KR20210060992A - Composition for preventing or treating of neuroinflammation comprising Protaetia brevitarsis seulensis larva ethanol extract - Google Patents
Composition for preventing or treating of neuroinflammation comprising Protaetia brevitarsis seulensis larva ethanol extract Download PDFInfo
- Publication number
- KR20210060992A KR20210060992A KR1020190148688A KR20190148688A KR20210060992A KR 20210060992 A KR20210060992 A KR 20210060992A KR 1020190148688 A KR1020190148688 A KR 1020190148688A KR 20190148688 A KR20190148688 A KR 20190148688A KR 20210060992 A KR20210060992 A KR 20210060992A
- Authority
- KR
- South Korea
- Prior art keywords
- ethanol extract
- composition
- disease
- white spotted
- neuroinflammation
- Prior art date
Links
- 239000000469 ethanolic extract Substances 0.000 title claims abstract description 74
- 230000003959 neuroinflammation Effects 0.000 title claims abstract description 35
- 208000036110 Neuroinflammatory disease Diseases 0.000 title claims abstract description 34
- 239000000203 mixture Substances 0.000 title claims description 36
- 241000111850 Protaetia brevitarsis seulensis Species 0.000 title abstract description 11
- 230000014509 gene expression Effects 0.000 claims abstract description 27
- 208000019736 Cranial nerve disease Diseases 0.000 claims abstract description 18
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 17
- 208000014826 cranial nerve neuropathy Diseases 0.000 claims abstract description 9
- 241000220259 Raphanus Species 0.000 claims description 69
- 235000006140 Raphanus sativus var sativus Nutrition 0.000 claims description 69
- MWUXSHHQAYIFBG-UHFFFAOYSA-N Nitric oxide Chemical compound O=[N] MWUXSHHQAYIFBG-UHFFFAOYSA-N 0.000 claims description 50
- 210000000274 microglia Anatomy 0.000 claims description 21
- 238000011282 treatment Methods 0.000 claims description 19
- 239000002158 endotoxin Substances 0.000 claims description 16
- 235000013305 food Nutrition 0.000 claims description 16
- 229920006008 lipopolysaccharide Polymers 0.000 claims description 16
- 108060008682 Tumor Necrosis Factor Proteins 0.000 claims description 14
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 claims description 14
- 108090001005 Interleukin-6 Proteins 0.000 claims description 13
- 102100029438 Nitric oxide synthase, inducible Human genes 0.000 claims description 12
- 101710089543 Nitric oxide synthase, inducible Proteins 0.000 claims description 12
- 102100038280 Prostaglandin G/H synthase 2 Human genes 0.000 claims description 12
- 108050003267 Prostaglandin G/H synthase 2 Proteins 0.000 claims description 12
- 229940079593 drug Drugs 0.000 claims description 11
- 239000003814 drug Substances 0.000 claims description 11
- 230000002265 prevention Effects 0.000 claims description 10
- 238000000034 method Methods 0.000 claims description 8
- 230000028709 inflammatory response Effects 0.000 claims description 6
- 208000024827 Alzheimer disease Diseases 0.000 claims description 5
- 208000000044 Amnesia Diseases 0.000 claims description 5
- 208000031091 Amnestic disease Diseases 0.000 claims description 5
- 208000018737 Parkinson disease Diseases 0.000 claims description 5
- 230000006986 amnesia Effects 0.000 claims description 5
- 206010002026 amyotrophic lateral sclerosis Diseases 0.000 claims description 5
- 206010015037 epilepsy Diseases 0.000 claims description 5
- 208000020406 Creutzfeldt Jacob disease Diseases 0.000 claims description 4
- 208000003407 Creutzfeldt-Jakob Syndrome Diseases 0.000 claims description 4
- 208000010859 Creutzfeldt-Jakob disease Diseases 0.000 claims description 4
- 208000023105 Huntington disease Diseases 0.000 claims description 4
- 206010029260 Neuroblastoma Diseases 0.000 claims description 4
- 208000006011 Stroke Diseases 0.000 claims description 4
- 201000006417 multiple sclerosis Diseases 0.000 claims description 4
- 208000028173 post-traumatic stress disease Diseases 0.000 claims description 4
- 201000000980 schizophrenia Diseases 0.000 claims description 4
- 201000010901 lateral sclerosis Diseases 0.000 claims 2
- 208000005264 motor neuron disease Diseases 0.000 claims 2
- 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 claims 1
- 230000036541 health Effects 0.000 abstract description 19
- 235000013376 functional food Nutrition 0.000 abstract description 17
- 108090000623 proteins and genes Proteins 0.000 abstract description 15
- 102000004127 Cytokines Human genes 0.000 abstract description 13
- 108090000695 Cytokines Proteins 0.000 abstract description 13
- 102000004169 proteins and genes Human genes 0.000 abstract description 11
- 230000002314 neuroinflammatory effect Effects 0.000 abstract description 10
- 231100000135 cytotoxicity Toxicity 0.000 abstract description 7
- 230000003013 cytotoxicity Effects 0.000 abstract description 7
- 239000004480 active ingredient Substances 0.000 abstract description 5
- 230000003215 anti-neuroinflammatory effect Effects 0.000 abstract description 3
- 239000003112 inhibitor Substances 0.000 abstract description 3
- 239000000463 material Substances 0.000 abstract description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 23
- 210000004027 cell Anatomy 0.000 description 14
- 239000000284 extract Substances 0.000 description 13
- 238000002360 preparation method Methods 0.000 description 13
- 102000004889 Interleukin-6 Human genes 0.000 description 12
- 229940100601 interleukin-6 Drugs 0.000 description 12
- 239000000126 substance Substances 0.000 description 12
- 201000010099 disease Diseases 0.000 description 9
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 9
- 230000002757 inflammatory effect Effects 0.000 description 9
- 210000002569 neuron Anatomy 0.000 description 8
- 239000000546 pharmaceutical excipient Substances 0.000 description 8
- 239000000843 powder Substances 0.000 description 8
- 206010061218 Inflammation Diseases 0.000 description 7
- 230000004913 activation Effects 0.000 description 7
- 230000000694 effects Effects 0.000 description 7
- 230000004054 inflammatory process Effects 0.000 description 7
- 238000004519 manufacturing process Methods 0.000 description 7
- 108090000790 Enzymes Proteins 0.000 description 6
- 102000004190 Enzymes Human genes 0.000 description 6
- 208000012902 Nervous system disease Diseases 0.000 description 6
- 208000025966 Neurological disease Diseases 0.000 description 6
- 241000767511 Protaetia Species 0.000 description 6
- 239000008187 granular material Substances 0.000 description 6
- 230000002401 inhibitory effect Effects 0.000 description 6
- 239000000654 additive Substances 0.000 description 5
- 239000011230 binding agent Substances 0.000 description 5
- 239000002775 capsule Substances 0.000 description 5
- 238000011161 development Methods 0.000 description 5
- 230000018109 developmental process Effects 0.000 description 5
- 238000010586 diagram Methods 0.000 description 5
- 239000007884 disintegrant Substances 0.000 description 5
- 239000000796 flavoring agent Substances 0.000 description 5
- 235000013373 food additive Nutrition 0.000 description 5
- 239000002778 food additive Substances 0.000 description 5
- 235000013355 food flavoring agent Nutrition 0.000 description 5
- 230000006870 function Effects 0.000 description 5
- 238000005259 measurement Methods 0.000 description 5
- 208000014644 Brain disease Diseases 0.000 description 4
- 108010010803 Gelatin Proteins 0.000 description 4
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 4
- 241000238631 Hexapoda Species 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
- 230000001405 anti-neuronal effect Effects 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 4
- 230000008859 change Effects 0.000 description 4
- 238000002474 experimental method Methods 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
- 230000006872 improvement 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
- 150000003180 prostaglandins Chemical class 0.000 description 4
- 235000018102 proteins Nutrition 0.000 description 4
- 230000002829 reductive effect Effects 0.000 description 4
- 238000011160 research Methods 0.000 description 4
- 239000003826 tablet Substances 0.000 description 4
- LOGFVTREOLYCPF-KXNHARMFSA-N (2s,3r)-2-[[(2r)-1-[(2s)-2,6-diaminohexanoyl]pyrrolidine-2-carbonyl]amino]-3-hydroxybutanoic acid Chemical compound C[C@@H](O)[C@@H](C(O)=O)NC(=O)[C@H]1CCCN1C(=O)[C@@H](N)CCCCN LOGFVTREOLYCPF-KXNHARMFSA-N 0.000 description 3
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 3
- 241000282412 Homo Species 0.000 description 3
- 102000003777 Interleukin-1 beta Human genes 0.000 description 3
- 108090000193 Interleukin-1 beta Proteins 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 229920002472 Starch Polymers 0.000 description 3
- 210000003169 central nervous system Anatomy 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- 239000003153 chemical reaction reagent Substances 0.000 description 3
- 239000011248 coating agent Substances 0.000 description 3
- 238000012790 confirmation Methods 0.000 description 3
- 238000007796 conventional method Methods 0.000 description 3
- 230000001419 dependent effect Effects 0.000 description 3
- 239000000839 emulsion Substances 0.000 description 3
- 238000000605 extraction Methods 0.000 description 3
- 239000012091 fetal bovine serum Substances 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 239000000314 lubricant Substances 0.000 description 3
- 230000004770 neurodegeneration Effects 0.000 description 3
- 239000002547 new drug Substances 0.000 description 3
- 239000006187 pill Substances 0.000 description 3
- 239000003755 preservative agent Substances 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 239000003642 reactive oxygen metabolite Substances 0.000 description 3
- 239000008107 starch Substances 0.000 description 3
- 235000019698 starch Nutrition 0.000 description 3
- 239000005720 sucrose Substances 0.000 description 3
- 239000000829 suppository Substances 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- 238000003786 synthesis reaction Methods 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
- 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
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 2
- 238000002965 ELISA Methods 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
- 108010001336 Horseradish Peroxidase 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
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 2
- 239000002033 PVDF binder Substances 0.000 description 2
- 102000004005 Prostaglandin-endoperoxide synthases Human genes 0.000 description 2
- 108090000459 Prostaglandin-endoperoxide synthases Proteins 0.000 description 2
- 244000299461 Theobroma cacao Species 0.000 description 2
- 210000001642 activated microglia Anatomy 0.000 description 2
- 230000000996 additive effect Effects 0.000 description 2
- 239000003125 aqueous solvent Substances 0.000 description 2
- 239000002585 base 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
- 239000001913 cellulose Substances 0.000 description 2
- 235000010980 cellulose Nutrition 0.000 description 2
- 229920002678 cellulose Polymers 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 239000003086 colorant Substances 0.000 description 2
- 235000009508 confectionery Nutrition 0.000 description 2
- 230000006378 damage Effects 0.000 description 2
- 230000003247 decreasing effect Effects 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 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
- 239000001963 growth medium Substances 0.000 description 2
- 239000007902 hard capsule Substances 0.000 description 2
- 241000411851 herbal medicine Species 0.000 description 2
- 230000036737 immune function Effects 0.000 description 2
- 230000028993 immune response Effects 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- 210000002540 macrophage Anatomy 0.000 description 2
- 235000019359 magnesium stearate Nutrition 0.000 description 2
- 239000002609 medium Substances 0.000 description 2
- 239000012528 membrane Substances 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 210000000653 nervous system Anatomy 0.000 description 2
- 239000003592 new natural product Substances 0.000 description 2
- 235000012149 noodles Nutrition 0.000 description 2
- 239000002953 phosphate buffered saline Substances 0.000 description 2
- 239000000049 pigment Substances 0.000 description 2
- 229920002981 polyvinylidene fluoride Polymers 0.000 description 2
- 230000002335 preservative effect Effects 0.000 description 2
- 230000001737 promoting effect Effects 0.000 description 2
- 238000003757 reverse transcription PCR Methods 0.000 description 2
- 230000028327 secretion Effects 0.000 description 2
- 239000007901 soft capsule Substances 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
- -1 specifically Substances 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- 239000003765 sweetening agent Substances 0.000 description 2
- 208000024891 symptom Diseases 0.000 description 2
- 239000006188 syrup Substances 0.000 description 2
- 235000020357 syrup Nutrition 0.000 description 2
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 2
- 239000003053 toxin Substances 0.000 description 2
- 231100000765 toxin Toxicity 0.000 description 2
- 108700012359 toxins Proteins 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
- 244000144730 Amygdalus persica Species 0.000 description 1
- 108010011485 Aspartame Proteins 0.000 description 1
- 208000023275 Autoimmune disease Diseases 0.000 description 1
- 238000009020 BCA Protein Assay Kit Methods 0.000 description 1
- 241000894006 Bacteria Species 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
- 241000254173 Coleoptera Species 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
- 238000008157 ELISA kit Methods 0.000 description 1
- 241000196324 Embryophyta 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
- 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
- CEAZRRDELHUEMR-URQXQFDESA-N Gentamicin Chemical compound O1[C@H](C(C)NC)CC[C@@H](N)[C@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](NC)[C@@](C)(O)CO2)O)[C@H](N)C[C@@H]1N CEAZRRDELHUEMR-URQXQFDESA-N 0.000 description 1
- 229930182566 Gentamicin Natural products 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 229920002907 Guar gum Polymers 0.000 description 1
- 229920000084 Gum arabic Polymers 0.000 description 1
- 206010019851 Hepatotoxicity Diseases 0.000 description 1
- 101000611183 Homo sapiens Tumor necrosis factor Proteins 0.000 description 1
- ODKSFYDXXFIFQN-BYPYZUCNSA-N L-arginine Chemical compound OC(=O)[C@@H](N)CCCN=C(N)N ODKSFYDXXFIFQN-BYPYZUCNSA-N 0.000 description 1
- 229930064664 L-arginine Natural products 0.000 description 1
- 235000014852 L-arginine Nutrition 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
- 241000699670 Mus sp. Species 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 206010029350 Neurotoxicity Diseases 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 235000006040 Prunus persica var persica Nutrition 0.000 description 1
- 241000220324 Pyrus Species 0.000 description 1
- 244000305267 Quercus macrolepis Species 0.000 description 1
- 238000011529 RT qPCR Methods 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 208000034189 Sclerosis Diseases 0.000 description 1
- 239000006180 TBST buffer Substances 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
- 206010044221 Toxic encephalopathy Diseases 0.000 description 1
- 102100040247 Tumor necrosis factor Human genes 0.000 description 1
- 241000700605 Viruses 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
- 240000008042 Zea mays Species 0.000 description 1
- 235000005824 Zea mays ssp. parviglumis Nutrition 0.000 description 1
- 235000002017 Zea mays subsp mays Nutrition 0.000 description 1
- 230000005856 abnormality Effects 0.000 description 1
- 235000010489 acacia gum Nutrition 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 230000032683 aging Effects 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
- 239000003513 alkali Substances 0.000 description 1
- 230000002421 anti-septic effect Effects 0.000 description 1
- 239000003146 anticoagulant agent Substances 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
- 230000009286 beneficial effect Effects 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
- 235000013361 beverage Nutrition 0.000 description 1
- 230000000975 bioactive effect Effects 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 230000023555 blood coagulation Effects 0.000 description 1
- 230000036772 blood pressure Effects 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 210000004958 brain cell Anatomy 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
- 201000011510 cancer Diseases 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
- 230000005754 cellular signaling Effects 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 235000019219 chocolate Nutrition 0.000 description 1
- 208000037976 chronic inflammation Diseases 0.000 description 1
- 230000006020 chronic inflammation Effects 0.000 description 1
- 235000013985 cinnamic acid Nutrition 0.000 description 1
- 229930016911 cinnamic acid Natural products 0.000 description 1
- 239000007931 coated granule Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 239000002299 complementary DNA Substances 0.000 description 1
- 239000002361 compost Substances 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 238000007906 compression Methods 0.000 description 1
- 230000006835 compression Effects 0.000 description 1
- 235000008504 concentrate Nutrition 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 238000010924 continuous production Methods 0.000 description 1
- 230000001276 controlling effect Effects 0.000 description 1
- 235000005822 corn Nutrition 0.000 description 1
- 235000013365 dairy product Nutrition 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 230000008260 defense mechanism Effects 0.000 description 1
- 230000003412 degenerative effect Effects 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
- 229940000406 drug candidate Drugs 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 235000013399 edible fruits Nutrition 0.000 description 1
- 239000003792 electrolyte Substances 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 239000012156 elution solvent Substances 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
- 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
- 235000011389 fruit/vegetable juice Nutrition 0.000 description 1
- 238000012812 general test Methods 0.000 description 1
- 229960002518 gentamicin Drugs 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
- 239000000665 guar gum Substances 0.000 description 1
- 235000010417 guar gum Nutrition 0.000 description 1
- 229960002154 guar gum Drugs 0.000 description 1
- 210000003494 hepatocyte Anatomy 0.000 description 1
- 230000007686 hepatotoxicity Effects 0.000 description 1
- 231100000304 hepatotoxicity Toxicity 0.000 description 1
- 238000010842 high-capacity cDNA reverse transcription kit Methods 0.000 description 1
- 235000015243 ice cream Nutrition 0.000 description 1
- 210000002865 immune cell Anatomy 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 208000015181 infectious disease Diseases 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
- 229940069445 licorice extract Drugs 0.000 description 1
- 230000037356 lipid metabolism Effects 0.000 description 1
- 229940057995 liquid paraffin Drugs 0.000 description 1
- 239000006193 liquid solution Substances 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 208000019423 liver disease Diseases 0.000 description 1
- 229960003511 macrogol Drugs 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
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 239000003550 marker Substances 0.000 description 1
- 230000013011 mating Effects 0.000 description 1
- 235000013372 meat Nutrition 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 230000001404 mediated effect Effects 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
- 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
- 239000002480 mineral oil Substances 0.000 description 1
- 235000010446 mineral oil Nutrition 0.000 description 1
- 150000002772 monosaccharides Chemical class 0.000 description 1
- 238000000465 moulding Methods 0.000 description 1
- 235000019462 natural additive Nutrition 0.000 description 1
- 235000021096 natural sweeteners Nutrition 0.000 description 1
- 210000005036 nerve Anatomy 0.000 description 1
- 210000000944 nerve tissue Anatomy 0.000 description 1
- 208000015122 neurodegenerative disease Diseases 0.000 description 1
- 230000003962 neuroinflammatory response Effects 0.000 description 1
- 231100000189 neurotoxic Toxicity 0.000 description 1
- 230000002887 neurotoxic effect Effects 0.000 description 1
- 230000007135 neurotoxicity Effects 0.000 description 1
- 231100000228 neurotoxicity Toxicity 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
- 235000015097 nutrients 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
- 239000005416 organic matter Substances 0.000 description 1
- 229940094443 oxytocics prostaglandins Drugs 0.000 description 1
- 239000003002 pH adjusting agent Substances 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 235000021017 pears Nutrition 0.000 description 1
- 239000008188 pellet Substances 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
- 230000002250 progressing effect Effects 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 238000011321 prophylaxis Methods 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
- 238000000751 protein extraction Methods 0.000 description 1
- 239000012264 purified product Substances 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 230000004044 response Effects 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
- 230000003248 secreting effect Effects 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 235000020183 skimmed milk Nutrition 0.000 description 1
- 235000011888 snacks Nutrition 0.000 description 1
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 1
- 239000002689 soil Substances 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 235000014347 soups Nutrition 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 230000005062 synaptic transmission Effects 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
- 230000002537 thrombolytic effect Effects 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect 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
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil 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
- 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
- A61P25/00—Drugs for disorders of the nervous 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
- 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
- A23V2200/322—Foods, ingredients or supplements having a functional effect on health having an effect on the health of the nervous system or on mental function
-
- 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)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Insects & Arthropods (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Nutrition Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Mycology (AREA)
- Zoology (AREA)
- Epidemiology (AREA)
- Food Science & Technology (AREA)
- Polymers & Plastics (AREA)
- Animal Husbandry (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Medicines Containing Plant Substances (AREA)
Abstract
Description
본 발명은 흰점박이꽃무지 유충 에탄올 추출물을 포함하는 신경염증의 예방 또는 치료용 조성물에 관한 것이다.The present invention relates to a composition for preventing or treating neuroinflammation comprising ethanol extract of white spotted radish larva.
세계가 점차 노령화 사회로 변화하면서 파킨슨병, 알츠하이머병, 간질, 기억상실증 등 각종 뇌질환에 관련된 병에 걸리는 사람들이 급증하고 있다. 뇌는 생명유지에 필수적인 정보를 주관하고 신경 신호에 이상이 생기면 각종 신경성 장애를 일으키게 되는데 많은 연구에도 불구하고 현재 정확한 기전을 이해하고 치료하는 뇌질환은 극소수에 불과하다. 따라서, 신경세포가 손상되면서 유도된 신경염증반응의 제어가 신경퇴행성 질환의 치료 및 예방의 원인으로 인식되면서 미세아교세포의 과도한 활성 억제를 위한 소재 개발 연구가 다양하게 진행되고 있다.As the world gradually changes into an aging society, people suffering from diseases related to various brain diseases such as Parkinson's disease, Alzheimer's disease, epilepsy, and amnesia are increasing rapidly. The brain is responsible for information essential for life maintenance, and if there is an abnormality in the nerve signal, it causes various neurological disorders. Despite many studies, only a few brain diseases currently understand and treat the exact mechanism. Therefore, as the control of the neuroinflammatory response induced by damage to the neurons is recognized as the cause of the treatment and prevention of neurodegenerative diseases, various researches on developing materials for inhibiting excessive activity of microglia are being conducted.
미세아교세포(microglia)는 전체 뇌 세포의 12%를 차지하는 중추신경계(central nervous system, CNS)의 일차적인 면역 기능을 수행하는 세포로서, 외부에서 유입되거나 내부에서 발생하는 독소들이 존재하게 되면 이들 독소로부터 신경세포를 보호하기 위해 활성화된다. 미세아교세포의 활성화는 손상된 세포를 제거하고 외부에서 침입하는 박테리아나 바이러스로부터 신경세포를 보호하는 역할을 가지고 있으나, 과도한 활성화는 iNOS의 발현 증가를 통한 NO(Nitric Oxide) 합성과 COX-2에 의한 프로스타글란딘(Prostaglandin, PG), TNF-α 등의 합성 증가로 인해 신경세포에 독성을 나타내기 때문에 결과적으로 미세아교세포의 활성화는 신경세포의 손상을 악화시키게 된다. 나아가, 사멸 중인 신경세포가 방출하는 물질들이 미세아교세포의 활성을 다시 유발하게 되므로, 신경퇴행은 지속적인 악순환에 빠지게 된다.Microglia are cells that perform the primary immune function of the central nervous system (CNS), which accounts for 12% of all brain cells.When toxins introduced from the outside or generated inside are present, these toxins It is activated to protect nerve cells from The activation of microglia has the role of removing damaged cells and protecting nerve cells from invading bacteria or viruses, but excessive activation is caused by NO (Nitric Oxide) synthesis and COX-2 through increased expression of iNOS. Because prostaglandin (PG) and TNF-α are toxic to neurons due to increased synthesis, as a result, activation of microglia worsens damage to neurons. Furthermore, since the substances released by the dying neurons re-induce the activation of microglia, neurodegeneration falls into a continuous vicious cycle.
LPS(Lipopolysaccharide) 등의 자극에 의해 과하게 활성화된 미세아교세포는 NO, IL-1β(interleukin-1β), IL-6(interleukin-6), TNF-α(Tumor necrosis factor-α) 등과 같은 염증성 매개 인자 및 활성 산소종(reactive oxygen species, ROS)의 분비를 촉진하여 신경독성을 유발한다. 활성 산소종의 일종인 NO(Nitric oxide)는 무기 저분자 라디칼로써 신경전달 기능, 혈액응고 및 혈압 조절 기능, 암세포에 대항하는 면역기능 등의 역할을 하며 대식세포 및 간세포에서 NO 합성 경로인 NOS(nitric oxide synthase)를 통해 L-아르기닌(L-arginine)으로부터 합성된다. 그러나 면역반응에서 숙주의 방어기전으로 만들어지는 과량의 NO는 오히려 자가 면역질환이나 만성 염증의 원인이 되며, COX(cyclooxygenase)의 활성을 촉진시켜 프로스타글란딘 등의 생합성을 유도하여 염증반응을 심화시키는 것으로 보고되었다. 따라서 미세아교세포의 염증반응 관련 유전자의 발굴이나 이들의 조절을 통한 퇴행성 뇌질환 치료에 대한 연구가 활발하게 이루어지고 있으며, 염증반응이 진행되는 동안 유의적으로 증가하는 NO의 분비를 효과적으로 억제할 수 있는 억제제의 개발은 각종 뇌질환을 치료하는 유용한 치료방법으로 여겨지고 있다.Excessively activated microglia by stimulation of LPS (Lipopolysaccharide), etc., mediates inflammation such as NO, IL-1β (interleukin-1β), IL-6 (interleukin-6), and TNF-α (Tumor necrosis factor-α). It induces neurotoxicity by promoting the secretion of factors and reactive oxygen species (ROS). NO (Nitric oxide), a type of reactive oxygen species, is an inorganic low-molecular radical that plays a role in neurotransmission, blood coagulation and blood pressure control, and immune function against cancer cells. It is NOS (nitric oxide), a pathway for NO synthesis in macrophages and hepatocytes. oxide synthase) from L-arginine. However, it is reported that excessive NO, which is made as a defense mechanism of the host in the immune response, rather causes autoimmune diseases or chronic inflammation, and induces biosynthesis of prostaglandins, etc. by promoting the activity of COX (cyclooxygenase), which intensifies the inflammatory response. Became. Therefore, research on the treatment of degenerative brain diseases through the discovery of genes related to the inflammatory response of microglia or their regulation is being actively conducted, and it is possible to effectively suppress the secretion of NO, which is significantly increased during the inflammatory response. The development of inhibitors is considered to be a useful treatment method to treat various brain diseases.
한편, 최근 다양한 천연물 추출물을 이용하여 대식세포 활성화를 조절함으로써 염증반응을 억제시키는 물질에 대한 연구가 진행되고 있는데, 주로 식물을 이용한 연구가 진행되고 있는 실정이다. 그러나 신약 개발과 관련하여 천연자원을 이용한 염증관련 신약 개발 연구가 활발하게 진행되면서 지구상에서 다수 종을 차지하고 있는 곤충의 기능에 대한 관심도 증대되고 있다. Meanwhile, studies on substances that suppress inflammatory reactions by regulating macrophage activation using various natural extracts are currently being conducted, and studies are mainly conducted using plants. However, in connection with the development of new drugs, as research on the development of new drugs related to inflammation using natural resources is actively progressing, interest in the function of insects, which occupy many species on the planet, is also increasing.
흰점박이꽃무지(Protaetia brevitarsis seulensis)는 민간 및 동의보감 등의 전통 한방의서에서 "제조" 또는 "굼벵이" 라는 속명으로 불리고 있는 딱정벌레목, 풍뎅이과, 꽃무지아과에 속하며, 크기는 17 내지 24센티미터의 초식성 곤충으로서, 우리나라를 비롯하여 중국, 일본 및 시베리아 동부 지역에 서식하며, 5월에서 10월에 걸쳐 1 내지 2년에 1회 발생한다고 알려졌다. 3령의 성숙유충 상태로 월동하며, 성충은 주간에 활동하고 복숭아, 배 등의 성숙한 과일이나 옥수수, 상수리나무 등의 즙액을 먹이로 하며, 항상 군집성이다. 또한, 이들의 유충은 퇴비나 건초더미 등의 유기물이 풍부한 부식성 토양 속에서 서식한다. 흰점박이꽃무지는 오래전부터 간질환 등의 치료를 위한 한방 약재로서 이용되어 왔다. 또한, 최근에 유용한 생체 활성물질의 탐색 및 개발을 위한 곤충자원으로 크게 주목을 받고 있으며, 항생활성물질의 생산, 흰쥐(mouse)를 이용한 실험에서 알코올 과량섭취에 의해 손상된 간지질대사의 회복작용 등이 알려졌으며 혈전용해성 효소에 대한 연구와 집쥐(rat)에서 사염화탄소의 투여에 의해 유도된 간독성에 대한 간 보호효과를 나타내는 등 유용성이 확인된 바 있다. 그러나 흰점박이꽃무지 유충 추출물이 미세아교세포에 미치는 영향 및 그에 따른 흰점박이꽃무지 유충 추출물의 신경염증 개선 가능성에 대하여는 아직까지 보고된 바가 없고, 이에 대한 연구는 미미한 실정이다.White Spotted Flower ignorance (Protaetia brevitarsis seulensis) belongs to the genus "manufacturing" or "slug" in traditional herbal medicines such as private and Donguibogam, belonging to the order of beetle, chaferaceae, and the subfamily. It is a herbivorous insect of 17 to 24 centimeters in size, including Korea. It lives in China, Japan, and eastern Siberia, and is known to occur once every 1-2 years from May to October. It winters in the state of 3 instar mature larvae, and adults are active during the day and feed on mature fruits such as peaches and pears, or juices such as corn and oak trees, and are always clustered. In addition, their larvae live in corrosive soils rich in organic matter such as compost and haystacks. White spotted radish has long been used as a herbal medicine for the treatment of liver disease and the like. In addition, recently, it is attracting great attention as an insect resource for the search and development of useful bioactive substances, the production of anti-living substances, and the recovery effect of liver lipid metabolism damaged by excessive intake of alcohol in experiments using mice. This has been known, and its usefulness has been confirmed, including studies on thrombolytic enzymes and liver-protective effects against hepatotoxicity induced by the administration of carbon tetrachloride in rats. However, the effect of white spotted radish larvae extract on microglia and the possibility of improving neuroinflammation of white spotted radish larvae extract accordingly has not yet been reported, and research on this is insignificant.
이에, 본 발명자들은 신경염증의 효과적인 예방과 치료를 가능하게 하는 곤충 유래의 새로운 신약 후보물질을 연구하던 중, 흰점박이꽃무지(Protaetia brevitarsis seulensis) 유충의 에탄올 추출물이 NO(Nitric Oxide) 및 신경염증 사이토카인의 발현을 억제하여 항신경염증 활성을 가짐을 확인하고, 본 발명을 완성하였다.Accordingly, the inventors of the present invention were studying new drug candidates derived from insects that enable effective prevention and treatment of neuroinflammation , while the ethanol extract of the larvae of Protaetia brevitarsis seulensis was NO (Nitric Oxide) and neuroinflammation. By inhibiting the expression of cytokines, it was confirmed that it has anti-neuronal inflammatory activity, and the present invention was completed.
따라서 본 발명의 목적은 흰점박이꽃무지 유충 에탄올 추출물을 포함하는 신경염증 또는 뇌신경질환의 예방 또는 치료용 약학적 조성물을 제공하는 것이다.Accordingly, an object of the present invention is to provide a pharmaceutical composition for the prevention or treatment of neuroinflammation or cranial nerve disease comprising ethanol extract of white spotted flower radish larvae.
본 발명의 또 다른 목적은 흰점박이꽃무지 유충 에탄올 추출물을 포함하는 신경염증 또는 뇌신경질환의 예방 또는 개선용 식품 조성물을 제공하는 것이다.Another object of the present invention is to provide a food composition for preventing or improving neuroinflammation or cranial nerve disease comprising ethanol extract of white spotted flower radish larvae.
본 발명의 또 다른 목적은 흰점박이꽃무지 유충 에탄올 추출물을 포함하는 신경염증 또는 뇌신경질환의 예방 또는 개선용 의약외품 조성물을 제공하는 것이다.Another object of the present invention is to provide a quasi-drug composition for preventing or improving neuroinflammation or cranial nerve disease comprising ethanol extract of white spotted flower radish larvae.
상기 목적을 달성하기 위하여, 본 발명은 흰점박이꽃무지 유충 에탄올 추출물을 포함하는 신경염증의 예방 또는 치료용 약학적 조성물을 제공한다.In order to achieve the above object, the present invention provides a pharmaceutical composition for preventing or treating neuroinflammation comprising an ethanol extract of white spotted flower radish larva.
또한, 본 발명은 흰점박이꽃무지 유충 에탄올 추출물을 포함하는 뇌신경질환의 예방 또는 치료용 약학적 조성물을 제공한다.In addition, the present invention provides a pharmaceutical composition for preventing or treating cranial nerve diseases comprising ethanol extract of white spotted flower radish larva.
또한, 본 발명은 흰점박이꽃무지 유충 에탄올 추출물을 포함하는 신경염증의 예방 또는 개선용 식품 조성물을 제공한다.In addition, the present invention provides a food composition for preventing or improving neuroinflammation comprising ethanol extract of white spotted flower radish larva.
또한, 본 발명은 흰점박이꽃무지 유충 에탄올 추출물을 포함하는 뇌신경질환의 예방 또는 개선용 식품 조성물을 제공한다.In addition, the present invention provides a food composition for preventing or improving cranial nerve diseases comprising ethanol extract of white spotted flower radish larva.
또한, 본 발명은 흰점박이꽃무지 유충 에탄올 추출물을 포함하는 신경염증의 예방 또는 개선용 의약외품 조성물을 제공한다.In addition, the present invention provides a quasi-drug composition for preventing or improving neuroinflammation comprising ethanol extract of white spotted flower radish larva.
또한, 본 발명은 흰점박이꽃무지 유충 에탄올 추출물을 포함하는 뇌신경질환의 예방 또는 개선용 의약외품 조성물을 제공한다.In addition, the present invention provides a quasi-drug composition for preventing or improving cranial nerve diseases comprising ethanol extract of white spotted flower radish larva.
본 발명은 항신경염증 활성을 갖는 흰점박이꽃무지 유충 에탄올 추출물을 유효성분으로 포함하여, 세포독성을 나타내지 않으면서도 신경염증성 사이토카인의 발현을 단백질 및 유전자 발현 수준에서 현저히 억제시킬 수 있어 새로운 천연물 유래 신경염증 억제 물질, 뇌신경질환의 예방과 개선을 위한 약학적 조성물 또는 건강기능식품으로 유용하게 사용될 수 있을 것으로 기대된다. The present invention contains an ethanol extract of white spotted radish larvae having anti-neuro-inflammatory activity as an active ingredient, and can significantly inhibit the expression of neuroinflammatory cytokines at the level of protein and gene expression without showing cytotoxicity. It is expected to be useful as a neuroinflammation inhibitor, a pharmaceutical composition for the prevention and improvement of neurological diseases, or a health functional food.
도 1은 흰점박이꽃무지(Protaetia brevitarsis seulensis) 유충 에탄올 추출물(Protaetia brevitarsis seulensis Extract, PBE) 농도(100, 500, 1000, 2000 μg/mL)에 따른 세포독성 확인 결과를 나타낸 도이다.
도 2는 LPS(100 ng/mL) 처리한 미세아교세포(microglia)에 대하여, 농도(0, 100, 500, 1000, 2000 μg/mL)별 흰점박이꽃무지(Protaetia brevitarsis seulensis) 유충 에탄올 추출물(Protaetia brevitarsis seulensis Extract, PBE) 처리에 따른 NO(Nitric Oxide) 발현량 변화를 확인한 도이다.
도 3은 LPS(100 ng/mL) 처리한 미세아교세포(microglia)에 대하여, 농도(0, 100, 500, 1000, 2000 μg/mL)별 흰점박이꽃무지(Protaetia brevitarsis seulensis) 유충 에탄올 추출물(Protaetia brevitarsis seulensis Extract, PBE) 처리에 따른 신경염증성 사이토카인(TNF-α, IL-6) 발현량 변화를 확인한 도이다.
도 4는 LPS(100 ng/mL) 처리한 미세아교세포(microglia)에 대하여, 농도(0, 100, 500, 1000, 2000 μg/mL)별 흰점박이꽃무지(Protaetia brevitarsis seulensis) 유충 에탄올 추출물(Protaetia brevitarsis seulensis Extract, PBE) 처리에 따른 염증효소(iNOS, COX-2) 및 신경염증성 사이토카인(TNF-α, IL-6) 유전자 발현량 변화를 확인한 도이다.
도 5는 LPS(100 ng/mL) 처리한 미세아교세포(microglia)에 대하여, 농도(0, 100, 500, 1000, 2000 μg/mL)별 흰점박이꽃무지(Protaetia brevitarsis seulensis) 유충 에탄올 추출물(Protaetia brevitarsis seulensis Extract, PBE) 처리에 따른 염증효소(iNOS, COX-2) 단백질 발현량 변화를 확인한 도이다. 1 is a white spotted flower ( Protaetia) brevitarsis seulensis ) is a diagram showing the cytotoxicity confirmation results according to the concentration (100, 500, 1000, 2000 μg/mL) of ethanol extract of larvae (Protaetia brevitarsis seulensis Extract, PBE).
2 is a white spotted flower radish (Protaetia ) by concentration (0, 100, 500, 1000, 2000 μg/mL) for microglia treated with LPS (100 ng/mL). brevitarsis seulensis ) is a diagram confirming the change in the expression level of NO (Nitric Oxide) according to the treatment of ethanol extract of larvae (Protaetia brevitarsis seulensis Extract, PBE).
3 is a white spotted flower radish (Protaetia ) by concentration (0, 100, 500, 1000, 2000 μg/mL) for microglia treated with LPS (100 ng/mL). brevitarsis seulensis ) This is a diagram confirming the change in the expression level of neuroinflammatory cytokines (TNF-α, IL-6) according to the treatment of ethanol extract of larvae (Protaetia brevitarsis seulensis Extract, PBE).
4 is a white spotted flower radish (Protaetia ) by concentration (0, 100, 500, 1000, 2000 μg/mL) for microglia treated with LPS (100 ng/mL). brevitarsis seulensis ) This is a diagram confirming the change in the expression level of inflammatory enzymes (iNOS, COX-2) and neuroinflammatory cytokines (TNF-α, IL-6) genes according to the treatment of larvae ethanol extract (Protaetia brevitarsis seulensis Extract, PBE).
5 is a white spotted flower radish (Protaetia ) by concentration (0, 100, 500, 1000, 2000 μg/mL) for microglia treated with LPS (100 ng/mL). brevitarsis seulensis ) This is a diagram confirming the change in the expression level of inflammatory enzyme (iNOS, COX-2) protein according to the treatment of ethanol extract of larvae (Protaetia brevitarsis seulensis Extract, PBE).
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 that are not otherwise defined in the present specification have the meanings commonly used in the technical field to which the present invention pertains.
본 발명은 흰점박이꽃무지 유충 에탄올 추출물을 포함하는 신경염증의 예방 또는 치료용 약학적 조성물을 제공한다.The present invention provides a pharmaceutical composition for preventing or treating neuroinflammation comprising ethanol extract of white spotted flower radish larva.
상기 흰점박이꽃무지 유충 에탄올 추출물은 에탄올을 사용하여 흰점박이꽃무지 유충으로부터 추출하여 수득한 추출물을 의미한다. 본 발명은 일 실시예에서 상기 흰점박이꽃무지 유충 에탄올 추출물이 현저한 항신경염증 효과가 있음을 확인하였다.The ethanol extract of white spotted radish larva refers to an extract obtained by extracting from white spotted radish larva using ethanol. In one embodiment of the present invention, it was confirmed that the ethanol extract of the white spotted radish larva had a remarkable anti-neuro-inflammatory effect.
상기 흰점박이꽃무지 유충 에탄올 추출물은 건조 중량의 약 1 내지 10배에 달하는 부피의 에탄올을 용출 용매로써 사용하여 수득될 수 있다. 상기 에탄올은 50 내지 100%(농도)의 에탄올일 수 있으며, 바람직하게는 70% 에탄올이나 이에 제한되지 않는다. 추출 온도는 20 내지 100℃에서 다양한 추출방법을 사용하여 추출할 수 있으며, 항신경염증 억제 활성이 있는 물질을 추출하는 방법이라면 제한없이 이용될 수 있다. The ethanol extract of white spotted radish larva can be obtained by using ethanol in a volume of about 1 to 10 times the dry weight as an elution solvent. The ethanol may be 50 to 100% (concentration) of ethanol, preferably 70% ethanol, but is not limited thereto. The extraction temperature may be extracted using various extraction methods at 20 to 100°C, and any method of extracting a substance having anti-neuronal inflammation inhibitory activity may be used without limitation.
본 발명의 일 실시예에서는, 흰점박이꽃무지(Protaetia brevitarsis seulensis) 유충 분말을 70% 에탄올의 10%(v/v)가 되게 혼합한 후, 초음파 처리하여 30분간 실온에서 방치한 뒤 에탄올 추출액을 회수하고 감압증류하여 흰점박이꽃무지 유충 에탄올 추출물을 수득하였다. In one embodiment of the present invention, white spotted flower radish ( Protaetia brevitarsis seulensis ) larvae powder was mixed to 10% (v/v) in 70% ethanol, sonicated and left at room temperature for 30 minutes, and then the ethanol extract was recovered and distilled under reduced pressure to obtain ethanol extract of white spotted radish larva. I did.
본 발명에 있어서, 상기 흰점박이꽃무지 유충 에탄올 추출물은 추출액, 추출액의 희석액 또는 농축액, 추출액을 건조하여 얻어지는 건조물, 또는 이들의 조정제물 또는 정제물을 모두 포함한다.In the present invention, the ethanol extract of white-spotted flower radish larvae includes an extract, a dilute or concentrate of the extract, a dried product obtained by drying the extract, or a prepared product or purified product thereof.
본 발명에 있어서, 상기 흰점박이꽃무지 유충 에탄올 추출물은 NO(Nitric Oxide)의 방출을 저해하며, 신경염증 관련 사이토카인인 TNF-α 또는 IL-6의 발현 및 염증효소인 iNOS 또는 COX-2의 발현을 억제하는 것을 특징으로 한다. In the present invention, the ethanol extract of the white spotted radish larva inhibits the release of NO (Nitric Oxide), and the expression of TNF-α or IL-6, a neuroinflammation-related cytokine, and an inflammatory enzyme of iNOS or COX-2 It is characterized by inhibiting expression.
또한, 본 발명에 있어서, 상기 흰점박이꽃무지 유충 에탄올 추출물은LPS(Lipopolysaccharide)로 유도된 미세아교세포(microglia)의 염증반응을 저해하는 것을 특징으로 한다. In addition, in the present invention, the ethanol extract of white spotted radish larva is characterized in that it inhibits the inflammatory response of microglia induced by LPS (Lipopolysaccharide).
본 발명의 일 실시예에 따르면, 본 발명의 흰점박이꽃무지 유충 에탄올 추출물은 신경염증성 사이토카인의 발현을 단백질 및 유전자 발현 수준에서 현저히 억제시킬 수 있어 새로운 천연물 유래 신경염증 억제 물질, 뇌신경질환의 예방과 개선을 위한 약학적 조성물 또는 건강기능식품으로 유용하게 사용될 수 있음을 확인하였다. According to an embodiment of the present invention, the ethanol extract of white spotted radish larvae of the present invention can significantly inhibit the expression of neuroinflammatory cytokines at the level of protein and gene expression, so that a new natural product-derived neuroinflammation inhibitory substance, prevention of cranial nerve diseases It was confirmed that it can be usefully used as a pharmaceutical composition or health functional food for improvement.
본 발명에 있어서, 상기 흰점박이꽃무지 유충 에탄올 추출물은 세포독성을 일으키지 않고 미세아교세포에서 항신경염증 활성을 나타낼 수 있다면 농도에 제한 없이 사용될 수 있으나, 바람직하게는 0.1 내지 2000 μg/mL, 보다 바람직하게는 500 내지 2000 μg/mL, 보다 더 바람직하게는 1000 내지 2000 μg/mL의 농도로 사용될 수 있다.In the present invention, the ethanol extract of white spotted radish larvae can be used without limitation in concentration as long as it does not cause cytotoxicity and can exhibit anti-neuronal inflammatory activity in microglia, but preferably 0.1 to 2000 μg/mL, more Preferably, it may be used at a concentration of 500 to 2000 μg/mL, even more preferably 1000 to 2000 μg/mL.
본 발명에서, 용어 "신경염증"은 신경계, 즉 신경세포, 신경조직 등에 발생하는 염증성 반응을 총칭한다. 중추신경계에 존재하는 면역세포인 미세아교세포가 다양한 외인성, 내인성 물질로 인해 활성화되어, 염증성 사이토카인인 TNF-α, IL-1β일산화질소, 프로스타글란딘 등의 물질을 생산, 방출하는 현상을 포함할 수 있다. 이러한 물질들의 생성은 단기적으로는 면역반응을 유발하지만, 그 과도한 생산이나 지속적인 생산은 근접한 신경세포들의 사멸을 유도하여 결국 신경퇴행을 유발한다고 알려져 있다.In the present invention, the term "neural inflammation" collectively refers to an inflammatory reaction occurring in the nervous system, that is, nerve cells, nerve tissues, and the like. Microglia, which are immune cells present in the central nervous system, are activated by various exogenous and endogenous substances, which can include the production and release of substances such as inflammatory cytokines such as TNF-α, IL-1β nitric oxide, and prostaglandin. have. It is known that the production of these substances induces an immune response in the short term, but excessive production or continuous production induces the death of adjacent nerve cells and eventually causes neurodegeneration.
본 발명에 있어서, 상기 신경염증은 알츠하이머병, 파킨슨병, 루게릭병, 헌팅턴병, 간질, 기억상실증, 다발성 경화증, 신경모세포종, 뇌졸중, 크로이츠펠트야콥병, 외상 후 스트레스 장애, 우울증, 정신분열증 또는 근위축성측색경화증에 수반되는 신경염증일 수 있으나, 이에 제한되는 것은 아니다. In the present invention, the neuroinflammation is Alzheimer's disease, Parkinson's disease, Lou Gehrig's disease, Huntington's disease, epilepsy, amnesia, multiple sclerosis, neuroblastoma, stroke, Creutzfeldt-Jakob disease, post-traumatic stress disorder, depression, schizophrenia or amyotrophic measurement It may be neuroinflammation accompanying sclerosis, but is not limited thereto.
또한, 본 발명은 흰점박이꽃무지 유충 에탄올 추출물을 포함하는 뇌신경질환의 예방 또는 치료용 약학적 조성물을 제공한다. In addition, the present invention provides a pharmaceutical composition for preventing or treating cranial nerve diseases comprising ethanol extract of white spotted flower radish larva.
본 발명에 있어서, 상기 뇌신경질환은 신경계의 염증에 의하여 발생하는 질환이라면 제한 없이 포함할 수 있으며, 예컨대 알츠하이머병, 파킨슨병, 루게릭병, 헌팅턴병, 간질, 기억상실증, 다발성 경화증, 신경모세포종, 뇌졸중, 크로이츠펠트야콥병, 외상 후 스트레스 장애, 우울증, 정신분열증 및 근위축성측색경화증으로 이루어진 군에서 선택되는 하나 이상일 수 있으나, 이에 제한되는 것은 아니다.In the present invention, the cranial nerve disease may include without limitation, as long as it is a disease caused by inflammation of the nervous system, such as Alzheimer's disease, Parkinson's disease, Lou Gehrig's disease, Huntington's disease, epilepsy, amnesia, multiple sclerosis, neuroblastoma, stroke, It may be one or more selected from the group consisting of Creutzfeldt-Jakob disease, post-traumatic stress disorder, depression, schizophrenia, and amyotrophic lateral sclerosis, but is not limited thereto.
본 명세서에서, 용어 "예방"은 신경염증 또는 뇌신경질환을 보유하고 있다고 진단된 적은 없으나, 이러한 질환에 걸리기 쉬운 경향이 있는 개체에서 질환의 발생을 억제하는 것을 의미한다. In the present specification, the term "prevention" has not been diagnosed as having neuroinflammation or neurological disorders, but it means suppressing the occurrence of a disease in an individual who is prone to such a disease.
본 명세서에서, 용어 "치료"라 함은 신경염증 또는 뇌신경질환의 발전의 억제, 질환의 경감 및 질환의 제거를 의미한다.In the present specification, the term "treatment" refers to inhibition of the development of neuroinflammation or cranial nerve disease, alleviation of disease, and elimination of disease.
본 발명에 있어서, 상기 약학적 조성물은 신경염증의 예방 또는 치료, 뇌신경질환의 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 prepared and processed in the form of tablets, capsules, powders, granules, liquids, pills, etc. for the purpose of preventing or treating neuroinflammation, preventing or treating neurological 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 as a pharmaceutical composition including a pharmaceutically acceptable carrier, and oral dosage forms such as powders, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols, etc. according to a conventional method , It can be formulated in the form of external preparations, suppositories, and sterile injectable 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 carriers are 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, mineral oil, and the like. In addition, diluents or excipients such as fillers, extenders, binders, wetting agents, disintegrants, and surfactants are included. Oral solid preparations include tablets, pills, powders, granules, capsules, and the like, and these solid preparations include at least one or more excipients, such as starch, calcium carbonate, sucrose, or lactose. ), gelatin, and the like, and may include a lubricant such as magnesium stearate and talc. Liquid preparations for oral use include suspensions, liquid solutions, emulsions, syrups, and the like, and may include diluents such as water and liquid paraffin, wetting agents, sweetening agents, fragrances, preservatives, and the like. Parenteral preparations include sterilized aqueous solutions, non-aqueous solvents, suspensions, emulsions, freeze-dried preparations, and suppositories. Non-aqueous solvents and suspensions include propylene glycol, polyethylene glycol, vegetable oils such as olive oil, ethyl And injectable esters such as oleate. As a base for suppositories, witepsol, macrogol, tween 61, cacao butter, laurin paper, glycero gelatin, and the like may 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 can be administered orally or parenterally, and in the case of parenteral administration, it can be administered by intravenous injection, subcutaneous injection, intramuscular injection, intraperitoneal injection, transdermal administration, etc., preferably oral administration to be.
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.The suitable dosage of the pharmaceutical composition varies depending on factors such as formulation method, mode of administration, age, weight, sex, pathological condition, food, administration time, route of administration, excretion rate and response sensitivity of the patient, and is usually A skilled practitioner can readily determine and prescribe a dosage effective for the desired treatment or prophylaxis. The daily dosage of the pharmaceutical composition is generally sufficient in a 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.
또한, 본 발명은 흰점박이꽃무지 유충 에탄올 추출물을 포함하는 신경염증의 예방 또는 개선용 식품 조성물 및 흰점박이꽃무지 유충 에탄올 추출물을 포함하는 뇌신경질환의 예방 또는 개선용 식품 조성물을 제공한다.In addition, the present invention provides a food composition for preventing or improving neuroinflammation comprising ethanol extract of white spotted flower radish larvae, and a food composition for preventing or improving neurological disorders including ethanol extract of white spotted flower radish larvae.
본 발명에서, 용어 "개선"은 흰점박이꽃무지 유충 에탄올 추출물을 유효성분으로 포함하는 조성물을 이용하여 예방 또는 치료되는 신경염증 또는 뇌신경질환과 같은 질환의 의심 및 발병 개체의 증상이 호전되거나 이롭게 되는 모든 행위를 말한다.In the present invention, the term "improvement" refers to a symptom of a disease such as neuroinflammation or cranial nerve disease that is prevented or treated by using a composition comprising ethanol extract of white spotted radish larvae as an active ingredient and improves or benefits the symptoms of the individual It refers to all actions.
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 after being formulated as a health functional food, or may be included in other health functional foods as an additive of 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, gum, dairy products including ice cream, various soups, beverages, tea, drinks, There are alcoholic beverages and vitamin complexes, and all health functional foods in the usual sense are included.
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, specifically, flavoring agents used in the preparation of foods or food additives; 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; Electrolytes; coloring agent; Organic acids; Protective colloidal thickeners; pH adjuster; Stabilizers; antiseptic; glycerin; Alcohol; Carbonating agents used in carbonated beverages may be included.
본 발명에 있어서, 상기 식품 조성물 또는 건강기능식품은 항신경염증 활성 발휘를 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 exerting anti-neuronal inflammatory activity.
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 having useful functions for the human body according to the Health Functional Food Act No.6727, and with respect to the structure and function of the human body It refers to ingestion for the purpose of controlling or obtaining beneficial effects for health purposes such as physiological effects. The mixing 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 contain ordinary food additives, and the suitability as the "food additive" is determined according to the general rules of the food additive code approved by the Food and Drug Administration and the general test method, etc., 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.Items listed in the "Food Additives Code" include, for example, chemical compounds such as ketones, glycine, potassium citrate, nicotinic acid, and cinnamic acid, natural additives such as dark pigments, licorice extract, crystalline cellulose, high color pigments, and guar gum, Mixed preparations, such as a sodium L-glutamate preparation, an alkali additive for noodles, a preservative preparation, and a tar color preparation, etc. are mentioned.
예를 들어, 정제 형태의 건강기능식품은 흰점박이꽃무지 유충 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, in a health functional food in the form of a tablet, an ethanol extract of white spotted radish larva is granulated by a conventional method of a mixture of an excipient, a binder, a disintegrant, and other additives, and then compression-molded by adding a lubricant or the like, The mixture can be directly compression molded.
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 a tablet may contain a mating agent or the like, if necessary, and may be coated with a suitable coating agent if necessary.
캅셀 형태의 건강기능식품 중 경질캅셀제는 통상의 경질캅셀에 흰점박이꽃무지 유충 에탄올 추출물을 부형제 등의 첨가제와의 혼합물 또는 그의 입상물 또는 제피한 입상물을 충진하여 제조할 수 있으며, 연질캅셀제는 흰점박이꽃무지 유충 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 the capsule-type health functional foods, hard capsules can be prepared by filling ordinary hard capsules with ethanol extract of white spotted radish larva with additives such as excipients, granules thereof, or coated granules, and soft capsules It can be prepared by filling a mixture of ethanol extract of white spotted radish larvae with additives such as excipients in a capsule base such as gelatin. The soft capsule may contain a plasticizer such as glycerin or sorbitol, a colorant, a preservative, and the like, if necessary.
환 형태의 건강기능식품은 흰점박이꽃무지 유충 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.Ring-shaped health functional foods can be prepared by molding a mixture of white spotted radish larvae ethanol extract and excipients, binders, disintegrants, etc. by appropriate methods, and if necessary, coating with white sugar or other suitable coating agents, or starch, Talc or a suitable substance can also be used to dress the ring.
과립형태의 건강기능식품은 상기 흰점박이꽃무지 유충 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 a granular form by a mixture of the ethanol extract of white spotted radish larvae, excipients, binders, disintegrants, etc., and may contain flavoring agents, flavoring agents, etc., if 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 definitions of terms for the excipients, binders, disintegrants, lubricants, flavoring agents, flavoring agents, and the like of the present invention are described in documents known in the art and include those having the same or similar functions.
또한, 본 발명은 흰점박이꽃무지 유충 에탄올 추출물을 포함하는 신경염증의 예방 또는 개선용 의약외품 조성물 및 흰점박이꽃무지 유충 에탄올 추출물을 포함하는 뇌신경질환의 예방 또는 개선용 의약외품 조성물을 제공한다.In addition, the present invention provides a quasi-drug composition for preventing or improving neuroinflammation comprising ethanol extract of white spotted flower radish larvae, and a quasi-drug composition for preventing or improving cranial nerve disease comprising ethanol extract of white spotted flower radish larvae.
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.In the present invention, 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. Or non-machine and similar, as an article corresponding to one of the preparations used for sterilization, insecticide, and similar purposes to prevent infection, and used for the purpose of diagnosing, treating, alleviating, treating or preventing diseases of humans or animals. It refers to items that are not instruments, machines, or devices among the items that are used, and items that are not instruments, machines or devices among items used for the purpose of pharmacologically affecting the structure and function of humans or animals, and are for external use for skin and personal hygiene. Includes supplies.
본 발명의 흰점박이꽃무지 유충 에탄올 추출물을 신경염증 또는 뇌신경질환 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 white spotted radish larva of the present invention is added to a quasi-drug composition for the purpose of preventing or improving neuroinflammation or neurological disease, the extract may be added as it is or used with other fractions or other quasi-drug components, and a conventional method It can be used appropriately according to. The mixing amount of the active ingredient can be appropriately determined according to the intended use.
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 describing the present invention in more detail, and it will be apparent to those of ordinary skill 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. Preparation for experiment
흰점박이꽃무지(Protaetia brevitarsis seulensis) 유충은 동결건조하여 분쇄기로 분쇄한 후 분말로 사용하였다. 시료의 추출을 위해 흰점박이꽃무지 분말에 70% 에탄올을 혼합하였으며, 이때 분말의 양이 용매의 10%(v/v)가 되게 혼합하였다. 초음파 분쇄기로 에탄올 추출액을 얻고, 상기 에탄올 추출액을 감압증류하여 갈색을 띠는 에탄올 추출물을 얻었다. 이하 실험에서는 본 발명에 따른 흰점박이꽃무지 유충 에탄올 추출물을 PBE로 명명하였다. White-spotted flower ( Protaetia) brevitarsis seulensis ) larvae were lyophilized, pulverized with a grinder, and used as powder. For the extraction of the sample, 70% ethanol was mixed with the white spotted radish powder, and at this time, the amount of the powder was mixed to be 10% (v/v) of the solvent. An ethanol extract was obtained by an ultrasonic grinder, and the ethanol extract was distilled under reduced pressure to obtain a brownish ethanol extract. In the following experiment, the ethanol extract of white spotted radish larvae according to the present invention was named PBE.
BV-2 미세아교세포는 5% FBS(fetal bovine serum)와 50 μg/mL 겐타마이신(gentamicin)이 첨가된 DMEM(Dulbecco's modified eagle's medium) 배지를 사용하여 37℃, 5% CO2 조건하에서 배양하였다.BV-2 microglia were cultured under conditions of 37°C and 5% CO 2 using DMEM (Dulbecco's modified eagle's medium) medium supplemented with 5% FBS (fetal bovine serum) and 50 μg/mL gentamicin. .
실시예Example 2. 2. 흰점박이꽃무지White spotted flower 유충 에탄올 추출물의 세포독성 확인 Confirmation of cytotoxicity of ethanol extract of larvae
본 발명에 따른 흰점박이꽃무지 유충 에탄올 추출물이 미세아교세포 BV-2의 증식 및 독성에 미치는 영향을 확인하기 위하여 세포 독성 실험을 수행하였다. 구체적으로, BV-2 세포를 96-웰 플레이트에 2.0 × 104 cells/웰로 분주하여 세포 밀도(confluence)가 약 80%에 도달할 때까지 5% FBS가 들어있는 배지에서 약 24시간 동안 배양하였다. 그 후 흰점박이꽃무지 유충 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.Cytotoxicity experiments were performed to confirm the effect of the ethanol extract of white spotted radish larvae according to the present invention on the proliferation and toxicity of microglia BV-2. Specifically, BV-2 cells were distributed in a 96-well plate at 2.0 × 10 4 cells/well and cultured in a medium containing 5% FBS for about 24 hours until the cell density (confluence) reached about 80%. . Then, the ethanol extract of white spotted radish larvae was treated according to the concentration (100, 500, 1000, 2000 μg/mL), and after further incubation for 24 and 48 hours, MTS (3-(4,5-dimethylthiazol-2- Cell viability was measured using yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium) reagent. The results are shown in FIG. 1.
도 1에 나타낸 바와 같이, 본 발명의 흰점박이꽃무지 유충 에탄올 추출물은 2000 μg/mL까지 BV-2 세포 독성을 유발하지 않음을 확인하였다. As shown in Figure 1, it was confirmed that the ethanol extract of white spotted radish larvae of the present invention did not induce BV-2 cytotoxicity up to 2000 μg/mL.
실시예Example 3. 3. 흰점박이꽃무지White spotted flower 유충 에탄올 추출물의 미세아교세포 활성화 억제 확인 Confirmation of inhibition of microglia activation by ethanol extract of larvae
3-1. NO 생성수준 측정3-1. NO generation level measurement
활성화된 미세아교세포는 NO(Nitric Oxide)와 같은 신경독성 인자를 분비함으로써 신경염증 반응을 유발하므로, NO의 생성은 소교세포 내 염증반응의 강력한 표지이다. 이에, 흰점박이꽃무지 유충 에탄올 추출물이 미세아교세포 활성화를 억제하는지 여부를 확인하기 위하여, LPS(100 ng/mL)로 24시간 동안 처리한 BV-2 세포에 대하여 본 발명의 흰점박이꽃무지 유충 에탄올 추출물을 농도 별로(0, 100, 500, 1000, 2000 μg/mL) 처리하고, Greiss 반응을 이용해서 NO의 양을 측정하였다. 그 결과를 도 2에 나타내었다.Activated microglia induce a neuroinflammatory reaction by secreting neurotoxic factors such as NO (Nitric Oxide), so the production of NO is a strong marker of the inflammatory response in microglia. Thus, in order to confirm whether the ethanol extract of white spotted radish larva inhibits microglia activation, the white spotted radish larva of the present invention for BV-2 cells treated with LPS (100 ng/mL) for 24 hours. The ethanol extract was treated by concentration (0, 100, 500, 1000, 2000 μg/mL), and the amount of NO was measured using a Greiss reaction. The results are shown in FIG. 2.
도 2에 나타낸 바와 같이, LPS에 의해 유도되는 NO의 양이 본 발명의 흰점박이꽃무지 유충 에탄올 추출물 처리에 따라 농도의존적으로 감소함을 확인하였다. 상기 결과를 통해, 본 발명의 흰점박이꽃무지 유충 에탄올 추출물은 신경염증을 효과적으로 억제할 수 있음을 확인하였다.As shown in Fig. 2, it was confirmed that the amount of NO induced by LPS decreased in a concentration-dependent manner according to the ethanol extract treatment of white spotted radish larvae of the present invention. Through the above results, it was confirmed that the ethanol extract of white spotted radish larvae of the present invention can effectively suppress neuroinflammation.
3-2. 신경염증 사이토카인 발현 측정3-2. Neuroinflammatory cytokine expression measurement
본 발명에 따른 흰점박이꽃무지 유충 에탄올 추출물이 염증 매개 사이토카인인 TNF-α 및 IL-6 발현을 억제하는지 확인하기 위하여, 효소결합 면역흡착 측정법(ELISA)을 수행하였다. 구체적으로, BV-2 세포를 4×105 cells/웰로 6-웰 플레이트에 분주하여 약 24시간 동안 배양한 후 본 발명의 흰점박이꽃무지 유충 에탄올 추출물을 농도 별로(0, 100, 500, 1000, 2000 μg/mL) 1시간 동안 전처리하고, 100 ng/ml의 LPS를 처리하여 24시간 동안 배양하였다. 그 후 배양액을 회수하여 배양액에 유리된 TNF-α와 IL-6을 ELISA 키트(Thermo Fisher, Waltham, MA)를 이용하여 측정하였다. 그 결과를 도 3에 나타내었다.In order to confirm whether the ethanol extract of white spotted radish larvae according to the present invention inhibits the expression of TNF-α and IL-6, which are inflammation-mediated cytokines, an enzyme-linked immunosorbent assay (ELISA) was performed. Specifically, BV-2 cells were dispensed into a 6-well plate at 4×10 5 cells/well, cultured for about 24 hours, and then the ethanol extract of white spotted radish larvae of the present invention was added by concentration (0, 100, 500, 1000 , 2000 μg/mL) was pretreated for 1 hour, and 100 ng/ml of LPS was treated and incubated for 24 hours. Thereafter, the culture medium was recovered, and TNF-α and IL-6 freed from the culture medium were measured using an ELISA kit (Thermo Fisher, Waltham, MA). The results are shown in FIG. 3.
도 3에 나타낸 바와 같이, 미세아교세포에서 LPS에 의해 유도된 TNF-α 및 IL-6의 생성은 본 발명의 흰점박이꽃무지 유충 에탄올 추출물 처리에 따라 농도의존적으로 감소함을 확인하였다. As shown in Figure 3, it was confirmed that the production of TNF-α and IL-6 induced by LPS in microglia was reduced in a concentration-dependent manner according to the ethanol extract treatment of the white spotted radish larva of the present invention.
3-3. 3-3. iNOSiNOS , COX-2, , COX-2, TNFTNF -α 및 IL-6 유전자 발현 측정-α and IL-6 gene expression measurement
본 발명에 따른 흰점박이꽃무지 유충 에탄올 추출물이 염증효소(iNOS, COX-2) 및 신경염증성 사이토카인(TNF-α, IL-6) 유전자 발현을 억제하는지 확인하기 위하여 RT-PCR을 수행하였다. 구체적으로, BV-2 세포를 4×105 cells/웰로 6-웰 플레이트에 분주하여 약 24시간 동안 배양한 후 본 발명의 흰점박이꽃무지 유충 에탄올 추출물을 농도 별로(0, 100, 500, 1000, 2000 μg/mL) 1시간 동안 전처리하고, 100 ng/mL의 LPS를 처리하여 5시간 동안 배양하였다. 배양한 BV-2를 PBS(phosphate buffered saline)로 2회 세척하고 TRIzol 시약(Invitrogen, Carlsbad, CA)로 총 RNA를 추출한 후, 동량의 RNA(2 μg)로부터 High Capacity cDNA Reverse Transcription Kit(Applied Biosystems, Foster city, CA)를 이용하여 cDNA를 합성하였다. iNOS, COX-2, TNF-α 및 IL-6에 대한 각각의 프라이머와 함께 AMPIGENE®qPCR Green Mix Lo-ROX (Enzo Life Sciences, USA)를 이용하여 각 유전자의 발현량을 RT-PCR로 확인하였다. 그 결과를 도 4에 나타내었다.RT-PCR was performed to confirm whether the ethanol extract of white spotted radish larvae according to the present invention inhibits the expression of inflammatory enzymes (iNOS, COX-2) and neuroinflammatory cytokines (TNF-α, IL-6) genes. Specifically, BV-2 cells were dispensed into a 6-well plate at 4×10 5 cells/well, cultured for about 24 hours, and then the ethanol extract of white spotted radish larvae of the present invention was added by concentration (0, 100, 500, 1000 , 2000 μg/mL) was pretreated for 1 hour, and 100 ng/mL of LPS was treated and incubated for 5 hours. The cultured BV-2 was washed twice with PBS (phosphate buffered saline) and total RNA was extracted with TRIzol reagent (Invitrogen, Carlsbad, CA), and then High Capacity cDNA Reverse Transcription Kit (Applied Biosystems) from the same amount of RNA (2 μg). , Foster city, CA) was used to synthesize cDNA. The expression level of each gene was confirmed by RT-PCR using AMPIGENE®qPCR Green Mix Lo-ROX (Enzo Life Sciences, USA) with respective primers for iNOS, COX-2, TNF-α, and IL-6. . The results are shown in FIG. 4.
도 4에 나타낸 바와 같이, 염증효소(iNOS, COX-2) 및 신경염증성 사이토카인(TNF-α, IL-6)은 본 발명의 흰점박이꽃무지 유충 에탄올 추출물 처리에 의해 유전자 발현이 현저히 감소됨을 확인하였다.As shown in Figure 4, inflammatory enzymes (iNOS, COX-2) and neuroinflammatory cytokines (TNF-α, IL-6) are significantly reduced gene expression by the ethanol extract treatment of white spotted radish larva of the present invention. Confirmed.
3-4. 3-4. iNOSiNOS , COX-2 단백질 발현 측정, COX-2 protein expression measurement
본 발명에 따른 흰점박이꽃무지 유충 에탄올 추출물이 신경염증과 관련된iNOS, COX-2 단백질 발현에 미치는 영향을 확인하였다. BV-2 세포를 수득한 후 원심 분리하여 그 상등액을 버리고 세포 펠렛을 수거하였다. M-PER™Mammalian Protein Extraction Reagent(Thermo)를 이용하여 세포를 용해(lysis)시킨 후 원심분리(12,000 rpm, 15 min)하여 상등액을 수거하였다. 단백질량은 BCA protein assay kit(Pierce, Rockford, IL, USA)로 정량하였으며 동일 량의 단백질을 SDS-PAGE로 분리한 후, PVDF 막으로 이동시켰다. 상기 PVDF 막을 5% 탈지분유로 1시간 동안 반응시켜 비특이적 단백질에 대한 반응성을 차단하고 항-iNOS와 항-COX-2(Cell signaling, MA) 항체를 각각 반응시킨 후 HRP(horse radish peroxidase)가 결합되어 있는 2차 항체로 1시간 동안 반응시켰다. 각 반응 사이에 0.05% TBST로 10분씩 3회 수세하였다. 그 후 항체에 대한 대응 단백질 밴드를 ECL kit(Amersham phar-macia Biotech, UK)를 사용하여 확인하였다. 단백질 밴드의 강도는 Image J(version, 1.52) 프로그램을 이용하여 측정하였다. 그 결과를 도 5에 나타내었다.It was confirmed the effect of the ethanol extract of white spotted radish larvae according to the present invention on the expression of iNOS and COX-2 proteins related to neuroinflammation. After obtaining the BV-2 cells, centrifugation was performed, the supernatant was discarded, and a cell pellet was collected. The cells were lysed using M-PER™ Mammalian Protein Extraction Reagent (Thermo) and then centrifuged (12,000 rpm, 15 min) to collect the supernatant. The amount of protein was quantified with a BCA protein assay kit (Pierce, Rockford, IL, USA), and the same amount of protein was separated by SDS-PAGE, and then transferred to a PVDF membrane. The PVDF membrane was reacted with 5% skim milk for 1 hour to block reactivity to non-specific proteins, reacted with anti-iNOS and anti-COX-2 (Cell signaling, MA) antibodies, respectively, and then horse radish peroxidase (HRP) was bound. The secondary antibody was reacted for 1 hour. Between each reaction, it was washed three times with 0.05% TBST for 10 minutes each. Then, the corresponding protein band for the antibody was confirmed using the ECL kit (Amersham phar-macia Biotech, UK). The intensity of the protein band was measured using the Image J (version, 1.52) program. The results are shown in FIG. 5.
도 5에 나타낸 바와 같이, LPS 처리에 따라 증가한 iNOS 및 COX-2는 본 발명의 흰점박이꽃무지 유충 에탄올 추출물 1000 ug/mL의 농도부터 단백질 발현량이 농도의존적으로 감소됨을 확인하였다. As shown in Figure 5, iNOS and COX-2 increased according to the LPS treatment was confirmed that the protein expression level was decreased in a concentration-dependent manner from the concentration of the ethanol extract of white spotted radish larvae of the
상기 결과를 통해, 본 발명의 흰점박이꽃무지 유충 에탄올 추출물은 신경염증성 사이토카인의 발현을 단백질 및 유전자 발현 수준에서 현저히 억제시킬 수 있어 새로운 천연물 유래 신경염증 억제 물질, 뇌신경질환의 예방과 개선을 위한 약학적 조성물 또는 건강기능식품으로 유용하게 사용될 수 있음을 확인하였다. Through the above results, the ethanol extract of white spotted radish larvae of the present invention can significantly inhibit the expression of neuroinflammatory cytokines at the level of protein and gene expression, and thus a new natural product-derived neuroinflammation inhibitory substance, for the prevention and improvement of cranial nerve diseases. It was confirmed that it can be usefully used as a pharmaceutical composition or health functional food.
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, specific parts of the present invention have been described in detail, and for those of ordinary skill in the art, it is clear that these specific techniques are only preferred embodiments, and the scope of the present invention is not limited thereto. Accordingly, it will be said that the substantial scope of the present invention is defined by the appended claims and their equivalents.
Claims (12)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| KR1020190148688A KR20210060992A (en) | 2019-11-19 | 2019-11-19 | Composition for preventing or treating of neuroinflammation comprising Protaetia brevitarsis seulensis larva ethanol extract |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| KR1020190148688A KR20210060992A (en) | 2019-11-19 | 2019-11-19 | Composition for preventing or treating of neuroinflammation comprising Protaetia brevitarsis seulensis larva ethanol extract |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| KR20210060992A true KR20210060992A (en) | 2021-05-27 |
Family
ID=76135713
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR1020190148688A KR20210060992A (en) | 2019-11-19 | 2019-11-19 | Composition for preventing or treating of neuroinflammation comprising Protaetia brevitarsis seulensis larva ethanol extract |
Country Status (1)
| Country | Link |
|---|---|
| KR (1) | KR20210060992A (en) |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR101758718B1 (en) | 2016-07-08 | 2017-07-18 | 대한민국(농촌진흥청장) | Composition comprising compound isolated from Protaetia brevitarsis seulensis larva for antithrombosis |
-
2019
- 2019-11-19 KR KR1020190148688A patent/KR20210060992A/en not_active Application Discontinuation
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR101758718B1 (en) | 2016-07-08 | 2017-07-18 | 대한민국(농촌진흥청장) | Composition comprising compound isolated from Protaetia brevitarsis seulensis larva for antithrombosis |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP5300167B2 (en) | Composition for treating mood disorders | |
| KR101756943B1 (en) | Pharmaceutical composition for prevention or treatment neuro-inflammation or neurodegenerative diseases comprising Vaccinium bracteatum Thunb extracts or fractions thereof | |
| WO2014058142A1 (en) | Pharmaceutical composition containing aster glehni extract as active ingredientfor preventing or treating obesity or metabolic diseases | |
| KR101026528B1 (en) | Compositions for prevention and treatment of inflammatory diseases containing the extracts of seaweeds as an active ingredient | |
| KR20200048057A (en) | Antiinflammatory composition comprising Locusta migratoria extract | |
| KR20170010303A (en) | A pharmaceutical composition comprising extract from flower of Rosa rugosa for preventing or treating IL-6-mediated disease | |
| KR101802970B1 (en) | A composition for treating or preventing liver disease comprising Sicyos angulatus extract | |
| CN107106621B (en) | Pharmaceutical composition for preventing or treating neuroinflammation or neurodegenerative disease comprising Portulaca grandiflora extract or fraction thereof as active ingredient | |
| KR102089490B1 (en) | Composition for improving memory or composition for preventing and treating Alzheimer's dementia containing boiled silkworm products having silk protein and angelica extracts | |
| KR20170116846A (en) | Composition for treatment, improvement or prevention of neuroinflammatory diseases comprising extract of lacquer tree as an effective component | |
| KR20200046772A (en) | Composition comprising Locusta migratoria extract for preventing or treating Neuritis | |
| KR101487065B1 (en) | A pharmaceutical composition for prevention or treatment of inflammatory disease comprising Myagropsis myagroides extracts or fraction thereof as an effective ingredient | |
| KR102266287B1 (en) | Anti-obese composition comprising Gymnaster koraiensis | |
| KR20210060992A (en) | Composition for preventing or treating of neuroinflammation comprising Protaetia brevitarsis seulensis larva ethanol extract | |
| KR20180131770A (en) | A composition comprising extract of Coptis chinensis F. for treating and preventing muscle-related disorder | |
| KR101332824B1 (en) | Pharmaceutical Compositions for Preventing or Treating Arthritis Comprising Euphorbia ebracteolata Extracts | |
| JP2022535353A (en) | A composition for prevention, amelioration and treatment of metabolic syndrome associated with obesity and/or diabetes, containing a compound of an Indian gooseberry extract and a young barley leaf extract (IB compound) as an active ingredient | |
| KR101854960B1 (en) | Composition for anti-diabete comprising extract of hull and sprout parts from germinated rough rice as an effective component | |
| KR20200089527A (en) | Composition comprising extracts of Acorus gramineus and Dendropanax morbifera for anti-inflammation | |
| KR20160020638A (en) | Compostion for preventing or improving the metabolic syndrome containing Aeschynanthus acuminatus Wall. ex A. DC extract as agonist of GPR119 | |
| US20240082331A1 (en) | Anti-obesity composition containing, as active ingredient, moringa oleifera fermentation product prepared using novel monascus purpureus sl1 | |
| KR102429980B1 (en) | Composition comprising Locusta migratoria extract for preventing or treating Neuritis | |
| KR101537579B1 (en) | Neuroprotective composition for comprising extracts or fractions of Aspergillus terreus as an active ingredient | |
| KR101226881B1 (en) | A composition comprising the extract of Proso millet as an active ingredient for preventing and treating inflammatory disease | |
| KR20170090935A (en) | A composition comprising Fomitopsis pinicola for preventing or treating diabetes mellitus |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| E601 | Decision to refuse application |