10
- 210000003098 myoblast Anatomy 0.000 claims description 8
- 230000001737 promoting effect Effects 0.000 claims description 4
- 238000000338 in vitro Methods 0.000 claims 1
- 201000010099 disease Diseases 0.000 abstract description 28
- 240000000249 Morus alba Species 0.000 abstract description 13
- 235000008708 Morus alba Nutrition 0.000 abstract description 13
- 230000003466 anti-cipated effect Effects 0.000 abstract 1
- 230000014509 gene expression Effects 0.000 description 62
- 210000004262 dental pulp cavity Anatomy 0.000 description 29
- 230000000694 effects Effects 0.000 description 24
- MZOFCQQQCNRIBI-VMXHOPILSA-N (3s)-4-[[(2s)-1-[[(2s)-1-[[(1s)-1-carboxy-2-hydroxyethyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-[[2-[[(2s)-2,6-diaminohexanoyl]amino]acetyl]amino]-4-oxobutanoic acid Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@@H](N)CCCCN MZOFCQQQCNRIBI-VMXHOPILSA-N 0.000 description 22
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 22
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 22
- 102100037850 Interferon gamma Human genes 0.000 description 21
- 108010074328 Interferon-gamma Proteins 0.000 description 21
- 101710191029 F-box only protein 32 Proteins 0.000 description 20
- 102100040669 F-box only protein 32 Human genes 0.000 description 18
- 108010059343 MM Form Creatine Kinase Proteins 0.000 description 17
- 108090000623 proteins and genes Proteins 0.000 description 16
- 210000004027 cell Anatomy 0.000 description 15
- 230000007423 decrease Effects 0.000 description 13
- 206010003694 Atrophy Diseases 0.000 description 12
- 108090000723 Insulin-Like Growth Factor I Proteins 0.000 description 12
- 108010084498 Myosin Heavy Chains Proteins 0.000 description 12
- 230000037444 atrophy Effects 0.000 description 12
- 238000001262 western blot Methods 0.000 description 12
- 102000005604 Myosin Heavy Chains Human genes 0.000 description 11
- 108010052419 NF-KappaB Inhibitor alpha Proteins 0.000 description 10
- 102100039337 NF-kappa-B inhibitor alpha Human genes 0.000 description 10
- 102000005747 Transcription Factor RelA Human genes 0.000 description 10
- 108010031154 Transcription Factor RelA Proteins 0.000 description 10
- 239000000796 flavoring agent Substances 0.000 description 10
- 235000019634 flavors Nutrition 0.000 description 9
- 210000002027 skeletal muscle Anatomy 0.000 description 9
- 102100025014 E3 ubiquitin-protein ligase TRIM63 Human genes 0.000 description 8
- 101710164910 E3 ubiquitin-protein ligase TRIM63 Proteins 0.000 description 8
- 102000004218 Insulin-Like Growth Factor I Human genes 0.000 description 8
- 102000003945 NF-kappa B Human genes 0.000 description 8
- 108010057466 NF-kappa B Proteins 0.000 description 8
- 101710089543 Nitric oxide synthase, inducible Proteins 0.000 description 8
- 102100029438 Nitric oxide synthase, inducible Human genes 0.000 description 8
- 108020004999 messenger RNA Proteins 0.000 description 8
- 102100032970 Myogenin Human genes 0.000 description 7
- 108010056785 Myogenin Proteins 0.000 description 7
- 238000000034 method Methods 0.000 description 7
- 238000003757 reverse transcription PCR Methods 0.000 description 7
- 206010006895 Cachexia Diseases 0.000 description 6
- 101100239693 Dictyostelium discoideum myoD gene Proteins 0.000 description 6
- 108010031794 IGF Type 1 Receptor Proteins 0.000 description 6
- 102000038455 IGF Type 1 Receptor Human genes 0.000 description 6
- 108050003267 Prostaglandin G/H synthase 2 Proteins 0.000 description 6
- 102100038280 Prostaglandin G/H synthase 2 Human genes 0.000 description 6
- 230000003247 decreasing effect Effects 0.000 description 6
- 239000003814 drug Substances 0.000 description 6
- 238000011156 evaluation Methods 0.000 description 6
- 235000013376 functional food Nutrition 0.000 description 6
- 230000036541 health Effects 0.000 description 6
- -1 myigenin Proteins 0.000 description 6
- 210000000107 myocyte Anatomy 0.000 description 6
- 102000004127 Cytokines Human genes 0.000 description 5
- 108090000695 Cytokines Proteins 0.000 description 5
- 206010061218 Inflammation Diseases 0.000 description 5
- 101001023030 Toxoplasma gondii Myosin-D Proteins 0.000 description 5
- 230000004054 inflammatory process Effects 0.000 description 5
- 239000000843 powder Substances 0.000 description 5
- 102000004169 proteins and genes Human genes 0.000 description 5
- 230000001105 regulatory effect Effects 0.000 description 5
- 230000035899 viability Effects 0.000 description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 description 4
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 4
- 108090001005 Interleukin-6 Proteins 0.000 description 4
- 102000004889 Interleukin-6 Human genes 0.000 description 4
- 102100038380 Myogenic factor 5 Human genes 0.000 description 4
- 101710099061 Myogenic factor 5 Proteins 0.000 description 4
- 102100038379 Myogenic factor 6 Human genes 0.000 description 4
- 102000013275 Somatomedins Human genes 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 4
- 230000006378 damage Effects 0.000 description 4
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
- 238000000386 microscopy Methods 0.000 description 4
- 108010084677 myogenic factor 6 Proteins 0.000 description 4
- 230000000770 proinflammatory effect Effects 0.000 description 4
- 208000001076 sarcopenia Diseases 0.000 description 4
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- 208000031229 Cardiomyopathies Diseases 0.000 description 3
- 206010014561 Emphysema Diseases 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 3
- 208000031886 HIV Infections Diseases 0.000 description 3
- 208000037357 HIV infectious disease Diseases 0.000 description 3
- 206010021143 Hypoxia Diseases 0.000 description 3
- 206010024229 Leprosy Diseases 0.000 description 3
- 208000002720 Malnutrition Diseases 0.000 description 3
- 206010028980 Neoplasm Diseases 0.000 description 3
- 238000010240 RT-PCR analysis Methods 0.000 description 3
- 229920002472 Starch Polymers 0.000 description 3
- 102000004987 Troponin T Human genes 0.000 description 3
- 108090001108 Troponin T Proteins 0.000 description 3
- 230000009471 action Effects 0.000 description 3
- 239000000654 additive Substances 0.000 description 3
- 235000010443 alginic acid Nutrition 0.000 description 3
- 229920000615 alginic acid Polymers 0.000 description 3
- 210000003719 b-lymphocyte Anatomy 0.000 description 3
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 3
- 201000011510 cancer Diseases 0.000 description 3
- 230000024245 cell differentiation Effects 0.000 description 3
- 239000001913 cellulose Substances 0.000 description 3
- 235000010980 cellulose Nutrition 0.000 description 3
- 229920002678 cellulose Polymers 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 230000001684 chronic effect Effects 0.000 description 3
- 208000020832 chronic kidney disease Diseases 0.000 description 3
- 230000001086 cytosolic effect Effects 0.000 description 3
- 206010012601 diabetes mellitus Diseases 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 208000028208 end stage renal disease Diseases 0.000 description 3
- 201000000523 end stage renal failure Diseases 0.000 description 3
- 208000033519 human immunodeficiency virus infectious disease Diseases 0.000 description 3
- 230000007954 hypoxia Effects 0.000 description 3
- 230000028709 inflammatory response Effects 0.000 description 3
- 230000005764 inhibitory process Effects 0.000 description 3
- 208000017169 kidney disease Diseases 0.000 description 3
- 230000001071 malnutrition Effects 0.000 description 3
- 235000000824 malnutrition Nutrition 0.000 description 3
- 230000007246 mechanism Effects 0.000 description 3
- 210000000663 muscle cell Anatomy 0.000 description 3
- 201000006938 muscular dystrophy Diseases 0.000 description 3
- 208000015380 nutritional deficiency disease Diseases 0.000 description 3
- 208000005368 osteomalacia Diseases 0.000 description 3
- 239000003755 preservative agent Substances 0.000 description 3
- 230000002335 preservative effect Effects 0.000 description 3
- 150000003839 salts Chemical class 0.000 description 3
- 239000008107 starch Substances 0.000 description 3
- 235000019698 starch Nutrition 0.000 description 3
- 239000006188 syrup Substances 0.000 description 3
- 235000020357 syrup Nutrition 0.000 description 3
- 229940124597 therapeutic agent Drugs 0.000 description 3
- 239000011782 vitamin Substances 0.000 description 3
- 235000013343 vitamin Nutrition 0.000 description 3
- 229930003231 vitamin Natural products 0.000 description 3
- 229940088594 vitamin Drugs 0.000 description 3
- PUPZLCDOIYMWBV-UHFFFAOYSA-N (+/-)-1,3-Butanediol Chemical compound CC(O)CCO PUPZLCDOIYMWBV-UHFFFAOYSA-N 0.000 description 2
- FHVDTGUDJYJELY-UHFFFAOYSA-N 6-{[2-carboxy-4,5-dihydroxy-6-(phosphanyloxy)oxan-3-yl]oxy}-4,5-dihydroxy-3-phosphanyloxane-2-carboxylic acid Chemical compound O1C(C(O)=O)C(P)C(O)C(O)C1OC1C(C(O)=O)OC(OP)C(O)C1O FHVDTGUDJYJELY-UHFFFAOYSA-N 0.000 description 2
- 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 2
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 2
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 2
- 238000009007 Diagnostic Kit Methods 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- 108010010803 Gelatin Proteins 0.000 description 2
- 108010051696 Growth Hormone Proteins 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
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 2
- 102100031790 Myelin expression factor 2 Human genes 0.000 description 2
- 101710107751 Myelin expression factor 2 Proteins 0.000 description 2
- 102100038803 Somatotropin Human genes 0.000 description 2
- 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 2
- 229930006000 Sucrose Natural products 0.000 description 2
- 102000040945 Transcription factor Human genes 0.000 description 2
- 108091023040 Transcription factor Proteins 0.000 description 2
- 102100035100 Transcription factor p65 Human genes 0.000 description 2
- 102000006275 Ubiquitin-Protein Ligases Human genes 0.000 description 2
- 108010083111 Ubiquitin-Protein Ligases Proteins 0.000 description 2
- 230000032683 aging Effects 0.000 description 2
- 229940072056 alginate Drugs 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 239000001506 calcium phosphate Substances 0.000 description 2
- 229910000389 calcium phosphate Inorganic materials 0.000 description 2
- 235000011010 calcium phosphates Nutrition 0.000 description 2
- 239000000378 calcium silicate Substances 0.000 description 2
- 229910052918 calcium silicate Inorganic materials 0.000 description 2
- 235000012241 calcium silicate Nutrition 0.000 description 2
- OYACROKNLOSFPA-UHFFFAOYSA-N calcium;dioxido(oxo)silane Chemical compound [Ca+2].[O-][Si]([O-])=O OYACROKNLOSFPA-UHFFFAOYSA-N 0.000 description 2
- 150000001720 carbohydrates Chemical class 0.000 description 2
- 235000014633 carbohydrates Nutrition 0.000 description 2
- 230000001925 catabolic effect Effects 0.000 description 2
- 210000003169 central nervous system Anatomy 0.000 description 2
- 239000003086 colorant Substances 0.000 description 2
- 210000000805 cytoplasm Anatomy 0.000 description 2
- 230000003013 cytotoxicity Effects 0.000 description 2
- 231100000135 cytotoxicity Toxicity 0.000 description 2
- 230000034994 death Effects 0.000 description 2
- 231100000517 death Toxicity 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 230000018109 developmental process Effects 0.000 description 2
- 239000008121 dextrose Substances 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- 239000012153 distilled water Substances 0.000 description 2
- 239000003937 drug carrier Substances 0.000 description 2
- 239000003792 electrolyte Substances 0.000 description 2
- 239000002158 endotoxin Substances 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- 235000013305 food Nutrition 0.000 description 2
- 229920000159 gelatin Polymers 0.000 description 2
- 239000008273 gelatin Substances 0.000 description 2
- 235000019322 gelatine Nutrition 0.000 description 2
- 235000011852 gelatine desserts Nutrition 0.000 description 2
- 235000011187 glycerol Nutrition 0.000 description 2
- 239000008187 granular material Substances 0.000 description 2
- 239000000122 growth hormone Substances 0.000 description 2
- 230000006698 induction Effects 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 229910052500 inorganic mineral Inorganic materials 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- 229920006008 lipopolysaccharide Polymers 0.000 description 2
- 235000019359 magnesium stearate Nutrition 0.000 description 2
- 230000001404 mediated effect Effects 0.000 description 2
- 229920000609 methyl cellulose Polymers 0.000 description 2
- 239000001923 methylcellulose Substances 0.000 description 2
- 235000010981 methylcellulose Nutrition 0.000 description 2
- LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 2
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 2
- 239000008108 microcrystalline cellulose Substances 0.000 description 2
- 229940016286 microcrystalline cellulose Drugs 0.000 description 2
- 239000011707 mineral Substances 0.000 description 2
- 235000010755 mineral Nutrition 0.000 description 2
- 239000002480 mineral oil Substances 0.000 description 2
- 235000010446 mineral oil Nutrition 0.000 description 2
- 230000002107 myocardial effect Effects 0.000 description 2
- 230000004070 myogenic differentiation Effects 0.000 description 2
- 235000015097 nutrients Nutrition 0.000 description 2
- 239000003002 pH adjusting agent Substances 0.000 description 2
- 230000037361 pathway Effects 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 2
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 2
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 2
- 229960003415 propylparaben Drugs 0.000 description 2
- HELXLJCILKEWJH-NCGAPWICSA-N rebaudioside A Chemical compound O([C@H]1[C@H](O)[C@@H](CO)O[C@H]([C@@H]1O[C@H]1[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O1)O)O[C@]12C(=C)C[C@@]3(C1)CC[C@@H]1[C@@](C)(CCC[C@]1([C@@H]3CC2)C)C(=O)O[C@H]1[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O1)O)[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O HELXLJCILKEWJH-NCGAPWICSA-N 0.000 description 2
- 230000002829 reductive effect Effects 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 235000010356 sorbitol Nutrition 0.000 description 2
- 239000000600 sorbitol Substances 0.000 description 2
- 229960002920 sorbitol Drugs 0.000 description 2
- 239000003381 stabilizer Substances 0.000 description 2
- 239000005720 sucrose Substances 0.000 description 2
- 235000000346 sugar Nutrition 0.000 description 2
- 208000024891 symptom Diseases 0.000 description 2
- 239000003826 tablet Substances 0.000 description 2
- 239000000454 talc Substances 0.000 description 2
- 229910052623 talc Inorganic materials 0.000 description 2
- 235000012222 talc Nutrition 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- 230000002103 transcriptional effect Effects 0.000 description 2
- 230000005945 translocation Effects 0.000 description 2
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 2
- LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 description 1
- 229940058015 1,3-butylene glycol Drugs 0.000 description 1
- OWEGMIWEEQEYGQ-UHFFFAOYSA-N 100676-05-9 Natural products OC1C(O)C(O)C(CO)OC1OCC1C(O)C(O)C(O)C(OC2C(OC(O)C(O)C2O)CO)O1 OWEGMIWEEQEYGQ-UHFFFAOYSA-N 0.000 description 1
- 208000030507 AIDS Diseases 0.000 description 1
- 241000238876 Acari Species 0.000 description 1
- 208000007848 Alcoholism Diseases 0.000 description 1
- 108091093088 Amplicon Proteins 0.000 description 1
- 235000003261 Artemisia vulgaris Nutrition 0.000 description 1
- 240000006891 Artemisia vulgaris Species 0.000 description 1
- 108010011485 Aspartame Proteins 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- DKPFZGUDAPQIHT-UHFFFAOYSA-N Butyl acetate Natural products CCCCOC(C)=O DKPFZGUDAPQIHT-UHFFFAOYSA-N 0.000 description 1
- 208000018380 Chemical injury Diseases 0.000 description 1
- 229920000858 Cyclodextrin Polymers 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- 229920001353 Dextrin Polymers 0.000 description 1
- 239000004375 Dextrin Substances 0.000 description 1
- 206010013801 Duchenne Muscular Dystrophy Diseases 0.000 description 1
- 241000283073 Equus caballus Species 0.000 description 1
- 239000004386 Erythritol Substances 0.000 description 1
- UNXHWFMMPAWVPI-UHFFFAOYSA-N Erythritol Natural products OCC(O)C(O)CO UNXHWFMMPAWVPI-UHFFFAOYSA-N 0.000 description 1
- 239000001512 FEMA 4601 Substances 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 229930091371 Fructose Natural products 0.000 description 1
- 239000005715 Fructose Substances 0.000 description 1
- RFSUNEUAIZKAJO-ARQDHWQXSA-N Fructose Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O RFSUNEUAIZKAJO-ARQDHWQXSA-N 0.000 description 1
- 239000004378 Glycyrrhizin Substances 0.000 description 1
- 101001123331 Homo sapiens Peroxisome proliferator-activated receptor gamma coactivator 1-alpha Proteins 0.000 description 1
- 108060003951 Immunoglobulin Proteins 0.000 description 1
- 108700005091 Immunoglobulin Genes Proteins 0.000 description 1
- 108010002350 Interleukin-2 Proteins 0.000 description 1
- 102000000588 Interleukin-2 Human genes 0.000 description 1
- 102000007351 Interleukin-2 Receptor alpha Subunit Human genes 0.000 description 1
- 108010032774 Interleukin-2 Receptor alpha Subunit Proteins 0.000 description 1
- 235000010643 Leucaena leucocephala Nutrition 0.000 description 1
- 240000007472 Leucaena leucocephala Species 0.000 description 1
- 208000008930 Low Back Pain Diseases 0.000 description 1
- 208000019693 Lung disease Diseases 0.000 description 1
- GUBGYTABKSRVRQ-PICCSMPSSA-N Maltose Natural products O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@@H](CO)OC(O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-PICCSMPSSA-N 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 102000008934 Muscle Proteins Human genes 0.000 description 1
- 108010074084 Muscle Proteins Proteins 0.000 description 1
- 208000000112 Myalgia Diseases 0.000 description 1
- 206010068871 Myotonic dystrophy Diseases 0.000 description 1
- 208000023137 Myotoxicity Diseases 0.000 description 1
- 208000008589 Obesity Diseases 0.000 description 1
- 102100028960 Peroxisome proliferator-activated receptor gamma coactivator 1-alpha Human genes 0.000 description 1
- 241000009328 Perro Species 0.000 description 1
- 208000000474 Poliomyelitis Diseases 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- HELXLJCILKEWJH-SEAGSNCFSA-N Rebaudioside A Natural products O=C(O[C@H]1[C@@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1)[C@@]1(C)[C@@H]2[C@](C)([C@H]3[C@@]4(CC(=C)[C@@](O[C@H]5[C@H](O[C@H]6[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O6)[C@@H](O[C@H]6[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O6)[C@H](O)[C@@H](CO)O5)(C4)CC3)CC2)CCC1 HELXLJCILKEWJH-SEAGSNCFSA-N 0.000 description 1
- 206010039020 Rhabdomyolysis Diseases 0.000 description 1
- 244000178231 Rosmarinus officinalis Species 0.000 description 1
- 244000228451 Stevia rebaudiana Species 0.000 description 1
- 244000269722 Thea sinensis Species 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 201000007930 alcohol dependence Diseases 0.000 description 1
- 239000000783 alginic acid Substances 0.000 description 1
- 229960001126 alginic acid Drugs 0.000 description 1
- 150000004781 alginic acids Chemical class 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 230000003078 antioxidant effect Effects 0.000 description 1
- 206010003246 arthritis Diseases 0.000 description 1
- 239000000605 aspartame Substances 0.000 description 1
- 235000010357 aspartame Nutrition 0.000 description 1
- IAOZJIPTCAWIRG-QWRGUYRKSA-N aspartame Chemical compound OC(=O)C[C@H](N)C(=O)N[C@H](C(=O)OC)CC1=CC=CC=C1 IAOZJIPTCAWIRG-QWRGUYRKSA-N 0.000 description 1
- 229960003438 aspartame Drugs 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- GUBGYTABKSRVRQ-QUYVBRFLSA-N beta-maltose Chemical compound OC[C@H]1O[C@H](O[C@H]2[C@H](O)[C@@H](O)[C@H](O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@@H]1O GUBGYTABKSRVRQ-QUYVBRFLSA-N 0.000 description 1
- 235000019437 butane-1,3-diol Nutrition 0.000 description 1
- 235000010216 calcium carbonate Nutrition 0.000 description 1
- 229910000019 calcium carbonate Inorganic materials 0.000 description 1
- 229960001714 calcium phosphate Drugs 0.000 description 1
- 229960003340 calcium silicate Drugs 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 235000014171 carbonated beverage Nutrition 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 230000005779 cell damage Effects 0.000 description 1
- 208000037887 cell injury Diseases 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 239000000084 colloidal system Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 231100000433 cytotoxic Toxicity 0.000 description 1
- 230000001472 cytotoxic effect Effects 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 235000019425 dextrin Nutrition 0.000 description 1
- 150000002016 disaccharides Chemical class 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- HELXLJCILKEWJH-UHFFFAOYSA-N entered according to Sigma 01432 Natural products C1CC2C3(C)CCCC(C)(C(=O)OC4C(C(O)C(O)C(CO)O4)O)C3CCC2(C2)CC(=C)C21OC(C1OC2C(C(O)C(O)C(CO)O2)O)OC(CO)C(O)C1OC1OC(CO)C(O)C(O)C1O HELXLJCILKEWJH-UHFFFAOYSA-N 0.000 description 1
- 235000019414 erythritol Nutrition 0.000 description 1
- 229940009714 erythritol Drugs 0.000 description 1
- UNXHWFMMPAWVPI-ZXZARUISSA-N erythritol Chemical compound OC[C@H](O)[C@H](O)CO UNXHWFMMPAWVPI-ZXZARUISSA-N 0.000 description 1
- 230000029142 excretion Effects 0.000 description 1
- 230000037080 exercise endurance Effects 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 235000015203 fruit juice Nutrition 0.000 description 1
- 230000004927 fusion Effects 0.000 description 1
- 229940014259 gelatin Drugs 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- LPLVUJXQOOQHMX-UHFFFAOYSA-N glycyrrhetinic acid glycoside Natural products C1CC(C2C(C3(CCC4(C)CCC(C)(CC4C3=CC2=O)C(O)=O)C)(C)CC2)(C)C2C(C)(C)C1OC1OC(C(O)=O)C(O)C(O)C1OC1OC(C(O)=O)C(O)C(O)C1O LPLVUJXQOOQHMX-UHFFFAOYSA-N 0.000 description 1
- UYRUBYNTXSDKQT-UHFFFAOYSA-N glycyrrhizic acid Natural products CC1(C)C(CCC2(C)C1CCC3(C)C2C(=O)C=C4C5CC(C)(CCC5(C)CCC34C)C(=O)O)OC6OC(C(O)C(O)C6OC7OC(O)C(O)C(O)C7C(=O)O)C(=O)O UYRUBYNTXSDKQT-UHFFFAOYSA-N 0.000 description 1
- 229960004949 glycyrrhizic acid Drugs 0.000 description 1
- 235000019410 glycyrrhizin Nutrition 0.000 description 1
- LPLVUJXQOOQHMX-QWBHMCJMSA-N glycyrrhizinic acid Chemical compound O([C@@H]1[C@@H](O)[C@H](O)[C@H](O[C@@H]1O[C@@H]1C([C@H]2[C@]([C@@H]3[C@@]([C@@]4(CC[C@@]5(C)CC[C@@](C)(C[C@H]5C4=CC3=O)C(O)=O)C)(C)CC2)(C)CC1)(C)C)C(O)=O)[C@@H]1O[C@H](C(O)=O)[C@@H](O)[C@H](O)[C@H]1O LPLVUJXQOOQHMX-QWBHMCJMSA-N 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid Chemical compound CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 1
- 102000018358 immunoglobulin Human genes 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 230000002779 inactivation Effects 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 230000002458 infectious effect Effects 0.000 description 1
- 230000004968 inflammatory condition Effects 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 210000002901 mesenchymal stem cell Anatomy 0.000 description 1
- HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 description 1
- 208000030159 metabolic disease Diseases 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 230000002297 mitogenic effect Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 150000002772 monosaccharides Chemical class 0.000 description 1
- 230000009756 muscle regeneration Effects 0.000 description 1
- 230000005996 muscular dysfunction Effects 0.000 description 1
- 230000001114 myogenic effect Effects 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 230000000926 neurological effect Effects 0.000 description 1
- 235000020824 obesity Nutrition 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 229940124595 oriental medicine Drugs 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 230000037081 physical activity Effects 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 229920001184 polypeptide Polymers 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 150000004804 polysaccharides Chemical class 0.000 description 1
- 230000002028 premature Effects 0.000 description 1
- 230000002672 pro-cachectic effect Effects 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 230000002797 proteolythic effect Effects 0.000 description 1
- 235000019203 rebaudioside A Nutrition 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 102000037983 regulatory factors Human genes 0.000 description 1
- 108091008025 regulatory factors Proteins 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 235000019204 saccharin Nutrition 0.000 description 1
- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
- 229940081974 saccharin Drugs 0.000 description 1
- 239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 1
- HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical compound O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 238000004904 shortening Methods 0.000 description 1
- 230000019491 signal transduction Effects 0.000 description 1
- 210000002363 skeletal muscle cell Anatomy 0.000 description 1
- 208000020431 spinal cord injury Diseases 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 150000005846 sugar alcohols Chemical class 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 230000001256 tonic effect Effects 0.000 description 1
- 238000013518 transcription Methods 0.000 description 1
- 230000035897 transcription Effects 0.000 description 1
- 238000002137 ultrasound extraction Methods 0.000 description 1
- 235000013311 vegetables Nutrition 0.000 description 1
- 150000003722 vitamin derivatives Chemical class 0.000 description 1
- 238000003809 water extraction Methods 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 239000000811 xylitol Substances 0.000 description 1
- 235000010447 xylitol Nutrition 0.000 description 1
- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 description 1
- 229960002675 xylitol Drugs 0.000 description 1
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/46—Eucommiaceae (Eucommia family), e.g. hardy rubber tree
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
- A23L33/105—Plant extracts, their artificial duplicates or their derivatives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
-
- 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
- A23V2200/316—Foods, ingredients or supplements having a functional effect on health having an effect on regeneration or building of ligaments or muscles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
- A61K2236/30—Extraction of the material
- A61K2236/33—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones
- A61K2236/331—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones using water, e.g. cold water, infusion, tea, steam distillation or decoction
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
- A61K2236/30—Extraction of the material
- A61K2236/33—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones
- A61K2236/333—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones using mixed solvents, e.g. 70% EtOH
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Natural Medicines & Medicinal Plants (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Botany (AREA)
- Mycology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Medical Informatics (AREA)
- Microbiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Neurology (AREA)
- Alternative & Traditional Medicine (AREA)
- Biotechnology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Organic Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Physical Education & Sports Medicine (AREA)
- Epidemiology (AREA)
- Nutrition Science (AREA)
- Food Science & Technology (AREA)
- Polymers & Plastics (AREA)
- Medicines Containing Plant Substances (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
본 발명은 근육 소모 관련 질환의 예방 또는 치료에 유용하게 사용될 수 있는 두충 추출물을 포함 하는 약학적 조성물에 관한 것이다. 본 발명의 두충추출물을 이용하여 근육 소모 관련 질환을 효과적으로 치료할 수 있는 조성물을 생산할 수 있다. 따라서 근육 소모 관련 질환의 치료에 있어서 보다 근본적으로 접근하여 타겟 치료를 할 수 있을 것으로 기대된다.The present invention relates to a pharmaceutical composition comprising a mulberry extract which can be usefully used for preventing or treating muscle wasting-related diseases. The extract of the present invention can be used to produce a composition capable of effectively treating muscle wasting-related diseases. Therefore, it is anticipated that the target treatment will be more fundamentally approachable in the treatment of muscle wasting related diseases.
Description
본 발명은 근육 소모 관련 질환의 예방 또는 치료에 유용하게 사용될 수 있는 두충 추출물을 포함하는 약학적 조성물에 관한 것이다.The present invention relates to a pharmaceutical composition comprising a mulberry extract which can be usefully used for preventing or treating muscle wasting-related diseases.
두충은 장미목 두충과 낙엽교목으로 원산지는 중국이지만, 한국, 일본에서도 재배하고 있다. 두충나무는 자르면 끈끈한 점질의 실이 나온다. 한방에서는 두충나무 껍질을 건조시킨 것을 두충 또는 당두충이라고 하여, 강장제, 관절염, 류머티즘 진통제로 사용하고 있으며, 근래에는 나무껍질 이외에도 잎과 더불어 씨의 사용도 점차적으로 증가하고 있다.
It is a Chinese rosemary and a deciduous arboreous tree. Its origin is China, but it is also cultivated in Korea and Japan. When cutting the mulberry tree, a thread of sticky consistency comes out. In the oriental medicine, it is used as a tonic, arthritis, and rheumatism painkiller, which is dried by the bark of the mulberry tree. In recent years, besides the bark, the use of the seed with the leaf is gradually increasing.
노화성 근육 감소증(Sarcopenia)은 나이가 증가함에 따라 동반되는 골격근의 감소와 근력의 감소로 정의된다. 노화에 의한 근육량과 근육력의 감소는 운동 지구력을 감소시키고, 신체 활동의 저하로 이어져 다양한 대사질환과 낙상으로 인한 사망을 유발한다. Sarcopenia is defined as a decrease in skeletal muscle and a decrease in muscle strength accompanied by an increase in age. Decreases in muscle mass and muscle strength due to aging decrease exercise endurance and lead to lowering of physical activity, resulting in various metabolic diseases and deaths due to falls.
현대사회에서 조기 사망의 감소로 인한 평균 수명의 연장은 이와 같은 근육 감소증 환자의 발생율을 증가시키는 요인이 되며, 이로 인한 노인 의존적 생활의 연장은 사회적 부담으로 작용할 것으로 보인다. 근육량과 근육의 감소는 30대부터 시작되며, 60대에 15%, 80세 이상은 40%의 근육 감소증을 보이며, 이로 인한 의료비용은 2000년 미국의 경우 185불이 소요되었으며, 이는 건강관리비용의 1.5%에 해당하는 수치이다.In the modern society, the prolongation of life expectancy due to the decrease of premature death is a factor that increases the incidence of such hypochondriaced patients, and the extension of the elderly dependent life is expected to be a social burden. Muscle weight and muscle loss begin in their 30s, 15% in their 60s, and 40% in those over 80 years of age, resulting in a US $ 185 health care cost in 2000, Which is 1.5% of the total.
노화성 근육 감소증을 효율적으로 제어하는 방법에 대해 다양한 연구가 수행되고 있다. 그러나, 예를 들어 성장 호르몬(GH)에 의한 치료가 근육 질량을 증가시킬 수 있는 것으로 나타났지만, 이러한 치료는 매우 고가이며, 평균 연령의 단축 등과 같은 바람직하지 않는 몇몇 부작용을 발생시켰다. 또한 환자 또는 병상에 누워있는 환자등에 있어서는 매우 부적절한 방법으로서, 근육의 재생 및 분화를 유도할 수 있는 근육 감소증 치료 약물 및 기술개발이 주요한 과제의 대상이 되고 있고, 이에 대한 연구가 이루어지고 있으나(한국 특허공개번호 10-2012-0058457), 아직 미비한 실정이다.A variety of studies have been conducted on how to effectively control aging muscular dysfunction. However, treatment with growth hormone (GH), for example, has been shown to increase muscle mass, but this treatment is very expensive and has produced some undesirable side effects, such as shortening of the average age. In addition, as a very inadequate method for a patient or a patient lying on a sickbed, the development of drugs and techniques for treating muscle hypoxia that can induce muscle regeneration and differentiation have been the subject of major researches, and studies have been conducted Patent Publication No. 10-2012-0058457).
본 발명은 상기와 같은 문제점을 해결하기 위해 안출된 것으로서, 두충(Eucommiae cortex) 추출물을 유효성분으로 포함하는, 근육 소모 관련 질환의 예방 또는 치료용 약학적 조성물을 제공하는 것을 목적으로 한다.Disclosure of Invention Technical Problem [8] Accordingly, the present invention has been made to solve the above-mentioned problems, and it is an object of the present invention to provide a pharmaceutical composition for preventing or treating muscle wasting-related diseases comprising Eucommiae cortex extract as an active ingredient.
또한, 본 발명은 두충(Eucommiae cortex) 추출물을 유효성분으로 포함하는, 근육 소모 관련 질환의 예방 또는 개선용 건강기능식품 조성물을 제공하는 것을 또 다른 목적으로 한다.
It is another object of the present invention to provide a health functional food composition for preventing or ameliorating muscle wasting-related diseases, which comprises an extract of Eucommiae cortex as an active ingredient.
그러나 본 발명이 이루고자 하는 기술적 과제는 이상에서 언급한 과제에 제한되지 않으며, 언급되지 않은 또 다른 과제들은 아래의 기재로부터 당업자에게 명확하게 이해될 수 있을 것이다.However, the technical problem to be solved by the present invention is not limited to the above-mentioned problems, and other matters not mentioned can be clearly understood by those skilled in the art from the following description.
본 발명은 두충(Eucommiae cortex) 추출물을 유효성분으로 포함하는, 근육 소모 관련 질환의 예방 또는 치료용 약학적 조성물을 제공한다.The present invention provides a pharmaceutical composition for preventing or treating muscle wasting-related diseases, comprising an extract of Eucommiae cortex as an active ingredient.
본 발명의 다른 구현예로서, 상기 근육 소모 관련 질환은 근이영양증(Muscle Dystrophy), 근육 위축증(Muscle Atropy), 카켁시아(Cachexia), 영양실조, 나병, 당뇨병, 신장병, 만성 폐쇄성 폐병(Chronic Ostructive Pulmonary Disease; COPD), 암, 말기 신부전, 사르코페니아(Sarcopenia), 기종(Emphysema), 골연화증(Osteomalacia), HIV감염 및 심근증(Cardiomyopathy)으로 이루어진 군으로부터 선택되는 것을 특징으로 한다.As another embodiment of the present invention, the muscle wasting-related diseases include muscular dystrophy, muscular atrophy, cachexia, malnutrition, leprosy, diabetes, nephropathy, chronic obstructive pulmonary disease ; COPD), cancer, end-stage renal failure, Sarcopenia, Emphysema, osteomalacia, HIV infection and cardiomyopathy.
본 발명의 또 다른 구현예로서, 상기 조성물은 근원성 분화를 촉진하는 것을 특징으로 한다.In another embodiment of the present invention, the composition is characterized by promoting myogenic differentiation.
본 발명의 또 다른 구현예로서, 상기 조성물은 근관 위축을 감소시키는 것을 특징으로 한다.In another embodiment of the present invention, the composition is characterized by reducing root canal atrophy.
본 발명의 또 다른 구현 예로서, 상기 조성물은 염증 반응을 저하시키는 것을 특징으로 한다.In another embodiment of the present invention, the composition is characterized by lowering the inflammatory response.
본 발명의 또 다른 구현 예로서 상기 조성물은 NF-κB기전을 억제시키는 것을 특징으로 한다.In another embodiment of the present invention, the composition is characterized by inhibiting the NF-κB mechanism.
본 발명은 두충(Eucommiae cortex) 추출물을 유효성분으로 포함하는, 근육 소모 관련 질환의 예방 또는 개선용 건강기능식품 조성물을 제공한다.The present invention provides a health functional food composition for preventing or ameliorating a muscle wasting-related disease, comprising an extract of Eucommiae cortex as an active ingredient.
본 발명의 다른 구현예로서 상기 근육 소모 관련 질환은 근이영양증(Muscle Dystrophy), 근육 위축증(Muscle Atropy), 카켁시아(Cachexia), 영양실조, 나병, 당뇨병, 신장병, 만성 폐쇄성 폐병(Chronic Ostructive Pulmonary Disease; COPD), 암, 말기 신부전, 사르코페니아(Sarcopenia), 기종(Emphysema), 골연화증(Osteomalacia), HIV감염 및 심근증(Cardiomyopathy)으로 이루어진 군으로부터 선택되는 것을 특징으로 한다.In another embodiment of the present invention, the muscle wasting-related diseases include muscular dystrophy, muscular atrophy, cachexia, malnutrition, leprosy, diabetes, nephropathy, chronic obstructive pulmonary disease COPD), cancer, end stage renal failure, Sarcopenia, Emphysema, osteomalacia, HIV infection and cardiomyopathy.
본 발명은 상기 약학적 조성물을 개체에 투여하는 단계를 포함하는 근육 소모 관련 질환의 치료방법을 제공한다.The present invention provides a method for treating a muscle wasting-related disease comprising administering the above pharmaceutical composition to a subject.
본 발명은 상기 두충 추출물을 포함하는 조성물의 근육 소모 관련 질환의 치료용도를 제공한다.The present invention provides a therapeutic use of a muscle wasting-related disease of a composition comprising the mulberry extract.
본 발명에 따른 조성물은 두충(Eucommiae cortex) 추출물을 유효성분으로 포함하고, 상기 두충 추출물은 근원성 분화 촉진, 근관 위축 감소 및 염증반응을 억제시킬 수 있는 바, 근육 소모 관련 질환을 예방 또는 치료하기 위한 약학적 조성물로 유용하게 사용될 수 있을 것으로 기대된다. The composition according to the present invention contains an extract of Eucommiae cortex as an active ingredient. The extract of the mulberry extract can promote root differentiation, reduce root canal atrophy and inhibit the inflammatory reaction, prevent or treat muscle wasting-related diseases It is expected that it can be usefully used as a pharmaceutical composition.
도 1은 EC(Eucommiae cortex) 추출물 처리에 의한 C2C12 근원세포와 근관의 생존능력을 나타낸 결과이다.
도 2는 근관의 형성을 Contrast microscopy로 확인한 실험결과이다.
도 3은 EC 추출물 처리에 의한 형성된 근관의 muscle creatine kinase 활성을 나타낸 결과이다.
도 4는 EC 추출물 처리에 의한 MHC, HES-6, N-CAD, MEF-2a 및 MEF-2D의 발현을 RT-PCR로 확인한 실험결과이다.
도 5는 EC 추출물 처리에 의한 myoD, myigenin, MRF4, myf5, IGF-1, IGF-1R의 발현을 RT-PCR로 확인한 실험결과이다.
도 6은 EC 추출물 처리에 의한 myoD, myigenin, MRF4, myf5, IGF-1, IGF-1R 발현의 실험결과이다.
도 7은 (a) 대조군, (b) TNF-α(10ng/ml)와 INF-γ(100IU/ml)를 처리한 경우, (c) EC 추출물 0.1mg/ml를 첨가한 경우, (d) EC 추출물 0.5mg/ml를 첨가한 경우, (e) EC 추출물 1.0mg/ml를 첨가한 경우, 근관 위축을 Contrast microscopy로 확인한 실험결과이다.
도 8은 EC 추출물 처리에 의한 위축된 근관의 muscle creatine kinase 활성을 나타낸 결과이다.
도 9는 EC 추출물 처리에 의한 Myosin heavy chain(MHC), Troponin-T의 발현을 Western blot으로 확인한 실험결과이다.
도 10은 EC 추출물 처리에 의한 Atrogin-1/MAFbx, MuRF1 mRNA의 발현을 RT-PCR로 확인한 실험결과이다.
도 11은 EC 추출물 처리에 의한 Atrogin-1/MAFbx, MuRF1, myoD, myogenin 단백질의 발현을 Western blot으로 확인한 실험결과이다.
도 12는 EC 추출물 처리에 의한 근원세포의 (a) IL-1β, IL-6, iNOS, COX-2 mRNA의 발현을 RT-PCR로 확인한 실험결과 및 (b) iNOS, COX-2 단백질의 발현을 Western blot으로 확인한 실험결과이다.
도 13은 EC 추출물 처리에 의한 근관의 (a) IL-1β, IL-6, iNOS, COX-2 mRNA의 발현을 RT-PCR로 확인한 실험결과 및 (b) iNOS, COX-2 단백질의 발현을 Western blot으로 확인한 실험결과이다.
도 14는 EC 추출물 처리에 의한 근원세포의 NF-κB p65(세포질), NF-κB p65(핵), IκB-α, P-IκB-α의 발현을 Western blot으로 확인한 실험결과이다.
도 15는 EC 추출물 처리에 의한 근관의 NF-κB p65(세포질), NF-κB p65(핵), IκB-α, P-IκB-α의 발현을 Western blot으로 확인한 실험결과이다.Figure 1 shows the viability of C2C12 myocytes and root canal by EC (Eucommiae cortex) extract treatment.
Fig. 2 is a result of an experiment in which the formation of a root canal was confirmed by contrast microscopy.
Fig. 3 shows the results of muscle creatine kinase activity of the root canal formed by EC extract treatment.
FIG. 4 shows the results of RT-PCR analysis of expression of MHC, HES-6, N-CAD, MEF-2a and MEF-2D by EC extract treatment.
FIG. 5 shows the results of RT-PCR analysis of expression of myoD, myigenin, MRF4, myf5, IGF-1 and IGF-1R by EC extract treatment.
FIG. 6 shows experimental results of myoD, myigenin, MRF4, myf5, IGF-1 and IGF-1R expression by EC extract treatment.
7 shows the results of (a) treatment with (b) TNF-α (10 ng / ml) and INF-γ (100 IU / ml) EC extract (0.5 mg / ml), (e) EC extract (1.0 mg / ml) was added to the root canal atrophy by contrast microscopy.
FIG. 8 shows the results of muscle creatine kinase activity of atrophy root canal by EC extract treatment.
FIG. 9 shows the results of Western blot analysis of Myosin heavy chain (MHC) and Troponin-T expression by EC extract treatment.
FIG. 10 shows the results of RT-PCR analysis of expression of Atrogin-1 / MAFbx and MuRF1 mRNA by EC extract treatment.
FIG. 11 shows the results of Western blot analysis of the expression of Atrogin-1 / MAFbx, MuRF1, myoD and myogenin protein by EC extract treatment.
12 shows the results of RT-PCR of (a) expression of IL-1β, IL-6, iNOS and COX-2 mRNA in the myocardial cells by EC extract treatment and (b) expression of iNOS and COX- Were confirmed by Western blot analysis.
13 shows the results of RT-PCR of (a) expression of IL-1β, IL-6, iNOS and COX-2 mRNA in the root canal by EC extract treatment and (b) expression of iNOS and COX- Western blot.
Fig. 14 shows the results of Western blotting the expression of NF-κB p65 (cytoplasm), NF-κB p65 (nucleus), IκB-α, and P-IκB-α in myoblasts by EC extract treatment.
FIG. 15 shows the results of Western blot analysis of the expression of NF-κB p65 (cytoplasm), NF-κB p65 (nucleus), IκB-α and P-IκB-α in root canal by EC extract treatment.
본 발명자들은 근육 소모 관련 질환을 예방 또는 치료하기 위한 방법에 대해 연구 노력한 결과, 두충 추출물이 근원성 분화의 촉진, 근관 위축의 감소, 염증반응의 억제효과가 있음을 확인하고 이에 기초 하여 본 발명을 완성하게 되었다.
As a result of efforts to prevent or treat muscle wasting-related diseases, the inventors of the present invention have found that the mulberry extract has an effect of promoting root differentiation, reducing root canal atrophy, and inhibiting an inflammatory reaction, It was completed.
이하 본 발명을 상세히 설명한다.
Hereinafter, the present invention will be described in detail.
본 발명은 두충(Eucommiae cortex) 추출물을 유효성분으로 포함하는, 근육소모 관련 질환의 예방 또는 치료용 약학적 조성물을 제공한다.The present invention provides a pharmaceutical composition for preventing or treating muscle wasting-related diseases, comprising an extract of Eucommiae cortex as an active ingredient.
본 발명에서 사용되는 용어, "예방"이란 본 발명에 따른 약학적 조성물의 투여에 의해 근육 소모 관련 질환을 억제시키거나 발병을 지연시키는 모든 행위를 의미한다.As used herein, the term "prophylactic " means any action that inhibits or slows the onset of muscle wasting-related diseases by administration of the pharmaceutical composition according to the present invention.
본 발명에서 사용되는 용어, "치료"란 본 발명에 따른 약학적 조성물의 투여에 의해 근육 소모 관련 질환에 대한 증세가 호전되거나 이롭게 변경되는 모든 행위를 의미한다.The term "treatment" as used in the present invention means all the actions for improving or alleviating symptoms of muscle wasting-related diseases by administration of the pharmaceutical composition according to the present invention.
근육 소모 관련 질환은 만성적인 신경병성(neurological), 유전성, 또는 감염성 병리상태(pathology), 질병(disease), 또는 증상(condition)과 관련이 있다. Muscle wasting-related disorders are associated with chronic neurological, hereditary, or infectious pathology, disease, or condition.
근육 소모 관련 질환의 예로는, 이로 제한되는 것은 아니나, 근이영양증(Muscle Dystrophy), 근육 위축증(Muscle Atropy), 카켁시아(Cachexia), 영양실조, 나병, 당뇨병, 신장병, 만성 폐쇄성 폐병(Chronic Ostructive Pulmonary Disease; COPD), 암, 말기 신부전, 사르코페니아(Sarcopenia), 기종(Emphysema), 골연화증(Osteomalacia), HIV감염 및 심근증(Cardiomyopathy)으로 이루어진 군으로부터 선택될 수 있다.Examples of muscle wasting related diseases include, but are not limited to, Muscle Dystrophy, Muscle Atropy, Cachexia, malnutrition, leprosy, diabetes, nephropathy, Chronic Ostructive Pulmonary Disease ; COPD), cancer, end-stage renal failure, Sarcopenia, Emphysema, osteomalacia, HIV infection and cardiomyopathy.
보다 구체적으로, 상기 근이영양증은 뒤센느 근이영양증(Duchenne Muscular Dystrophy) 또는 근육 긴장성 이영양증(Myotonic Dystrophy)일 수 있고, 상기 근육 위축증은 포스트 폴리오 근 위축증(Post-polio Muscle Atropy)일 수 있으며, 상기 카켁시아는 심장 카켁시아(Cachexia), AIDS 카켁시아 또는 카켁시아일 수 있으나, 이것으로 제한되는 것은 아니다. More specifically, the muscular dystrophy may be Duchenne Muscular Dystrophy or Myotonic Dystrophy, and the muscular atrophy may be Post-polio Muscle Atropy, Heart Cachexia, AIDS cachexia, or cachexia.
또한, 기타 환경 및 조건도 근육 소모 관련 질환과 관련이 있으며, 이를 유발할 수 있는데, 이러한 것에는 만성적인 하부요통(chronic lower back pain), 고령(advanced age), 중추신경계 손상(CNS damage), 말초 신경 손상, 척수 손상, 화학적 손상, 화상, 다리 고정시 발생하는 불사용 탈조건화(disuse deconditioning), 질환 또는 상해로 인한 장기 입원, 및 알코올 중독등이 포함될 수 있다. Other conditions and conditions may also be associated with and associated with muscle wasting related diseases including chronic lower back pain, advanced age, central nervous system damage (CNS damage), peripheral Nasal damage, spinal cord injury, chemical injury, burns, disuse deconditioning that occurs during leg fixation, long-term hospitalization due to disease or injury, and alcoholism.
본 발명에서 두충 추출물은 천연물로부터 추출물을 추출하는 당업계에 공지된 통상적인 방법에 따라, 즉, 통상적인 온도, 압력의 조건 하에서 통상적인 용매를 사용하여 추출할 수 있다. 예컨대, 본 발명에서, 두충 추출물은 물, 탄소수 1-4개의 무수 또는 함수 저급 알코올, 아세톤, 에틸아세테이트, 부틸아세테이트 및 1,3-부틸렌 글리콜로 구성된 군으로부터 선택되는 용매를 사용하여 추출할 수 있다. 또한, 두충으로부터 추출물을 추출하는 방법은 열수 추출, 냉침 추출, 환류 추출, 초음파 추출 등의 다양한 방법을 통하여 추출할 수 있지만, 이것으로 제한되는 것은 아니다(실시예 1).
In the present invention, the mulberry extract can be extracted by a conventional method known in the art for extracting an extract from a natural product, that is, using a conventional solvent under the conditions of ordinary temperature and pressure. For example, in the present invention, the mulberry extract can be extracted using a solvent selected from the group consisting of water, an anhydrous or a lower alcohol having 1 to 4 carbon atoms, acetone, ethyl acetate, butyl acetate and 1,3-butylene glycol have. In addition, the method for extracting the extract from mites can be extracted through various methods such as hot water extraction, cold extraction, reflux extraction, and ultrasonic extraction, but the present invention is not limited thereto (Example 1).
본 발명의 약학적 조성물은 근원성 분화를 촉진할 수 있다.The pharmaceutical composition of the present invention can promote source differentiation.
상기 약학적 조성물은 MHC, HES-6 및 MEF-2와 같은 근육 특이성 유전자의 발현을 증가시킬 수 있으며, MyoD, Myogenin 및 MRF-4와 같은 근육조절인자의 발현을 증가시킬 수 있다. 또한, IGF-1과 같은 근육 비특이적 전사인자의 발현을 증가시킬 수 있다. 근육세포 분화는 MyoD, Myf5, 미오게닌(myogenin), MRF4와 같은 다양한 근육 조절 인자(muscle regulatory factors; MRFs)에 의해 조절된다. MyoD는 근육-특이 유전자의 발현을 개시하게 하고 중간엽줄기세포가 근육세포 계열로 분화하는 것을 유도한다. myogenin 발현의 유도는 MyoD 활성에 의해 조절되고, 최종 분화와 MHC(myosin heavy chain), MCK(muscle creatine kinase)와 같은 근육 특이 유전자의 유도에 중요한 요소이다. IGF-1은 고농도에서 혈장에서 순화되고 대부분의 조직에서 검출되는 7.5-kD의 폴리펩타이드이며, 인슐린-유사 성장 인자로서 세포 분화 및 세포증식과 같은 여러 조직의 성장 및 발달에 중요한 역할을 하고 전체 성장을 조절한다. IGF-1에 자극된 세포 증식 또는 분화를 유도하는 형질도입 경로는 IGF-1 수용체와의 결합이며, IGF-1 수용체(IGF-1R)는 2개의 하위단위로 알파 서브유닛(전체적으로 세포외이고 리간드 결합작용을 하는 130 내지 135-kD의 단백질) 및 베타 서브유닛(막간 및 세포질 도메인을 갖은 95-kD 의 막간 단백질)으로 구성되어 있다. 본 발명의 실시예에 따르면, 두충 추출물의 근원세포 및 근관에 대한 세포 독성여부를 확인하였으며(실시예 2), 근원세포의 분화 촉진효과를 확인하였다(실시예 3).The pharmaceutical composition may increase the expression of muscle specific genes such as MHC, HES-6 and MEF-2 and may increase the expression of muscle regulators such as MyoD, Myogenin and MRF-4. It may also increase the expression of nonspecific transcription factors such as IGF-1. Muscle cell differentiation is regulated by various muscle regulatory factors (MRFs) such as MyoD, Myf5, myogenin, and MRF4. MyoD induces the expression of muscle-specific genes and induces mesenchymal stem cells to differentiate into muscle cell lines. Induction of myogenin expression is regulated by MyoD activity and is an important factor in the final differentiation and induction of muscle specific genes such as MHC (myosin heavy chain) and MCK (muscle creatine kinase). IGF-1 is a 7.5-kD polypeptide that is purified in plasma at high concentrations and detected in most tissues. It plays an important role in the growth and development of various tissues such as cell differentiation and cell proliferation as an insulin-like growth factor, . The IGF-1 receptor (IGF-1R) is composed of two subunits, the alpha subunit (which is totally extracellular and the ligand is the extracellular domain of the IGF-1 receptor) And a beta subunit (a 95-kD interstitial protein with intercellular and cytoplasmic domains). According to the embodiment of the present invention, it was confirmed that the mulberry extract was cytotoxic to root cells and root canal (Example 2), and the promoting effect of differentiation of root cells was confirmed (Example 3).
본 발명의 약학적 조성물은 근관 위축을 감소시킬 수 있다. The pharmaceutical composition of the present invention can reduce root canal atrophy.
위축된 근관은 근관의 수가 감소할 뿐 아니라, 근관의 직경의 감소가 관찰된다. 또한, 근관의 위축에 의해서 CK(muscle creatine kinase)의 활성이 감소하며, Myosin heavy chain(MHC), Troponin-T와 같은 골격근 특이 단백질을 발현이 저하될 수 있다. 상기 약학적 조성물은 근육 특이성 Ubiquitin-Ligase인 Atrogin-1/MAFbx의 발현을 감소시킬 수 있다. Atrogin-1 유전자의 발현은 근육통, 근육세포 손상, 나아가 횡문근융해의 근육 독성을 일으키며, PGC-1α전사인사 활성은 Atrogin-1 유전자의 발현에 연관성이 있다. 본 발명의 실시예에 따르면, 두충 추출물의 근관세포 위축(myotube atrophy) 감소효과를 확인하였다(실시예 4).Atrophied root canal not only reduces the number of root canals, but also decreases the diameter of root canals. In addition, activity of CK (muscle creatine kinase) is decreased by cancellous atrophy, Myosin heavy chain (MHC), and Troponin-T. The pharmaceutical composition may reduce the expression of Atrogin-1 / MAFbx, a muscle-specific Ubiquitin-Ligase. Expression of the Atrogin-1 gene causes myotoxicity of myalgia, muscle cell damage and further rhabdomyolysis, and the PGC-1α transcriptional activity is related to the expression of the Atrogin-1 gene. According to the embodiment of the present invention, the effect of reducing the myotube atrophy of the mulberry extract was confirmed (Example 4).
본 발명의 약학적 조성물은 염증반응을 억제할 수 있다. The pharmaceutical composition of the present invention can inhibit the inflammatory reaction.
근원세포로 불리는 근육조직에서 발견되는 미성숙 세포는 새로운 근관을 형성하기 위해서 길게 늘어진 배열되어 있거나 융합된 상태로 존재하며, 이는 muscle regulatory Factor(MRF)/insuline-like growth factor(IGF)에 의하여 조절된다, MRF/IGF는 염증성 cytokine에 의하여 하향 조절되며, 이에 따라, 근원세포의 분화를 늦추며, 융합단계를 지연시킨다. 또한, 염증은 ubiquitin-proteasome system에 의해서 근육감소증의 발생을 증가시킬 수 있으며, Ubiquitin-proteasome proteolytic pathway의 활성에 의하여 급격한 골격근 단백질의 분해가 일어난다. 본 발명의 실시예에 따르면, 두충추출물의 염증반응 감소효과를 확인하였다(실시예 5).Immature cells found in muscle tissue, called myoblasts, are elongated or fused to form a new root canal, which is regulated by muscle regulatory factor (MRF) / insulin-like growth factor (IGF) , MRF / IGF is downregulated by inflammatory cytokines, thereby slowing the differentiation of myocytes and delaying the fusion phase. In addition, inflammation can increase the incidence of myopenia by the ubiquitin-proteasome system, and the activity of the ubiquitin-proteasome proteolytic pathway leads to rapid degradation of the skeletal muscle protein. According to the example of the present invention, the anti-inflammatory effect of the mulberry extract was confirmed (Example 5).
본 발명의 약학적 조성물은 NF-κB기전을 억제시킬 수 있다.The pharmaceutical composition of the present invention can inhibit the NF-κB mechanism.
NF-κB는 면역글로불린 κL사슬유전자의 인트론증폭자에 결합하는 전사인자이며, 결합하는 배열은 κB모티프로서, 10염기쌍(GGGACTTTCC)으로 구성된다. NF-κB는 B세포에 특이적이며, B세포 분화에 따라 발현하는 세포 특이적 유전자의 발현을 제어할 수 있다. 또한, NF-κB는 면역글로불린유전자 외에 인터류킨2, 인터류킨2 수용체α등 여러 가지 유전자의 전사조절영역에서도 결합하고, 이들 유전자의 전사를 활성화한다. 이 밖에도 비-B세포(Non-B cell)에서도 바이러스, 세균, 사이토카인, 지질다당(LPS)와 같은 세포외 자극에 의해서 유도될 수도 있다. 본 발명의 실시예에 따르면, NF-κB기전 활성의 억제를 확인하였다(실시예 6).NF-κB is a transcription factor that binds to the intron amplicon of the immunoglobulin κL chain gene, and the binding sequence is κB motif, consisting of 10 base pairs (GGGACTTTCC). NF-κB is specific for B cells and can control the expression of cell-specific genes expressed by B cell differentiation. In addition, NF-κB binds to the transcriptional regulatory regions of various genes such as
본 발명에 따른 약학적 조성물은 유효성분 이외에 약제학적으로 허용되는 담체를 포함할 수 있다. 이때, 약제학적으로 허용되는 담체는 제제시에 통상적으로 이용되는 것으로서, 락토스, 덱스트로스, 수크로스, 솔비톨, 만니톨, 전분, 아카시아고무, 인산 칼슘, 알기네이트, 젤라틴, 규산 칼슘, 미세 결정성 셀룰로스, 폴리비닐피로리돈, 셀룰로스, 물, 시럽, 메틸 셀룰로스, 메틸히드록시벤조에이트, 프로필 히드록시벤조에이트, 활석, 스테아르산 마그네슘 및 미네랄 오일등을 포함하나, 이에 한정되는 것은 아니다. 또한, 상기성분들 이외에 윤활제, 습윤제, 감미제, 향미제, 유화제, 현탁제, 보존제 등을 추가로 포함할 수 있다. The pharmaceutical composition according to the present invention may contain, in addition to the active ingredient, a pharmaceutically acceptable carrier. Herein, the pharmaceutically acceptable carriers are those conventionally used in the present invention and include lactose, dextrose, sucrose, sorbitol, mannitol, starch, acacia rubber, calcium phosphate, alginate, gelatin, calcium silicate, microcrystalline cellulose But are not limited to, polyvinylpyrrolidone, cellulose, water, syrup, methylcellulose, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil. Further, in addition to the above components, a lubricant, a wetting agent, a sweetener, a flavoring agent, an emulsifying agent, a suspending agent, a preservative, and the like may be further included.
본 발명의 약제학적 조성물은 목적하는 방법에 따라 경구 투여하거나 비경구투여(예를 들어, 정맥 내, 피하, 복강 내 또는 국소에 적용)할 수 있으며, 투여량은 환자의 상태 및 체중, 질병의 정도, 약물형태, 투여경로 및 시간에 따라 다르지만, 당업자에 의해 적절하게 선택될 수 있다. The pharmaceutical composition of the present invention may be administered orally or parenterally (for example, intravenously, subcutaneously, intraperitoneally or topically) depending on the intended method, and the dose may vary depending on the condition and weight of the patient, The mode of administration, the route of administration, and the time, but may be appropriately selected by those skilled in the art.
본 발명의 약제학적 조성물은 약학적으로 유효한 양으로 투여한다. 본 발명에 있어서 "약학적으로 유효한 양"은 의학적 치료에 적용 가능한 합리적인 수혜/위험 비율로 질환을 치료하기에 충분한 양을 의미하며, 유효용량 수준은 환자의 질환의 종류, 중증도, 약물의 활성, 약물에 대한 민감도, 투여 시간, 투여 경로 및 배출비율, 치료기간, 동시 사용되는 약물을 포함한 요소 및 기타 의학 분야에 잘 알려진 요소에 따라 결정될 수 있다. 본 발명에 다른 약학적 조성물은 개별 치료제로 투여하거나 다른 치료제와 병용하여 투여될 수 있고 종래의 치료제와는 순차적 또는 동시에 투여될 수 있으며, 단일 또는 다중 투여될 수 있다. 상기한 요소들을 모두 고려하여 부작용없이 최소한의 양으로 최대 효과를 얻을 수 있는 양을 투여하는 것이 중요하며, 이는 당업자에 의해 용이하게 결정될 수 있다. 구체적으로 본 발명의 약제학적 조성물의 유효량은 환자의 연령, 성별, 상태, 체중, 체내에 활성 성분의 흡수도, 불활성율 및 배설속도, 질병종류, 병용되는 약물에 따라 달라질 수 있으며, 일반적으로는 체중 1 kg 당 0.001 내지 150 mg, 바람직하게는 0.01 내지 100mg을 매일 또는 격일 투여하거나, 1일 1회 내지 3회로 나누어 투여할 수 있다. 그러나 투여 경로, 비만의 중증도, 성별, 체중, 연령 등에 따라서 증감될 수 있으므로 상기 투여량이 어떠한 방법으로도 본 발명의 범위를 한정하는 것은 아니다.The pharmaceutical composition of the present invention is administered in a pharmaceutically effective amount. In the present invention, the term "pharmaceutically effective amount" means an amount sufficient to treat a disease at a reasonable benefit / risk ratio applicable to medical treatment, and the effective dose level will depend on the type of disease, severity, The sensitivity to the drug, the time of administration, the route of administration and the rate of release, the duration of the treatment, factors including co-administered drugs, and other factors well known in the medical arts. The pharmaceutical composition according to the present invention may be administered as an individual therapeutic agent or in combination with other therapeutic agents, sequentially or concurrently with conventional therapeutic agents, and may be administered singly or in multiple doses. It is important to take into account all of the above factors and to administer the amount in which the maximum effect can be obtained in a minimal amount without side effects, which can be easily determined by those skilled in the art. Specifically, the effective amount of the pharmaceutical composition of the present invention may vary depending on the age, sex, condition, body weight, absorbency, inactivation rate and excretion rate of the active ingredient in the body, type of disease, It is possible to administer 0.001 to 150 mg, preferably 0.01 to 100 mg per kg body weight daily or every other day, or one or three times a day. However, the dosage may be varied depending on the route of administration, the severity of obesity, sex, weight, age, etc. Therefore, the dosage is not limited to the scope of the present invention by any means.
본 발명의 다른 양태로서, 본 발명은 상기 약학적 조성물을 개체에 투여하는 단계를 포함하는 근육 소모 질환 치료방법을 제공한다. 본 발명에서 "개체"란 질병의 치료를 필요로 하는 대상을 의미하고, 보다 구체적으로는, 인간 또는 비-인간인 영장류, 생쥐(mouse), 개, 고양이, 말 및 소 등의 포유류를 의미한다.
In another aspect of the present invention, the present invention provides a method for treating muscle wasting disease comprising administering the pharmaceutical composition to a subject. The term " individual "as used herein refers to a subject in need of treatment for a disease, and more specifically refers to a mammal such as a human or non-human primate, mouse, dog, cat, horse and cattle .
본 발명은 두충(Eucommiae cortex)추출물을 유효성분으로 포함하는, 근육 소모 관련 질환의 예방 또는 개선용 건강기능식품 조성물을 제공한다.The present invention provides a health functional food composition for preventing or ameliorating a muscle wasting-related disease, comprising an extract of Eucommiae cortex as an active ingredient.
본 발명에서 사용되는 용어, "개선"이란 치료되는 상태와 관련된 파라미터, 예를 들면 증상의 정도를 적어도 감소시키는 모든 행위를 의미한다. 이때 상기 기능성 식품 조성물은 근육 소모 관련 질환의 예방 또는 개선을 위하여 해당 질환의 발병 단계 이전 또는 발병 후, 치료를 위한 약제와 동시에 또는 별개로서 사용될 수 있다. As used herein, the term "improvement" means all actions that at least reduce the degree of symptom associated with the condition being treated. Herein, the functional food composition may be used either simultaneously with or separately from the agent for treatment before or after the onset of the disease to prevent or ameliorate the muscle wasting-related diseases.
본 발명에서 사용되는 용어, "건강기능 식품 조성물"은 담체, 희석제, 부형제 및 첨가제 중 하나 이상을 포함하여 정제, 환제, 산제, 과립제, 분말제, 켑슐제 및 액제 제형으로 이루어진 군에서 선택된 하나로 제형된 것을 특징으로 한다. 본 발명의 추출물에 첨가할 수 있는 식품으로는, 각종 식품류, 분말, 과립, 정제, 캡슐, 시럽제, 음료, 껌, 차, 비타민 복합제, 건강 기능성 식품류 등이 있다. 상기 본 발명에 더 포함될 수 있는 첨가제로는, 천연 탄수 화물, 향미제, 영양제, 비타민, 광물(전해질), 풍미제(합성 풍미제, 천연 풍미제 등), 착색제, 충진제, 팩트산 및 그의 염, 일간산 및 그의 염, 유기산, 보호성 콜오이드 증점제, PH조절제, 안정화제, 방부제, 산화 방지제, 글리세린, 알콜, 탄산화제 및 과육으로 이루어진 구으로부터 선택된 1종 이상의 성분을 사용할 수 있다. 상술한 천연 탄수화물의 예는 모노사카라이드, 예를 들어, 포도당, 과당등; 디사카라이드, 예를 들어 말토스, 슈크로스 등; 및 폴리사카라이드, 예를 들어 덱스트린, 시클로덱스트린 등과 같은 통상적인 당, 및 자일리톨, 소르비톨, 에리트리톨 등의 당알콜이다. 상기 향미제로서 천연 향미제(타우마틴, 스테비아추출물(예를 들어 레바우디오시드 A, 글리시르히진 등) 및 합성 향미제(사카린, 아스파르탐 등)를 유리하게 사용할 수 있다. 상기 외에 본 발명에 따른 조성물은 여러 가지 영양제, 비타민, 광물(전해질), 합성 풍미제 및 천연 풍미제 등의 풍미제, 착색제 및 중진제, 팩트산 및 그의 염, 알긴산 및 그의 염, 유기산, 보호성 콜로이드 증점제, PH 조절제, 안정화제, 방부제, 글리세린, 알콜, 탄산 음료에 사용되는 탄산화제 등을 함유할 수 있다. 그밖에 본 발명에 다른 조성물은 천영 과일 주스 및 야채 음료의 제조를 위한 과육을 함유할 수 있다. 이러한 성분은 독립적으로 또는 조합하여 사용할 수 있다. 상기 담체, 부형제, 희석제 및 첨가제의 구체적인 예로는 이에 한정하는 것은 아니나, 락토스, 덱스트로즈, 슈크로즈, 솔비톨, 만니톨, 에리스리톨, 전분, 아카시아 고무, 인산칼슘, 알지네이트, 젤라틴, 칼슘 포스페이트, 칼슘 실리케이트, 미세결정성 셀룰로즈, 폴리비닐키롤리돈, 셀룰로즈, 폴리비닐피로리돈, 메틸셀룰로즈, 물, 설탕시럽, 메틸 하이드록시 벤조에이트, 프로필하이드록시 벤조에이트, 활석, 스테아트산 마그네슘 및 미네랄 오일로 이루어진 그룹으로부터 선택된 1종 이상이 사용되는 것이 바람직하다.
The term "health functional food composition" used in the present invention includes at least one of carriers, diluents, excipients and additives, and is formulated into one selected from the group consisting of tablets, pills, powders, granules, powders, . Examples of foods that can be added to the extract of the present invention include various foods, powders, granules, tablets, capsules, syrups, drinks, gums, tea, vitamin complexes, and health functional foods. Examples of the additive that can be further included in the present invention include natural carbohydrates, flavors, nutrients, vitamins, minerals (electrolytes), flavors (synthetic flavors, natural flavors and the like), colorants, fillers, , At least one component selected from the group consisting of an inorganic acid and a salt thereof, an organic acid, a protective colloid thickening agent, a pH adjusting agent, a stabilizer, a preservative, an antioxidant, glycerin, an alcohol, a carbonating agent and a pulp. Examples of the above-mentioned natural carbohydrates include monosaccharides such as glucose, fructose and the like; Disaccharides such as maltose, sucrose and the like; And polysaccharides, for example, conventional sugars such as dextrin, cyclodextrin and the like, and sugar alcohols such as xylitol, sorbitol and erythritol. As the above-mentioned flavors, natural flavors (tautatin, stevia extract (for example, rebaudioside A and glycyrrhizin) and synthetic flavors (saccharin, aspartame, etc.) can be advantageously used. The composition according to the present invention can be used in various forms such as flavorings such as various nutrients, vitamins, minerals (electrolytes), synthetic flavors and natural flavors, colorants and heavies, factic acid and its salts, alginic acid and its salts, , A pH adjusting agent, a stabilizer, a preservative, a carbonating agent used in glycerin, an alcohol, a carbonated beverage, etc. In addition, the composition according to the present invention may contain flesh for the preparation of fruit juice and vegetable drinks . These ingredients may be used independently or in combination. Specific examples of the carrier, excipient, diluent and additives include, but are not limited to, lactose, dextrose, Cellulose, calcium carbonate, alginate, gelatin, calcium phosphate, calcium silicate, microcrystalline cellulose, polyvinylquilolidone, cellulose, polyvinylpyrrolidone, methyl cellulose, water, sugar, starch, starch, It is preferable to use at least one selected from the group consisting of syrup, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil.
이하, 본 발명의 이해를 돕기 위하여 바람직한 실시예를 제시한다. 그러나 하기의 실시예는 본 발명을 보다 쉽게 이해하기 위하여 제공되는 것일 뿐, 하기 실시예에 의해 본 발명의 내용이 한정되는 것은 아니다.
Hereinafter, preferred embodiments of the present invention will be described in order to facilitate understanding of the present invention. However, the following examples are provided only for the purpose of easier understanding of the present invention, and the present invention is not limited by the following examples.
실시예 1. 두충추출물의 제조Example 1. Preparation of mulberry extract
두충 20 g에 200 ml의 증류수를 가하여 3시간 동안 가열하여 추출하였다. 추출된 용액을 0.2 mm 여과지(Whatman International, Maidstone, UK) 에서 여과한 후, rotary evaporator (VV2000, Heidolph, Walpersdorfer, Germany)를 이용하여 감압농축한 후, 동결건조하여 분말을 얻었다. 분말은 실험직전 증류수나 배지에 희석하여 0.2 μm syringe filter(Thermo Fisher Scientific, Roskilde, Denmark)에 여과하여 사용하였다.
200 g of distilled water was added to 20 g of mugwort, and the mixture was extracted by heating for 3 hours. The extracted solution was filtered through a 0.2 mm filter paper (Whatman International, Maidstone, UK), concentrated under reduced pressure using a rotary evaporator (VV2000, Heidolph, Walpersdorfer, Germany) and lyophilized to obtain a powder. The powder was diluted in distilled water or medium immediately before the experiment and filtered through a 0.2 μm syringe filter (Thermo Fisher Scientific, Roskilde, Denmark).
실시예 2. EC의 세포독성 확인Example 2. Cytotoxicity of EC
분화되지 않은 근원세포와 분화된 근관에 대한 EC(Eucommiae cortex) 추출물의 세포독성을 조사하기 위하여 쥐의 C2C12 골격근 cell line과 TNF-α/IFN-γ 혼합제를 이용하여 근원세포와 근관의 생존능력을 측정하였다. 근원세포와 근관을 24시간 동안 TNF-α(10ng/ml) 및 IFN-γ(100IU/ml)와 EC(0, 0.1, 0.5, 1.0 mg/ml)로 처리 하였으며, 이 후 근원세포와 근관의 생존능력을 확인하기 위하여, XTT assay를 수행하였으며, 그 결과를 도 1에 나타내었다.To investigate the cytotoxicity of EC (Eucommiae cortex) extracts on differentiated root cells and differentiated root canals, the viability of myocytes and root canals was assessed using the C2C12 skeletal muscle cell line and TNF-α / IFN-γ mixture in rats Respectively. The myocytes and root canal were treated with TNF-α (10 ng / ml), IFN-γ (100 IU / ml) and EC (0, 0.1, 0.5 and 1.0 mg / ml) for 24 h, To confirm viability, XTT assay was performed and the results are shown in FIG.
도 1에 나타난 바와 같이 근관의 생존능력은 EC의 투여용량과 관계없이 80%이상이었으며, 근원세포의 생존능력은 EC 1.0 mg/ml 처리한 군에서 생존능력 감소를 확인하였다.
As shown in Fig. 1, viability of root canals was more than 80% regardless of the dose of EC, and the viability of myoblasts was EC 1.0 mg / ml The survival rate was decreased in the treated group.
실시예 3. EC가 근원성 분화에 미치는 영향Example 3. Effect of EC on myogenic differentiation
배양된 C2C12 근원세포(myoblast)는 80% 이상의 confluence에 도달하였으며, 이 후 differentiation media로 교체하였다. 배지는 매일 교체해주었으며, TNF-α(10ng/ml) 및 IFN-γ(100IU/ml)와 EC(0, 0.1, 0.5mg/ml)를 보충해 주었다.
Cultured C2C12 myoblasts reached confluence> 80% and were then replaced with differentiation media. The medium was replaced daily and supplemented with TNF-α (10 ng / ml), IFN-γ (100 IU / ml) and EC (0, 0.1, 0.5 mg / ml).
가. end. 근관Root canal 형성 평가. Formation evaluation.
근관 형성에 대한 EC의 효과를 확인하기 위하여, 분화 96시간 후, Contrast microscopy의 영상을 관찰하였으며, 그 결과는 도 2에 나타내었다.In order to confirm the effect of EC on root canal formation, images of contrast microscopy were observed after 96 hours of differentiation, and the results are shown in Fig.
도 2에 나타난 바와 같이 TNF-α/IFN-γ에 노출된 근관은 근관형성의 감소를 확인하였으며, 분화 중인 근원세포에 EC(0.5 and 1.0 mg/ml)를 추가로 처리한 경우, 근관의 형성이 발달됨을 확인하였다.
As shown in Fig. 2, the root canals exposed to TNF-α / IFN-γ showed a decrease in root canal formation. When ECs (0.5 and 1.0 mg / ml) .
나. I. CKCK (( musclemuscle creatinecreatine kinasekinase )의 활성 평가) ≪ / RTI &
분화 96시간 후, 진단키트를 이용하여, 성숙한 골격근에서 발현되는 효소인 muscle creatine kinase의 활성을 평가 하였으며, 그 결과는 도 3에 나타내었다.After 96 hours of differentiation, the activity of muscle creatine kinase, an enzyme expressed in mature skeletal muscle, was evaluated using a diagnostic kit. The results are shown in FIG.
도 3에 나타난 바와 같이 TNF-α/IFN-γ에 노출된 경우, CK 활성의 급격한 감소를 확인하였으며, EC(0.5 and 1.0 mg/ml)를 추가로 처리한 경우, CK 활성의 증가를 확인하였다.
As shown in FIG. 3, when the cells were exposed to TNF-α / IFN-γ, a sharp decrease in CK activity was observed, and an increase in CK activity was observed when EC (0.5 and 1.0 mg / ml) .
다. skeletal muscle specfic gene의 발현 평가All. Expression evaluation of skeletal muscle specfic gene
골격근 특이적 유전자인 MHC, HES-6, N-CAD, MEF-2a 및 MEF-2D의 발현을 측정하기 위하여 RT-PCR을 수행하였다. 그 결과는 도 4에 나타내었다.RT-PCR was performed to measure the expression of the skeletal muscle specific genes MHC, HES-6, N-CAD, MEF-2a and MEF-2D. The results are shown in Fig.
도 4에 나타난 바와 같이 TNF-α/IFN-γ에 노출된 경우, 유전자의 발현이 감소된 반면, EC(0.5 and 1.0 mg/ml)를 추가로 처리한 경우, 유전자의 발현이 증가 하였다. 또한, CK활성의 증가는 MHC, HES-6, MEF-2등과 같은 근육 특이성 유전자의 발현 증가와 일치하였다.
As shown in FIG. 4, expression of the gene was decreased when exposed to TNF-α / IFN-γ, whereas expression of the gene was increased when EC (0.5 and 1.0 mg / ml) was further treated. In addition, the increase in CK activity was consistent with increased expression of muscle specific genes such as MHC, HES-6, and MEF-2.
라. MRF 와 IGF-1 family mRNA의 발현 평가la. Expression of MRF and IGF-1 family mRNA
분화 24, 48, 72시간 후, myoD, myigenin, MRF4, myf5, IGF-1, IGF-1R의 발현을 측정하기 위하여, RT-PCR을 수행하였으며, 그 결과는 도 5 및 도 6에 나타내었다.RT-PCR was performed to measure the expression of myoD, myigenin, MRF4, myf5, IGF-1 and IGF-1R at 24, 48 and 72 hours after the differentiation. The results are shown in FIG. 5 and FIG.
도 5 및 도 6에 나타난 바와 같이, TNF-α/IFN-γ에 노출된 경우, 분화 72시간 동안 MyoD, Myogenin 및 MRF-4와 같은 근원성 조절인자의 발현을 감소시키는 반면, EC(0.5 and 1.0 mg/ml)를 추가로 처리한 경우, 상대적으로 유전자 발현이 증가하였다. 또한, TNF-α/IFN-γ에 노출된 경우, IGF-1의 발현이 분화 후 72 시간 동안 거의 관찰되지 않았지만, EC(0.5 and 1.0 mg/ml)를 추가로 처리한 경우, 분화 72시간 후, IGF-1의 발현이 관찰되었다.
As shown in FIG. 5 and FIG. 6, when exposed to TNF-α / IFN-γ, the expression of myogenic factors such as MyoD, Myogenin and MRF-4 is reduced during 72 hours of differentiation whereas EC 1.0 mg / ml), the relative gene expression was increased. In addition, when exposed to TNF-α / IFN-γ, the expression of IGF-1 was scarcely observed for 72 hours after the differentiation. However, when EC (0.5 and 1.0 mg / ml) , And IGF-1 expression was observed.
실시예 4. EC가 근관 위축에 미치는 영향Example 4. Effect of EC on canalicular atrophy
배양된 C2C12 근원세포(myoblast)는 80% 이상의 confluence에 도달하였으며, 이 후 differentiation media로 교체하였다. 배지는 매일 교체 해주었으며, TNF-α(10ng/ml) 및 IFN-γ(100IU/ml)와 EC(0, 0.1, 0.5, 1.0 mg/ml)를 보충해 주었다.
Cultured C2C12 myoblasts reached confluence> 80% and were then replaced with differentiation media. The medium was replaced daily and supplemented with TNF-α (10 ng / ml), IFN-γ (100 IU / ml) and EC (0, 0.1, 0.5, 1.0 mg / ml).
가. 근관 위축 평가end. Assessment of root canal atrophy
근관 위축에 대한 EC의 효과를 확인하기 위하여, 분화 72시간 후, Contrast microscopy의 영상을 관찰하였으며, 그 결과는 도 7에 나타내었다.In order to confirm the effect of EC on canalicular atrophy, 72 hours after the differentiation, images of the contrast microscopy were observed, and the results are shown in FIG.
도 7에 나타난 바와 같이, TNF-α/IFN-γ에 노출된 경우, 근관 직경의 현저한 감소를 확인하였으며, EC(0.1, 0.5 and 1.0 mg/ml)를 추가로 처리한 경우, 근관의 직경의 증가를 확인하였다.
As shown in FIG. 7, significant reduction in root canal diameter was observed when exposed to TNF-α / IFN-γ, and when further treatment of EC (0.1, 0.5 and 1.0 mg / ml) Respectively.
나.I. CK(muscle creatine kinase)의 활성 평가Activity evaluation of CK (muscle creatine kinase)
진단키트를 이용하여, 성숙한 골격근에서 발현되는 효소인 muscle creatine kinase의 활성을 평가 하였으며 그 결과는 도 8에 나타내었다.The activity of muscle creatine kinase, an enzyme expressed in mature skeletal muscle, was evaluated using a diagnostic kit. The results are shown in FIG.
도 8에 나타난 바와 같이, TNF-α/IFN-γ에 노출된 경우, CK 활성의 급격한 감소를 확인하였으며, EC(0.5 and 1.0 mg/ml)를 추가로 처리한 경우, CK 활성의 증가를 확인하였다.
As shown in FIG. 8, when the cells were exposed to TNF-α / IFN-γ, a sharp decrease in CK activity was confirmed, and an increase in CK activity was confirmed when EC (0.5 and 1.0 mg / ml) Respectively.
다. skeletal muscle specfic protein의 농도 평가All. Evaluation of concentration of skeletal muscle specfic protein
골격근 특이 단백질인 Myosin heavy chain(MHC), Troponin-T의 농도를 검출하기 위해서 Western Blot을 수행하였으며, 그 결과는 도 9에 나타내었다.Western blot was performed to detect the concentration of Myosin heavy chain (MHC) and Troponin-T, which are skeletal muscle specific proteins, and the results are shown in FIG.
도 9에 나타난 바와 같이, TNF-α/IFN-γ에 노출된 경우, 단백질 농도의 감소를 확인하였으며, EC(0.5 and 1.0 mg/ml)를 추가로 처리한 경우, 단백질의 농도의 증가를 확인하였다.
As shown in FIG. 9, when the cells were exposed to TNF-α / IFN-γ, a decrease in the protein concentration was confirmed. When EC (0.5 and 1.0 mg / ml) was further treated, Respectively.
라. la. ProcachecticProcachectic andand promyogenicpromyogenic factorfactor 의 발현 평가Expression
E3 ubiquitin ligase에 속하는 Atrogin-1/MAFbx, MuRF1의 발현은 염증조건하에서 근육 감소증을 초래하기 때문에, 근관위축에 대한 EC의 저해효과와 상기 신호와 관련성을 확인하고자 하였다. Atrogin-1/MAFbx, MuRF1 mRNA 발현을 평가하기 위해 RT-PCR을 수행하였으며, 그 결과는 도 10에 나타내었다.Because the expression of Atrogin-1 / MAFbx, MuRF1 belonging to the E3 ubiquitin ligase causes muscle hypoxia under inflammatory conditions, the effect of EC on inhibition of cancellous atrophy and the relationship with the signal were examined. RT-PCR was performed to evaluate Atrogin-1 / MAFbx, MuRF1 mRNA expression, and the results are shown in FIG.
도 10에 나타난 바와 같이, TNF-α/IFN-γ에 노출된 경우, Atrogin-1/MAFbx, MuRF1 mRNA 발현의 증가를 확인하였으며, EC(0, 0.1, 0.5, 1.0 mg/ml)를 추가로 처리한 경우, Atrogin-1/MAFbx 발현 감소를 확인하였지만, MuRF1 발현에는 큰 차이가 없었다.
As shown in FIG. 10, the expression of Atrogin-1 / MAFbx and MuRF1 mRNA was increased when exposed to TNF-α / IFN-γ and EC (0, 0.1, 0.5, 1.0 mg / ml) Treated mice showed a decrease in Atrogin-1 / MAFbx expression, but there was no significant difference in MuRF1 expression.
Atrogin-1/MAFbx, MuRF1, myoD, myogenin의 단백질 발현을 평가하기 위해 Western Blot을 수행하였으며, 그 결과는 도 11에 나타내었다.Western blot was performed to evaluate protein expression of Atrogin-1 / MAFbx, MuRF1, myoD, myogenin, and the results are shown in FIG.
도 11에 나타난 바와 같이 EC(0, 0.1, 0.5, 1.0 mg/ml)를 추가로 처리한 경우 Atrogin-1/MAFbx 발현 감소를 확인하였지만, MuRF1 발현에는 큰 차이가 없었으며, myoD, myogenin 발현 증가를 확인하였다.
As shown in FIG. 11, when the ECs (0, 0.1, 0.5, 1.0 mg / ml) were further treated, the expression of Atrogin-1 / MAFbx was decreased, but there was no significant difference in expression of MuRF1 and increased expression of myoD, myogenin Respectively.
실시예 5. EC가 염증반응에 미치는 영향Example 5. Influence of EC on inflammatory reaction
염증반응은 직접적인 이화성 효과 및/또는 근원세포에서 근관으로 분화의 저해를 통하여, 골격근에 부정적으로 영향을 미치며, EC가 분화계속 중 또는 분화 후 염증반응을 저해시킬 수 있는지 여부에 대하여 확인하였다.
The inflammatory response negatively affects the skeletal muscle through direct mitogenic effects and / or inhibition of differentiation into root canals in myoblasts, confirming whether EC can inhibit the inflammatory response during or after differentiation.
가. C2C12 근원세포에서 Pro-inflammatory cytokine의 발현 평가end. Evaluation of pro-inflammatory cytokine expression in C2C12 myocytes
근원세포에 24시간 동안 TNF-α(10ng/ml)와 IFN-γ(100IU/ml)와 EC(0, 0.1, 0.5, 1.0 mg/ml)를 보충해 주었다. catabolic pro-inflammatory mediator인 IL-1β, IL-6, iNOS, COX-2 mRNA 발현을 평가하기 위하여 RT-PCR을 수행하였으며, iNOS, COX-2 단백질 발현을 평가하기 위하여 Western Blot을 수행하였다. 그 결과는 도 12에 나타내었다. TNF-α (10 ng / ml), IFN-γ (100 IU / ml) and EC (0, 0.1, 0.5, and 1.0 mg / ml) were supplemented to the myocardial cells for 24 hours. RT-PCR was performed to evaluate the catabolic pro-inflammatory mediators IL-1β, IL-6, iNOS and COX-2 mRNA expression and Western blot was performed to evaluate iNOS and COX-2 protein expression. The results are shown in Fig.
도 12에 나타난 바와 같이, TNF-α/IFN-γ에 노출된 경우, 발현의 증가를 확인하였으며, EC(0, 0.1, 0.5, 1.0 mg/ml)를 추가로 처리한 경우, 발현의 감소를 확인하였다.
As shown in FIG. 12, when the cells were exposed to TNF-α / IFN-γ, the increase in expression was confirmed, and further treatment of EC (0, 0.1, 0.5, 1.0 mg / ml) Respectively.
나. C2C12 근관세포에서 Pro-inflammatory cytokine의 발현 평가I. Evaluation of pro-inflammatory cytokine expression in C2C12 canalicular cells
근관에 24시간 동안 TNF-α(10ng/ml)와 IFN-γ(100IU/ml)와 EC(0, 0.1, 0.5, 1.0 mg/ml)를 보충해 주었다. catabolic pro-inflammatory mediator인 IL-1β, IL-6, iNOS, COX-2 mRNA 발현을 평가하기 위하여 RT-PCR을 수행하였으며, iNOS, COX-2 단백질 발현을 평가하기 위하여 Western Blot을 수행하였다. 그 결과는 도 13에 나타내었다. The root canal was supplemented with TNF-α (10 ng / ml), IFN-γ (100 IU / ml) and EC (0, 0.1, 0.5, 1.0 mg / ml) for 24 h. RT-PCR was performed to evaluate the catabolic pro-inflammatory mediators IL-1β, IL-6, iNOS and COX-2 mRNA expression and Western blot was performed to evaluate iNOS and COX-2 protein expression. The results are shown in Fig.
도 13에 나타난 바와 같이, TNF-α/IFN-γ에 노출된 경우, 발현의 증가를 확인하였으며, EC(0, 0.1, 0.5, 1.0 mg/ml)를 추가로 처리한 경우, 발현의 감소를 확인하였다.
As shown in Fig. 13, when the cells were exposed to TNF-α / IFN-γ, the expression was increased, and the expression of EC (0, 0.1, 0.5, 1.0 mg / ml) Respectively.
실시예 6. EC가 NF-κB pathway에 미치는 영향Example 6. Effect of EC on NF-κB pathway
cytokine 매개 근육감소증의 근원적인 메카니즘을 조사하기 위해서, NF-κB신호 pathway에 초점을 두어 실험을 하였다.
To investigate the underlying mechanism of cytokine mediated hypoxia, we focused on the NF-κB signal pathway.
가. end. C2C12C2C12 근원세포에서 IκB-α, P-IκB-α, In myoblasts, IκB-α, P-IκB-α, NFNF -κB -KB p65p65 의 발현 평가Expression
근원세포를 1시간 동안 EC(0, 0.1, 0.5, 1.0 mg/ml)로 전 처리를 한 후, TNF-α(10ng/ml) 및 IFN-γ(100IU/ml)로 1시간 동안 처리 하였다. IκB-α, P-IκB-α, NF-κB p65 단백질 발현을 평가하기 위하여 Western Blot을 수행하였다. 그 결과는 도 14에 나타내었다.The myocytes were pretreated with EC (0, 0.1, 0.5, 1.0 mg / ml) for 1 hour and treated with TNF-α (10 ng / ml) and IFN-γ (100 IU / ml) for 1 hour. Western blot analysis was performed to evaluate IκB-α, P-IκB-α, and NF-κB p65 protein expression. The results are shown in Fig.
도 14에 나타난 바와 같이, TNF-α/IFN-γ에 노출된 경우, NF-κB p65는 translocation에 의해 핵내 발현이 증가하며, IκB-α 발현의 감소와 P-IκB-α의 농도의 증가를 확인하였다. EC(0, 0.1, 0.5, 1.0 mg/ml)를 추가로 처리한 경우, NF-κB p65은 세포질내 발현이 증가하며, IκB-α 발현의 증가와 P-IκB-α의 농도의 감소를 확인하였다.
As shown in FIG. 14, when exposed to TNF-α / IFN-γ, NF-κB p65 is increased by translocation in the nucleus and decreases in IκB-α expression and increase in P-IκB- Respectively. NF-κB p65 increased the cytoplasmic expression and increased IκB-α expression and decreased P-IκB-α concentration when EC (0, 0.1, 0.5, 1.0 mg / Respectively.
나. I. C2C12C2C12 근관세포에서In root canal cells IκB-α, P-IκB-α, IκB-α, P-IκB-α, NFNF -κB -KB p65p65 의 발현 평가Expression
근관세포를 1시간 동안 EC(0, 0.1, 0.5, 1.0 mg/ml)로 전 처리를 한 후, TNF-α(10ng/ml)와 IFN-γ(100IU/ml)로 1시간 동안 처리 하였다. IκB-α, P-IκB-α, NF-κB p65 단백질 발현을 평가하기 위하여 Western Blot을 수행하였다. 그 결과는 도 15에 나타내었다.The canaliculus cells were pretreated with EC (0, 0.1, 0.5, 1.0 mg / ml) for 1 hour and then treated with TNF-α (10 ng / ml) and IFN-γ (100 IU / ml) for 1 hour. Western blot analysis was performed to evaluate IκB-α, P-IκB-α, and NF-κB p65 protein expression. The results are shown in Fig.
도 15에 나타난 바와 같이, TNF-α/IFN-γ에 노출된 경우, NF-κB p65은 translocation에 의해 핵내 발현이 증가하며, IκB-α 발현의 감소와 P-IκB-α의 농도의 증가를 확인하였다. EC(0, 0.1, 0.5, 1.0 mg/ml)를 추가로 처리한 경우, NF-κB p65은 세포질내 발현이 증가하며, IκB-α 발현의 증가와 P-IκB-α의 농도의 감소를 확인하였다.
As shown in FIG. 15, when exposed to TNF-α / IFN-γ, NF-κB p65 increases translocation-induced nuclear expression and decreases IκB-α expression and increases P-IκB- Respectively. NF-κB p65 increased the cytoplasmic expression and increased IκB-α expression and decreased P-IκB-α concentration when EC (0, 0.1, 0.5, 1.0 mg / Respectively.
전술한 본 발명의 설명은 예시를 위한 것이며, 본 발명이 속하는 기술분야의 통상의 지식을 가진 자는 본 발명의 기술적 사상이나 필수적인 특징을 변경하지 않고서 다른 구체적인 형태로 쉽게 변형이 가능하다는 것을 이해할 수 있을 것이다. 그러므로 이상에서 기술한 실시예들은 모든 면에서 예시적인 것이며 한정적이 아닌 것으로 이해해야만 한다.It will be understood by those skilled in the art that the foregoing description of the present invention is for illustrative purposes only and that those of ordinary skill in the art can readily understand that various changes and modifications may be made without departing from the spirit or essential characteristics of the present invention. will be. It is therefore to be understood that the above-described embodiments are illustrative in all aspects and not restrictive.
Claims (8)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| KR1020140054193A KR101614205B1 (en) | 2014-05-07 | 2014-05-07 | Pharmaceutical composition comprising extract of Eucommiae coretex for prevention or treatment of muscle wasting disease |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| KR1020140054193A KR101614205B1 (en) | 2014-05-07 | 2014-05-07 | Pharmaceutical composition comprising extract of Eucommiae coretex for prevention or treatment of muscle wasting disease |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| KR20150127910A KR20150127910A (en) | 2015-11-18 |
| KR101614205B1 true KR101614205B1 (en) | 2016-05-02 |
Family
ID=54838611
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR1020140054193A KR101614205B1 (en) | 2014-05-07 | 2014-05-07 | Pharmaceutical composition comprising extract of Eucommiae coretex for prevention or treatment of muscle wasting disease |
Country Status (1)
| Country | Link |
|---|---|
| KR (1) | KR101614205B1 (en) |
Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR101898688B1 (en) * | 2016-07-21 | 2018-09-13 | 경희대학교 산학협력단 | Composition for preventing, treating or improving muscle atrophy comprising complex extracts |
| KR102689865B1 (en) * | 2020-06-03 | 2024-07-31 | 주식회사 한국인삼공사 | Pharmaceutical Composition Comprising Extracts of Eucommia ulmoides Oliver and Cervus elaphus Linne for Preventing or Treating Muscular Disease |
| KR20220151285A (en) | 2021-05-06 | 2022-11-15 | 주식회사 바이오의생명공학연구소 | Muscle function composition using bacteria fermentation-inclusion extract of eucommia ulmoides |
| KR102366919B1 (en) * | 2021-05-28 | 2022-02-24 | 농업회사법인 주식회사 이비채 | Functional health food composition for inhibiting muscle reduction comprising a mixed extract of mulberry twig, Eucommia bark, Acanthopanax, and black bean |
| KR20230089598A (en) * | 2021-12-13 | 2023-06-21 | 한국한의약진흥원 | Composition for improvement, prevention or treatment of myopathy |
| CN116173093B (en) * | 2022-07-26 | 2024-05-14 | 浙江大学 | Application of eucommia male flower extract in preparing food or medicine for resisting muscle aging |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR100950564B1 (en) * | 2008-03-03 | 2010-04-01 | 동아대학교 산학협력단 | Anti-Cancer Composition Containing an Extract of Chinese Herb as an Effective Ingredient |
-
2014
- 2014-05-07 KR KR1020140054193A patent/KR101614205B1/en active IP Right Grant
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR100950564B1 (en) * | 2008-03-03 | 2010-04-01 | 동아대학교 산학협력단 | Anti-Cancer Composition Containing an Extract of Chinese Herb as an Effective Ingredient |
Also Published As
| Publication number | Publication date |
|---|---|
| KR20150127910A (en) | 2015-11-18 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| KR101944985B1 (en) | Composition for differentiating muscle stem cell to muscle cell, pharmaceutical composition for preventing or treating muscle weakness diseases and health functional food composition for enhancing exercise capacity comprising Lithospermum erythrorhizon extract | |
| KR101614205B1 (en) | Pharmaceutical composition comprising extract of Eucommiae coretex for prevention or treatment of muscle wasting disease | |
| US20100105766A1 (en) | Composition for inhibition or prevention of bone density reduction | |
| JP2019513382A (en) | Composition for the prevention, amelioration or treatment of hyperuricemia or hyperuricemia-related metabolic disorders, which comprises the extract of Yuchichi as an active ingredient | |
| JP7132344B2 (en) | Compositions for preventing, ameliorating or treating cachexia and muscle loss | |
| KR101269208B1 (en) | Composition comprising sauchinone as an active ingredient for preventing or treating insulin resistance | |
| KR102465894B1 (en) | Composition for preventing, ameliorating or treating bone disease comprising salvianolic acid as effective component | |
| KR101710780B1 (en) | Pharmaceutical composition for preventing or treating obesity or lipid related metabolic disease comprising extract of Atractylodis macrocephalae rhizoma | |
| KR101913828B1 (en) | Composition for differentiating muscle stem cell to muscle cell, pharmaceutical composition for preventing or treating muscle weakness diseases and health functional food composition for enhancing exercise capacity comprising Lithospermum erythrorhizon extract | |
| KR20120112973A (en) | A composition for preventing or treating obesity or type 2 diabetes | |
| KR102634982B1 (en) | Composition for preventing, ameliorating or treating parkinson's disease comprising osmotin protein as effective component | |
| KR20180050272A (en) | Composition for preventing or treating obesity comprising Chrysanthemum leaf | |
| KR101778227B1 (en) | Composition for anti-obesity comprising extract of Morus alba as effective component | |
| KR20070091928A (en) | Composition for prevention or treatment of diseases in central nervous system comprising extract of cimicifuga heracleifolia komarow | |
| KR102242400B1 (en) | Functional Food for preventing Composition for preventing inflammatory disease due to stress | |
| KR101402921B1 (en) | Use of resveratol derivatives for treating obesity or type 2 diabetes | |
| US20100093852A1 (en) | Pharmaceutical composition comprising shikonin derivatives from lithospermum erythrorhizon for treating or preventing diabetes mellitus and the use thereof | |
| CN106822152B (en) | Pharmaceutical composition and application thereof | |
| KR20110099369A (en) | Agastache rugosa extract for the thrapy of diabetes mellitus | |
| KR101542694B1 (en) | Composition comprising water extract of hulled barley for preventing and treating obesity | |
| KR101862032B1 (en) | Composition comprising scirpusin a and b isolated from extracts of cyperus rotundus l. for preventing or treating of neurodegenerative disease and stress disease | |
| KR20160016030A (en) | Pharmaceutical composition for prevention or treatment of colorectal cancer comprising ethylacetate fraction of jubak ethanol extract as an effective component and health functional food comprising the same | |
| KR20200085070A (en) | Composition for preventing, improving or treating cachexia comprising natural product as effective component | |
| KR102599530B1 (en) | A composition for weight control comprising benzopyran | |
| KR101215797B1 (en) | A composition comprising a morus extract for preventing and treating liver cirrhosis |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A201 | Request for examination | ||
| E902 | Notification of reason for refusal | ||
| AMND | Amendment | ||
| E601 | Decision to refuse application | ||
| AMND | Amendment | ||
| X701 | Decision to grant (after re-examination) | ||
| FPAY | Annual fee payment |
Payment date: 20190326 Year of fee payment: 4 |