KR102292696B1 - Locusta Migratoria ethanol extract for inhibiting osteoclast differentiation and uses therof - Google Patents
Locusta Migratoria ethanol extract for inhibiting osteoclast differentiation and uses therof Download PDFInfo
- Publication number
- KR102292696B1 KR102292696B1 KR1020190148669A KR20190148669A KR102292696B1 KR 102292696 B1 KR102292696 B1 KR 102292696B1 KR 1020190148669 A KR1020190148669 A KR 1020190148669A KR 20190148669 A KR20190148669 A KR 20190148669A KR 102292696 B1 KR102292696 B1 KR 102292696B1
- Authority
- KR
- South Korea
- Prior art keywords
- ethanol extract
- ethanol
- bone
- present
- osteoclast differentiation
- Prior art date
Links
- 210000002997 osteoclast Anatomy 0.000 title claims abstract description 65
- 239000000469 ethanolic extract Substances 0.000 title claims abstract description 64
- 230000004069 differentiation Effects 0.000 title claims abstract description 44
- 230000002401 inhibitory effect Effects 0.000 title claims abstract description 14
- 241000254022 Locusta migratoria Species 0.000 title description 6
- 240000004160 Capsicum annuum Species 0.000 claims abstract description 53
- 235000008534 Capsicum annuum var annuum Nutrition 0.000 claims abstract description 53
- 208000020084 Bone disease Diseases 0.000 claims abstract description 24
- 230000000694 effects Effects 0.000 claims abstract description 21
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 15
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 43
- 239000000203 mixture Substances 0.000 claims description 29
- 230000014509 gene expression Effects 0.000 claims description 22
- 210000000988 bone and bone Anatomy 0.000 claims description 21
- 239000000284 extract Substances 0.000 claims description 21
- 102100034404 Nuclear factor of activated T-cells, cytoplasmic 1 Human genes 0.000 claims description 18
- 101710151542 Nuclear factor of activated T-cells, cytoplasmic 1 Proteins 0.000 claims description 18
- 235000013305 food Nutrition 0.000 claims description 18
- 108090000623 proteins and genes Proteins 0.000 claims description 15
- 241000332371 Abutilon x hybridum Species 0.000 claims description 11
- 208000001132 Osteoporosis Diseases 0.000 claims description 10
- 239000003814 drug Substances 0.000 claims description 10
- 229940079593 drug Drugs 0.000 claims description 8
- 206010031264 Osteonecrosis Diseases 0.000 claims description 7
- 102000001332 SRC Human genes 0.000 claims description 7
- 108060006706 SRC Proteins 0.000 claims description 7
- 239000003153 chemical reaction reagent Substances 0.000 claims description 6
- 238000000338 in vitro Methods 0.000 claims description 5
- 206010068975 Bone atrophy Diseases 0.000 claims description 4
- 102000004171 Cathepsin K Human genes 0.000 claims description 4
- 108090000625 Cathepsin K Proteins 0.000 claims description 4
- 208000029725 Metabolic bone disease Diseases 0.000 claims description 4
- 206010049088 Osteopenia Diseases 0.000 claims description 4
- 230000007547 defect Effects 0.000 claims description 4
- 208000005368 osteomalacia Diseases 0.000 claims description 4
- 238000002525 ultrasonication Methods 0.000 claims description 3
- 210000000689 upper leg Anatomy 0.000 claims 3
- 208000035896 Twin-reversed arterial perfusion sequence Diseases 0.000 claims 1
- 238000002604 ultrasonography Methods 0.000 claims 1
- 230000036541 health Effects 0.000 abstract description 18
- 235000013376 functional food Nutrition 0.000 abstract description 16
- 230000002265 prevention Effects 0.000 abstract description 10
- 231100000135 cytotoxicity Toxicity 0.000 abstract description 6
- 230000003013 cytotoxicity Effects 0.000 abstract description 6
- 239000004480 active ingredient Substances 0.000 abstract description 5
- 229930014626 natural product Natural products 0.000 abstract description 3
- 102000007591 Tartrate-Resistant Acid Phosphatase Human genes 0.000 description 16
- 108010032050 Tartrate-Resistant Acid Phosphatase Proteins 0.000 description 16
- 210000004027 cell Anatomy 0.000 description 16
- 241000238631 Hexapoda Species 0.000 description 14
- 102000014128 RANK Ligand Human genes 0.000 description 12
- 108010025832 RANK Ligand Proteins 0.000 description 12
- -1 RANK Proteins 0.000 description 9
- 238000002360 preparation method Methods 0.000 description 9
- 102000004169 proteins and genes Human genes 0.000 description 9
- 239000000546 pharmaceutical excipient Substances 0.000 description 8
- 238000000034 method Methods 0.000 description 7
- 239000002775 capsule Substances 0.000 description 6
- 230000003247 decreasing effect Effects 0.000 description 6
- 239000008187 granular material Substances 0.000 description 6
- 239000002609 medium Substances 0.000 description 6
- 239000000843 powder Substances 0.000 description 6
- 239000000243 solution Substances 0.000 description 6
- 239000003826 tablet Substances 0.000 description 6
- 239000011230 binding agent Substances 0.000 description 5
- 239000007884 disintegrant Substances 0.000 description 5
- 238000000605 extraction Methods 0.000 description 5
- 235000013373 food additive Nutrition 0.000 description 5
- 239000002778 food additive Substances 0.000 description 5
- 108010010803 Gelatin Proteins 0.000 description 4
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 4
- 108010055717 JNK Mitogen-Activated Protein Kinases Proteins 0.000 description 4
- 102000043136 MAP kinase family Human genes 0.000 description 4
- 108091054455 MAP kinase family Proteins 0.000 description 4
- 102100037808 Mitogen-activated protein kinase 8 Human genes 0.000 description 4
- 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 4
- 229930006000 Sucrose Natural products 0.000 description 4
- 239000000654 additive Substances 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 4
- 238000010586 diagram Methods 0.000 description 4
- 239000000796 flavoring agent Substances 0.000 description 4
- 235000013355 food flavoring agent Nutrition 0.000 description 4
- 229920000159 gelatin Polymers 0.000 description 4
- 239000008273 gelatin Substances 0.000 description 4
- 235000019322 gelatine Nutrition 0.000 description 4
- 235000011852 gelatine desserts Nutrition 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
- 238000005259 measurement Methods 0.000 description 4
- 230000011164 ossification Effects 0.000 description 4
- 210000000963 osteoblast Anatomy 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- 239000005720 sucrose Substances 0.000 description 4
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- 208000006386 Bone Resorption Diseases 0.000 description 3
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 3
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 229920002472 Starch Polymers 0.000 description 3
- 230000024279 bone resorption Effects 0.000 description 3
- 230000008859 change Effects 0.000 description 3
- 238000012790 confirmation Methods 0.000 description 3
- 230000001419 dependent effect Effects 0.000 description 3
- 201000010099 disease Diseases 0.000 description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
- 239000000839 emulsion Substances 0.000 description 3
- 239000012091 fetal bovine serum Substances 0.000 description 3
- 230000006870 function Effects 0.000 description 3
- 230000013632 homeostatic process Effects 0.000 description 3
- GUBGYTABKSRVRQ-QKKXKWKRSA-N lactose group Chemical group OC1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@H](O)[C@@H](O)[C@@H](O)[C@H](O2)CO)[C@H](O1)CO GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 3
- 239000000314 lubricant Substances 0.000 description 3
- 239000006187 pill Substances 0.000 description 3
- 239000003755 preservative agent Substances 0.000 description 3
- 230000011664 signaling Effects 0.000 description 3
- 235000019698 starch Nutrition 0.000 description 3
- 239000008107 starch Substances 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 239000000829 suppository Substances 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- 239000000454 talc Substances 0.000 description 3
- 229910052623 talc Inorganic materials 0.000 description 3
- 235000012222 talc Nutrition 0.000 description 3
- 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
- 102100024230 Dendritic cell-specific transmembrane protein Human genes 0.000 description 2
- 101710190014 Dendritic cell-specific transmembrane protein Proteins 0.000 description 2
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 2
- 206010017076 Fracture Diseases 0.000 description 2
- 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 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- 241000254023 Locusta Species 0.000 description 2
- 102000007651 Macrophage Colony-Stimulating Factor Human genes 0.000 description 2
- 108010046938 Macrophage Colony-Stimulating Factor Proteins 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 2
- 244000299461 Theobroma cacao Species 0.000 description 2
- 238000002835 absorbance Methods 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 230000004913 activation Effects 0.000 description 2
- 239000003125 aqueous solvent Substances 0.000 description 2
- 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 2
- 239000003086 colorant Substances 0.000 description 2
- 235000009508 confectionery Nutrition 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- 210000004748 cultured cell Anatomy 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 230000018109 developmental process Effects 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- 239000003937 drug carrier Substances 0.000 description 2
- 238000011049 filling Methods 0.000 description 2
- 235000003599 food sweetener Nutrition 0.000 description 2
- 235000011187 glycerol Nutrition 0.000 description 2
- 230000012010 growth Effects 0.000 description 2
- 239000007902 hard capsule Substances 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 235000019359 magnesium stearate Nutrition 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 235000015097 nutrients Nutrition 0.000 description 2
- 208000028169 periodontal disease Diseases 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 230000001105 regulatory effect Effects 0.000 description 2
- 102000034285 signal transducing proteins Human genes 0.000 description 2
- 108091006024 signal transducing proteins Proteins 0.000 description 2
- 230000019491 signal transduction Effects 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 239000000600 sorbitol Substances 0.000 description 2
- 235000010356 sorbitol Nutrition 0.000 description 2
- 239000003765 sweetening agent Substances 0.000 description 2
- 239000006188 syrup Substances 0.000 description 2
- 235000020357 syrup Nutrition 0.000 description 2
- 235000013343 vitamin Nutrition 0.000 description 2
- 239000011782 vitamin Substances 0.000 description 2
- 229940088594 vitamin Drugs 0.000 description 2
- 229930003231 vitamin Natural products 0.000 description 2
- 150000003722 vitamin derivatives Chemical class 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- 239000000080 wetting agent Substances 0.000 description 2
- WBYWAXJHAXSJNI-VOTSOKGWSA-M .beta-Phenylacrylic acid Natural products [O-]C(=O)\C=C\C1=CC=CC=C1 WBYWAXJHAXSJNI-VOTSOKGWSA-M 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
- 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 1
- 244000215068 Acacia senegal Species 0.000 description 1
- 235000006491 Acacia senegal Nutrition 0.000 description 1
- 241000254032 Acrididae Species 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 108010011485 Aspartame Proteins 0.000 description 1
- 208000010392 Bone Fractures Diseases 0.000 description 1
- 206010065687 Bone loss Diseases 0.000 description 1
- 108010001789 Calcitonin Receptors Proteins 0.000 description 1
- 102100038520 Calcitonin receptor Human genes 0.000 description 1
- PTHCMJGKKRQCBF-UHFFFAOYSA-N Cellulose, microcrystalline Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC)C(CO)O1 PTHCMJGKKRQCBF-UHFFFAOYSA-N 0.000 description 1
- WBYWAXJHAXSJNI-SREVYHEPSA-N Cinnamic acid Chemical compound OC(=O)\C=C/C1=CC=CC=C1 WBYWAXJHAXSJNI-SREVYHEPSA-N 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- 229920000858 Cyclodextrin Polymers 0.000 description 1
- 102000004127 Cytokines Human genes 0.000 description 1
- 108090000695 Cytokines Proteins 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
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- 238000002965 ELISA Methods 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
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 1
- 239000004606 Fillers/Extenders Substances 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
- 239000004471 Glycine Substances 0.000 description 1
- 229920000084 Gum arabic Polymers 0.000 description 1
- 102000008379 I-kappa B Proteins Human genes 0.000 description 1
- 108010021699 I-kappa B Proteins Proteins 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
- 229930195725 Mannitol Natural products 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- 241000238814 Orthoptera Species 0.000 description 1
- 208000010191 Osteitis Deformans Diseases 0.000 description 1
- 208000027868 Paget disease Diseases 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 102000001253 Protein Kinase Human genes 0.000 description 1
- 244000088415 Raphanus sativus Species 0.000 description 1
- 235000006140 Raphanus sativus var sativus Nutrition 0.000 description 1
- 208000005250 Spontaneous Fractures Diseases 0.000 description 1
- 210000001744 T-lymphocyte Anatomy 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- 244000269722 Thea sinensis Species 0.000 description 1
- 235000005764 Theobroma cacao ssp. cacao Nutrition 0.000 description 1
- 235000005767 Theobroma cacao ssp. sphaerocarpum Nutrition 0.000 description 1
- 102000040945 Transcription factor Human genes 0.000 description 1
- 108091023040 Transcription factor Proteins 0.000 description 1
- 235000021307 Triticum Nutrition 0.000 description 1
- 244000098338 Triticum aestivum Species 0.000 description 1
- TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 description 1
- 235000010489 acacia gum Nutrition 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 235000013334 alcoholic beverage Nutrition 0.000 description 1
- 229940072056 alginate Drugs 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 230000002421 anti-septic effect Effects 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 239000007900 aqueous suspension Substances 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
- 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
- 235000013361 beverage Nutrition 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 230000037182 bone density Effects 0.000 description 1
- 230000037180 bone health Effects 0.000 description 1
- 210000002805 bone matrix Anatomy 0.000 description 1
- 230000010072 bone remodeling Effects 0.000 description 1
- 235000008429 bread Nutrition 0.000 description 1
- 235000014121 butter Nutrition 0.000 description 1
- 235000001046 cacaotero Nutrition 0.000 description 1
- 229910000019 calcium carbonate Inorganic materials 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 229910000389 calcium phosphate Inorganic materials 0.000 description 1
- 235000011010 calcium phosphates Nutrition 0.000 description 1
- 239000000378 calcium silicate Substances 0.000 description 1
- 229910052918 calcium silicate Inorganic materials 0.000 description 1
- 235000012241 calcium silicate Nutrition 0.000 description 1
- OYACROKNLOSFPA-UHFFFAOYSA-N calcium;dioxido(oxo)silane Chemical compound [Ca+2].[O-][Si]([O-])=O OYACROKNLOSFPA-UHFFFAOYSA-N 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 235000014633 carbohydrates Nutrition 0.000 description 1
- 235000014171 carbonated beverage Nutrition 0.000 description 1
- 230000003833 cell viability Effects 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 235000010980 cellulose Nutrition 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 235000019219 chocolate Nutrition 0.000 description 1
- 229930016911 cinnamic acid Natural products 0.000 description 1
- 235000013985 cinnamic acid Nutrition 0.000 description 1
- 239000007979 citrate buffer Substances 0.000 description 1
- 239000007931 coated granule Substances 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 238000000748 compression moulding Methods 0.000 description 1
- 230000001276 controlling effect Effects 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 231100000263 cytotoxicity test Toxicity 0.000 description 1
- 235000013365 dairy product Nutrition 0.000 description 1
- 235000019425 dextrin Nutrition 0.000 description 1
- 239000008121 dextrose Substances 0.000 description 1
- 150000002016 disaccharides Chemical class 0.000 description 1
- PXEDJBXQKAGXNJ-QTNFYWBSSA-L disodium L-glutamate Chemical compound [Na+].[Na+].[O-]C(=O)[C@@H](N)CCC([O-])=O PXEDJBXQKAGXNJ-QTNFYWBSSA-L 0.000 description 1
- VIYFPAMJCJLZKD-UHFFFAOYSA-L disodium;(4-nitrophenyl) phosphate Chemical compound [Na+].[Na+].[O-][N+](=O)C1=CC=C(OP([O-])([O-])=O)C=C1 VIYFPAMJCJLZKD-UHFFFAOYSA-L 0.000 description 1
- 229940000406 drug candidate Drugs 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 230000004821 effect on bone Effects 0.000 description 1
- 239000003792 electrolyte Substances 0.000 description 1
- 239000012156 elution solvent Substances 0.000 description 1
- 230000007613 environmental effect Effects 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
- 235000019414 erythritol Nutrition 0.000 description 1
- 229940009714 erythritol Drugs 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 230000029142 excretion Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000000835 fiber Substances 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 230000037406 food intake Effects 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 239000003205 fragrance Substances 0.000 description 1
- 238000010230 functional analysis Methods 0.000 description 1
- 230000004927 fusion Effects 0.000 description 1
- 238000012812 general test Methods 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 125000005639 glycero group Chemical group 0.000 description 1
- 229960002449 glycine Drugs 0.000 description 1
- 235000015243 ice cream Nutrition 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 239000002917 insecticide Substances 0.000 description 1
- 238000010255 intramuscular injection Methods 0.000 description 1
- 239000007927 intramuscular injection Substances 0.000 description 1
- 239000007928 intraperitoneal injection Substances 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- VMPHSYLJUKZBJJ-UHFFFAOYSA-N lauric acid triglyceride Natural products CCCCCCCCCCCC(=O)OCC(OC(=O)CCCCCCCCCCC)COC(=O)CCCCCCCCCCC VMPHSYLJUKZBJJ-UHFFFAOYSA-N 0.000 description 1
- 239000012669 liquid formulation Substances 0.000 description 1
- 229940057995 liquid paraffin Drugs 0.000 description 1
- 229960003511 macrogol Drugs 0.000 description 1
- 210000002540 macrophage Anatomy 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 239000000845 maltitol Substances 0.000 description 1
- 235000010449 maltitol Nutrition 0.000 description 1
- VQHSOMBJVWLPSR-WUJBLJFYSA-N maltitol Chemical compound OC[C@H](O)[C@@H](O)[C@@H]([C@H](O)CO)O[C@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O VQHSOMBJVWLPSR-WUJBLJFYSA-N 0.000 description 1
- 229940035436 maltitol Drugs 0.000 description 1
- 208000027202 mammary Paget disease Diseases 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000013011 mating Effects 0.000 description 1
- 235000013372 meat Nutrition 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
- 230000002503 metabolic effect Effects 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- WBYWAXJHAXSJNI-UHFFFAOYSA-N methyl p-hydroxycinnamate Natural products OC(=O)C=CC1=CC=CC=C1 WBYWAXJHAXSJNI-UHFFFAOYSA-N 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 239000002480 mineral oil Substances 0.000 description 1
- 235000010446 mineral oil Nutrition 0.000 description 1
- 239000011259 mixed solution Substances 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 150000002772 monosaccharides Chemical class 0.000 description 1
- 238000000465 moulding Methods 0.000 description 1
- 210000005088 multinucleated cell Anatomy 0.000 description 1
- 235000021096 natural sweeteners Nutrition 0.000 description 1
- 239000002547 new drug Substances 0.000 description 1
- 239000011664 nicotinic acid Substances 0.000 description 1
- 229960003512 nicotinic acid Drugs 0.000 description 1
- 235000001968 nicotinic acid Nutrition 0.000 description 1
- 235000012149 noodles Nutrition 0.000 description 1
- 229940049964 oleate Drugs 0.000 description 1
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
- 235000008390 olive oil Nutrition 0.000 description 1
- 239000004006 olive oil Substances 0.000 description 1
- 239000006186 oral dosage form Substances 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 201000008482 osteoarthritis Diseases 0.000 description 1
- 230000003256 osteocytic effect Effects 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 229940116257 pepper extract Drugs 0.000 description 1
- 230000026731 phosphorylation Effects 0.000 description 1
- 238000006366 phosphorylation reaction Methods 0.000 description 1
- 238000013081 phylogenetic analysis Methods 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 235000013550 pizza Nutrition 0.000 description 1
- 239000004014 plasticizer Substances 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229920000136 polysorbate Polymers 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 239000001508 potassium citrate Substances 0.000 description 1
- 229960002635 potassium citrate Drugs 0.000 description 1
- QEEAPRPFLLJWCF-UHFFFAOYSA-K potassium citrate (anhydrous) Chemical compound [K+].[K+].[K+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O QEEAPRPFLLJWCF-UHFFFAOYSA-K 0.000 description 1
- 235000011082 potassium citrates Nutrition 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 208000034133 primary 1 avascular necrosis of femoral head Diseases 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 1
- 229960003415 propylparaben Drugs 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 108060006633 protein kinase Proteins 0.000 description 1
- 239000012264 purified product Substances 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 108091006084 receptor activators Proteins 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 238000003757 reverse transcription PCR Methods 0.000 description 1
- 206010039073 rheumatoid arthritis Diseases 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
- 235000013580 sausages Nutrition 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
- 229930000044 secondary metabolite Natural products 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 235000011888 snacks Nutrition 0.000 description 1
- 239000007901 soft capsule Substances 0.000 description 1
- 238000000527 sonication Methods 0.000 description 1
- 235000014347 soups Nutrition 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 210000000130 stem cell Anatomy 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 238000005728 strengthening Methods 0.000 description 1
- 229960005322 streptomycin Drugs 0.000 description 1
- 238000012916 structural analysis Methods 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000013616 tea Nutrition 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 230000017423 tissue regeneration Effects 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 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 1
- 238000002137 ultrasound extraction Methods 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 238000003809 water extraction Methods 0.000 description 1
- 238000001262 western blot Methods 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
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/56—Materials from animals other than mammals
- A61K35/63—Arthropods
- A61K35/64—Insects, e.g. bees, wasps or fleas
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2200/00—Function of food ingredients
- A23V2200/30—Foods, ingredients or supplements having a functional effect on health
- A23V2200/306—Foods, ingredients or supplements having a functional effect on health having an effect on bone mass, e.g. osteoporosis prevention
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2250/00—Food ingredients
- A23V2250/20—Natural extracts
- A23V2250/204—Animal extracts
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Insects & Arthropods (AREA)
- Veterinary Medicine (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Physical Education & Sports Medicine (AREA)
- Mycology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nutrition Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Chemical & Material Sciences (AREA)
- Polymers & Plastics (AREA)
- Animal Husbandry (AREA)
- Food Science & Technology (AREA)
- Zoology (AREA)
- Epidemiology (AREA)
- Medicines Containing Plant Substances (AREA)
- Coloring Foods And Improving Nutritive Qualities (AREA)
Abstract
본 발명은 파골세포 분화 억제용 풀무치 에탄올 추출물에 관한 것이다. 본 발명은 파골세포 분화를 억제하는 풀무치 에탄올 추출물을 유효성분으로 포함하여, 천연물로 세포독성을 나타내지 않으면서도 파골세포 분화 활성을 현저하게 억제시킬 수 있어 골형성 촉진, 골소실 또는 골 대사 불균형으로 인한 골질환의 효과적인 예방 및 치료를 위한 약학적 조성물 또는 건강기능식품으로 유용하게 사용될 수 있을 것으로 기대된다. The present invention relates to an ethanol extract of bell pepper for inhibiting osteoclast differentiation. The present invention contains an ethanol extract of bell pepper that inhibits osteoclast differentiation as an active ingredient, and can significantly inhibit osteoclast differentiation activity without showing cytotoxicity as a natural product. It is expected to be usefully used as a pharmaceutical composition or health functional food for the effective prevention and treatment of bone diseases.
Description
본 발명은 파골세포 분화 억제용 풀무치 에탄올 추출물 및 이의 용도에 관한 것이다.The present invention relates to an ethanol extract of bell pepper for inhibiting osteoclast differentiation and use thereof.
골조직은 골 재형성(bone remodeling) 과정을 통해 골 항상성(skeletal homeostasis)을 유지하며 골량(bone mass)은 노화된 골을 흡수하는 파골세포(osteoclast)와 뼈기질을 합성하고 채우는 조골세포(osteoblast)의 상반된 작용에 의해 결정된다. 파골세포와 조골세포 활성 간의 균형은 뼈의 항상성 유지를 위해 중요하며, 뼈의 항상성에서 파골세포의 활성 또는 수 증가는 골다공증, 파젯 병, 류마티스 관절염 및 치주 질환과 같은 뼈 질환에서 골질량 감소의 원인이 된다. 골 대사 불균형으로 인한 골질환의 예방 또는 치료 측면에서 젊은 때부터 골질량을 높이는 것이 상당히 중요하며, 뼈의 건강을 유지하는 것은 성별이나 연령과 관계없이 중요한 문제이다.Bone tissue maintains skeletal homeostasis through the process of bone remodeling, and bone mass consists of osteoclasts that absorb aged bone and osteoblasts that synthesize and fill the bone matrix. determined by the opposing action of A balance between osteoclast and osteoblast activity is important for the maintenance of bone homeostasis, and an increase in the activity or number of osteoclasts in bone homeostasis may cause a decrease in bone mass in bone diseases such as osteoporosis, Paget's disease, rheumatoid arthritis and periodontal disease. do. It is very important to increase bone mass from a young age in terms of prevention or treatment of bone diseases caused by bone metabolic imbalance, and maintaining bone health is an important issue regardless of gender or age.
이에, 최근 가장 흔한 골질환인 골다공증의 예방 및 치료를 위해서도 골형성 증가 및 골조직 재생능력에 미치는 영향 등에 대한 연구가 활발하게 이루어지고 있다. 골다공증은 세계적으로 가장 흔한 뼈 질환으로 골질량 감소와 골절 위험 증가와 관련이 있다. 골다공증 환자는 골밀도가 낮아져 뼈의 미세 구조가 약화되는 특징을 가지고 있어서 병리학적인 골절을 경험할 가능성이 크다. 골다공증의 주요 원인은 파골세포 수가 증가하여 골 흡수가 증가하는 것과 관련이 깊다. 파골세포는 여러 단핵전구체의 융합으로 형성된 TRAP(tartrate-resistant acid phosphatase) 양성 다핵세포로서 뼈의 재흡수를 담당하며, 오래되거나 약해진 뼈를 제거하거나 혈중 미네랄의 항성성을 유지한다.Accordingly, recent studies on the increase in bone formation and the effect on bone tissue regeneration ability have been actively conducted for the prevention and treatment of osteoporosis, which is the most common bone disease. Osteoporosis is the most common bone disease worldwide and is associated with decreased bone mass and increased risk of fractures. Osteoporosis patients are more likely to experience pathological fractures because their bone density is lowered and the microstructure of the bones is weakened. The main cause of osteoporosis is closely related to an increase in bone resorption due to an increase in the number of osteoclasts. Osteoclasts are tartrate-resistant acid phosphatase (TRAP)-positive multinucleated cells formed by the fusion of several mononuclear precursors. They are responsible for bone resorption, remove old or weakened bones, or maintain the constancy of minerals in the blood.
파골세포의 분화는 두 개의 사이토카인인 M-CSF(macrophage colony stimulating factor)와 RANKL(receptor activator of nuclear factor-κ(NF-κ)에 의해 조절된다. 면역세포/조골세포에서 생성되는 M-CSF는 파골세포 전구세포에서 RANK 발현 및 파골세포의 생존 신호를 유도하며, 조골세포/활성 T 세포에 의해 분비되는 RANKL는 파골세포의 수용체 RANK와 결합하여 MAPK(mitogen-activated protein kinase) 및 NFATc1의 활성화를 유도한다. 상기 NFATc1은 파골세포 형성의 핵심 전사 인자로서 TRAP, cathepsin K, DC-STAMP(dendritic cell-specific transmembrane protein)와 같은 파골세포 분화 및 활성화 인자의 발현을 조절한다.Osteoclast differentiation is regulated by two cytokines, macrophage colony stimulating factor (M-CSF) and receptor activator of nuclear factor-κ (NF-κ). induces RANK expression and osteoclast survival signals in osteoclast progenitor cells, and RANKL secreted by osteoblasts/activated T cells binds to osteoclast receptor RANK and activates mitogen-activated protein kinase (MAPK) and NFATc1 As a key transcription factor for osteoclast formation, NFATc1 regulates the expression of osteoclast differentiation and activation factors such as TRAP, cathepsin K, and DC-STAMP (dendritic cell-specific transmembrane protein).
한편, 현재 지구상에 존재하는 곤충은 130만 종으로 알려져 있으나 그에 비해 곤충을 이용한 소재 개발은 미비한 실정이다. 과거 동의보감, 본초강목을 통해 다양한 효능이 보고되었으며, 극한 외부 환경 조건에서 살아가는 곤충의 특성상 체내에 기능성을 가진 2차 대사산물을 함유하고 있을 것으로 추정되고 있다. 뿐만 아니라 미래 인구 증가에 따른 식량 부족에 대한 대안으로써 식용곤충이 각광받고 있으며, 현재 국내에 7종의 식용곤충이 일반식품으로 식품공전에 등록되어 있다. 최근에는 다양한 곤충 유래의 생리활성 물질에 대한 연구가 활발히 진행되고 있으며 곤충의 기능성 연구를 통해 식용 및 약용으로 곤충의 이용이 증가할 것으로 사료된다.On the other hand, it is known that there are 1.3 million kinds of insects on the earth, but development of materials using insects is insufficient. Various effects have been reported in the past through Donguibogam and Bonchogangmok, and it is estimated that the insect contains functional secondary metabolites in the body due to the nature of insects living in extreme external environmental conditions. In addition, edible insects are in the spotlight as an alternative to food shortages due to future population growth. Currently, 7 types of edible insects are registered as general foods in Korea. Recently, research on various insect-derived physiologically active substances is being actively conducted, and it is thought that the use of insects for food and medicine will increase through functional studies of insects.
이 중, 풀무치(Locusta migratoria)는 메뚜기목(Orthoptera) 메뚜기과(Acrididae)의 곤충으로 우리나라를 포함하여 아시아, 아프리카, 오스트레일리아, 유럽 등 전세계적으로 분포한다. 크기는 4-6 cm 정도이고, 하루에 100 km를 이동할 수 있을 정도로 이동성이 강한 것으로 알려져 있다. 풀무치는 사료용, 식·약용 등으로 사용되는 유용한 곤충 종 중 하나로 다양한 목적으로의 연구를 위하여 실험실에서 흔하게 사육되고 있고, 체코, 폴란드, 터키 등 유럽 국가에서는 수출용으로 사육되고 있다. 현재까지 풀무치를 이용한 연구로는 집단형 풀무치에 대한 방제 연구, 국내 풀무치의 계통 분석, 풀무치 유래 펩타이드 및 GST의 구조 및 기능 분석 등이 진행되었으나 풀무치 추출물의 파골세포 분화 억제에 미치는 영향에 대하여는 아직까지 보고된 바가 없고, 이에 대한 연구는 미미한 실정이다. Among them, the bellows ( Locusta) migratoria ) is an insect of the Orthoptera family, Acrididae, distributed worldwide including Korea, Asia, Africa, Australia, and Europe. It is about 4-6 cm in size and is known to be highly mobile enough to travel 100 km in a day. Bellows is one of the useful insect species used for feed, food and medicine, and it is commonly bred in laboratories for various purposes, and is bred for export in European countries such as the Czech Republic, Poland and Turkey. Until now, studies using bellflower have been conducted such as control studies on group-type bellflowers, phylogenetic analysis of domestic bellflowers, and structural and functional analysis of bellows-derived peptides and GST. It has not been reported, and studies on it are insignificant.
이에, 본 발명자들은 골소실로 인한 골질환의 효과적인 예방과 치료를 가능하게 하는 곤충 유래의 새로운 신약 후보물질을 연구하던 중, 풀무치 에탄올 추출물이 파골세포의 분화를 억제하는 효과가 우수함을 확인하여 본 발명을 완성하였다.Accordingly, the present inventors confirmed that the ethanol extract of bell pepper is excellent in inhibiting the differentiation of osteoclasts while researching new drug candidates derived from insects that enable the effective prevention and treatment of bone diseases caused by bone loss. The invention was completed.
따라서 본 발명의 목적은 풀무치 에탄올 추출물을 포함하는 파골세포 분화 억제용 조성물을 제공하는 것이다.Accordingly, an object of the present invention is to provide a composition for inhibiting osteoclast differentiation comprising an ethanol extract of bell pepper.
본 발명의 또 다른 목적은 풀무치 에탄올 추출물을 포함하는 골질환 예방 또는 치료용 약학적 조성물, 골질환 예방 또는 개선용 식품 조성물, 골질환 예방 또는 개선용 의약외품 조성물을 제공하는 것이다.Another object of the present invention is to provide a pharmaceutical composition for preventing or treating bone disease, a food composition for preventing or improving bone disease, and a quasi-drug composition for preventing or improving bone disease, comprising an ethanol extract of bell pepper.
본 발명의 또 다른 목적은 풀무치 에탄올 추출물을 함유하는 시험관 내(in vitro) 파골세포 분화 억제용 시약 조성물을 제공하는 것이다.Another object of the present invention is to provide a reagent composition for inhibiting osteoclast differentiation in vitro containing an ethanol extract of bell pepper.
상기 목적을 달성하기 위하여, 본 발명은 풀무치 에탄올 추출물을 포함하는 파골세포 분화 억제용 조성물을 제공한다.In order to achieve the above object, the present invention provides a composition for inhibiting osteoclast differentiation comprising an ethanol extract of bell pepper.
또한, 본 발명은 풀무치 에탄올 추출물을 포함하는 골질환 예방 또는 치료용 약학적 조성물을 제공한다.In addition, the present invention provides a pharmaceutical composition for preventing or treating bone disease comprising an ethanol extract of bell pepper.
또한, 본 발명은 풀무치 에탄올 추출물을 포함하는 골질환 예방 또는 개선용 식품 조성물을 제공한다.In addition, the present invention provides a food composition for preventing or improving bone disease comprising an ethanol extract of bell pepper.
또한, 본 발명은 풀무치 에탄올 추출물을 포함하는 골질환 예방 또는 개선용 의약외품 조성물을 제공한다.In addition, the present invention provides a quasi-drug composition for preventing or improving bone disease comprising an ethanol extract of bell pepper.
또한, 본 발명은 풀무치 에탄올 추출물을 함유하는 시험관 내(in vitro) 파골세포 분화 억제용 시약 조성물을 제공한다.In addition, the present invention provides a reagent composition for inhibiting osteoclast differentiation in vitro containing an ethanol extract of bell pepper.
본 발명은 파골세포 분화를 억제하는 풀무치 에탄올 추출물을 유효성분으로 포함하여, 천연물로 세포독성을 나타내지 않으면서도 파골세포 분화 활성을 현저하게 억제시킬 수 있어 골형성 촉진, 골소실 또는 골 대사 불균형으로 인한 골질환의 효과적인 예방 및 치료를 위한 약학적 조성물 또는 건강기능식품으로 유용하게 사용될 수 있을 것으로 기대된다. The present invention contains an ethanol extract of bell pepper that inhibits osteoclast differentiation as an active ingredient, and can significantly inhibit osteoclast differentiation activity without showing cytotoxicity as a natural product. It is expected to be usefully used as a pharmaceutical composition or health functional food for the effective prevention and treatment of bone diseases.
도 1은 풀무치 에탄올 추출물(Locusta Migratoria Extract, LME) 농도(100, 500, 1000, 2000 μg/mL)에 따른 세포독성 확인 결과를 나타낸 도이다.
도 2는 RANKL(100 ng/mL)를 처리한 파골세포에 대하여, 농도(0, 100, 500, 1000, 2000 μg/mL)별 풀무치 에탄올 추출물(Locusta Migratoria Extract, LME) 처리에 따른 TRAP 활성 변화를 확인한 도이다.
도 3은 RANKL(100 ng/mL)를 처리한 파골세포에 대하여, 농도(0, 100, 500, 1000, 2000 μg/mL)별 풀무치 에탄올 추출물(Locusta Migratoria Extract, LME) 처리에 따른 파골세포 분화 관련 유전자(TRAP, RANK, NFATc1 및 CathepsinK) 발현 변화를 확인한 도이다.
도 4는 RANKL(100 ng/mL)를 처리한 파골세포에 대하여, 농도(0, 100, 500, 1000, 2000 μg/mL)별 풀무치 에탄올 추출물(Locusta Migratoria Extract, LME) 처리에 따른 파골세포 분화 관련 단백질(NFATc1 및 c-Src) 발현 변화를 확인한 도이다.
도 5는 RANKL(100 ng/mL)를 처리한 파골세포에 대하여, 농도(0, 100, 500, 1000, 2000 μg/mL)별 풀무치 에탄올 추출물(Locusta Migratoria Extract, LME) 처리에 따른 파골세포 분화 관련 시그널링 단백질 발현 변화를 확인한 도이다. 1 is a diagram showing the cytotoxicity confirmation results according to the concentration (100, 500, 1000, 2000 μg/mL) of an ethanol extract of bell pepper (Locusta Migratoria Extract, LME).
Figure 2 is for osteoclasts treated with RANKL (100 ng/mL), TRAP activity changes according to concentration (0, 100, 500, 1000, 2000 μg/mL) treatment with ethanol extract (Locusta Migratoria Extract, LME) is a confirmation of
Figure 3 is for osteoclasts treated with RANKL (100 ng/mL), osteoclast differentiation according to concentration (0, 100, 500, 1000, 2000 μg/mL) by treatment with ethanol extract (Locusta Migratoria Extract, LME) A diagram confirming the expression changes of related genes (TRAP, RANK, NFATc1 and CathepsinK).
4 shows osteoclast differentiation according to ethanol extract (Locusta Migratoria Extract, LME) treatment for each concentration (0, 100, 500, 1000, 2000 μg/mL) of osteoclasts treated with RANKL (100 ng/mL); A diagram confirming the expression change of related proteins (NFATc1 and c-Src).
Figure 5 is for osteoclasts treated with RANKL (100 ng/mL), osteoclast differentiation according to concentration (0, 100, 500, 1000, 2000 μg/mL) by treatment with ethanol extract (Locusta Migratoria Extract, LME) It is a diagram confirming the change in the expression of the related signaling protein.
이하, 본 발명을 상세히 설명한다.Hereinafter, the present invention will be described in detail.
본 명세서에서 달리 정의되지 않은 용어들은 본 발명이 속하는 기술분야에서 통상적으로 사용되는 의미를 갖는 것이다.Terms not otherwise defined herein have meanings commonly used in the art to which the present invention pertains.
본 발명은 풀무치 에탄올 추출물을 포함하는 파골세포 분화 억제용 조성물을 제공한다.The present invention provides a composition for inhibiting osteoclast differentiation comprising an ethanol extract of bell pepper.
상기 풀무치 에탄올 추출물은 에탄올을 사용하여 풀무치로부터 추출하여 수득한 추출물을 의미한다. 본 발명은 일 실시예에서 상기 풀무치 에탄올 추출물이 현저한 파골세포 분화 억제 효과가 있음을 확인하였다.The ethanol extract of bellflower refers to an extract obtained by extracting from bellflower using ethanol. In one embodiment, the present invention confirmed that the ethanol extract of bell pepper has a significant inhibitory effect on osteoclast differentiation.
상기 풀무치 에탄올 추출물은 건조 중량의 약 2 내지 20배, 구체적으로는, 약 3 내지 5배에 달하는 부피의 에탄올을 용출 용매로써 사용하는 것이 바람직하다. 상기 에탄올은 50 내지 100%(농도) 에탄올일 수 있으며, 바람직하게는 70% 에탄올일 수 있으나, 이에 제한되지 않는다. 상기 추출 온도는 20 내지 100℃, 예를 들어 실온일 수 있고, 추출 기간은 약 12시간 내지 4일 동안 이루어질 수 있으나 이에 제한되지 않는다. 추출방법으로는 열수 추출, 냉침 추출, 환류 냉각 추출 또는 초음파 추출 등을 사용하여 추출할 수 있으며 파골세포 억제 활성이 있는 물질을 추출하는 방법이라면 제한없이 이용될 수 있다. It is preferred that the ethanol extract of bell peppers uses about 2 to 20 times the dry weight, specifically, about 3 to 5 times the volume of ethanol as the elution solvent. The ethanol may be 50 to 100% (concentration) ethanol, preferably 70% ethanol, but is not limited thereto. The extraction temperature may be 20 to 100° C., for example, room temperature, and the extraction period may be made for about 12 hours to 4 days, but is not limited thereto. The extraction method can be extracted using hot water extraction, chilled extraction, reflux cooling extraction, or ultrasonic extraction, and any method for extracting a substance having osteoclast inhibitory activity can be used without limitation.
본 발명의 일 실시예에서는, 풀무치 동결건조 분말을 70% 에탄올과 10%(v/v)가 되게 혼합한 후, 초음파 처리하여 30분간 실온에서 방치한 뒤 에탄올 추출액을 회수하고 감압증류하여 풀무치 에탄올 추출물을 수득하였다. In an embodiment of the present invention, the freeze-dried powder of bell peppers is mixed with 70% ethanol and 10% (v/v), followed by sonication and left at room temperature for 30 minutes, then the ethanol extract is recovered and distilled under reduced pressure to ethanol with bellows An extract was obtained.
본 발명에 있어서, 상기 풀무치 에탄올 추출물은 추출액, 추출액의 희석액 또는 농축액, 추출액을 건조하여 얻어지는 건조물, 또는 이들의 조정제물 또는 정제물을 모두 포함한다.In the present invention, the bellows ethanol extract includes all of an extract, a diluted or concentrated solution of the extract, a dried product obtained by drying the extract, or a crude or purified product thereof.
본 발명에 있어서, 상기 풀무치 에탄올 추출물은 파골세포에서 TRAP, RANK, NFATc1 및 카텝신(Cathepsin) K로 이루어진 군으로부터 선택되는 하나 이상 유전자의 발현을 감소시키는 것을 특징으로 한다.In the present invention, the ethanol extract of bell pepper is characterized in that it reduces the expression of one or more genes selected from the group consisting of TRAP, RANK, NFATc1 and cathepsin K in osteoclasts.
또한, 본 발명에 있어서, 상기 풀무치 에탄올 추출물은 파골세포에서 NFATc1 또는 c-Src 단백질의 발현을 감소시키는 것을 특징으로 한다.In addition, in the present invention, the ethanol extract of bell pepper is characterized in that it reduces the expression of NFATc1 or c-Src protein in osteoclasts.
본 발명의 일 실시예에 따르면, 본 발명의 풀무치 에탄올 추출물은 파골세포 분화 관련 유전자(TRAP, RANK, NFATc1 및 카텝신 K) 및 파골세포 분화 관련 단백질(NFATc1 및 c-Src)의 발현을 현저히 감소시키며, 상기 결과를 통해 골질환의 예방 및 치료가 가능함을 확인하였다.According to an embodiment of the present invention, the ethanol extract of bell pepper of the present invention significantly reduces the expression of osteoclast differentiation-related genes (TRAP, RANK, NFATc1 and cathepsin K) and osteoclast differentiation-related proteins (NFATc1 and c-Src) Through the above results, it was confirmed that the prevention and treatment of bone diseases are possible.
또한, 본 발명은 풀무치 에탄올 추출물을 포함하는 골질환 예방 또는 치료용 약학적 조성물을 제공한다.In addition, the present invention provides a pharmaceutical composition for preventing or treating bone disease comprising an ethanol extract of bell pepper.
본 발명에 있어서, 상기 풀무치 에탄올 추출물은 파골세포 분화 활성을 억제하는 것을 특징으로 하며, 본 발명의 일 실시예에서는 본 발명의 풀무치 에탄올 추출물이 파골세포 분화와 관련된 RAP, RANK, NFATc1 및 CathepsinK의 유전자 발현을 감소시키고, 골세포 분화와 관련된 NFATc1 및 c-Src 단백질 발현을 감소시킴을 확인하여, 상기 추출물이 골질환 예방 또는 치료용도로 사용될 수 있음을 확인하였다.In the present invention, the ethanol extract of bellflower extract is characterized in that it inhibits osteoclast differentiation activity, and in one embodiment of the present invention, the ethanol extract of bell pepper of the present invention is related to osteoclast differentiation-related RAP, RANK, NFATc1 and CathepsinK genes By reducing the expression and reducing the expression of NFATc1 and c-Src proteins related to osteocytic differentiation, it was confirmed that the extract can be used for the prevention or treatment of bone diseases.
본 발명에 있어서, 용어 “골질환”은 골형성과 골흡수의 균형이 깨짐으로써 발병하는 모든 골 관련 질환을 제한 없이 포함하며, 예를 들어 골다공증(osteoporosis), 불유합(non-union) 골절, 골괴사증(osteonecrosis), 골연화증(osteomalacia), 골결손, 골감소증(osteopenia), 골위축(bone atrophy), 골관절염(osteoarthritis), 치주질환(periodontal disease), 무혈성 대퇴골괴사(Avascular necrosis of the Femoral Head)로 이루어진 군으로부터 선택되는 어느 하나일 수 있고, 바람직하게는 골다공증인 것을 특징으로 할 수 있다.In the present invention, the term “bone disease” includes, without limitation, all bone-related diseases that occur due to the disruption of the balance between bone formation and bone resorption, for example, osteoporosis, non-union fracture, bone Consists of osteonecrosis, osteomalacia, bone defects, osteopenia, bone atrophy, osteoarthritis, periodontal disease, and avascular necrosis of the Femoral Head. It may be any one selected from the group, and may preferably be characterized as osteoporosis.
본 발명에 있어서, 상기 약학적 조성물은 골형성의 촉진 또는 골질환의 예방 또는 치료를 목적으로 정제, 캅셀, 분말, 과립, 액상, 환 등의 형태로 제조 및 가공할 수 있다.In the present invention, the pharmaceutical composition may be manufactured and processed in the form of tablets, capsules, powders, granules, liquids, pills, etc. for the purpose of promoting bone formation or preventing or treating bone diseases.
본 발명에 따른 조성물은 약학적으로 허용 가능한 담체를 포함하여 약학적 조성물로 제제화될 수 있으며, 통상의 방법에 따라 산제, 과립제, 정제, 캡슐제, 현탁액, 에멀젼, 시럽, 에어로졸 등의 경구형 제형, 외용제, 좌제 및 멸균 주사용액의 형태로 제제화될 수 있다.The composition according to the present invention may be formulated into a pharmaceutical composition including a pharmaceutically acceptable carrier, and oral dosage forms such as powders, granules, tablets, capsules, suspensions, emulsions, syrups, and aerosols according to conventional methods , it can be formulated in the form of external preparations, suppositories and sterile injection solutions.
상기 약학적으로 허용가능한 담체는 락토즈, 덱스트로즈, 수크로스, 솔비톨, 만니톨, 자일리톨, 에리스리톨, 말티톨, 전분, 아카시아 고무, 알지네이트, 젤라틴, 칼슘 포스페이트, 칼슘 실리케이트, 셀룰로즈, 메틸 셀룰로즈, 미정질 셀룰로스, 폴리비닐 피롤리돈, 물, 메틸히드록시벤조에이트, 프로필히드록시벤조에이트, 탈크, 마그네슘 스테아레이트 및 광물유 등을 포함한다. 또한, 충진제, 증량제, 결합제, 습윤제, 붕해제, 계면활성제 등의 희석제 또는 부형제를 포함한다. 경구용 고형 제제는 정제, 환제, 산제, 과립제, 캡슐제 등을 포함하며, 이러한 고형제제는 적어도 하나 이상의 부형제 예를 들면, 전분, 칼슘카보네이트 (calcium carbonate), 수크로스(sucrose) 또는 락토오스(lactose), 젤라틴 등을 포함할 수 있으며, 마그네슘 스테아레이트, 탈크 같은 윤활제 등을 포함할 수 있다. 경구용 액상 제제는 현탁제, 내용액제, 유제, 시럽제 등을 포함하며, 물, 리퀴드 파라핀 등의 희석제, 습윤제, 감미제, 방향제, 보존제 등을 포함할 수 있다. 비경구용 제제는 멸균된 수용액, 비수성용제, 현탁제, 유제, 동결건조 제제, 좌제를 포함하며, 비수성 용제, 현탁제로는 프로필렌글리콜(propylene glycol), 폴리에틸렌 글리콜, 올리브 오일과 같은 식물성 기름, 에틸올레이트와 같은 주사 가능한 에스테르류 등을 포함한다. 좌제의 기제로는 위텝솔(witepsol), 마크로골, 트윈 (tween) 61, 카카오지, 라우린지, 글리세로 젤라틴 등이 사용될 수 있다.The pharmaceutically acceptable carrier is lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, gum acacia, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methyl cellulose, microcrystalline cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil and the like. It also includes diluents or excipients such as fillers, extenders, binders, wetting agents, disintegrants, surfactants, and the like. Solid preparations for oral use include tablets, pills, powders, granules, capsules, and the like, and such solid preparations include at least one excipient, for example, starch, calcium carbonate, sucrose or lactose. ), gelatin, and the like, and lubricants such as magnesium stearate and talc. Liquid formulations for oral use include suspensions, solutions, emulsions, syrups, and the like, and may include water and diluents such as liquid paraffin, wetting agents, sweetening agents, fragrances, and preservatives. Parenteral preparations include sterile aqueous solutions, non-aqueous solvents, suspensions, emulsions, freeze-dried preparations, and suppositories, and non-aqueous solvents and suspensions include propylene glycol, polyethylene glycol, vegetable oil such as olive oil, ethyl injectable esters such as oleate; and the like. As the base of the suppository, witepsol, macrogol, tween 61, cacao butter, laurin, glycero gelatin, and the like can be used.
본 발명에 따른 약학적 조성물은 경구 또는 비경구로 투여할 수 있고, 비경구 투여인 경우에는 정맥내 주입, 피하 주입, 근육 주입, 복강 주입, 경피 투여 등으로 투여할 수 있으며, 바람직하게는 경구 투여이다.The pharmaceutical composition according to the present invention may be administered orally or parenterally, and in the case of parenteral administration, it may be administered by intravenous injection, subcutaneous injection, intramuscular injection, intraperitoneal injection, transdermal administration, etc., preferably oral administration am.
상기 약학적 조성물의 적합한 투여량은 제제화 방법, 투여 방식, 환자의 연령, 체중, 성, 병적 상태, 음식, 투여시간, 투여 경로, 배설 속도 및 반응 감응성과 같은 요인들에 의해 다양하며, 보통으로 숙련된 의사는 소망하는 치료 또는 예방에 효과적인 투여량을 용이하게 결정 및 처방할 수 있다. 상기 약학적 조성물의 1일 투여량은 0.1 내지 300 ㎎/㎏/일 또는 약 0.5 내지 50 ㎎/㎏/일 또는 약 1 내지 10 ㎎/㎏/일의 투여량이 일반적으로 충분하다.A suitable dosage of the pharmaceutical composition varies depending on factors such as formulation method, administration mode, age, weight, sex, pathological condition, food, administration time, route of administration, excretion rate, and response sensitivity of the patient, usually A skilled practitioner can readily determine and prescribe a dosage effective for the desired treatment or prevention. A daily dosage of 0.1 to 300 mg/kg/day or about 0.5 to 50 mg/kg/day or about 1 to 10 mg/kg/day of the pharmaceutical composition is generally sufficient.
또한, 본 발명은 풀무치 에탄올 추출물을 포함하는 골질환 예방 또는 개선용 식품 조성물을 제공한다.In addition, the present invention provides a food composition for preventing or improving bone disease comprising an ethanol extract of bell pepper.
본 발명에 따른 조성물이 식품용으로 사용되는 경우, 상기 식품 조성물은 건강기능식품으로서 그 자체로 제형화를 거쳐 사용되거나, 건강기능식품의 첨가물로서 다른 건강기능식품에 포함될 수 있다.When the composition according to the present invention is used for food, the food composition may be used as a health functional food by itself after being formulated, or may be included in other health functional food as an additive to a health functional food.
상기 식품의 종류에는 특별한 제한은 없다. 상기 물질을 첨가할 수 있는 식품의 예로는 육류, 소시지, 빵, 초콜릿, 캔디류, 스낵류, 과자류, 피자, 라면, 기타 면류, 껌류, 아이스크림류를 포함한 낙농제품, 각종 수프, 음료수, 차, 드링크제, 알코올 음료 및 비타민 복합제 등이 있으며, 통상적인 의미에서의 건강기능식품을 모두 포함한다.There is no particular limitation on the type of the food. Examples of foods to which the above substances can be added include meat, sausage, bread, chocolate, candy, snacks, confectionery, pizza, ramen, other noodles, gums, dairy products including ice cream, various soups, beverages, tea, drinks, There are alcoholic beverages and vitamin complexes, and includes all health functional foods in the ordinary sense.
본 발명의 식품 조성물은 식품 또는 식품 첨가물의 제조에 사용되는 통상의 성분들, 구체적으로, 향미제; 천연 탄수화물로서 포도당, 과당과 같은 모노사카라이드, 말토오스, 수크로오스와 같은 디사카라이드 및 덱스트린, 사이클로덱스트린과 같은 천연 감미제나, 사카린, 아스파르탐과 같은 합성 감미제; 영양제; 비타민; 전해질; 착색제; 유기산; 보호성 콜로이드 증점제; pH 조절제; 안정화제; 방부제; 글리세린; 알코올; 탄산 음료에 사용되는 탄산화제 등을 포함할 수 있다.The food composition of the present invention includes conventional ingredients used in the manufacture of food or food additives, specifically, a flavoring agent; As natural carbohydrates, monosaccharides such as glucose and fructose, disaccharides such as maltose and sucrose, and natural sweeteners such as dextrin and cyclodextrin, and synthetic sweeteners such as saccharin and aspartame; Nutrients; vitamin; electrolyte; coloring agent; organic acids; protective colloidal thickeners; pH adjusters; stabilizers; antiseptic; glycerin; Alcohol; Carbonating agents used in carbonated beverages, etc. may be included.
본 발명에 있어서, 상기 식품 조성물 또는 건강기능식품은 골형성, 골강화 또는 성장발육 촉진을 목적으로 정제, 캅셀, 분말, 과립, 액상, 환 등의 형태로 제조 및 가공할 수 있다.In the present invention, the food composition or health functional food can be manufactured and processed in the form of tablets, capsules, powders, granules, liquids, pills, etc. for the purpose of bone formation, bone strengthening or growth and development promotion.
본 발명에서, 용어 "건강기능식품"은 건강기능식품에 관한 법률 제6727호에 따른 인체에 유용한 기능성을 가진 원료나 성분을 사용하여 제조 및 가공한 식품을 말하며, 인체의 구조 및 기능에 대하여 영양소를 조절하거나 생리학적 작용 등과 같은 보건 용도에 유용한 효과를 얻을 목적으로 섭취하는 것을 의미한다. 유효성분의 혼합양은 사용 목적 (예방, 건강 또는 치료적 처치)에 따라 적합하게 결정될 수 있다.In the present invention, the term "health functional food" refers to a food manufactured and processed using raw materials or ingredients useful in the human body according to Act No. 6727 of the Health Functional Food Act, and provides nutrients for the structure and function of the human body. It refers to ingestion for the purpose of obtaining useful effects for health purposes, such as controlling or physiological effects. The mixed amount of the active ingredient may be appropriately determined according to the purpose of use (prevention, health or therapeutic treatment).
본 발명에 따른 건강기능식품은 통상의 식품 첨가물을 포함할 수 있으며, 상기 "식품 첨가물"로서의 적합 여부는 다른 규정이 없는 한, 식품의약품안정청에 승인된 식품 첨가물 공전의 총칙 및 일반시험법 등에 따라 해당 품목에 관한 규격 및 기준에 의하여 판정한다.The health functional food according to the present invention may include normal food additives, and the suitability as the "food additive" is determined according to the general rules and general test methods of food additives approved by the Food and Drug Administration, unless otherwise specified. It is judged according to the standards and standards for the relevant item.
상기 "식품 첨가물 공전"에 수재된 품목으로는 예를 들어, 케톤류, 글리신, 구연산칼륨, 니코틴산, 계피산 등의 화학적 합성물, 감색소, 감초추출물, 결정셀룰로오스, 고량색소, 구아검 등의 천연첨가물, L-글루타민산나트륨 제제, 면류첨가알칼리제, 보존료제제, 타르색소제제 등의 혼합제제류 등을 들 수 있다.The items listed in the "Food Additives Code" include, for example, chemical compounds such as ketones, glycine, potassium citrate, nicotinic acid, and cinnamic acid; and mixed preparations such as sodium L-glutamate preparations, noodle-added alkalis, preservatives, and tar dye preparations.
예를 들어, 정제 형태의 건강기능식품은 풀무치 에탄올 추출물을 부형제, 결합제, 붕해제 및 다른 첨가제와의 혼합물을 통상의 방법으로 과립화한 다음, 활택제 등을 넣어 압축성형하거나, 상기 혼합물을 직접 압축 성형할 수 있다.For example, a health functional food in the form of a tablet is granulated by a mixture of an ethanol extract of bell pepper, an excipient, a binder, a disintegrant, and other additives in a conventional manner, and then compression-molded by adding a lubricant, or the mixture directly Compression molding is possible.
또한, 상기 정제 형태의 건강기능식품은 필요에 따라 교미제 등을 함유할 수 있으며, 필요에 따라 적당한 제피제로 제피할 수도 있다.In addition, the health functional food in the form of tablets may contain a mating agent, etc., if necessary, and may be coated with a suitable skinning agent if necessary.
캅셀 형태의 건강기능식품 중 경질캅셀제는 통상의 경질캅셀에 풀무치 에탄올 추출물을 부형제 등의 첨가제와의 혼합물 또는 그의 입상물 또는 제피한 입상물을 충진하여 제조할 수 있으며, 연질캅셀제는 풀무치 에탄올 추출물을 부형제 등의 첨가제와의 혼합물을 젤라틴 등 캅셀기제에 충진하여 제조할 수 있다. 상기 연질캅셀제는 필요에 따라 글리세린 또는 소르비톨 등의 가소제, 착색제, 보존제 등을 함유할 수 있다.Among health functional foods in the form of capsules, hard capsules can be prepared by filling conventional hard capsules with a mixture of ethanol extract from bellflower radish with additives such as excipients, or their granules or coated granules. It can be prepared by filling a mixture with additives such as excipients in a capsule base such as gelatin. The soft capsules may contain a plasticizer such as glycerin or sorbitol, a colorant, a preservative, and the like, if necessary.
환 형태의 건강기능식품은 풀무치 에탄올 추출물과 부형제, 결합제, 붕해제 등과의 혼합물을 적당한 방법으로 성형하여 조제할 수 있으며, 필요에 따라 백당이나 다른 적당한 제피제로 제피를, 또는 전분, 탈크 또는 적당한 물질로 환의를 입힐 수도 있다.A health functional food in the form of a ring can be prepared by molding a mixture of an ethanol extract of bell pepper and an excipient, binder, disintegrant, etc. in an appropriate way, and if necessary, the skin is coated with sucrose or other suitable skinning agent, or starch, talc, or a suitable substance. You can also dress up with
과립형태의 건강기능식품은 상기 풀무치 에탄올 추출물과 부형제, 결합제, 붕해제 등과의 혼합물을 적당한 방법으로 입상으로 제조할 수 있으며, 필요에 따라 착향제, 교미제 등을 함유할 수 있다.The health functional food in the form of granules may be prepared in granular form by a suitable method of a mixture of the ethanol extract of bell pepper and excipients, binders, disintegrants, and the like, and may contain flavoring agents, flavoring agents, etc. as necessary.
본 발명의 상기 부형제, 결합제, 붕해제, 활택제, 교미제, 착향제 등에 대한 용어 정의는 당업계에 공지된 문헌에 기재된 것으로 그 기능 등이 동일 내지 유사한 것들을 포함한다.The term definitions for the excipients, binders, disintegrants, lubricants, flavoring agents, and the like of the present invention are those described in documents known in the art and include those having the same or similar functions.
또한, 본 발명은 풀무치 에탄올 추출물을 포함하는 골질환 예방 또는 개선용 의약외품 조성물을 제공한다.In addition, the present invention provides a quasi-drug composition for preventing or improving bone disease comprising an ethanol extract of bell pepper.
본 발명에서 용어, "의약외품"은 사람이나 동물의 질병을 치료, 경감, 처치 또는 예방할 목적으로 사용되는 섬유, 고무제품 또는 이와 유사한 것, 인체에 대한 작용이 약하거나 인체에 직접 작용하지 아니며, 기구 또는 기계가 아닌 것과 이와 유사한 것, 감염 예방을 위하여 살균, 살충 및 이와 유사한 용도로 사용되는 제제 중 하나에 해당하는 물품으로서, 사람이나 동물의 질병을 진단, 치료, 경감, 처치 또는 예방할 목적으로 사용하는 물품 중 기구, 기계 또는 장치가 아닌 것 및 사람이나 동물의 구조와 기능에 약리학적 영향을 줄 목적으로 사용하는 물품 중 기구, 기계 또는 장치가 아닌 것을 제외한 물품을 의미하며, 피부 외용제 및 개인위생용품도 포함한다.As used herein, the term "quasi-drug" refers to fibers, rubber products or the like, which are used for the purpose of treating, alleviating, treating or preventing diseases of humans or animals, have weak action on the human body or do not directly act on the human body, or non-machines and similar products, which are products that are used for sterilization, insecticide, and similar purposes to prevent infection It refers to items that are not instruments, machines, or devices, and items used for the purpose of pharmacologically affecting the structure and function of humans or animals, other than those that are not instruments, machines, or devices. Also includes supplies.
본 발명의 풀무치 에탄올 추출물을 골질환 예방 또는 개선을 목적으로 의약외품 조성물에 첨가할 경우, 상기 추출물을 그대로 첨가하거나 다른 분획물이나 다른 의약외품 성분과 함께 사용할 수 있고, 통상적인 방법에 따라 적절하게 사용할 수 있다. 유효 성분의 혼합량은 사용 목적에 따라 적합하게 결정할 수 있다.When the ethanol extract of bell pepper of the present invention is added to a quasi-drug composition for the purpose of preventing or improving bone disease, the extract may be added as it is or used with other fractions or other quasi-drug components, and may be used appropriately according to a conventional method. . The mixing amount of the active ingredient can be appropriately determined according to the purpose of use.
또한, 본 발명은 풀무치 에탄올 추출물을 함유하는 시험관 내(in vitro) 파골세포 분화 억제용 시약 조성물을 제공한다.In addition, the present invention provides a reagent composition for inhibiting osteoclast differentiation in vitro containing an ethanol extract of bell pepper.
본 발명의 풀무치 에탄올 추출물은 시험관 내(in vitro)에서 파골세포의 분화를 억제하는 것을 특징으로 하는 파골세포 분화 억제용 시약 조성물로 활용할 수 있다.The ethanol extract of bell pepper of the present invention can be used as a reagent composition for inhibiting osteoclast differentiation, characterized in that it inhibits osteoclast differentiation in vitro.
이하, 실시예를 통하여 본 발명을 더욱 상세히 설명하고자 한다. 이들 실시예는 오로지 본 발명을 보다 구체적으로 설명하기 위한 것으로, 본 발명의 요지에 따라 본 발명의 범위가 이들 실시예에 의해 제한되지 않는다는 것은 당업계에서 통상의 지식을 가진 자에 있어서 자명할 것이다.Hereinafter, the present invention will be described in more detail through examples. These examples are only for illustrating the present invention in more detail, and it will be apparent to those skilled in the art that the scope of the present invention is not limited by these examples according to the gist of the present invention. .
실시예Example 1. 실험 준비 1. Experimental Preparation
풀무치(Locusta migratoria)는 국립농업과학원 곤충산업과에서 실내 계대 사육한 해남 6세대를 사용하였다. 실험 곤충은 밀을 먹이로 사용하였으며 30℃65% R.H., 9L/15D, 1,800 Lux의 조건에서 사육하였다. 풀무치 추출물은 상기 풀무치를 동결건조 한 후 분말화 하여 Baek 등(J. Life Sci. 2017, 27, 1269-1275.)의 방법에 따라 추출하였다. 구체적으로, 풀무치 동결건조 분말을 70% 에탄올의 10%(v/v)가 되게 혼합하여 초음파 처리(250 J, 10초, 2회)한 후 30분간 실온에서 방치하였다. 혼합액의 상등액을 걸러 원심농축기(EYELA, Tokyo, Japan)를 이용하여 완전히 건조한 후 사용 전까지 -20℃에서 냉동보관하였다. 상기 과정을 통해 수득한 풀무치 추출물을 LME로 명명하였다. Bellows ( Locusta) migratoria ) used the 6th generation Haenam, which was bred indoors in the Department of Insect Industry at the National Academy of Agricultural Sciences. The experimental insects used wheat as food, and were reared at 30℃ 65% RH, 9L/15D, and 1,800 Lux. The bellflower extract was lyophilized and then powdered and extracted according to the method of Baek et al. (J. Life Sci. 2017, 27, 1269-1275.). Specifically, the freeze-dried powder of bell peppers was mixed so as to be 10% (v/v) of 70% ethanol, followed by ultrasonication (250 J, 10 seconds, twice), and then left at room temperature for 30 minutes. The supernatant of the mixed solution was filtered, dried completely using a centrifugal concentrator (EYELA, Tokyo, Japan), and then stored frozen at -20°C until use. The bellflower extract obtained through the above process was named LME.
파골세포(마우스 대식세포주 유래 Raw264.7)는 ATCC에서 구입하였으며 10% FBS (fetal bovine serum) (Hyclone, Logan, UT, USA)와 1× 페니실린-스트렙토마이신 (Hyclone)이 첨가된 DMEM 배지(Dulbecco's Modified Eagle Medium) (Hyclone)를 사용하여 배양하였고 세포는 37℃, 5% CO2의 배양조건을 유지하였다. 세포가 충분히 성장하는 2-3일 간격으로 계대 배양하며 실험을 진행하였다.Osteoclasts (Raw264.7 derived from a mouse macrophage cell line) were purchased from ATCC and added with 10% FBS (fetal bovine serum) (Hyclone, Logan, UT, USA) and 1× penicillin-streptomycin (Hyclone) in DMEM medium (Dulbecco's). Modified Eagle Medium) (Hyclone) was used and the cells were maintained at 37° C. and 5% CO 2 culture conditions. The experiment was carried out by subculture at intervals of 2-3 days when the cells were sufficiently grown.
실시예Example 2. 풀무치 에탄올 추출물의 세포독성 확인 2. Confirmation of cytotoxicity of ethanol extract of bell pepper
본 발명에 따른 풀무치 에탄올 추출물이 Raw264.7 세포의 증식 및 독성에 미치는 영향을 확인하기 위하여 세포 독성 실험을 수행하였다. 구체적으로, Raw264.7 세포를 96-웰 플레이트에 5.0 × 103 cells/웰로 분주하여 세포밀도(confluence)가 약 80%에 도달할 때까지 10% FBS가 들어있는 배지에서 약 24시간 동안 배양하였다. 그 후 풀무치 에탄올 추출물을 농도(100, 500, 1000, 2000 μg/mL)에 따라 처리하고 24시간 및 48시간 동안 추가 배양한 후 MTS(3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium) 시약을 사용하여 세포 생존율을 측정하였다. 그 결과를 도 1에 나타내었다.A cytotoxicity test was performed to confirm the effect of the ethanol extract of bell pepper according to the present invention on the proliferation and toxicity of Raw264.7 cells. Specifically, Raw264.7 cells were seeded in a 96-well plate at 5.0 × 10 3 cells/well and cultured in a medium containing 10% FBS for about 24 hours until the cell density (confluence) reached about 80%. . After that, the ethanol extract of bell peppers was treated according to the concentration (100, 500, 1000, 2000 μg/mL), and after further incubation for 24 hours and 48 hours, MTS(3-(4,5-dimethylthiazol-2-yl)-5 Cell viability was measured using -(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium) reagent. The results are shown in FIG. 1 .
도 1에 나타낸 바와 같이, 본 발명의 풀무치 에탄올 추출물은 2000 μg/mL까지 Raw264.7 세포 독성을 유발하지 않음을 확인하였다. As shown in FIG. 1 , it was confirmed that the ethanol extract of bell pepper of the present invention did not induce Raw264.7 cytotoxicity up to 2000 μg/mL.
실시예Example 3. 풀무치 에탄올 추출물이 파골세포의 분화에 미치는 영향 관찰 3. Observation of Effect of Ethanol Extract of Bellulberry on Osteoclast Differentiation
3-1. TRAP 활성 측정3-1. TRAP activity measurement
파골세포는 분화가 진행되면서 단핵의 전 파골세포를 형성하지만, 세포가 융합되면서 다핵의 성숙 파골세포를 형성하게 되고 이는 골 표면에 부착하여 골을 흡수하는 작용을 한다. 파골세포는 TRAP와 칼시토닌 수용체를 가지며, 산 생성이 활발한 특징을 가져, 파골세포의 표지 인자로 널리 사용되고 있다. 이에, Raw 264.7 세포를 이용하여 TRAP 염색을 하고 TRAP 활성 변화를 측정하였다. 구체적으로, Raw 264.7 세포를 5 × 104 cells/ml로 조정하여 96-웰 플레이트에 분주하여 24시간 배양하였다. 배지를 제거하고 DMEM 배지에 분화 인자인 RANKL 100 ng/mL와 시료로써 본 발명의 풀무치 에탄올 추출물을 농도 별로(0, 100, 500, 1000, 2000 μg/mL) 처리하여 4일간 배양하였다. 이후 배지를 제거하고 PBS로 세척한 후 고정 용액(시트레이트 용액 + 아세톤 + 포름알데히드)으로 세포를 고정한 뒤, 기질 용액으로 1.36 mg/ml 4-니트로페닐 포스페이트 디소듐 염(4-nitrophenyl phosphate disodium salt), 10 mM 타르타르산(tartrate)을 포함하는 50 mM 시트레이트 완충용액(pH 4.6)을 제조하여 고정한 세포에 분주하였다. 37℃, 5% CO2 배양기에서 30분간 반응 후 효소 반응액을 0.1 N NaOH로 반응을 중지시키고 ELISA 리더로 405 nm에서 흡광도를 측정하였다. TRAP 활성은 시료의 흡광도를 대조군에 대한 백분율로 표시하였다. 그 결과를 도 2에 나타내었다.As osteoclasts differentiate, they form mononuclear pro-osteoclasts, but as the cells fuse, they form multinucleated mature osteoclasts, which attach to the bone surface and absorb bone. Osteoclasts have TRAP and calcitonin receptors, have an active acid production feature, and are widely used as markers for osteoclasts. Accordingly, TRAP staining was performed using Raw 264.7 cells and the change in TRAP activity was measured. Specifically, Raw 264.7 cells were adjusted to 5 × 10 4 cells/ml, aliquoted in a 96-well plate, and cultured for 24 hours. After removing the medium, 100 ng/mL of RANKL, a differentiation factor, and an ethanol extract of the present invention as a sample were treated in DMEM medium by concentration (0, 100, 500, 1000, 2000 μg/mL) and cultured for 4 days. After removing the medium and washing with PBS, the cells were fixed with a fixing solution (citrate solution + acetone + formaldehyde), and 1.36 mg/ml 4-nitrophenyl phosphate disodium salt as a substrate solution ), a 50 mM citrate buffer (pH 4.6) containing 10 mM tartaric acid was prepared and dispensed into the fixed cells. After reacting for 30 minutes at 37° C., 5% CO 2 incubator, the reaction was stopped with 0.1 N NaOH and absorbance was measured at 405 nm with an ELISA reader. TRAP activity was expressed as a percentage of the absorbance of the sample relative to the control. The results are shown in FIG. 2 .
도 2에 나타낸 바와 같이, RANKL에 의해 증가된 TRAP 활성이 본 발명의 풀무치 에탄올 추출물 처리에 의해 농도의존적으로 감소함을 확인하였다. 상기 결과를 통해, 본 발명의 풀무치 에탄올 추출물은 파골세포의 분화를 효과적으로 억제함을 확인하였다. As shown in FIG. 2 , it was confirmed that the TRAP activity increased by RANKL was decreased in a concentration-dependent manner by treatment with the ethanol extract of the present invention. From the above results, it was confirmed that the ethanol extract of bell pepper of the present invention effectively inhibited the differentiation of osteoclasts.
3-2. 파골세포 분화 관련 유전자 발현 측정3-2. Measurement of osteoclast differentiation-related gene expression
본 발명에 따른 풀무치 에탄올 추출물이 파골세포 분화 유전자 마커인 TRAP, RANK, NFATc1 및 CathepsinK의 발현에 미치는 영향을 확인하였다. 구체적으로, Raw 264.7 세포를 1 x 104 cells/웰의 농도로 48-웰 플레이트에 시딩하고, 100 ng/mL RANKL과 시료로써 본 발명의 풀무치 에탄올 추출물을 농도 별로(0, 100, 500, 1000, 2000 μg/mL) 처리하여 5일 동안 37℃ 배양기에서 배양하였다. 배양 완료된 세포를 회수하고 RNA를 추출하여 RT-PCR을 수행하였다. 그 결과를 도 3에 나타내었다.The effect of the ethanol extract of bell pepper according to the present invention on the expression of osteoclast differentiation gene markers TRAP, RANK, NFATc1 and CathepsinK was confirmed. Specifically, Raw 264.7 cells were seeded in a 48-well plate at a concentration of 1 x 10 4 cells/well, and 100 ng/mL RANKL and an ethanol extract of the present invention as a sample were added to each concentration (0, 100, 500, 1000). , 2000 μg/mL) and incubated in an incubator at 37° C. for 5 days. RT-PCR was performed by recovering cultured cells and extracting RNA. The results are shown in FIG. 3 .
도 3에 나타낸 바와 같이, RANKL 처리에 의해 증가된 TRAP, RANK, NFATc1 및 CathepsinK의 유전자 발현이 본 발명의 풀무치 에탄올 추출물을 처리함에 따라 감소함을 확인하였다. TRAP, NFATc1 및 CathepsinK의 경우 풀무치 에탄올 추출물 처리에 의해 발현량이 농도의존적으로 감소하였다. 상기 결과를 통해, 본 발명의 풀무치 에탄올 추출물은 파골세포의 분화를 효과적으로 억제함을 확인하였다.As shown in FIG. 3 , it was confirmed that the gene expression of TRAP, RANK, NFATc1 and CathepsinK increased by RANKL treatment was decreased by treatment with the ethanol extract of the present invention. In the case of TRAP, NFATc1 and CathepsinK, the expression levels were decreased in a concentration-dependent manner by treatment with an ethanol extract of bell pepper. From the above results, it was confirmed that the ethanol extract of bell pepper of the present invention effectively inhibited the differentiation of osteoclasts.
3-3. 파골세포 분화 관련 단백질 발현 측정3-3. Measurement of osteoclast differentiation-related protein expression
본 발명에 따른 풀무치 에탄올 추출물이 파골세포 분화와 관련된 NFATc1 및 c-Src 단백질 발현에 미치는 영향을 확인하였다. 구체적으로, Raw 264.7 세포를 1 x 104 cells/웰의 농도로 48-웰 플레이트에 시딩하고, 100 ng/mL RANKL과 시료로써 본 발명의 풀무치 에탄올 추출물을 농도 별로(0, 100, 500, 1000, 2000 μg/mL) 처리하여 5일 동안 37℃ 배양기에서 배양하였다. 배양완료된 세포를 회수하고 단백질을 추출하여 웨스턴 블랏을 수행하였다. 그 결과를 도 4에 나타내었다.The effect of the ethanol extract of bell pepper according to the present invention on the expression of NFATc1 and c-Src proteins related to osteoclast differentiation was confirmed. Specifically, Raw 264.7 cells were seeded in a 48-well plate at a concentration of 1 x 10 4 cells/well, and 100 ng/mL RANKL and an ethanol extract of the present invention as a sample were added to each concentration (0, 100, 500, 1000). , 2000 μg/mL) and incubated in an incubator at 37° C. for 5 days. Cultured cells were recovered, proteins were extracted, and Western blot was performed. The results are shown in FIG. 4 .
도 4에 나타낸 바와 같이, RANKL 처리 시 증가한 NFATc1 및 c-Src 단백질 발현량이 본 발명의 풀무치 에탄올 추출물 처리에 의해 감소함을 확인하였다. NFATc1의 경우 풀무치 에탄올 추출물 처리에 의해 단백질 발현량이 농도의존적으로 감소하였다. 상기 결과를 통해, 본 발명의 풀무치 에탄올 추출물은 파골세포의 분화를 효과적으로 억제함을 확인하였다.As shown in FIG. 4 , it was confirmed that the expression levels of NFATc1 and c-Src proteins increased during RANKL treatment were decreased by the treatment with the ethanol extract of the present invention. In the case of NFATc1, the protein expression level was decreased in a concentration-dependent manner by treatment with the ethanol extract of bell pepper. From the above results, it was confirmed that the ethanol extract of bell pepper of the present invention effectively inhibited the differentiation of osteoclasts.
3-4. 파골세포 분화 관련 3-4. Related to osteoclast differentiation 시그널링signaling 단백질 발현 측정 Protein expression measurement
본 발명에 따른 풀무치 에탄올 추출물이 파골세포 분화와 관련된 MAPK 신호전달 관련 단백질(ERK, JNK) 및 NF-κ신호전달인자의 발현에 미치는 영향을 확인하였다. 구체적으로, 100 ng/mL RANKL과 농도별 풀무치 에탄올 추출물(0, 100, 500, 1000, 2000 μg/mL) 처리에 따른 MAPK 신호전달경로 및 NF-κ 신호전달경로 관련 단백질의 활성화를 확인하기 위하여, ERK(extracellular signal-regulated protein kinase) 단백질, JNK(Jun-N-terminal kinase) 단백질, p-38 및 IκB 단백질의 인산화를 각각 관찰하였다. 그 결과를 도 5에 나타내었다.The effect of the ethanol extract of bell pepper according to the present invention on the expression of MAPK signaling related proteins (ERK, JNK) and NF-κ signaling factors related to osteoclast differentiation was confirmed. Specifically, in order to confirm the activation of the MAPK signaling pathway and NF-κ signaling pathway-related proteins following treatment with 100 ng/mL RANKL and ethanol extract of bell pepper (0, 100, 500, 1000, 2000 μg/mL) for each concentration , phosphorylation of extracellular signal-regulated protein kinase (ERK) protein, Jun-N-terminal kinase (JNK) protein, p-38 and IκB protein was observed, respectively. The results are shown in FIG. 5 .
도 5에 나타낸 바와 같이, 본 발명의 풀무치 에탄올 추출물은 ERK, JNK 및 IκB 활성의 감소를 유발함을 확인하였다. 상기 결과를 통해, 본 발명의 풀무치 에탄올 추출물은 파골세포 분화의 신호전달과정을 억제할 수 있음을 확인하였다.As shown in FIG. 5 , it was confirmed that the ethanol extract of bell pepper of the present invention induced a decrease in ERK, JNK and IκB activities. Through the above results, it was confirmed that the ethanol extract of bell pepper of the present invention can inhibit the signaling process of osteoclast differentiation.
따라서, 파골세포 분화를 억제하는 풀무치 에탄올 추출물을 유효성분으로 포함하여, 천연물로 세포독성을 나타내지 않으면서도 파골세포 분화 활성을 현저하게 억제시킬 수 있어 골형성 촉진, 골소실 또는 골 대사 불균형으로 인한 골질환의 효과적인 예방 및 치료를 위한 약학적 조성물 또는 건강기능식품으로 유용하게 사용될 수 있다.Therefore, by including the bell pepper extract that inhibits osteoclast differentiation as an active ingredient, it can significantly inhibit osteoclast differentiation activity without showing cytotoxicity as a natural product. It can be usefully used as a pharmaceutical composition or health functional food for the effective prevention and treatment of diseases.
이상으로 본 발명의 특정한 부분을 상세히 기술하였는바, 당업계의 통상의 지식을 가진 자에게 있어서 이러한 구체적인 기술은 단지 바람직한 구현 예일 뿐이며, 이에 본 발명의 범위가 제한되는 것이 아닌 점은 명백하다. 따라서, 본 발명의 실질적인 범위는 첨부된 청구항과 그의 등가물에 의하여 정의된다고 할 것이다.As described above in detail a specific part of the present invention, for those of ordinary skill in the art, this specific description is only a preferred embodiment, and it is clear that the scope of the present invention is not limited thereto. Accordingly, the substantial scope of the present invention will be defined by the appended claims and their equivalents.
Claims (9)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| KR1020190148669A KR102292696B1 (en) | 2019-11-19 | 2019-11-19 | Locusta Migratoria ethanol extract for inhibiting osteoclast differentiation and uses therof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| KR1020190148669A KR102292696B1 (en) | 2019-11-19 | 2019-11-19 | Locusta Migratoria ethanol extract for inhibiting osteoclast differentiation and uses therof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| KR20210060983A KR20210060983A (en) | 2021-05-27 |
| KR102292696B1 true KR102292696B1 (en) | 2021-08-24 |
Family
ID=76135674
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR1020190148669A KR102292696B1 (en) | 2019-11-19 | 2019-11-19 | Locusta Migratoria ethanol extract for inhibiting osteoclast differentiation and uses therof |
Country Status (1)
| Country | Link |
|---|---|
| KR (1) | KR102292696B1 (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20220032504A (en) | 2020-09-07 | 2022-03-15 | 주식회사 성균바이오텍 | A composition for the prevention or treatment of depression or bone metabolism related diseases containing Hippophae rhamnoides fruits extract |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR100835214B1 (en) | 2006-09-01 | 2008-06-09 | 재단법인 제주하이테크산업진흥원 | Anomala albopilosa extracts having anti-oxidant activity and bone metabolism factor inhibition activity |
| JP2015047076A (en) | 2013-08-29 | 2015-03-16 | 独立行政法人産業技術総合研究所 | Cell culture substrate, method for differentiation-inducing of osteoblasts using the same and method for producing osteoblasts |
| KR101806474B1 (en) | 2016-10-25 | 2017-12-07 | 순천향대학교 산학협력단 | A composition for improving, preventing and treating of bone diseases comprising Tenebrio molitor extract |
| KR102185436B1 (en) * | 2018-10-25 | 2020-12-01 | 대한민국 | Composition comprising Locusta migratoria extract for promoting osteoblast differentiation |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20160041110A (en) * | 2014-10-06 | 2016-04-18 | 대한민국(농촌진흥청장) | Composition for Prevention or Treatment of Rheumatoid Arthritis Comprising extract suspension of Tenebrio molitor |
-
2019
- 2019-11-19 KR KR1020190148669A patent/KR102292696B1/en active IP Right Grant
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR100835214B1 (en) | 2006-09-01 | 2008-06-09 | 재단법인 제주하이테크산업진흥원 | Anomala albopilosa extracts having anti-oxidant activity and bone metabolism factor inhibition activity |
| JP2015047076A (en) | 2013-08-29 | 2015-03-16 | 独立行政法人産業技術総合研究所 | Cell culture substrate, method for differentiation-inducing of osteoblasts using the same and method for producing osteoblasts |
| KR101806474B1 (en) | 2016-10-25 | 2017-12-07 | 순천향대학교 산학협력단 | A composition for improving, preventing and treating of bone diseases comprising Tenebrio molitor extract |
| KR102185436B1 (en) * | 2018-10-25 | 2020-12-01 | 대한민국 | Composition comprising Locusta migratoria extract for promoting osteoblast differentiation |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20220032504A (en) | 2020-09-07 | 2022-03-15 | 주식회사 성균바이오텍 | A composition for the prevention or treatment of depression or bone metabolism related diseases containing Hippophae rhamnoides fruits extract |
Also Published As
| Publication number | Publication date |
|---|---|
| KR20210060983A (en) | 2021-05-27 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| KR101855423B1 (en) | A composition comprising 5,6-dichloroindirubin-3'-methoxime and 5-methoxylindirubin-3'-oxime | |
| KR101997060B1 (en) | Composition for prevention or treatment of muscular disorder, or improvement of muscular functions comprising fermented deer antler | |
| KR101269208B1 (en) | Composition comprising sauchinone as an active ingredient for preventing or treating insulin resistance | |
| US9655878B2 (en) | Composition comprising coumestrol or a bean extract containing coumestrol | |
| KR102292696B1 (en) | Locusta Migratoria ethanol extract for inhibiting osteoclast differentiation and uses therof | |
| US8865762B2 (en) | Method for the treatment of bone diseases comprising colforsin daropate | |
| KR101308144B1 (en) | Pharmaceutical composition for Prevention or Treatment of bone diseases comprising agelasin D | |
| KR101242635B1 (en) | Composition for Prevention or Treatment of Osteoporosis Comprising Extract of Selaginellae Herba | |
| KR102002260B1 (en) | A composition comprising the compounds isolated from an extract of Allium sativum L. for treating and preventing muscle-related disorder | |
| KR102465894B1 (en) | Composition for preventing, ameliorating or treating bone disease comprising salvianolic acid as effective component | |
| KR102372440B1 (en) | Phamaceutical Composition Comprising an Extract of Artemisia scoparia for Preventing or Treating Metabolic Bone Disease-induced Bone Loss | |
| KR20130009685A (en) | Composition comprising esculetin for inhibition of bone loss | |
| KR101167678B1 (en) | Composition for preventing and treating of diabetes containing glyceollin or glyceollin enhanced fermented soybean as an effective ingredient | |
| KR102521988B1 (en) | Pharmaceutical composition for treating or preventing cancer comprising gamma-glutamyltyrosine | |
| KR20210007401A (en) | Pharmaceutical composition for enhancing osteogenesis comprising Tenebrio molitor oil | |
| KR101539978B1 (en) | Chromen-4-one derivative or pharmaceutically acceptable salts thereof and pharmaceutical composition for stimulating bone-forming | |
| KR101655554B1 (en) | Pharmaceutical composition for prevention or treatment bone diseases comprising Alisma canaliculatum extract or fractions thereof, or compounds isolated from therefrom | |
| KR102410703B1 (en) | Composition for preventing, improving or treating bone disease comprising Pyrrosia lingua extract as effective component | |
| KR101996184B1 (en) | Adjuvant of anti-cancer agent comprising and an extract of Allium sativum L. for treating and preventing cachexia | |
| KR101575702B1 (en) | Pharmaceutical compositions containing extract of Phellinus baumii or fraction thereof of wound-healing or skin activation | |
| KR101965699B1 (en) | A composition comprising and an extract of Allium sativum L. for treating and preventing muscle-related disorder | |
| KR101888578B1 (en) | A pharmaceutical composition for promoting osteogenesis comprising thiacremonone | |
| KR20210004390A (en) | Pharmaceutical composition for prevention or treatment of osteoporosis comprising Sipholenol A | |
| KR102112753B1 (en) | Benzophenones and their use | |
| KR20220115062A (en) | Pharmaceutical Composition For Treating and Preventing Osteoporosis Comprising Compounds of Chromone Scaffold |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| E701 | Decision to grant or registration of patent right | ||
| GRNT | Written decision to grant |