KR101051085B1 - Parkinson's disease prevention and treatment composition containing cinnamon extract, fractions thereof or trans-cinnaaldehyde isolated from cinnamon as an active ingredient - Google Patents
Parkinson's disease prevention and treatment composition containing cinnamon extract, fractions thereof or trans-cinnaaldehyde isolated from cinnamon as an active ingredient Download PDFInfo
- Publication number
- KR101051085B1 KR101051085B1 KR1020080116692A KR20080116692A KR101051085B1 KR 101051085 B1 KR101051085 B1 KR 101051085B1 KR 1020080116692 A KR1020080116692 A KR 1020080116692A KR 20080116692 A KR20080116692 A KR 20080116692A KR 101051085 B1 KR101051085 B1 KR 101051085B1
- Authority
- KR
- South Korea
- Prior art keywords
- cinnamon
- parkinson
- extract
- disease
- trans
- Prior art date
Links
- 241000723347 Cinnamomum Species 0.000 title claims abstract description 69
- 235000017803 cinnamon Nutrition 0.000 title claims abstract description 69
- 208000018737 Parkinson disease Diseases 0.000 title claims abstract description 47
- 239000000203 mixture Substances 0.000 title claims abstract description 45
- 239000004480 active ingredient Substances 0.000 title claims abstract description 22
- 230000006806 disease prevention Effects 0.000 title claims description 10
- 235000020230 cinnamon extract Nutrition 0.000 title description 35
- KJPRLNWUNMBNBZ-QPJJXVBHSA-N (E)-cinnamaldehyde Chemical compound O=C\C=C\C1=CC=CC=C1 KJPRLNWUNMBNBZ-QPJJXVBHSA-N 0.000 claims abstract description 49
- 239000000284 extract Substances 0.000 claims abstract description 47
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 46
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 29
- 239000002904 solvent Substances 0.000 claims abstract description 11
- 244000037364 Cinnamomum aromaticum Species 0.000 claims abstract description 7
- 235000014489 Cinnamomum aromaticum Nutrition 0.000 claims abstract description 7
- 235000021511 Cinnamomum cassia Nutrition 0.000 claims abstract description 7
- 230000036541 health Effects 0.000 claims description 22
- 238000000034 method Methods 0.000 claims description 20
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 claims description 18
- 235000013376 functional food Nutrition 0.000 claims description 13
- 239000002038 ethyl acetate fraction Substances 0.000 claims description 11
- 150000003839 salts Chemical class 0.000 claims description 11
- 239000000469 ethanolic extract Substances 0.000 claims description 10
- 239000002034 butanolic fraction Substances 0.000 claims description 9
- 230000006872 improvement Effects 0.000 claims description 6
- 239000008194 pharmaceutical composition Substances 0.000 claims description 6
- 150000001298 alcohols Chemical class 0.000 claims description 2
- 241000124008 Mammalia Species 0.000 claims 2
- VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 abstract description 39
- 229960003638 dopamine Drugs 0.000 abstract description 20
- 210000002569 neuron Anatomy 0.000 abstract description 15
- 239000000126 substance Substances 0.000 abstract description 11
- 230000006378 damage Effects 0.000 abstract description 7
- 231100000189 neurotoxic Toxicity 0.000 abstract description 6
- 230000002887 neurotoxic effect Effects 0.000 abstract description 6
- 150000001875 compounds Chemical class 0.000 abstract description 5
- DIVDFFZHCJEHGG-UHFFFAOYSA-N oxidopamine Chemical compound NCCC1=CC(O)=C(O)C=C1O DIVDFFZHCJEHGG-UHFFFAOYSA-N 0.000 description 43
- KJPRLNWUNMBNBZ-UHFFFAOYSA-N cinnamic aldehyde Natural products O=CC=CC1=CC=CC=C1 KJPRLNWUNMBNBZ-UHFFFAOYSA-N 0.000 description 31
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 27
- 210000001577 neostriatum Anatomy 0.000 description 21
- 108091000117 Tyrosine 3-Monooxygenase Proteins 0.000 description 20
- 102000048218 Tyrosine 3-monooxygenases Human genes 0.000 description 20
- 238000002360 preparation method Methods 0.000 description 20
- 238000004519 manufacturing process Methods 0.000 description 19
- 239000002158 endotoxin Substances 0.000 description 18
- 229920006008 lipopolysaccharide Polymers 0.000 description 18
- 102000011779 Nitric Oxide Synthase Type II Human genes 0.000 description 17
- 108010076864 Nitric Oxide Synthase Type II Proteins 0.000 description 17
- CFFZDZCDUFSOFZ-UHFFFAOYSA-N 3,4-Dihydroxy-phenylacetic acid Chemical compound OC(=O)CC1=CC=C(O)C(O)=C1 CFFZDZCDUFSOFZ-UHFFFAOYSA-N 0.000 description 14
- 102100038280 Prostaglandin G/H synthase 2 Human genes 0.000 description 14
- 108050003267 Prostaglandin G/H synthase 2 Proteins 0.000 description 14
- 210000004027 cell Anatomy 0.000 description 14
- 230000014509 gene expression Effects 0.000 description 14
- 241000699666 Mus <mouse, genus> Species 0.000 description 10
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 10
- 230000000694 effects Effects 0.000 description 10
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
- 235000013361 beverage Nutrition 0.000 description 9
- 229940117916 cinnamic aldehyde Drugs 0.000 description 9
- 210000005064 dopaminergic neuron Anatomy 0.000 description 9
- -1 flavonoid compound Chemical class 0.000 description 9
- 238000005259 measurement Methods 0.000 description 9
- 239000000401 methanolic extract Substances 0.000 description 9
- 239000011780 sodium chloride Substances 0.000 description 9
- GIANIJCPTPUNBA-QMMMGPOBSA-N (2s)-3-(4-hydroxyphenyl)-2-nitramidopropanoic acid Chemical compound [O-][N+](=O)N[C@H](C(=O)O)CC1=CC=C(O)C=C1 GIANIJCPTPUNBA-QMMMGPOBSA-N 0.000 description 8
- 239000007864 aqueous solution Substances 0.000 description 8
- 239000000843 powder Substances 0.000 description 8
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 7
- AXMVYSVVTMKQSL-UHFFFAOYSA-N UNPD142122 Natural products OC1=CC=C(C=CC=O)C=C1O AXMVYSVVTMKQSL-UHFFFAOYSA-N 0.000 description 7
- 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 7
- 238000000605 extraction Methods 0.000 description 7
- 235000013305 food Nutrition 0.000 description 7
- 239000002953 phosphate buffered saline Substances 0.000 description 7
- 239000000243 solution Substances 0.000 description 7
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- 230000003247 decreasing effect Effects 0.000 description 6
- 238000012545 processing Methods 0.000 description 6
- 210000001519 tissue Anatomy 0.000 description 6
- 241000699670 Mus sp. Species 0.000 description 5
- 239000002253 acid Substances 0.000 description 5
- 238000004440 column chromatography Methods 0.000 description 5
- 238000011532 immunohistochemical staining Methods 0.000 description 5
- 238000001727 in vivo Methods 0.000 description 5
- 238000002347 injection Methods 0.000 description 5
- 239000007924 injection Substances 0.000 description 5
- 238000002156 mixing Methods 0.000 description 5
- 230000001681 protective effect Effects 0.000 description 5
- 235000018102 proteins Nutrition 0.000 description 5
- 108090000623 proteins and genes Proteins 0.000 description 5
- 102000004169 proteins and genes Human genes 0.000 description 5
- 230000009467 reduction Effects 0.000 description 5
- 230000002829 reductive effect Effects 0.000 description 5
- 239000006228 supernatant Substances 0.000 description 5
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 4
- WSMYVTOQOOLQHP-UHFFFAOYSA-N Malondialdehyde Chemical compound O=CCC=O WSMYVTOQOOLQHP-UHFFFAOYSA-N 0.000 description 4
- 239000000020 Nitrocellulose Substances 0.000 description 4
- 239000002775 capsule Substances 0.000 description 4
- 125000002871 cinnamic aldehydes group Chemical group 0.000 description 4
- 238000007796 conventional method Methods 0.000 description 4
- 235000015203 fruit juice Nutrition 0.000 description 4
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
- 229940118019 malondialdehyde Drugs 0.000 description 4
- 230000007246 mechanism Effects 0.000 description 4
- 239000002207 metabolite Substances 0.000 description 4
- 235000013336 milk Nutrition 0.000 description 4
- 239000008267 milk Substances 0.000 description 4
- 210000004080 milk Anatomy 0.000 description 4
- 229920001220 nitrocellulos Polymers 0.000 description 4
- 239000002245 particle Substances 0.000 description 4
- 239000000546 pharmaceutical excipient Substances 0.000 description 4
- 235000014347 soups Nutrition 0.000 description 4
- 239000003826 tablet Substances 0.000 description 4
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 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 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 3
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 3
- 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 3
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 210000001130 astrocyte Anatomy 0.000 description 3
- 235000015278 beef Nutrition 0.000 description 3
- 210000004556 brain Anatomy 0.000 description 3
- 235000014121 butter Nutrition 0.000 description 3
- 150000001720 carbohydrates Chemical class 0.000 description 3
- 235000014633 carbohydrates Nutrition 0.000 description 3
- 230000003833 cell viability Effects 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 235000013365 dairy product Nutrition 0.000 description 3
- 239000000835 fiber Substances 0.000 description 3
- 239000000945 filler Substances 0.000 description 3
- 229930003935 flavonoid Natural products 0.000 description 3
- 235000017173 flavonoids Nutrition 0.000 description 3
- 235000003599 food sweetener Nutrition 0.000 description 3
- 238000009472 formulation Methods 0.000 description 3
- 230000006870 function Effects 0.000 description 3
- 239000008103 glucose Substances 0.000 description 3
- 235000011187 glycerol Nutrition 0.000 description 3
- 239000008187 granular material Substances 0.000 description 3
- 238000004128 high performance liquid chromatography Methods 0.000 description 3
- 230000002401 inhibitory effect Effects 0.000 description 3
- 239000008101 lactose Substances 0.000 description 3
- 230000003902 lesion Effects 0.000 description 3
- 230000003859 lipid peroxidation Effects 0.000 description 3
- 239000002609 medium Substances 0.000 description 3
- 239000012528 membrane Substances 0.000 description 3
- 230000000877 morphologic effect Effects 0.000 description 3
- 210000000653 nervous system Anatomy 0.000 description 3
- 230000001537 neural effect Effects 0.000 description 3
- 230000000626 neurodegenerative effect Effects 0.000 description 3
- 235000012149 noodles Nutrition 0.000 description 3
- 150000007524 organic acids Chemical class 0.000 description 3
- 239000003960 organic solvent Substances 0.000 description 3
- 230000002265 prevention Effects 0.000 description 3
- 230000008569 process Effects 0.000 description 3
- 230000004083 survival effect Effects 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- 239000003765 sweetening agent Substances 0.000 description 3
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 2
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- 102000019034 Chemokines Human genes 0.000 description 2
- 108010012236 Chemokines Proteins 0.000 description 2
- 229920002261 Corn starch Polymers 0.000 description 2
- RGHNJXZEOKUKBD-SQOUGZDYSA-N D-gluconic acid Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O RGHNJXZEOKUKBD-SQOUGZDYSA-N 0.000 description 2
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- 108010010803 Gelatin Proteins 0.000 description 2
- 235000010469 Glycine max Nutrition 0.000 description 2
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 2
- 240000005979 Hordeum vulgare Species 0.000 description 2
- 235000007340 Hordeum vulgare Nutrition 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- 102000010909 Monoamine Oxidase Human genes 0.000 description 2
- 108010062431 Monoamine oxidase Proteins 0.000 description 2
- 235000004347 Perilla Nutrition 0.000 description 2
- 244000124853 Perilla frutescens Species 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- 229920002472 Starch Polymers 0.000 description 2
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
- 229930006000 Sucrose Natural products 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 244000299461 Theobroma cacao Species 0.000 description 2
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
- 239000013504 Triton X-100 Substances 0.000 description 2
- 229920004890 Triton X-100 Polymers 0.000 description 2
- TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 description 2
- 230000002159 abnormal effect Effects 0.000 description 2
- 238000002835 absorbance Methods 0.000 description 2
- 150000001299 aldehydes Chemical class 0.000 description 2
- 238000003975 animal breeding Methods 0.000 description 2
- 239000003125 aqueous solvent Substances 0.000 description 2
- 229960005070 ascorbic acid Drugs 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- 235000007215 black sesame Nutrition 0.000 description 2
- 229940098773 bovine serum albumin Drugs 0.000 description 2
- 210000005013 brain tissue Anatomy 0.000 description 2
- 235000008429 bread Nutrition 0.000 description 2
- 235000010633 broth Nutrition 0.000 description 2
- 235000021329 brown rice Nutrition 0.000 description 2
- 238000005119 centrifugation Methods 0.000 description 2
- 235000013339 cereals Nutrition 0.000 description 2
- 210000004720 cerebrum Anatomy 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 239000012141 concentrate Substances 0.000 description 2
- 235000009508 confectionery Nutrition 0.000 description 2
- 238000010411 cooking Methods 0.000 description 2
- 239000008120 corn starch Substances 0.000 description 2
- 230000001419 dependent effect Effects 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
- 230000003291 dopaminomimetic effect Effects 0.000 description 2
- 235000013399 edible fruits Nutrition 0.000 description 2
- 239000000839 emulsion Substances 0.000 description 2
- RRAFCDWBNXTKKO-UHFFFAOYSA-N eugenol Chemical compound COC1=CC(CC=C)=CC=C1O RRAFCDWBNXTKKO-UHFFFAOYSA-N 0.000 description 2
- 150000002215 flavonoids Chemical class 0.000 description 2
- 239000000796 flavoring agent Substances 0.000 description 2
- 235000019634 flavors Nutrition 0.000 description 2
- 235000013312 flour Nutrition 0.000 description 2
- 239000000499 gel Substances 0.000 description 2
- 239000008273 gelatin Substances 0.000 description 2
- 229920000159 gelatin Polymers 0.000 description 2
- 235000019322 gelatine Nutrition 0.000 description 2
- 235000011852 gelatine desserts Nutrition 0.000 description 2
- 229940093915 gynecological organic acid Drugs 0.000 description 2
- 235000015243 ice cream Nutrition 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 235000019359 magnesium stearate Nutrition 0.000 description 2
- HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- 210000000274 microglia Anatomy 0.000 description 2
- 230000002025 microglial effect Effects 0.000 description 2
- 150000007522 mineralic acids Chemical class 0.000 description 2
- RPUFERHPLAVBJN-UHFFFAOYSA-N n,n-dihydroxy-1-phenylmethanamine Chemical compound ON(O)CC1=CC=CC=C1 RPUFERHPLAVBJN-UHFFFAOYSA-N 0.000 description 2
- 230000004770 neurodegeneration Effects 0.000 description 2
- 210000004498 neuroglial cell Anatomy 0.000 description 2
- 230000000324 neuroprotective effect Effects 0.000 description 2
- 235000005985 organic acids Nutrition 0.000 description 2
- 230000003647 oxidation Effects 0.000 description 2
- 238000007254 oxidation reaction Methods 0.000 description 2
- 238000007911 parenteral administration Methods 0.000 description 2
- 229920001282 polysaccharide Polymers 0.000 description 2
- 239000005017 polysaccharide Substances 0.000 description 2
- 239000003755 preservative agent Substances 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 239000000741 silica gel Substances 0.000 description 2
- 229910002027 silica gel Inorganic materials 0.000 description 2
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 2
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 2
- 239000008107 starch Substances 0.000 description 2
- 235000019698 starch Nutrition 0.000 description 2
- UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 2
- 210000003523 substantia nigra Anatomy 0.000 description 2
- 239000005720 sucrose Substances 0.000 description 2
- 239000000829 suppository Substances 0.000 description 2
- XOAAWQZATWQOTB-UHFFFAOYSA-N taurine Chemical compound NCCS(O)(=O)=O XOAAWQZATWQOTB-UHFFFAOYSA-N 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- 235000015192 vegetable juice Nutrition 0.000 description 2
- 239000011782 vitamin Substances 0.000 description 2
- 229940088594 vitamin Drugs 0.000 description 2
- 235000013343 vitamin Nutrition 0.000 description 2
- 229930003231 vitamin Natural products 0.000 description 2
- 238000001262 western blot Methods 0.000 description 2
- 239000000080 wetting agent Substances 0.000 description 2
- 239000000811 xylitol Substances 0.000 description 2
- 235000010447 xylitol Nutrition 0.000 description 2
- 229960002675 xylitol Drugs 0.000 description 2
- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 description 2
- HFKPAXQHQKDLSU-MCDZGGTQSA-N (2r,3r,4s,5r)-2-(6-aminopurin-9-yl)-5-(hydroxymethyl)oxolane-3,4-diol;pyridine-3-carboxamide Chemical compound NC(=O)C1=CC=CN=C1.C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O HFKPAXQHQKDLSU-MCDZGGTQSA-N 0.000 description 1
- LSFCNJZMBBDBJT-YZMNHHIASA-N (e)-3-phenylprop-2-enal Chemical compound O=C\C=C\C1=CC=CC=C1.O=C\C=C\C1=CC=CC=C1 LSFCNJZMBBDBJT-YZMNHHIASA-N 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
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
- 108010011485 Aspartame Proteins 0.000 description 1
- 206010003591 Ataxia Diseases 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- 238000009010 Bradford assay Methods 0.000 description 1
- 101150071146 COX2 gene Proteins 0.000 description 1
- 101100114534 Caenorhabditis elegans ctc-2 gene Proteins 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 241001164374 Calyx Species 0.000 description 1
- 241001107116 Castanospermum australe Species 0.000 description 1
- NPBVQXIMTZKSBA-UHFFFAOYSA-N Chavibetol Natural products COC1=CC=C(CC=C)C=C1O NPBVQXIMTZKSBA-UHFFFAOYSA-N 0.000 description 1
- 241000723346 Cinnamomum camphora Species 0.000 description 1
- 241001573498 Compacta Species 0.000 description 1
- 229920000858 Cyclodextrin Polymers 0.000 description 1
- 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 1
- 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 1
- RGHNJXZEOKUKBD-UHFFFAOYSA-N D-gluconic acid Natural products OCC(O)C(O)C(O)C(O)C(O)=O RGHNJXZEOKUKBD-UHFFFAOYSA-N 0.000 description 1
- HCYAFALTSJYZDH-UHFFFAOYSA-N Desimpramine Chemical compound C1CC2=CC=CC=C2N(CCCNC)C2=CC=CC=C21 HCYAFALTSJYZDH-UHFFFAOYSA-N 0.000 description 1
- 229920001353 Dextrin Polymers 0.000 description 1
- 239000004375 Dextrin Substances 0.000 description 1
- 240000001879 Digitalis lutea Species 0.000 description 1
- 238000002965 ELISA Methods 0.000 description 1
- 239000004278 EU approved seasoning Substances 0.000 description 1
- LVGKNOAMLMIIKO-UHFFFAOYSA-N Elaidinsaeure-aethylester Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC LVGKNOAMLMIIKO-UHFFFAOYSA-N 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 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
- 239000005770 Eugenol Substances 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
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 1
- 244000068988 Glycine max Species 0.000 description 1
- 238000012404 In vitro experiment Methods 0.000 description 1
- 239000002211 L-ascorbic acid Substances 0.000 description 1
- 235000000069 L-ascorbic acid Nutrition 0.000 description 1
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
- 241000134253 Lanka Species 0.000 description 1
- 241000255777 Lepidoptera Species 0.000 description 1
- 238000000134 MTT assay Methods 0.000 description 1
- 231100000002 MTT assay Toxicity 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 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
- 102000008109 Mixed Function Oxygenases Human genes 0.000 description 1
- 108010074633 Mixed Function Oxygenases Proteins 0.000 description 1
- 206010052904 Musculoskeletal stiffness Diseases 0.000 description 1
- 240000007594 Oryza sativa Species 0.000 description 1
- 235000007164 Oryza sativa Nutrition 0.000 description 1
- 102000004316 Oxidoreductases Human genes 0.000 description 1
- 108090000854 Oxidoreductases Proteins 0.000 description 1
- 101150000187 PTGS2 gene Proteins 0.000 description 1
- 229930040373 Paraformaldehyde Natural products 0.000 description 1
- 229920002230 Pectic acid Polymers 0.000 description 1
- 229930182555 Penicillin Natural products 0.000 description 1
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 1
- 239000004952 Polyamide Substances 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- 102000004005 Prostaglandin-endoperoxide synthases Human genes 0.000 description 1
- 108090000459 Prostaglandin-endoperoxide synthases Proteins 0.000 description 1
- UVMRYBDEERADNV-UHFFFAOYSA-N Pseudoeugenol Natural products COC1=CC(C(C)=C)=CC=C1O UVMRYBDEERADNV-UHFFFAOYSA-N 0.000 description 1
- 229920005654 Sephadex Polymers 0.000 description 1
- 239000012507 Sephadex™ Substances 0.000 description 1
- 240000003768 Solanum lycopersicum Species 0.000 description 1
- 238000000944 Soxhlet extraction Methods 0.000 description 1
- 244000228451 Stevia rebaudiana Species 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
- 244000269722 Thea sinensis Species 0.000 description 1
- 235000005764 Theobroma cacao ssp. cacao Nutrition 0.000 description 1
- 235000005767 Theobroma cacao ssp. sphaerocarpum Nutrition 0.000 description 1
- 206010044565 Tremor Diseases 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 210000001642 activated microglia Anatomy 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 235000013334 alcoholic beverage Nutrition 0.000 description 1
- 239000000783 alginic acid Substances 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 229960001126 alginic acid Drugs 0.000 description 1
- 150000004781 alginic acids Chemical class 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 230000000202 analgesic effect Effects 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 230000001093 anti-cancer Effects 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 230000001754 anti-pyretic effect Effects 0.000 description 1
- 230000000840 anti-viral effect Effects 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 230000003078 antioxidant effect Effects 0.000 description 1
- 235000006708 antioxidants Nutrition 0.000 description 1
- 239000002221 antipyretic Substances 0.000 description 1
- 230000006907 apoptotic process Effects 0.000 description 1
- 235000015197 apple juice Nutrition 0.000 description 1
- 239000006286 aqueous extract Substances 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 239000011668 ascorbic acid 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
- 235000003704 aspartic acid Nutrition 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- 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 1
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 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
- 239000011230 binding agent Substances 0.000 description 1
- 235000021279 black bean Nutrition 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 210000004958 brain cell Anatomy 0.000 description 1
- 238000009395 breeding Methods 0.000 description 1
- 230000001488 breeding effect Effects 0.000 description 1
- SXDBWCPKPHAZSM-UHFFFAOYSA-N bromic acid Chemical compound OBr(=O)=O SXDBWCPKPHAZSM-UHFFFAOYSA-N 0.000 description 1
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
- 235000001046 cacaotero Nutrition 0.000 description 1
- 235000012970 cakes Nutrition 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 229910000019 calcium carbonate Inorganic materials 0.000 description 1
- 235000014171 carbonated beverage Nutrition 0.000 description 1
- 235000015190 carrot juice Nutrition 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 230000030833 cell death Effects 0.000 description 1
- 210000003710 cerebral cortex Anatomy 0.000 description 1
- 230000002490 cerebral effect Effects 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- WORJEOGGNQDSOE-UHFFFAOYSA-N chloroform;methanol Chemical compound OC.ClC(Cl)Cl WORJEOGGNQDSOE-UHFFFAOYSA-N 0.000 description 1
- 235000019219 chocolate Nutrition 0.000 description 1
- 229940002510 cinnamon preparation Drugs 0.000 description 1
- 229940069647 citric acid 1000 mg Drugs 0.000 description 1
- 239000000084 colloidal system Substances 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 235000008504 concentrate Nutrition 0.000 description 1
- 235000014510 cooky Nutrition 0.000 description 1
- 210000000877 corpus callosum Anatomy 0.000 description 1
- 235000012495 crackers Nutrition 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 230000007850 degeneration Effects 0.000 description 1
- 230000003412 degenerative effect Effects 0.000 description 1
- 210000004443 dendritic cell Anatomy 0.000 description 1
- 229960003914 desipramine Drugs 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 235000019425 dextrin Nutrition 0.000 description 1
- WGLUMOCWFMKWIL-UHFFFAOYSA-N dichloromethane;methanol Chemical compound OC.ClCCl WGLUMOCWFMKWIL-UHFFFAOYSA-N 0.000 description 1
- 150000002016 disaccharides Chemical class 0.000 description 1
- 235000021186 dishes Nutrition 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 210000004002 dopaminergic cell Anatomy 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 239000003792 electrolyte Substances 0.000 description 1
- 230000027721 electron transport chain Effects 0.000 description 1
- 235000019414 erythritol Nutrition 0.000 description 1
- 229940009714 erythritol Drugs 0.000 description 1
- UNXHWFMMPAWVPI-ZXZARUISSA-N erythritol Chemical compound OC[C@H](O)[C@H](O)CO UNXHWFMMPAWVPI-ZXZARUISSA-N 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- UREBWPXBXRYXRJ-UHFFFAOYSA-N ethyl acetate;methanol Chemical compound OC.CCOC(C)=O UREBWPXBXRYXRJ-UHFFFAOYSA-N 0.000 description 1
- LVGKNOAMLMIIKO-QXMHVHEDSA-N ethyl oleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC LVGKNOAMLMIIKO-QXMHVHEDSA-N 0.000 description 1
- 229940093471 ethyl oleate Drugs 0.000 description 1
- 229960002217 eugenol Drugs 0.000 description 1
- 239000004060 excitotoxin Substances 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000004744 fabric Substances 0.000 description 1
- 238000011049 filling Methods 0.000 description 1
- 239000000834 fixative Substances 0.000 description 1
- 235000012041 food component Nutrition 0.000 description 1
- 239000005417 food ingredient Substances 0.000 description 1
- 235000011194 food seasoning agent Nutrition 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 239000003205 fragrance Substances 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 235000011087 fumaric acid Nutrition 0.000 description 1
- 239000007903 gelatin capsule Substances 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 239000000174 gluconic acid Substances 0.000 description 1
- 235000012208 gluconic acid Nutrition 0.000 description 1
- 235000013922 glutamic acid Nutrition 0.000 description 1
- 239000004220 glutamic acid Substances 0.000 description 1
- 229930182470 glycoside Natural products 0.000 description 1
- 150000002338 glycosides Chemical class 0.000 description 1
- 235000019674 grape juice Nutrition 0.000 description 1
- 235000013882 gravy Nutrition 0.000 description 1
- 235000013402 health food Nutrition 0.000 description 1
- 241000411851 herbal medicine Species 0.000 description 1
- 238000001794 hormone therapy Methods 0.000 description 1
- 238000005286 illumination Methods 0.000 description 1
- 230000028993 immune response Effects 0.000 description 1
- 239000000367 immunologic factor Substances 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 238000010255 intramuscular injection Methods 0.000 description 1
- 239000007927 intramuscular injection Substances 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- VMPHSYLJUKZBJJ-UHFFFAOYSA-N lauric acid triglyceride Natural products CCCCCCCCCCCC(=O)OCC(OC(=O)CCCCCCCCCCC)COC(=O)CCCCCCCCCCC VMPHSYLJUKZBJJ-UHFFFAOYSA-N 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 229940057995 liquid paraffin Drugs 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 239000012139 lysis buffer Substances 0.000 description 1
- 229960003511 macrogol Drugs 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 239000002075 main ingredient Substances 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 235000013372 meat Nutrition 0.000 description 1
- 235000013622 meat product Nutrition 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- 229940045641 monobasic sodium phosphate Drugs 0.000 description 1
- 150000002772 monosaccharides Chemical class 0.000 description 1
- 229910000403 monosodium phosphate Inorganic materials 0.000 description 1
- 235000019799 monosodium phosphate Nutrition 0.000 description 1
- 235000021096 natural sweeteners Nutrition 0.000 description 1
- 208000015122 neurodegenerative disease Diseases 0.000 description 1
- 230000019581 neuron apoptotic process Effects 0.000 description 1
- 230000004693 neuron damage Effects 0.000 description 1
- 230000016273 neuron death Effects 0.000 description 1
- 230000003955 neuronal function Effects 0.000 description 1
- 230000007512 neuronal protection Effects 0.000 description 1
- 229930027945 nicotinamide-adenine dinucleotide Natural products 0.000 description 1
- BOPGDPNILDQYTO-NNYOXOHSSA-N nicotinamide-adenine dinucleotide Chemical compound C1=CCC(C(=O)N)=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](COP(O)(=O)OP(O)(=O)OC[C@@H]2[C@H]([C@@H](O)[C@@H](O2)N2C3=NC=NC(N)=C3N=C2)O)O1 BOPGDPNILDQYTO-NNYOXOHSSA-N 0.000 description 1
- 150000007523 nucleic acids Chemical class 0.000 description 1
- 102000039446 nucleic acids Human genes 0.000 description 1
- 108020004707 nucleic acids Proteins 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- QXFHPLPMTXEJPV-UHFFFAOYSA-N octane-1-sulfonic acid;sodium Chemical compound [Na].CCCCCCCCS(O)(=O)=O QXFHPLPMTXEJPV-UHFFFAOYSA-N 0.000 description 1
- 229920001542 oligosaccharide Polymers 0.000 description 1
- 150000002482 oligosaccharides Chemical class 0.000 description 1
- 235000008390 olive oil Nutrition 0.000 description 1
- 239000004006 olive oil Substances 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 239000006186 oral dosage form Substances 0.000 description 1
- 239000011368 organic material Substances 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- WLJNZVDCPSBLRP-UHFFFAOYSA-N pamoic acid Chemical compound C1=CC=C2C(CC=3C4=CC=CC=C4C=C(C=3O)C(=O)O)=C(O)C(C(O)=O)=CC2=C1 WLJNZVDCPSBLRP-UHFFFAOYSA-N 0.000 description 1
- 229920002866 paraformaldehyde Polymers 0.000 description 1
- 239000006201 parenteral dosage form Substances 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- LCLHHZYHLXDRQG-ZNKJPWOQSA-N pectic acid Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)O[C@H](C(O)=O)[C@@H]1OC1[C@H](O)[C@@H](O)[C@@H](OC2[C@@H]([C@@H](O)[C@@H](O)[C@H](O2)C(O)=O)O)[C@@H](C(O)=O)O1 LCLHHZYHLXDRQG-ZNKJPWOQSA-N 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- 102000013415 peroxidase activity proteins Human genes 0.000 description 1
- 108040007629 peroxidase activity proteins Proteins 0.000 description 1
- 150000002978 peroxides Chemical class 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 235000013550 pizza Nutrition 0.000 description 1
- 229920002647 polyamide Polymers 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 239000010318 polygalacturonic acid Substances 0.000 description 1
- 150000004804 polysaccharides Chemical class 0.000 description 1
- 229920000136 polysorbate Polymers 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 210000000063 presynaptic terminal Anatomy 0.000 description 1
- 230000003449 preventive effect Effects 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- 238000002731 protein assay Methods 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 239000008213 purified water Substances 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- HELXLJCILKEWJH-NCGAPWICSA-N rebaudioside A Chemical compound O([C@H]1[C@H](O)[C@@H](CO)O[C@H]([C@@H]1O[C@H]1[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O1)O)O[C@]12C(=C)C[C@@]3(C1)CC[C@@H]1[C@@](C)(CCC[C@]1([C@@H]3CC2)C)C(=O)O[C@H]1[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O1)O)[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O HELXLJCILKEWJH-NCGAPWICSA-N 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 235000009566 rice Nutrition 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
- 238000010898 silica gel chromatography Methods 0.000 description 1
- 235000011888 snacks Nutrition 0.000 description 1
- AJPJDKMHJJGVTQ-UHFFFAOYSA-M sodium dihydrogen phosphate Chemical compound [Na+].OP(O)([O-])=O AJPJDKMHJJGVTQ-UHFFFAOYSA-M 0.000 description 1
- 235000010288 sodium nitrite Nutrition 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 235000010356 sorbitol Nutrition 0.000 description 1
- 229960002920 sorbitol Drugs 0.000 description 1
- 238000004611 spectroscopical analysis Methods 0.000 description 1
- 235000013599 spices Nutrition 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
- 229960005322 streptomycin Drugs 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 150000005846 sugar alcohols Chemical class 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 229960003080 taurine Drugs 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 235000015193 tomato juice Nutrition 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 229940035936 ubiquinone Drugs 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 235000013311 vegetables Nutrition 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- 238000003026 viability measurement method Methods 0.000 description 1
- 150000003722 vitamin derivatives Chemical class 0.000 description 1
- 210000002395 vitreous cell Anatomy 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 238000003809 water extraction Methods 0.000 description 1
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/54—Lauraceae (Laurel family), e.g. cinnamon or sassafras
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
- A23L33/105—Plant extracts, their artificial duplicates or their derivatives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
-
- A—HUMAN NECESSITIES
- 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
- A23V2250/21—Plant extracts
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
- A61K2236/30—Extraction of the material
- A61K2236/33—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Natural Medicines & Medicinal Plants (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Neurosurgery (AREA)
- Mycology (AREA)
- Botany (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Neurology (AREA)
- Animal Behavior & Ethology (AREA)
- Biomedical Technology (AREA)
- Alternative & Traditional Medicine (AREA)
- Polymers & Plastics (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Chemistry (AREA)
- Food Science & Technology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Psychology (AREA)
- Nutrition Science (AREA)
- Biotechnology (AREA)
- Medical Informatics (AREA)
- Microbiology (AREA)
- Epidemiology (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicines Containing Plant Substances (AREA)
- Coloring Foods And Improving Nutritive Qualities (AREA)
Abstract
본 발명은 녹나무과(Lauraceal)의 계피나무(Cinnamomum cassia)의 추출물, 이의 분획물 또는 계피나무로부터 분리한 트랜스-신남알데하이드(trans-cinnamaldeyde)를 유효성분으로 함유하는 파킨슨병 예방 및 치료용 조성물에 관한 것으로, 보다 상세하게는 물, 알코올 또는 이의 혼합물을 용매로 하여 추출되는 계피나무 가지 또는 껍질의 추출물, 이의 분획물 및 계피나무로부터 분리한 활성 화합물인 트랜스-신남알데하이드는 파킨슨병을 유발할 수 있는 신경독성물질에 의한 도파민 신경세포의 손상을 보호함으로써 파킨슨병 예방 및 치료용 조성물로 유용하게 사용될 수 있다.The present invention relates to a composition for preventing and treating Parkinson's disease, which contains a extract of Cinnamomum cassia , a fraction thereof, or a trans-cinnamaldehyde isolated from cinnamon as an active ingredient. More specifically, the extract of cinnamon branch or bark extracted from water, alcohol or a mixture thereof as a solvent, a fraction thereof and the active compound trans-cinnamaldehyde isolated from cinnamon tree are neurotoxic substances that can cause Parkinson's disease. It can be usefully used as a composition for preventing and treating Parkinson's disease by protecting the damage to dopamine neurons.
계피나무(Cinnamomum cassia), 트랜스-신남알데하이드(trans-cinnamaldeyde), 파킨슨병, 신경세포 보호. Cinnamomum cassia, trans-cinnamaldeyde, Parkinson's disease, neuronal cell protection.
Description
본 발명은 계피나무 추출물, 이의 분획물 또는 계피나무로부터 분리한 신남알데하이드(cinnamaldehyde)를 유효성분으로 함유하는 파킨슨병 예방 및 치료용 조성물에 관한 것으로, 보다 상세하게는 물, 알코올 또는 이의 혼합물을 용매로 하여 추출되는 계피나무 가지 또는 껍질 추출물, 이의 분획물 및 계피나무로부터 분리한 활성 화합물인 신남알데하이드를 유효성분으로 함유하는 파킨슨병 예방 및 치료용 조성물에 관한 것이다.The present invention relates to a composition for preventing and treating Parkinson's disease, which contains cinnamon extract, fractions thereof, or cinnamaldehyde isolated from cinnamon as an active ingredient, and more specifically, water, alcohol or a mixture thereof as a solvent. It relates to a composition for preventing and treating Parkinson's disease, which contains cinnamon branch or bark extract, fractions thereof and cinnamic aldehyde, which is an active compound isolated from cinnamon, as an active ingredient.
파킨슨병은 중뇌의 흑질 (substantia nigra pars compacta, SNpc)에 존재하는 도파민성 신경세포의 사멸과 선조체 (striatum)의 도파민 감소에 의하여, 근육 경직, 진전, 운동실조 등의 증상이 나타나는 퇴행성 신경질환이다.Parkinson's disease is a degenerative neurodegenerative symptom of muscle stiffness, tremor and ataxia caused by the death of dopaminergic neurons in the substantia nigra pars compacta (SNpc) and the reduction of dopamine in the striatum. .
파킨슨병에서의 도파민 신경세포의 선택적인 손상 기전은 아직 명확히 밝혀져 있지 않지만, 최근 연구에 의하면 미세아교세포의 활성이 흑질 밀집부의 신경 변성에 관여하는 중요한 기전 중의 하나로 제시되고 있다. 파킨슨병에서의 도파민 신경세포의 선택적인 손상 기전은 아직 명확히 밝혀져 있지는 않으나, 전자전달계 (electron transport chain)의 Complex I, 즉 니코틴산아미드 아데노신 디뉴클레오타이드 (NADH, Nicotinamide adenosine dinucleotide) - 유비퀴논(ubiquinone) 산화환원 효소의 차단으로 인한 도파민성 신경의 변성, 도파민의 자동 산화 또는 모노아민 산화 효소(MAO, MonoAmine Oxidase)에 의한 대사과정에서의 생성되는 활성산소, 세포 내 칼슘농도의 변화, 내인성 흥분독소(excitotoxin)의 독성, 흑질 부위에 신경교세포, 특히 활성화된 미세아교세포의 이상 발현 등의 병리적 소견을 나타내는 것으로 보고되고 있다.The mechanism of selective damage of dopamine neurons in Parkinson's disease is not yet clear, but recent studies suggest that microglial activity is one of the important mechanisms involved in neuronal degeneration in dendritic cells. The mechanism of selective damage of dopamine neurons in Parkinson's disease is not yet clear, but complex I of the electron transport chain, namely nicotinamide adenosine dinucleotide (NADH)-ubiquinone oxidation Degeneration of dopaminergic neurons due to blocking of reductase, automatic oxidation of dopamine or metabolism by monoamine oxidase (MAO), changes in intracellular calcium concentrations, endogenous excitotoxins ) And pathologic findings such as abnormal expression of glial cells, particularly activated microglia in the black matter region.
신경교세포 중 성상세포(astrocyte)는 신경계에 존재하는 세포의 일종으로 전체 뇌 세포의 90%를 차지하며, 신경세포의 기능을 유지하는데 관여하는 것으로 잘 알려져 있으나, 최근에는 성상세포의 새로운 기능이 보고가 되고 있다. 한편, 신경교세포의 하나인 미세아교세포(microglia)는 성상세포와 함께 중추 신경 변성에서 여러 종류의 케모카인(chemokines)과 유도산화질소합성효소(inducible nitric oxide synthase; iNOS), 사이클로옥시지나(cyclooxygenase; COX)-2 등의 유전자 발현이 증가되어 다양한 신경 변성 매개물질을 생성하는 것이 잘 알려져 있으며, 이렇게 증가된 신경 변성 매개물질은 다양한 기전을 통해 직접 또는 이차적으로 신경 세포의 세포사멸을 초래하는데 관여할 수 있음이 보고되고 있다. Astrocytes are a type of cells in the nervous system that account for 90% of all brain cells and are known to be involved in maintaining neuronal function. Recently, new functions of astrocytes have been reported. It is becoming. On the other hand, microglia, one of glial cells, together with astrocytes, have several types of chemokines, chemokines, inducible nitric oxide synthase (iNOS), and cyclooxygenase; It is well known that gene expression, such as COX) -2, is increased to produce a variety of neurodegenerative mediators, and these increased neurodegenerative mediators may be involved in inducing apoptosis of neurons directly or secondaryly through various mechanisms. Can be reported.
계피나무(Cinnamomum cassia PRESL)는 녹나무과에 속하며, 원산지는 중국이고, 스리랑카, 인도차이나 및 한국(제주)에 분포한다. 높이 7 m, 지름 1.3 m 정도로 곧게 자라고 굵은 가지가 많이 갈라지며 잔가지가 있다. 잎은 마주나고 달걀 모양으로 넓으며 잎의 길이는 4 내지 8 cm이며, 나비는 3 내지 7 cm 정도로 끝이 다소 둔하다. 앞면은 녹색, 뒷면은 분백색이고 5 내지 7개의 손바닥 모양의 맥이 있으며 가장자리에는 둔한 톱니가 있다. 계피나무의 꽃은 6월에 피고 연한 노란빛을 띤 녹색이며 새가지 끝 잎겨드랑이에 산형꽃차례로 달린다. 꽃받침은 통 모양이며 윗부분이 6개로 갈라진다. 수술은 3개씩 4줄로 늘어서고 가장 안쪽 줄은 꽃밥이 없다. 암술은 1개이고 열매는 3 내지 5개씩 달리고, 씨는 편평하며 한쪽에 날개가 있다. Cinnamomum cassia PRESL belongs to the camphor tree. It is native to China and is distributed in Sri Lanka, Indochina and Korea (Jeju). It grows straight up to 7 m in height and 1.3 m in diameter. There are many thick branches and twigs. The leaves are opposite each other, broad in the shape of an egg, the leaves are 4 to 8 cm in length, and the butterflies are slightly dull at the tips of 3 to 7 cm. The front is green, the back is white, and there are 5 to 7 palm-shaped veins with dull teeth on the edges. The cinnamon tree blossoms in June, light yellowish green, and hangs in the form of inflorescence on the axillary end of the new branch. Calyx is tubular and its upper part is divided into 6 pieces. The stamens are arranged in four rows of three, and the innermost row has no anther. Pistil is one, the fruit is running three to five, seeds are flat, with wings on one side.
주요성분으로는 19-아세틸신카시올 A, 안하이드로신젤알라닌, 카시오사이드, 유게놀, 신남알데하이드 및 시남 에틸아세테이트가 있으며, 해열 작용, 진통 작용, 건위 작용, 항균 작용, 항바이러스 작용 등에 효과가 있음이 알려져 있다(www.tradimed.co.kr; 지형준 등, 한약(생약)규격집 주해서, 87p, 1998). 그러나 계피나무 추출물 및 트랜스-신남알데하이드가 신경세포를 보호하여 파킨슨병 등의 퇴행성 신경질환 예방 및 치료 효과에 대한 보고는 전무하다. Its main ingredients include 19-acetylcincasiol A, anhydroscingelalanine, casioside, eugenol, cinnamic aldehyde and cinnamic ethyl acetate, which are effective in antipyretic, analgesic, dry, antibacterial and antiviral effects. (Www.tradimed.co.kr; Jik-Joon et al., Medicinal Herbal Medicines Reference Manual, 87p, 1998). However, there is no report on the effect of preventing and treating neurodegenerative diseases such as Parkinson's disease by extracting cinnamon tree and trans-cinnaaldehyde.
천연식물에 존재하는 플라보노이드(flavonoid)를 포함한 여러 물질들은 강력 한 항산화, 항염증 효과가 있으며, 항암작용을 발휘하는 것이 알려져 있으며, 특히 플라보노이드 화합물이 시험관 내(in vitro)와 일부 동물실험에서 많은 연구가 되었으나, 신경계의 손상을 보호할 수 있는 지의 여부, 또는 신경계 기능의 개선에 대한 효과는 밝혀져 있지 않은 실정이다.Several substances, including flavonoids (flavonoid) present in the natural plants and is a powerful antioxidant and anti-inflammatory effect, is known to exhibit an anticancer activity, in particular within the test tube flavonoid compound (in Many studies have been conducted in vitro and in some animal experiments, but it is not known whether or not it can protect the damage of the nervous system or the effects of improving the nervous system function.
이에, 본 발명자들은 신경세포를 보호하는 물질을 개발하던 중, 계피나무 추출물, 이의 분획물 및 상기 분획물로부터 분리한 트랜스-신남알데하이드가 생체 내외 실험에서 파킨슨병 양상을 유발할 수 있는 대표적인 신경독성물질인 6-하이드록시도파민(6-hydroxydopamine; 6-OHDA)에 의한 도파민 신경세포의 손상을 보호하고, 지질다당류인 LPS(lipopolysaccharide)에 의한 신경세포의 활성을 억제할 수 있음을 확인함으로써, 본 발명의 계피나무 추출물, 이의 분획물 및 상기 분획물로부터 분리한 트랜스-신남알데하이드를 파킨슨병 예방 및 치료용 조성물의 유효성분으로 사용될 수 있음을 발견함으로써 본 발명을 완성하였다.Thus, the inventors of the present invention, while developing a substance to protect neurons, cinnamon extract, its fractions and the trans-cinnamaldehyde isolated from the
본 발명의 목적은 본 발명은 계피나무(Cinnamomum cassia) 추출물, 이의 분획물, 또는 계피나무로부터 분리한 트랜스-신남알데하이드(trans-cinnamaldehyde) 또는 이의 약학적으로 허용가능한 염을 유효성분으로 함유하는 파킨슨병 예방 및 치료용 조성물, 또는 파킨슨병 개선용 건강기능식품을 제공하는 것이다.An object of the present invention is a Parkinson's disease containing Cinnamomum cassia extract, fractions thereof, or trans-cinnamaldehyde or its pharmaceutically acceptable salts isolated from cinnamon tree as an active ingredient. It is to provide a preventive and therapeutic composition, or a functional food for improving Parkinson's disease.
상기 목적을 달성하기 위하여, 본 발명은 물, 알코올 또는 이의 혼합물을 용매로 하여 추출된 계피나무(Cinnamomum cassia) 추출물을 유효성분으로 함유하는 파킨슨병 예방 및 치료용 조성물을 제공한다.In order to achieve the above object, the present invention provides a composition for preventing and treating Parkinson's disease containing cinnamomum cassia extract extracted with water, alcohol or a mixture thereof as a solvent as an active ingredient.
또한, 본 발명은 상기 추출물을 에틸아세테이트 및 부탄올 순으로 순차적으로 용매 분획한 각 분획물을 유효성분으로 함유하는 파킨슨병 예방 및 치료용 조성물을 제공한다.In addition, the present invention provides a composition for preventing and treating Parkinson's disease, containing each fraction of the extract sequentially solvent-sorted in the order of ethyl acetate and butanol as an active ingredient.
또한, 본 발명은 하기 화학식 1로 표시되는 트랜스-신남알데하이드(trans-cinnamaldehyde) 또는 이의 약학적으로 허용가능한 염을 유효성분으로 함유하는 파킨슨병 예방 및 치료용 조성물을 제공한다.In addition, the present invention provides a composition for preventing and treating Parkinson's disease, which contains a trans-cinnamaldehyde represented by the following formula (1) or a pharmaceutically acceptable salt thereof as an active ingredient.
또한, 물, 에탄올 또는 이의 혼합물을 용매로 하여 추출된 계피나무 추출물을 유효성분으로 함유하는 파킨슨병 예방 및 개선용 건강기능식품을 제공한다.In addition, the present invention provides a health functional food for preventing and improving Parkinson's disease containing cinnamon tree extract extracted using water, ethanol or a mixture thereof as a solvent as an active ingredient.
또한, 본 발명은 상기 추출물을 에틸아세테이트 및 부탄올 순으로 순차적으 로 용매 분획한 각 분획물을 유효성분으로 함유하는 파킨슨병 예방 및 개선용 건강기능식품을 제공한다.In another aspect, the present invention provides a functional food for preventing and improving Parkinson's disease containing each fraction of the extract sequentially solvent-sorted in the order of ethyl acetate and butanol as an active ingredient.
또한, 본 발명은 하기 화학식 1로 표시되는 트랜스-신남알데하이드 또는 이의 약학적으로 허용가능한 염을 유효성분으로 함유하는 파킨슨병 예방 및 개선용 건강기능식품을 제공한다.In addition, the present invention provides a functional food for preventing and improving Parkinson's disease, which contains a trans-cinnaaldehyde represented by the following formula (1) or a pharmaceutically acceptable salt thereof as an active ingredient.
또한, 본 발명은 약학적으로 유효한 양의 상기 조성물을 파킨슨병에 걸린 개체에 투여하는 단계를 포함하는 파킨슨병 치료방법을 제공한다.The present invention also provides a method for treating Parkinson's disease comprising administering a pharmaceutically effective amount of the composition to a subject with Parkinson's disease.
아울러, 본 발명은 약학적으로 유효한 양의 상기 조성물을 개체에 투여하는 단계를 포함하는 파킨슨병 예방방법을 제공한다.In addition, the present invention provides a method for preventing Parkinson's disease comprising administering to the individual a pharmaceutically effective amount of the composition.
본 발명의 계피나무 의 추출물, 이의 분획물 및 상기 분획물로부터 분리한 트랜스-신남알데하이드는 파킨슨병 양상을 유발할 수 있는 신경독성물질에 의한 도파민 신경세포의 손상을 보호하고, 병리적 원인에 의한 신경세포의 이상 활성을 억제할 수 있으므로 파킨슨병 예방 및 치료용 조성물로 유용하게 사용될 수 있다.Extract of cinnamon tree of the present invention, its fractions and the trans-cinnamaldehyde isolated from the fractions protects the damage of dopamine neurons by neurotoxic substances that can cause Parkinson's disease, and the pathogenesis of neurons Since abnormal activity can be suppressed, it can be usefully used as a composition for preventing and treating Parkinson's disease.
이하, 본 발명을 상세히 설명한다.Hereinafter, the present invention will be described in detail.
본 발명은 계피나무 추출물, 이의 분획물, 또는 하기 화학식 1로 기재되는 트랜스-신남알데하이드(trans cinnamaldeyde) 또는 이의 약학적으로 허용가능한 염을 유효성분으로 함유하는 파킨슨병 예방 및 치료용 조성물을 제공한다.The present invention provides a composition for preventing and treating Parkinson's disease, which comprises cinnamon extract, fractions thereof, or trans cinnamaldeyde represented by the following Chemical Formula 1 or a pharmaceutically acceptable salt thereof as an active ingredient.
[화학식 1][Formula 1]
상기 계피나무 추출물, 이의 분획물 및 활성 화합물은 The cinnamon extract, fractions and active compounds thereof
1) 계피나무를 물, 알코올 또는 이의 혼합물로 추출하는 단계;1) extracting the cinnamon tree with water, alcohol or a mixture thereof;
2) 단계 1)의 추출물에 추가적으로 유기용매를 가하여 유기용매 분획물을 제조하는 단계; 및2) adding an organic solvent to the extract of step 1) to prepare an organic solvent fraction; And
3) 단계 2)의 분획물을 컬럼 크로마토그래피하여 활성 화합물을 수득하는 단계를 포함하는 분리정제 방법에 의해 제조되는 것이 바람직하나 이에 한정되지 않는다. 3) Preferably, the fraction of step 2) is prepared by a separation purification method comprising column chromatography to obtain an active compound, but is not limited thereto.
상기 방법에 있어서, 단계 1)에서는 계피나무는 재배한 것 또는 시판되는 것에 제한 없이 모두 사용될 수 있다.In the above method, in step 1), the cinnamon tree can be used both without limitation, cultivated or commercially available.
상기 계피나무는 가지 또는 껍질 부위를 단독으로, 또는 함께 사용하는 것이 바람직하나 이에 한정되지 않는다. The cinnamon tree is preferably used alone or in combination with a branch or bark, but is not limited thereto.
상기 방법에 있어서, 단계 1)의 알코올은 C1 내지 C4 저급 알코올을 이용하는 것이 바람직하고, 저급 알코올로는 에탄올 또는 메탄올을 이용하는 것이 바람직하나 이에 한정되지 않는다. 유기물질은 100% 알코올에서 용출이 더 잘 되고 배당체는 알코올 수용액에서 용출이 더 잘 되므로 필요에 따라 알코올 또는 알코올 수용액으로 선택하여 사용할 수 있다. 추출시 용매를 건조 및 분쇄된 계피나무 분량의 5 내지 15배 첨가하여 추출하는 것이 바람직하며, 7 내지 10배 첨가하여 추출하는 것이 더욱 바람직하나 이에 한정되지 않는다. 추출시간은 2시간 내지 10시간인 것이 바람직하고, 3시간 내지 5시간인 것이 더욱 바람직하나 이에 한정되지 않는다. 추출 회수는 1 내지 5회인 것이 바람직하며, 3회 반복 추출하는 것이 더욱 바람직하나 이에 한정되지 않는다. 상기 추출방법은 열수추출, 환류추출, 진탕추 출 또는 Soxhlet 추출 등이 모두 가능하며 특정 방법에 한정되지 않는다. In the above method, the alcohol of step 1) is preferably C 1 to C 4 lower alcohol, it is preferable to use ethanol or methanol as the lower alcohol, but is not limited thereto. The organic material is better eluted in 100% alcohol and the glycoside is better eluted in an aqueous alcohol solution, so it can be used as an alcohol or an aqueous alcohol solution as needed. In the extraction, the solvent is preferably extracted by adding 5 to 15 times the amount of dried and ground cinnamon, and the extraction is preferably performed by adding 7 to 10 times, but is not limited thereto. The extraction time is preferably 2 hours to 10 hours, more preferably 3 hours to 5 hours, but is not limited thereto. The number of extraction is preferably 1 to 5 times, more preferably 3 times, but is not limited thereto. The extraction method may be hot water extraction, reflux extraction, shaking extraction or Soxhlet extraction, etc., but is not limited to a specific method.
상기 방법에 있어서, 단계 2)의 유기용매는 에틸아세테이트 또는 부탄올을 사용하는 것이 바람직하나 이에 한정되지 않는다. 본 발명에서는 계피나무 의 에탄올 수용액 추출물을 물에 현탁한 후 에틸아세테이트 및 부탄올로 순차적으로 용매 분획하여 각 분획물을 농축하였다.In the above method, the organic solvent of step 2) is preferably ethyl acetate or butanol, but is not limited thereto. In the present invention, an aqueous ethanol extract of cinnamon was suspended in water, and then solvent fractions were sequentially fractionated with ethyl acetate and butanol to concentrate each fraction.
상기 방법에 있어서, 단계 3)의 컬럼 크로마토그래피는 실리카겔, 세파덱스, RP-18, 폴리아미드, 도요펄(Toyopearl) 및 XAD 수지로 이루어진 그룹으로부터 선택된 충진제를 이용한 컬럼을 이용한 컬럼 크로마토그래피를 수행하여 활성화합물을 분리 및 정제할 수 있다. 컬럼 크로마토그래피는 필요에 따라 적절한 충진제를 선택하여 수차례 실시할 수 있으며, 용매로 클로로포름-메탄올, 에틸아세테이트-메탄올 또는 디클로로메탄-메탄올을 이용할 수 있으나 이에 한정하지 않는다. In the above method, the column chromatography of step 3) is performed by column chromatography using a column using a filler selected from the group consisting of silica gel, Sephadex, RP-18, polyamide, Toyopearl and XAD resin. The active compound can be isolated and purified. Column chromatography may be carried out several times by selecting an appropriate filler as needed, and may be used as a solvent, but not limited to chloroform-methanol, ethyl acetate-methanol or dichloromethane-methanol.
본 발명의 화학식 1의 트랜스-신남알데하이드는 계피나무 추출물로부터 컬럼 크로마토그래피를 사용하여 분리한 것 또는 Sigma-Aldrich(St. Louis, MO, USA) 등에서 구입한 것을 모두 사용할 수 있다. The trans-cinnaaldehyde of the formula (1) of the present invention can be used either from the cinnamon extract extracted by column chromatography or purchased from Sigma-Aldrich (St. Louis, MO, USA).
본 발명의 약학적으로 허용가능한 염은 유리산(free acid)에 의해 형성된 부가염이 유용하다. 적합한 유리산으로는 유기산과 무기산을 사용할 수 있으며, 무기산으로는 염산, 브롬산, 황산 및 인산 등을 사용할 수 있고 유기산으로는 구연산(citric acid), 초산, 젖산, 주석산(tartariac acid), 말레인산, 푸마르산(fumaric acid), 포름산, 프로피온산(propionic acid), 옥살산, 트리플루오로아세트산, 벤조산, 글루콘산, 메탄술폰산, 글리콜산, 숙신산, 4-톨루엔술폰산, 갈룩 투론산, 엠본산, 글루탐산 또는 아스파르트산 등을 사용할 수 있으나 이에 한정되지 않는다.As the pharmaceutically acceptable salt of the present invention, addition salts formed by free acid are useful. Suitable free acids may be organic and inorganic acids, inorganic acids may be hydrochloric acid, bromic acid, sulfuric acid and phosphoric acid, and organic acids may be citric acid, acetic acid, lactic acid, tartariac acid, maleic acid, Fumaric acid, formic acid, propionic acid, oxalic acid, trifluoroacetic acid, benzoic acid, gluconic acid, methanesulfonic acid, glycolic acid, succinic acid, 4-toluenesulfonic acid, gallux turonic acid, embonic acid, glutamic acid or aspartic acid Etc. may be used, but the present invention is not limited thereto.
본 발명에서는 계피나무 추출물, 이의 분획물 및 트랜스 신남 알데하이드가 LPS에 의한 신경세포의 활성을 억제할 수 있는지 알아보기 위해, 계피나무 추출물, 이의 분획물 및 트랜스 신남 알데하이드가 인지질다당류(LPS)에 의해 유발된 마우스 미세아교세포의 세포사멸 증가, NO 생성량 증가, 및 iNOS 및 COX-2 발현량 증가에 미치는 효과를 측정하였다. 그 결과, 본 발명의 계피나무 추출물, 이의 분획물 및 트랜스 신남 알데하이드는 NO 생성량 감소, 및 iNOS 및 COX-2 발현량 감소효과를 나타내었다. In the present invention, to determine whether the cinnamon tree extract, its fractions and trans cinnamic aldehyde can inhibit the activity of neurons by LPS, cinnamon tree extract, its fractions and trans cinnamic aldehyde is induced by phospholipid polysaccharide (LPS) The effects on increased apoptosis, increased NO production, and increased iNOS and COX-2 expression in mouse microglia were measured. As a result, the cinnamon extract, its fractions and trans cinnamic aldehyde of the present invention showed a reduction in NO production and a decrease in iNOS and COX-2 expression.
또한, 본 발명에서는 계피나무 추출물, 이의 분획물 및 트랜스 신남 알데하이드가 생체 내(in vivo)에서 신경세포 보호 효과를 나타낼 수 있는지 알아보기 위해, 생쥐를 이용하여 선조체 내 도파민 및 그 대사물질 함량, 뇌의 지질과산화 생성량, 및 선조체 및 흑질 내 TH(tyrosine hydroxylase), iNOS, COX-2 및 NT(Nitro tyrosine)의 발현량을 각각 측정하였다. 그 결과, 계피나무 추출물, 이의 분획물 및 트랜스 신남 알데하이드는 생쥐의 선조체에서 6-OHDA에 의해 유발된 도파민과 그 대사물질인 DOPAC(3-4-dihydroxyphenylacetic acid) 농도의 감소를 억제하였고, 6-OHDA에 의해 유발된 지질과산화물의 감소를 억제하였으며, 선조체 및 흑질에서 6-OHDA에 의해 유발된 TH(tyrosine hydroxylase)의 감소, iNOS의 증가 및 COX-2의 증가를 억제하였다.In addition, the present invention cinnamon extract, its fractions and trans cinnamic aldehyde is in vivo ( in To investigate the neuroprotective effects in vivo , mice were used to detect dopamine and its metabolites in the striatum, the amount of lipid peroxidation in the brain, and TH (tyrosine hydroxylase), iNOS, and COX-2 in striatum and black matter. And NT (Nitro tyrosine) expression levels were measured, respectively. As a result, cinnamon extract, its fractions and trans cinnamic aldehyde inhibited the decrease of 6-OHDA-induced dopamine and its metabolite, DOPAC (3-4-dihydroxyphenylacetic acid) in mouse striatum, and 6-OHDA Inhibition of the lipid peroxide induced by, inhibited the reduction of TH (tyrosine hydroxylase) induced by 6-OHDA, the increase of iNOS and the increase of COX-2 in the striatum and black matter.
또한, 본 발명에서는 트랜스 신남 알데하이드가 생체 내(in vivo)에서 신경 세포 보호 효과를 나타낼 수 있는지를 알아보기 위해, 면역조직화학염색을 통해 흑질의 도파민성 신경세포 형태 및 선조체의 신경섬유 형태를 관찰하였다. 그 결과, 트랜스 신남 알데하이드는 흑질에서 6-OHDA에 의해 유발된 TH(tyrosine hydroxylase) 양성 도파민성 신경세포의 감소를 억제하였고, 선조체에서 6-OHDA에 의해 유발된 TH 양성 도파민 섬유의 손실을 억제하였다(도 1, 도 2 및 도 3 참조). In the present invention, trans cinnamic aldehyde is in vivo ( in In vivo ), we examined the dopaminergic neuronal morphology and neurofibrillary morphology of the striatum by immunohistochemical staining. As a result, trans cinnamic aldehyde inhibited the reduction of tyrosine hydroxylase (TH) positive dopaminergic neurons induced by 6-OHDA in black matter and inhibited the loss of TH positive dopamine fibers induced by 6-OHDA in striatum. (See FIGS. 1, 2 and 3).
따라서, 본 발명의 계피나무 추출물, 이의 분획물 또는 트랜스 신남 알데하이드는 신경독성물질에 의한 도파민 신경세포의 손상을 보호함으로써 이들을 유효성분으로 하여 파킨슨병 예방 및 치료에 유용하게 사용할 수 있다.Therefore, the cinnamon tree extract, fractions thereof, or trans cinnamic aldehyde of the present invention can be useful for preventing and treating Parkinson's disease by using them as an active ingredient by protecting the damage of dopamine neurons caused by neurotoxic substances.
또한, 본 발명은 상기 조성물을 파킨슨병에 걸린 개체에 투여하는 단계를 포함하는 파킨슨병 치료방법을 제공한다.The present invention also provides a method for treating Parkinson's disease comprising administering the composition to an individual suffering from Parkinson's disease.
또한, 본 발명은 상기 조성물을 개체에 투여하는 단계를 포함하는 파킨슨병 예방방법을 제공한다.The present invention also provides a method for preventing Parkinson's disease comprising administering the composition to a subject.
상기 방법에 있어서, 조성물은 계피나무 추출물, 이의 분획물 또는 트랜스-신남알데하이드 중에서 하나 이상을 선택적으로 함유할 수 있으며, 상기 성분에 추가로 동일 또는 유사한 기능을 나타내는 유효성분을 1종 이상 함유할 수 있다.In the above method, the composition may optionally contain one or more of cinnamon extract, fractions thereof or trans-cinnaaldehyde, and may further contain one or more active ingredients exhibiting the same or similar functions in addition to the above components. .
상기 방법에 있어서, 조성물은 투여 시에 경구 또는 비경구로 투여가 가능하며 일반적인 의약품 제제의 형태로 사용될 수 있다. 즉, 본 발명의 조성물은 실제 임상 투여 시에 경구 및 비경구의 여러 가지 제형으로 투여될 수 있는데, 제제화할 경우에는 보통 사용하는 충진제, 증량제, 결합제, 습윤제, 붕해제 및 계면활성제 등의 희석제 또는 부형제를 사용하여 조제된다. 경구 투여를 위한 고형 제제에는 정제, 환제, 산제, 과립제 및 캡슐제 등이 포함되며, 이러한 고형 제제는 본 발명의 약학적 조성물에 적어도 하나 이상의 부형제 예를 들면, 전분, 탄산칼슘, 수크로스, 락토오스 및 젤라틴 등을 섞어 조제된다. 또한 단순한 부형제 이외에 마그네슘, 스티레이트, 탈크 같은 윤활제들도 사용된다. 경구 투여를 위한 액상 제제로는 현탁제, 내용액제, 유제 및 시럽제 등이 해당되는데 흔히 사용되는 단순 희석제인 물, 리퀴드 파라핀 이외에 여러 가지 부형제, 예를 들면 습윤제, 감미제, 방향제 및 보존제 등이 포함될 수 있다. 비경구 투여를 위한 제제에는 멸균된 수용액, 비수성용제, 현탁제, 유제, 동결건조제제 및 좌제가 포함된다. 비수성용제와 현탁용제로는 프로필렌글리콜, 폴리에틸렌 글리콜, 올리브 오일과 같은 식물성 기름, 에틸올레이트와 같은 주사 가능한 에스테르 등이 사용될 수 있다. 좌제의 기제로는 위텝솔(witepsol), 마크로골, 트윈(tween) 61, 카카오지, 라우린지, 글리세롤 및 젤라틴 등이 사용될 수 있다. 본 발명의 조성물은 비경구 투여시 피하주사, 정맥주사 또는 근육내 주사를 통할 수 있다.In the above method, the composition can be administered orally or parenterally, and can be used in the form of a general pharmaceutical formulation. That is, the composition of the present invention may be administered in various oral and parenteral dosage forms in actual clinical administration, and when formulated, diluents or excipients such as fillers, extenders, binders, wetting agents, disintegrating agents, and surfactants that are commonly used. Is prepared using. Solid preparations for oral administration include tablets, pills, powders, granules and capsules, and the like, which may be used in the pharmaceutical composition of the present invention at least one excipient such as starch, calcium carbonate, sucrose, lactose And gelatin etc. are mixed and prepared. In addition to simple excipients, lubricants such as magnesium, styrate and talc are also used. Liquid preparations for oral administration include suspensions, solutions, emulsions and syrups, and may include various excipients such as wetting agents, sweeteners, fragrances and preservatives, in addition to commonly used simple diluents such as water and liquid paraffin. have. Formulations for parenteral administration include sterile aqueous solutions, non-aqueous solvents, suspensions, emulsions, lyophilized preparations and suppositories. As the non-aqueous solvent and the suspension solvent, propylene glycol, polyethylene glycol, vegetable oil such as olive oil, injectable ester such as ethyl oleate, and the like can be used. As the base of the suppository, witepsol, macrogol, tween 61, cacao butter, laurin butter, glycerol and gelatin may be used. The compositions of the present invention may be via subcutaneous injection, intravenous injection or intramuscular injection during parenteral administration.
투약 단위는, 예를 들면 개별 투약량의 1, 2, 3 또는 4배를 함유하거나 또는 1/2, 1/3 또는 1/4배를 함유할 수 있다. 개별 투약량은 바람직하기로는 유효 약물이 1회에 투여되는 양을 함유하며, 이는 통상 1일 투여량의 전부, 1/2, 1/3 또는 1/4배에 해당한다. 본 발명의 조성물의 유효용량은 0.0001 ~ 10 g/㎏이고, 바람직하기로는 0.0001 g ~ 5 g/kg이며, 하루 1 ~ 6회 투여될 수 있다.Dosage units may contain, for example, one, two, three or four times the individual dosage, or they may contain 1/2, 1/3 or 1/4 times. The individual dosage preferably contains an amount in which the effective drug is administered at one time, which usually corresponds to all, 1/2, 1/3 or 1/4 times the daily dose. The effective dose of the composition of the present invention is 0.0001 to 10 g / kg, preferably 0.0001 g to 5 g / kg, may be administered 1 to 6 times a day.
본 발명의 조성물은 파킨슨병 예방 및 치료를 위하여 단독으로, 또는 수술, 호르몬 치료, 화학 치료 및 생물학적 반응 조절제를 사용하는 방법들과 병용하여 사용할 수 있다.The composition of the present invention can be used alone or in combination with methods using surgery, hormone therapy, chemotherapy and biological response modifiers for the prevention and treatment of Parkinson's disease.
아울러, 본 발명은 계피나무 추출물, 이의 분획물, 또는 화학식 1로 기재되는 트랜스-신남알데하이드(trans-cinnamaldehyde) 또는 이의 약학적으로 허용가능한 염을 유효성분으로 함유하는 파킨슨병 예방 및 개선용 건강기능식품을 제공한다.In addition, the present invention cinnamon extract, fractions thereof, or Parkinson's disease prevention and improvement health functional food containing a trans-cinnamaldehyde (trans-cinnamaldehyde) or a pharmaceutically acceptable salt thereof represented by the formula (1) as an active ingredient To provide.
본 발명의 건강기능식품은 계피나무 추출물, 이의 분획물 또는 트랜스-신남알데하이드를 그대로 첨가하거나 다른 식품 또는 식품 성분과 함께 사용될 수 있고, 통상적인 방법에 따라 적절하게 사용될 수 있다. 유효 성분의 혼합양은 사용 목적(예방, 건강 또는 치료적 처치)에 따라 적합하게 결정될 수 있다. 일반적으로, 식품 또는 음료의 제조시에 본 발명의 약학적 조성물은 원료에 대하여 15 중량부 이하, 바람직하게는 10 중량부 이하의 양으로 첨가된다. 그러나 건강 및 위생을 목적으로 하거나 또는 건강 조절을 목적으로 하는 장기간의 섭취의 경우에는 상기 양은 상기 범위 이하일 수 있으며, 안전성 면에서 아무런 문제가 없기 때문에 유효성분은 상기 범위 이상의 양으로도 사용될 수 있다.The health functional food of the present invention may be added with cinnamon extract, fractions thereof, or trans-cinnaaldehyde as it is, or used with other foods or food ingredients, and may be appropriately used according to a conventional method. The mixed amount of the active ingredient may be suitably determined depending on the purpose of use (prevention, health or therapeutic treatment). Generally, in the preparation of food or beverages, the pharmaceutical compositions of the present invention are added in an amount of up to 15 parts by weight, preferably up to 10 parts by weight based on the raw materials. However, in the case of long-term intake for health and hygiene or health control purposes, the amount may be below the above range, and the active ingredient may be used in an amount above the above range because there is no problem in terms of safety.
상기 식품의 종류에는 특별한 제한은 없다. 상기 물질을 첨가할 수 있는 식품의 예로는 육류, 소세지, 빵, 쵸코렛, 캔디류, 스넥류, 과자류, 피자, 라면, 기타 면류, 껌류, 아이스크림류를 포함한 낙농제품, 각종 스프, 음료수, 차, 드링크제, 알콜 음료 및 비타민 복합제 등이 있으며, 통상적인 의미에서의 건강식품을 모 두 포함한다.There is no particular limitation on the kind of food. Examples of the food to which the substance can be added include dairy products including meat, sausage, bread, chocolate, candy, snacks, confectionery, pizza, ramen, other noodles, gums, ice cream, various soups, drinks, tea, drinks, Alcoholic beverages and vitamin complexes, and includes all health foods in the conventional sense.
본 발명의 건강음료 조성물은 통상의 음료와 같이 여러 가지 향미제 또는 천연 탄수화물 등을 추가 성분으로서 함유할 수 있다. 상술한 천연 탄수화물은 포도당, 과당과 같은 모노사카라이드, 말토스, 슈크로스와 같은 디사카라이드, 및 덱스트린, 사이클로덱스트린과 같은 폴리사카라이드, 자일리톨, 소르비톨, 에리트리톨 등의 당알콜이다. 감미제로서는 타우마틴, 스테비아 추출물과 같은 천연 감미제나, 사카린, 아스파르탐과 같은 합성 감미제 등을 사용할 수 있다. 상기 천연 탄수화물의 비율은 본 발명의 조성물 100 ㎖당 일반적으로 약 0.01 ~ 0.04 g, 바람직하게는 약 0.02 ~ 0.03 g 이다.The health beverage composition of the present invention may contain various flavors or natural carbohydrates as an additional ingredient such as ordinary beverages. Such natural carbohydrates are monosaccharides such as glucose and fructose, disaccharides such as maltose and sucrose, and polysaccharides such as dextrin and cyclodextrin, and sugar alcohols such as xylitol, sorbitol and erythritol. Examples of sweeteners include natural sweeteners such as tau martin and stevia extract, synthetic sweeteners such as saccharin and aspartame, and the like. The proportion of the natural carbohydrate is generally about 0.01 to 0.04 g, preferably about 0.02 to 0.03 g per 100 ml of the composition of the present invention.
상기 외에 본 발명의 건강기능식품은 여러가지 영양제, 비타민, 전해질, 풍미제, 착색제, 펙트산 및 그의 염, 알긴산 및 그의 염, 유기산, 보호성 콜로이드 증점제, pH 조절제, 안정화제, 방부제, 글리세린, 알콜, 탄산 음료에 사용되는 탄산화제 등을 함유할 수 있다. 그밖에 본 발명의 건강기능식품은 천연 과일쥬스, 과일쥬스 음료 및 야채 음료의 제조를 위한 과육을 함유할 수 있다. 이러한 성분은 독립적으로 또는 조합하여 사용할 수 있다. 이러한 첨가제의 비율은 크게 중요하진 않지만 본 발명의 조성물 100 중량부당 0.01 ~ 0.1 중량부의 범위에서 선택되는 것이 일반적이다.In addition to the above, the health functional food of the present invention includes various nutrients, vitamins, electrolytes, flavors, coloring agents, pectic acid and salts thereof, alginic acid and salts thereof, organic acids, protective colloid thickeners, pH regulators, stabilizers, preservatives, glycerin, alcohols. And carbonation agents used in carbonated beverages. In addition, the health functional food of the present invention may contain fruit flesh for the production of natural fruit juice, fruit juice beverage and vegetable beverage. These components can be used independently or in combination. The proportion of such additives is not critical but is generally selected in the range of 0.01 to 0.1 parts by weight per 100 parts by weight of the composition of the present invention.
이하, 본 발명을 하기 실시예, 실험예 및 제조예에 의하여 상세히 설명한다.Hereinafter, the present invention will be described in detail by the following Examples, Experimental Examples and Preparation Examples.
단, 하기 실시예, 실험예 및 제조예는 본 발명을 구체적으로 예시하는 것이며, 본 발명의 내용이 하기의 실시예, 실험예 및 제조예에 의해 한정되는 것은 아니다. However, the following Examples, Experimental Examples, and Preparation Examples specifically illustrate the present invention, and the content of the present invention is not limited to the following Examples, Experimental Examples, and Preparation Examples.
<< 실시예Example 1> 1> 계피나무Cinnamon 추출물의 제조 Preparation of Extract
<1-1> 계피나무 에탄올 수용액 추출물<1-1> ethanol extract of cinnamon tree
경동시장에서 구입한 계피나무를 건조시킨 후 분쇄한 다음, 계피나무 시료 200 g을 3ℓ의 플라스크에 넣은 후 1.5 ℓ의 80% 에탄올 수용액을 가하여 3시간 동안 추출하였다. 이 과정을 3회 반복하여 상층액을 모은 후, 거름종이로 여과하고 진공감압하에 농축하여 계피나무 에탄올 수용액 추출물 7 g을 수득하였다. The cinnamon tree purchased from Gyeongdong market was dried and pulverized, and then 200 g of the cinnamon tree sample was placed in a 3 L flask, and 1.5 L of 80% ethanol aqueous solution was added thereto for 3 hours. This process was repeated three times, and the supernatant was collected, filtered through a filter paper and concentrated under vacuum to obtain 7 g of an aqueous extract of cinnamon ethanol.
<1-2> <1-2> 계피나무Cinnamon 물 추출물 Water extract
상기 실시예 <1-1>에서 80% 에탄올 수용액 대신 증류수를 가한 것을 제외하고 동일하게 하여 계피나무 물 추출물 10.2 g을 수득하였다. In Example <1-1>, 10.2 g of Cinnamon Water extract was obtained in the same manner except distilled water was added instead of an 80% ethanol aqueous solution.
<1-3> <1-3>
계피나무
상기 실시예 <1-1>에서 80% 에탄올 수용액 대신 100% 메탄올을 가한 것을 제외하고 동일하게 하여 계피나무 메탄올 추출물 8 g을 수득하였다. 8 g of cinnamon methanol extract was obtained in the same manner as in Example <1-1> except that 100% methanol was added instead of an 80% ethanol aqueous solution.
<< 실시예Example 2> 2> 계피나무Cinnamon 추출물로부터 From extract 분획물의Fraction 제조 Produce
상기 실시예 <1-1>에서 수득한 계피나무 에탄올 수용액 추출물 5.5 g을 물 1 ℓ에 현탁시킨 후에, 에틸아세테이트 및 부탄올로 순차적으로 용매 분획하였다. 먼저, 물 1ℓ에 현탁시킨 계피나무 에탄올 추출물에 에틸아세테이트 1ℓ를 첨가하여 용해한 다음, 이를 분획여두에서 에틸아세테이트 층에 용해되는 성분만 분리해서 진공건조하였다. 이 과정을 3회 반복 수행하여 에틸아세테이트 분획물을 수득하였다(0.7g). 남은 수층에 부탄올 1ℓ를 첨가하여 분획여두에서 부탄올 층에 용해되는 성분만 분리하여 진공건조하였다. 이 과정을 3회 반복 수행하여 부탄올 분획물을 수득하였다(3.5g).5.5 g of the cinnamon tree ethanol aqueous solution extract obtained in Example <1-1> was suspended in 1 L of water, and then solvent fractionated sequentially with ethyl acetate and butanol. First, 1 liter of ethyl acetate was added to the cinnamon ethanol extract suspended in 1 liter of water, and then dissolved. Then, only the components dissolved in the ethyl acetate layer in the fractional filter were separated and dried in vacuo. This process was repeated three times to obtain an ethyl acetate fraction (0.7 g). 1 liter of butanol was added to the remaining aqueous layer, and only the components dissolved in the butanol layer were separated and dried under vacuum. This process was repeated three times to obtain a butanol fraction (3.5 g).
<< 실시예Example 3> 트랜스- 3> trans- 신남알데하이드(trans-cinnamaldehyde)의Of cinnamic aldehyde (trans-cinnamaldehyde) 제조 Produce
상기 실시예 <1-3>에서 추출한 계피나무 메탄올 추출물을 메틸렌클로라이드에 녹인 후 실리카겔(Merck, Art No. 9385)에 가하여 활성물질을 흡착시킨 다음, 에틸아세테이트와 핵산의 비율을 95 : 5에서 80 : 20으로 변화시키면서 실리카겔 칼럼 크로마토그래피하여 활성분획을 분리하였다. 수득한 분획물을 C18 칼럼에 흡착시킨 다음 메탄올과 물로 용출시켜 부분 정제하여 화학식 1의 트랜스-신남알데하이드를 수득하였다.Cinnamon methanol extract extracted in Example <1-3> was dissolved in methylene chloride and added to silica gel (Merck, Art No. 9385) to adsorb the active substance, and then the ratio of ethyl acetate and nucleic acid was 95: 5 to 80. : The active fractions were separated by silica gel column chromatography changing to 20. The obtained fractions were adsorbed on a C18 column and then partially purified by eluting with methanol and water to obtain the trans-cinnaaldehyde of formula (1).
<< 실험예Experimental Example 1> 신경세포 보호효과 측정 1> Measurement of neuronal protective effect
<1-1> 세포 배양 <1-1> cell culture
본 발명자들은 마우스 미세아교 세포주(mouse microglial cell line)인 BV2 세포(Sigma, USA)를 100 U/mL 페니실린 및 100 ug/mL 스트렙토마이신이 들어있는 5% FBS(Gibsco, USA)와 DMEM(Sigma, USA) 배지로 5% CO2, 37℃에서 배양하였다. We used a mouse microglial cell line, BV2 cells (Sigma, USA), 5% FBS (Gibsco, USA) containing 100 U / mL penicillin and 100 ug / mL streptomycin and DMEM (Sigma, USA). USA) was incubated at 5% CO 2 , 37 ℃ medium.
<1-2> 세포생존율 측정<1-2> Cell viability measurement
본 발명자들은 계피나무 추출물, 이의 분획물 및 트랜스 신남 알데하이드가 신경독성물질에 대한 신경세포 보호효과를 가지는지 알아보기 위해서, MTT 분석법을 이용하여 세포생존률을 측정하였다. 먼저, 상기 실험예 <2-1>에서 배양한 BV2 세포를 96-웰 플레이트에 웰 당 5×103개로 깔고 1% FBS가 들어있는 DMEM(낮은 포도당) 배지에서 24시간 동안 전배양(pre-incubation)하였다. 상기 BV2 세포에 3 ~ 10 ug/mL의 계피나무 추출물, 3 ~ 10 ug/mL의 계피나무 추출물의 분획물, 및 1 ~ 3 uM의 트랜스 신남 알데하이드를 각각 처리한 후, 1시간 후 1 ug/ml의 LPS를 처리한 다음, 24시간 후 MTT로 세포생존율을 확인하였다.The present inventors measured the cell survival rate using the MTT assay to determine whether the cinnamon tree extract, its fractions and trans cinnamic aldehyde has a neuronal protective effect against neurotoxic substances. First, BV2 cells cultured in Experimental Example <2-1> were placed on 96-well plates at 5 × 10 3 per well and pre-cultured for 24 hours in DMEM (low glucose) medium containing 1% FBS. incubation). The BV2 cells were treated with 3 to 10 ug / mL cinnamon extract, 3 to 10 ug / mL cinnamon extract, and 1 to 3 uM trans cinnamic aldehyde, respectively, 1 ug / ml after 1 hour. After treatment with LPS, cell viability was confirmed by MTT after 24 hours.
그 결과, 표 1에서 보는 바와 같이 BV2 세포에 LPS만 처리한 군에 비해 3 ~ 10 ug/mL의 계피나무 추출물 및 이의 분획물, 및 1 ~ 3 uM의 트랜스 신남 알데하이드를 미리 처리한 군의 세포생존율이 약 35 ~ 45% 높았다. 따라서 본 발명의 계피나무 추출물, 이의 분획물 및 트랜스 신남 알데하이드는 LPS로 유발된 BV2 세포사멸에 대한 보호 효과가 있음을 알 수 있었다. As a result, as shown in Table 1, compared to the LPS-only group treated BV2 cells, 3 ~ 10 ug / mL of cinnamon extract and fractions thereof, and the cell survival rate of the group pre-treated with 1 ~ 3 uM trans cinnamic aldehyde This was about 35-45% higher. Therefore, the cinnamon extract, fractions and trans cinnamic aldehyde of the present invention was found to have a protective effect against BV2 cell death induced by LPS.
<1-3> <1-3> NONO 생성량 측정 Production measurement
본 발명자들은 계피나무 추출물, 이의 분획물 및 트랜스 신남 알데하이드가 LPS로 유도된 신경세포에서의 NO 생성을 억제하는지 알아보았다. 먼저, BV2 세포가 부착되어있는 60 디쉬에 1% FBS를 포함하는 DMEM로 배지를 갈아준 후, 3 ~ 10 ug/mL의 계피나무 추출물, 3 ~ 10 ug/mL의 계피나무 분획물, 및 1 ~ 3 uM의 트랜스 신남 알데하이드를 각각 전처리하였다. 1 시간 후에 1 ug/ml LPS를 처리하고 24시간 후, 상층액을 회수하여 그리스 시약(Griess reagent)을 동량 첨가하고 ELISA 리더기로 570 nm에서 흡광도를 측정하였다. 일정 농도의 아질산나트륨(sodium nitrite)의 표준 곡선을 이용하여 생성된 NO의 함량을 계산하였다.The inventors examined whether cinnamon extract, fractions thereof, and trans cinnamic aldehyde inhibit NO production in LPS-induced neurons. First, the medium was changed to DMEM containing 1% FBS in 60 dishes to which BV2 cells were attached, and then 3 to 10 ug / mL of cinnamon extract, 3 to 10 ug / mL of cinnamon fraction, and 1 to 1 3 uM of trans cinnamic aldehyde were pretreated respectively. After 1 hour, 1 ug / ml LPS was treated and after 24 hours, the supernatant was recovered, and the same amount of Greases reagent was added, and the absorbance was measured at 570 nm with an ELISA reader. The amount of NO produced was calculated using a standard curve of sodium nitrite at a certain concentration.
그 결과, 표 2에서 보는 바와 같이 NO 생성량은 LPS만 처리한 군이 대조군에 비해 약 4.5배 증가한 반면에, 1 ~ 10 ug/mL의 계피나무 추출물 및 이의 분획물, 및 1 ~ 3 uM의 트랜스 신남 알데하이드를 미리 처리한 군이 농도 의존적으로 감소하였다. 따라서 본 발명의 계피나무 추출물, 이의 분획물 및 트랜스 신남 알데하이드는 LPS로 유도된 BV2 세포에서의 NO 생성에 대한 억제 효과가 있음을 알 수 있었다. As a result, as shown in Table 2, the amount of NO production increased by about 4.5 times in the LPS-only group, compared to the control group, while the cinnamon extract and its fraction, and the transcinam of 1 ~ 3 uM of 1 ~ 10 ug / mL Groups pretreated with aldehydes decreased in a concentration dependent manner. Therefore, the cinnamon extract of the present invention, its fractions and trans cinnamic aldehyde was found to have an inhibitory effect on NO production in BV2 cells induced by LPS.
<1-4> <1-4> 웨스턴Weston 블랏팅( Blotting ( WesternWestern blottingblotting ))
본 발명자들은 계피나무 추출물, 이의 분획물 및 트랜스 신남 알데하이드가 LPS로 유도된 신경세포에서의 iNOS 및 COX-2 발현 증가를 억제하는지 알아보았다. 먼저, BV2 세포를 LPS로 처리한 후, 24시간 뒤 용해 완충용액(lysis buffer)을 이용하여 단백질을 분리하였다. 단백질 샘플을 단백질 분석 키트(protein assay kit)를 이용하여 정량한 후, SDS-PAGE를 시행한 다음, 전기영동이 끝난 겔(gel)은 니트로셀룰로오스막(nitrocellulose membrane)으로 이동시켰다. 단백질이 이동된 니트로셀룰로오스막은 항토끼 COX-2 항체(anti-rabbit COX-2 antibody)와 항마우스 iNOS(anti-mouse iNOS)를 1:1000로 희석하여 4℃에서 밤새 반응시켰다. TBST(Tris base solution, 0.1% triton X-100)로 10분간 3회 세척한 후, 2차 항체를 1:2000으로 희석하여 1시간 반응시키고, TBST로 10분씩 3번 세척한 뒤 ECL 키트로 반응하여 X-레이 필름(ray film)에 노출시켰다.The inventors examined whether cinnamon extract, fractions thereof and trans cinnamic aldehydes inhibited iNOS and COX-2 expression increase in LPS-induced neurons. First, after treating BV2 cells with LPS, proteins were separated using lysis buffer after 24 hours. Protein samples were quantified using a protein assay kit, followed by SDS-PAGE, and then the electrophoretic gels were transferred to nitrocellulose membranes. The protein-transferred nitrocellulose membrane was diluted 1: 1000 with anti-rabbit COX-2 antibody and anti-mouse iNOS and reacted at 4 ° C. overnight. After washing three times with TBST (Tris base solution, 0.1% triton X-100) for 10 minutes, the secondary antibody was diluted 1: 2000 and reacted for 1 hour, washed three times with TBST for 10 minutes, and then reacted with ECL kit. Was exposed to an X-ray film.
그 결과, LPS로 유도된 BV2 세포는 대조군에 비해 iNOS 및 COX-2의 발현이 유의성 있게 증가하였으나, 3 ~ 10 ug/mL의 계피나무 추출물 및 이의 분획물, 및 1 ~ 3 uM의 트랜스 신남 알데하이드를 미리 처리한 군의 경우 농도 의존적으로 유의성 있게 감소하였다. 따라서 본 발명의 계피나무 추출물, 이의 분획물 및 트랜스 신남 알데하이드는 LPS로 유도된 BV2 세포에서의 iNOS 및 COX-2 발현 증가를 억제시킬 수 있음을 알 수 있었다.As a result, LPS-induced BV2 cells significantly increased the expression of iNOS and COX-2 compared to the control group, but 3 to 10 ug / mL cinnamon extract and fractions thereof, and 1 to 3 uM of trans cinnamic aldehyde. The pretreatment group significantly decreased in a concentration dependent manner. Therefore, it was found that the cinnamon extract, fractions thereof, and trans cinnamic aldehyde of the present invention could inhibit the increase of iNOS and COX-2 expression in BV2 cells induced by LPS.
<< 실험예Experimental Example 2> 생체 내 도파민 신경세포 손상보호 효과 측정 2> Measurement of dopamine neuron damage protection effect in vivo
<2-1> 동물의 사육 및 시료투여<2-1> Animal Breeding and Sample Administration
본 발명자들은 6주령의 생쥐(ICR mouse)(Sigma, USA)를 구입하여 사육하였다. 사육조건은 국제보건기구(National Institute of Health; NIH) 및 대한의학과학회(The Korean Academy of Medical Sciences)의 동물사육지침을 따랐다. 생쥐에 노르에피네프린(norepineprine)의 재흡수를 막기 위하여 6-OHDA 투여 30분 전에 데시프라민(desipramine)(25 mg/kg)을 복강으로 주사하였다. 6-OHDA는 0.02% 아스코르빈산(ascorbic acid)에 녹이고 1 N NaOH를 이용하여 pH를 7.4로 맞춘 후, 6-OHDA 60 ug(10 ug/ul, Sigma, USA)을 생쥐의 뇌실에 주입하였다. 대조군은 6-OHDA 대신 pH 7.4의 식염수를 동일하게 주입하였다. 계피나무 추출물(50 및 100 mg/kg), 이의 분획물(50 mg/kg) 및 트랜스-신남알데하이드(30 mg/kg)를 복강으로 6-OHDA 주입 1시간 전, 주입 3시간, 7시간, 24시간 및 48시간 후로 총 5번 투여하였다. 대조군은 추출물 대신 0.5% DMSO를 동량 주입하였다. The present inventors purchased and bred 6-week-old mice (ICR mouse) (Sigma, USA). The conditions for breeding were followed by animal breeding guidelines of the National Institute of Health (NIH) and The Korean Academy of Medical Sciences. Mice were injected intraperitoneally with desipramine (25 mg / kg) 30 minutes prior to 6-OHDA administration to prevent reuptake of norepineprine. 6-OHDA was dissolved in 0.02% ascorbic acid, pH was adjusted to 7.4 using 1 N NaOH, and 6-OHDA 60 ug (10 ug / ul, Sigma, USA) was injected into the ventricles of mice. . The control group was injected with the same saline solution of pH 7.4 instead of 6-OHDA. Cinnamon extract (50 and 100 mg / kg), fractions thereof (50 mg / kg) and trans-cinnamaldehyde (30 mg / kg) intraperitoneally 1 hour before infusion, 3 hours, 7 hours, 24 hours A total of five doses were administered at time and 48 hours later. The control group was injected with the same amount of 0.5% DMSO instead of the extract.
<2-2> <2-2> 선조체Striatum 내 도파민 및 그 대사물질의 함량 측정 Determination of Dopamine and its Metabolites
본 발명자들은 계피나무 추출물, 이의 분획물 및 트랜스 신남 알데하이드가 신경독성물질에 대한 신경세포 보호효과를 가지는지 알아보기 위해서, 6-OHDA 투여에 따른 선조체 내에서의 도파민과 그 대사물질인 DOPAC(3-4-dihydroxyphenylacetic acid) 농도를 고성능 액체 크로마토그래피(HPLC)로 측정하였다. 병변 제작 7일 후, 생쥐를 경추 탈골하여 희생시킨 다음, 즉시 뇌 조직을 적출하였다. 냉각된 유리판 위에 대뇌 정중선을 따라 좌우 대뇌반구를 분리한 후, 뇌량을 경계로 하여 시상 및 대뇌피질로부터 선조체만을 분리 및 절취한 후, 이를 급속 동결시켜 측정시까지 -70℃에서 보관하였다. 동결된 검체에 냉각된 0.5 ml의 0.1 M 퍼클로릭산(percloric acid), 0.1 mM EDTA 용액을 첨가한 후, 초음파 마쇄기로 30초씩 3번 30-S 포즈(pause) 조건에서 조직 균등액을 제조한 다음, 12,000 rpm에서 10분 동안 원심 분리하여 그 상층액을 분리하였다. 상기 상층액을 니트로셀룰로스 막 여과지(nitrocellulose membrane filter; 0.2 um, Millipore)로 여과한 후, 10 ul를 HPLC 시스템에 주입하였다. HPLC의 분리조건은 Shisheido uBondapakTM C18 4.6 x150 mm 컬럼(particle size 10 um)을 사용하였고, 전기화학 검출기(electrochemical detector)(ICA-5000, TOA)는 700 mV의 Ag/Agcl 전극을 사용하며, 이동상(mobile phase)은 0.07 M 일염기 인산나트륨(monobasic sodium phosphate), 1 mM 옥탄설폰산 나트륨(sodium octansulfonic acid), 0.1 uM EDTA, 5% 아세토니트릴(acetonitrile)(pH 3.2) 용액으로 0.7 ml/min 유속으로 유지하였다. 도파민 및 DOPAC의 농도는 측정에 필요한 각 물질의 농도측정을 위해 조직 균등액 제조시 일정량의 디히드록시벤질아민(dihydroxybenzylamine; DHBA)을 내위 표준(internal standard)으로 조직균등액에 첨가하여 보관하였고, 원심분리 후 생성된 침전물은 0.4 ml PBS에 부유하여 단백 측정에 사용하였다.In order to find out whether cinnamon extract, its fractions and trans cinnamic aldehydes have neuroprotective effects against neurotoxic substances, dopamin and its metabolite DOPAC (3-) 4-dihydroxyphenylacetic acid) concentration was measured by high performance liquid chromatography (HPLC). Seven days after lesion preparation, mice were sacrificed by cervical dislocation and immediately brain tissue was extracted. After the left and right cerebral hemispheres were separated along the cerebral midline on the cooled glass plate, only the striatum was separated and cut off from the sagittal and cerebral cortex on the basis of the corpus callosum, and then rapidly frozen and stored at -70 ° C until measurement. After adding 0.5 ml of 0.1 M percloric acid and 0.1 mM EDTA solution cooled to the frozen specimen, tissue equalizers were prepared in 30-S pause conditions three times for 30 seconds using an ultrasonic mill. Next, the supernatant was separated by centrifugation at 12,000 rpm for 10 minutes. The supernatant was filtered through a nitrocellulose membrane filter (0.2 um, Millipore), and 10 ul was injected into the HPLC system. HPLC separation conditions were Shisheido uBondapak TM C18 4.6 x 150 mm column (particle size 10 um), electrochemical detector (ICA-5000, TOA) using 700 mV Ag / Agcl electrode, mobile phase The mobile phase is 0.07 M monobasic sodium phosphate, 1 mM sodium octansulfonic acid, 0.1 uM EDTA, 5% acetonitrile (pH 3.2) solution 0.7 ml / min Maintained at flow rate. The concentrations of dopamine and DOPAC were stored by adding a certain amount of dihydroxybenzylamine (DHBA) to the tissue homogenate as an internal standard when preparing the tissue homogenate to measure the concentration of each substance required for measurement. The precipitate produced after centrifugation was suspended in 0.4 ml PBS and used for protein determination.
그 결과, 표 3에서 보는 바와 같이 선조체 내 도파민 및 DOPAC의 농도는 6-OHDA만을 주입한 경우 대조군(0.02% L-아스코르빈산을 포함한 식염수 주입)에 비해 감소(대조군에 비해, 도파민: 63%, DOPAC: 45%)하였으나, 계피나무 추출물(50 및 100 mg/kg), 이의 분획물(50 mg/kg) 및 트랜스-신남알데하이드(30 mg/kg)를 미리 주입한 경우 상기 6-OHDA만을 주입한 경우에 비해 약 20 ~ 30% 증가하였다. 따라서 본 발명의 계피나무 추출물, 이의 분획물 및 트랜스 신남 알데하이드는 선조체 내에서 6-OHDA에 의해 유발된 도파민 및 DOPAC 농도의 감소를 억제함을 알 수 있었다.As a result, as shown in Table 3, the concentrations of dopamine and DOPAC in the striatum were reduced compared to the control group (saline injection with 0.02% L-ascorbic acid) when only 6-OHDA was injected (dopamine: 63% compared to the control). , DOPAC: 45%), but when the cinnamon extract (50 and 100 mg / kg), fractions thereof (50 mg / kg) and trans-cinnamaldehyde (30 mg / kg) was pre-injected injected only the 6-OHDA It was increased about 20-30% compared to one case. Therefore, the cinnamon extract of the present invention, its fractions and trans cinnamic aldehyde inhibited the decrease of dopamine and DOPAC concentration induced by 6-OHDA in the striatum.
(mg/kg)density
(mg / kg)
(대조군에 대한 %)Dopamine Concentration
(% Of control)
(대조군에 대한 %)DOPAC concentration
(% Of control)
<2-3> 지질과산화(<2-3> lipid peroxidation ( lipidlipid peroxidationperoxidation ) 생성량 측정) Production measurement
본 발명자들은 계피나무 추출물, 이의 분획물 및 트랜스 신남 알데하이드가 지질과산화물질인 말론디알데하이드(malondialdehyde; MDA)의 감소 억제효과를 가지는지 알아보기 위해, 생쥐 뇌 호모제네이트(brain homogenate)(2 ㎎/㎖)와 시료를 혼합한 후, 37℃에서 1시간 동안 진탕 수욕조에서 반응시켰다. 상기 반응물을 8.1% SDS, 20% 아세트산(pH 2.5), 0.8% TBA(0.01% BHT 첨가)를 넣고, 95℃에서 1시간 동안 끓인 후 식혀 5분 동안 3000 rpm으로 원심분리한 다음, 흡광도를 분광 광도계(UVIKON 933)를 이용하여 532 nm에서 측정하였다.In order to determine whether cinnamon extract, fractions thereof and trans cinnamic aldehydes have a reduced inhibitory effect on lipid peroxide malondialdehyde (MDA), mouse brain homogenate (2 mg / Ml) and the sample, followed by reaction in a shaking water bath at 37 ° C. for 1 hour. The reaction was added to 8.1% SDS, 20% acetic acid (pH 2.5), 0.8% TBA (0.01% BHT addition), boiled at 95 ℃ for 1 hour, cooled, centrifuged at 3000 rpm for 5 minutes, and then absorbance spectroscopy It was measured at 532 nm using a photometer (UVIKON 933).
그 결과, 표 4에서 보는 바와 같이 MDA의 농도는 6-OHDA만을 주입한 경우 대조군에 비해 약 50% 감소하였으나, 계피나무 추출물(50 및 100 mg/kg), 이의 분획물(50 mg/kg) 및 트랜스-신남알데하이드(30 mg/kg)를 미리 주입한 경우 상기 6-OHDA만을 주입한 경우에 비해 약 30 ~ 40% 증가하였다. 따라서 본 발명의 계피나무 추출물, 이의 분획물 및 트랜스 신남 알데하이드는 6-OHDA에 의해 유발된 지질과산화물의 감소를 억제함을 알 수 있었다.As a result, as shown in Table 4, the concentration of MDA was reduced by about 50% compared to the control group when 6-OHDA was injected, but the extract of cinnamon (50 and 100 mg / kg), fractions thereof (50 mg / kg) and Trans-cinnamaldehyde (30 mg / kg) pre-injected increased about 30-40% compared to the 6-OHDA only injection. Therefore, the cinnamon extract of the present invention, its fractions and trans cinnamic aldehyde was found to inhibit the reduction of lipid peroxide caused by 6-OHDA.
(mg/kg)density
(mg / kg)
출물Cinnamon tree ethanol aqueous solution weight
Exhibit
분획물Cinnamon ethyl acetate
Fraction
<2-4> <2-4> 웨스턴Weston 블랏팅( Blotting ( WesternWestern blottingblotting ))
본 발명자들은 계피나무 추출물, 이의 분획물 및 트랜스 신남 알데하이드가 6-OHDA로 유도된 선조체 및 흑질(substantia nigra)에서의 TH(tyrosine hydroxylase), iNOS, COX-2 및 NT(Nitro tyrosine) 발현 변화에 미치는 영향을 알아보았다. 먼저, 병변 제작 7일 후 지질과산화물을 측정할 때와 마찬가지의 방법으로 조직 균등액을 제조한 후, 4℃에서 5분간 13000 rpm으로 침전시킨 다음, 상층액을 취하여 브래드포드(bradford) 방법에 의하여 단백을 정량하고, 10 ug을 웨스턴 블랏하였다. 단백을 10% SDS PAGE 겔을 이용하여 니트로셀룰로오스(Bio-Rad Labolatories., CA, USA)에 이동시킨 후, 단클론 마우스 항 티로신 하이드록시라제(monoclonal mouse anti tyrosine hydroxylase)(Chemicon International, Temecula , USA; 1:3000), 단클론 마우스 항 iNOS(monoclonal mouse anti iNOS)(BD Biosciences Pharmingen, USA; 1:5000), 다클론 마우스 항 Cox-2(monoclonal mouse anti Cox-2)(Santa Cruz Biotechnology, Inc. USA; 1:1000) 및 단클론 마우스 항 니트로 티로신(monoclonal mouse anti Nitro tyrosine)(Upstate, USA; 1:1000)을 이용하여 확인하였다. 반응이 끝난 후에는 HRP가 결합된 이차항체(항 마우스 IgG; 1:2000)를 1시간 동안 반응시킨 후, ECL을 이용하여 확인하였다. We investigated the effects of cinnamon extract, fractions and trans cinnamic aldehydes on the expression of tyrosine hydroxylase (TH), iNOS, COX-2 and nitro tyrosine in 6-OHDA-induced striatum and substantia nigra. The impact was examined. First, after preparing the tissue homogenate in the same manner as the measurement of lipid peroxides 7 days after the preparation of the lesion, precipitated at 13000 rpm for 5 minutes at 4 ℃, the supernatant was taken by the Bradford method (bradford) method Protein was quantified and 10 ug western blotted. The protein was transferred to nitrocellulose (Bio-Rad Labolatories., CA, USA) using a 10% SDS PAGE gel, followed by monoclonal mouse anti tyrosine hydroxylase (Chemicon International, Temecula, USA; 1: 3000), monoclonal mouse anti iNOS (BD Biosciences Pharmingen, USA; 1: 5000), monoclonal mouse anti Cox-2 (Santa Cruz Biotechnology, Inc. USA) 1: 1000) and monoclonal mouse anti Nitro tyrosine (Upstate, USA; 1: 1000). After the reaction, HRP-bound secondary antibody (anti mouse IgG; 1: 2000) was reacted for 1 hour, and then confirmed using ECL.
그 결과, 표 5에서 보는 바와 같이 6-OHDA로 유도된 선조체 및 흑질에서 TH 및 NT의 발현이 대조군에 비해 유의성 있게 감소[대조군에 비해, TH(선조체: 약 25%, 흑질: 약 38%), NT(선조체: 약 28%, 흑질: 약 40%)]하였으나, 계피나무 추출물(50 및 100 mg/kg), 이의 분획물(50 mg/kg) 및 트랜스-신남알데하이드(30 mg/kg)를 미리 주입한 경우 상기 6-OHDA만을 주입한 경우에 비해 유의성 있게 증가하였다(대조군에 비해, 선조체: 약 65 ~ 75%, 흑질: 약 140 ~ 150%). 따라서 본 발명의 계피나무 추출물, 이의 분획물 및 트랜스 신남 알데하이드는 6-OHDA에 의해 유발된 TH 및 NT의 발현의 감소를 억제시킬 수 있음을 알 수 있었다. As a result, as shown in Table 5, expression of TH and NT in the 6-OHDA-induced striatum and black matter was significantly decreased compared to the control group (relative to the control group, TH (stratum: about 25%, black matter: about 38%). , NT (precursor: about 28%, black matter: about 40%)], but cinnamon extract (50 and 100 mg / kg), fractions thereof (50 mg / kg) and trans-cinnamaldehyde (30 mg / kg) In the case of pre-injection, the 6-OHDA was significantly increased compared to the case of injecting only 6-OHDA (compared to control group, about 65-75%, black matter: about 140-150%). Therefore, it was found that the cinnamon extract, fractions thereof, and trans cinnamic aldehyde of the present invention could inhibit the decrease in the expression of TH and NT induced by 6-OHDA.
또한, 표 6에서 보는 바와 같이 6-OHDA로 유도된 선조체 및 흑질에서 iNOS 및 COX-2의 발현이 대조군에 비해 유의성 있게 증가[대조군에 비해, iNOS(선조체: 약 650%, 흑질: 약 1100%), COX-2(선조체: 약 290%, 흑질: 약 160%)]하였으나, 계피나무 추출물(50 및 100 mg/kg), 이의 분획물(50 mg/kg) 및 트랜스-신남알데하이드(30 mg/kg)를 미리 주입한 경우 상기 6-OHDA만을 주입한 경우에 비해 유의성 있게 감소하였다[대조군에 비해, iNOS(선조체: 약 120 ~ 130%, 흑질: 약 170 ~ 180%), COX-2(선조체: 약 110 ~ 120%, 흑질: 약 110 ~ 120%)]. 따라서 본 발명의 계피나무 추출물, 이의 분획물 및 트랜스 신남 알데하이드는 6-OHDA에 의해 유발된 iNOS 및 COX-2 발현의 증가를 감소시킬 수 있음을 알 수 있었다.In addition, as shown in Table 6, the expression of iNOS and COX-2 in 6-OHDA-induced striatum and black matter was significantly increased compared to the control group [compared to the control group, iNOS (stratum: about 650%, nigra: about 1100%). ), COX-2 (column: about 290%, black matter: about 160%)], but cinnamon extract (50 and 100 mg / kg), fractions thereof (50 mg / kg) and The pre-injection of trans-cinnamaldehyde (30 mg / kg) was significantly reduced compared to the injection of 6-OHDA alone [compared to the control group, iNOS (column: about 120-130%, black matter: about 170-180). %), COX-2 (stratum: about 110-120%, blackness: about 110-120%)]. Therefore, it was found that the cinnamon extract, fractions thereof, and trans cinnamic aldehyde of the present invention could reduce the increase in iNOS and COX-2 expression induced by 6-OHDA.
(mg/kg)density
(mg / kg)
출물Cinnamon tree ethanol aqueous solution weight
Exhibit
분획물Keji ethyl acetate
Fraction
(mg/kg)density
(mg / kg)
출물Cinnamon tree ethanol aqueous solution weight
Exhibit
분획물Cinnamon ethyl acetate
Fraction
<2-5> 면역조직화학염색 및 형태학적 계측<2-5> Immunohistochemical Staining and Morphological Measurements
본 발명자들은 트랜스 신남 알데하이드의 신경세포 보호 여부를 알아보기 위해 6-OHDA로 유발한 파킨슨병 모델을 이용하였다. 병변 제작 7일 후, 동물을 마취하여 4% 파라포름알데하이드(paraformaldehyde)를 포함한 0.05 M PBS(phosphate-buffered saline)로 관류고정한 후 뇌를 적출하였다. 뇌 조직은 동일 고정액에 다시 처리한 후, 선조체와 흑질을 포함하는 40μm 두께의 절편으로 만들어 면역조직화학염색에 사용하였다. 조직절편을 항체에 반응시키기 전에 내재성 peroxidase를 제거하기 위하여 3% H2O2를 첨가한 0.05 M PBS에 반응시키고, 0.3% Triton X-100을 포함하는 PBS와 3% bovine serum albumin (BSA)을 포함한 0.1 M PBS에 반응시킨 후, 일차항체를 실온에서 하룻밤 동안 반응시켰다. 일차항체는 항 티로신 하이드록시라제(anti-tyrosine hydroxylase)(TH, 1:1000; Santa Cruz Biotechnology, Santa. Cruz, CA, USA)를 사용하였고, 이차항체를 위해 Vectastain elite ABC kit(Vector Laboratories, Burlingame, CA, USA)를 사용하였다. 면역반응이 끝난 조직은 0.5mg/ml의 DAB(3,3-diaminobezidine tetrahydrochloride) 용액(40 mg DAB, 0.045% H2O2 in 100 ml PBS)에서 발색시켜 관찰하였다. TH 면역반응 양성 신경세포의 수를 계측하기 위하여 흑질의 동일 레벨을 나타내는 절편을 선택하여, 100배 배율에서 광학 현미경 (Olympus, Japan)으로 관찰하였다. 선조체의 TH 면역양성 축삭종말의 상대적인 밀도는 일정한 현미경 조명으로 40배 배율에서 CCD 카메라 (software: Optimas, version 6.5, Media cybernetics, MD)를 이용하여 관찰하였다. 계측시에는 실험 내용을 모르게 하고 독립적으로 관찰하였다.The present inventors used a Parkinson's disease model induced by 6-OHDA to determine whether neuronal protection of trans cinnamic aldehyde. After 7 days of lesion preparation, animals were anesthetized, perfused with 0.05 M PBS (phosphate-buffered saline) containing 4% paraformaldehyde, and brains were extracted. Brain tissues were treated again in the same fixative, and then made into 40 μm thick sections containing striatum and black matter and used for immunohistochemical staining. Tissue sections were reacted with 0.05 M PBS with 3% H 2 O 2 added to remove endogenous peroxidase before reacting with antibodies, PBS containing 0.3% Triton X-100 and 3% bovine serum albumin (BSA). After reacting with 0.1 M PBS, the primary antibody was reacted overnight at room temperature. Primary antibody was used anti-tyrosine hydroxylase (TH, 1: 1000; Santa Cruz Biotechnology, Santa. Cruz, CA, USA), and Vectastain elite ABC kit (Vector Laboratories, Burlingame) for secondary antibody , CA, USA). After the immune response, the tissue was observed by color development in 0.5 mg / ml DAB (3,3-diaminobezidine tetrahydrochloride) solution (40 mg DAB, 0.045% H 2 O 2 in 100 ml PBS). In order to measure the number of TH immune-positive neurons, sections showing the same level of black matter were selected and observed under an optical microscope (Olympus, Japan) at 100-fold magnification. The relative density of the TH immunopositive axon terminal of the striatum was observed using a CCD camera (software: Optimas, version 6.5, Media cybernetics, MD) at 40x magnification with constant microscope illumination. During the measurement, the experimental contents were unknown and observed independently.
그 결과, 표 7에서 보는 바와 같이, 대조군과 각 실험군 사이에는 유의한 차이를 확인할 수 있었다. 6-OHDA 처리군에서 흑질의 TH 양성 도파민성 신경세포의 수는 대조군에 비하여 뚜렷하게 감소하여 대조군의 약 38% 수준이었다. 신남 알데하이드를 주사한 실험대조군은 생리식염수만으로 처리한 대조군과 유의한 차이를 보이지 않았다. 이는 신남 알데하이드 자체는 도파민성 세포의 형질 발현에 유의한 영향을 미치지 않음을 의미한다. 6-OHDA를 처리한 군에서 흑질의 도파민성 신경세포의 수가 뚜렷하게 감소하였는데 반해, 신남 알데하이드와 6-OHDA를 함께 처리한 실험군에서는 도파민성 신경세포수의 감소 정도가 유의하게 적게 나타나는 것을 관찰하였다. 즉, 신남 알데하이드가 도파민성 신경 세포 보호 효과가 있음을 확인할 수 있었다. As a result, as shown in Table 7, it was confirmed that a significant difference between the control group and each experimental group. In the 6-OHDA treatment group, the number of TH-positive dopaminergic neurons in the vitreous cells was markedly decreased compared to the control group, which was about 38% of the control group. The experimental control group injected with cinnamic aldehyde showed no significant difference from the control group treated with physiological saline only. This means that cinnamic aldehyde itself does not significantly affect the expression of dopaminergic cells. In the 6-OHDA-treated group, the number of dopaminergic neurons was significantly decreased, whereas in the experimental group treated with cinnamic aldehyde and 6-OHDA, the decrease in the number of dopaminergic neurons was significantly decreased. That is, it was confirmed that cinnamic aldehyde has a dopaminergic neuron protective effect.
평균±표준편차TH-IR cell count in the black matter
Mean ± Standard Deviation
*** p < 0.001 (대조군에 비해); ## p < 0.01 6-OHDA (처리군에 비해). *** p <0.001 (relative to control); ## p <0.01 6-OHDA (relative to treatment group).
하기에 본 발명의 조성물을 위한 제조예를 예시한다.The preparation examples for the compositions of the present invention are illustrated below.
<< 제조예Manufacturing example 1> : 약학적 제제의 제조 1>: Preparation of pharmaceutical preparation
1. 산제의 제조1. Preparation of powder
실시예 <1-1>의 추출물 2 g2 g of extract of Example <1-1>
유당 1 g1 g lactose
상기의 성분을 혼합하고 기밀포에 충진하여 산제를 제조하였다.The above components were mixed and packed in airtight bags to prepare powders.
2. 정제의 제조2. Preparation of Tablets
실시예 <1-1>의 추출물 100 ㎎100 mg of extract of Example <1-1>
옥수수전분 100 ㎎
유 당 100 ㎎100 mg of milk
스테아린산 마그네슘 2 ㎎2 mg magnesium stearate
상기의 성분을 혼합한 후, 통상의 정제의 제조방법에 따라서 타정하여 정제를 제조하였다.After mixing the above components, tablets were prepared by tableting according to a conventional method for producing tablets.
3. 캡슐제의 제조3. Preparation of Capsule
실시예 <1-2>의 추출물 100 ㎎100 mg of extract of Example <1-2>
옥수수전분 100 ㎎
유 당 100 ㎎100 mg of milk
스테아린산 마그네슘 2 ㎎2 mg magnesium stearate
상기의 성분을 혼합한 후, 통상의 캡슐제의 제조방법에 따라서 젤라틴 캡슐에 충전하여 캡슐제를 제조하였다.After mixing the above components, the capsule was prepared by filling in gelatin capsules according to the conventional method for producing a capsule.
4. 환의 제조4. Manufacture of rings
실시예 <1-2>의 추출물 1 g1 g of extract of Example <1-2>
유당 1.5 gLactose 1.5 g
글리세린 1 g1 g of glycerin
자일리톨 0.5 gXylitol 0.5 g
상기의 성분을 혼합한 후, 통상의 방법에 따라 1환 당 4 g이 되도록 제조하였다.After mixing the above components, it was prepared to be 4 g per ring in a conventional manner.
5. 과립의 제조5. Manufacture of granules
실시예 <1-3>의 추출물 150 ㎎150 mg of extract of Example <1-3>
대두추출물 50 ㎎Soy extract 50 mg
포도당 200 ㎎Glucose 200 mg
전분 600 ㎎Starch 600 mg
상기의 성분을 혼합한 후, 30 % 에탄올 100 ㎎을 첨가하여 섭씨 60℃에서 건조하여 과립을 형성한 후 포에 충진하였다.After mixing the above components, 100 mg of 30% ethanol was added, dried at 60 ° C. to form granules, and then filled into fabric.
<< 제제예Formulation example 2> : 식품의 제조 2>: Manufacture of food
1. 조리용 양념의 제조1. Preparation of Cooking Seasonings
본 발명의 <실시예 2>의 에틸아세테이트 분획물 20 ~ 95 중량부로 건강 증진용 조리용 양념을 제조하였다.20 to 95 parts by weight of the ethyl acetate fraction of <Example 2> of the present invention was prepared for cooking spices for health promotion.
2. 밀가루 식품의 제조2. Manufacturing of Flour Foods
본 발명의 <실시예 2>의 에틸아세테이트 분획물 0.5 ~ 5.0 중량부를 밀가루에 첨가하고, 이 혼합물을 이용하여 빵, 케이크, 쿠키, 크래커 및 면류를 제조하여 건강 증진용 식품을 제조하였다.0.5 to 5.0 parts by weight of the ethyl acetate fraction of <Example 2> of the present invention was added to flour, and bread, cake, cookies, crackers and noodles were prepared using this mixture to prepare foods for health promotion.
3. 스프 및 육즙(gravies)의 제조3. Preparation of soups and gravy
본 발명의 실시예 <1-1>의 추출물 0.1 ~ 5.0 중량부를 스프 및 육즙에 첨가하여 건강 증진용 육가공 제품, 면류의 수프 및 육즙을 제조하였다.0.1 ~ 5.0 parts by weight of the extract of Example <1-1> of the present invention was added to soups and broths to prepare meat products for health promotion, soups of noodles, and broths.
4. 그라운드 비프(ground beef)의 제조4. Preparation of Ground Beef
본 발명의 실시예 <1-1>의 추출물 10 중량부를 그라운드 비프에 첨가하여 건강 증진용 그라운드 비프를 제조하였다.10 parts by weight of the extract of Example <1-1> of the present invention was added to ground beef to prepare a ground beef for health promotion.
5. 유제품(dairy products)의 제조5. Manufacture of Dairy Products
본 발명의 실시예 <1-2>의 추출물 5 ~ 10 중량부를 우유에 첨가하고, 상기 우유를 이용하여 버터 및 아이스크림과 같은 다양한 유제품을 제조하였다.5 to 10 parts by weight of the extract of Example <1-2> of the present invention was added to milk, and various dairy products such as butter and ice cream were prepared using the milk.
6. 선식의 제조6. Manufacture of wire
현미, 보리, 찹쌀, 율무를 공지의 방법으로 알파화시켜 건조시킨 것을 배전한 후 분쇄기로 입도 60 메쉬의 분말로 제조하였다.Brown rice, barley, glutinous rice, and yulmu were dried by a known method and dried, and the mixture was granulated to a powder having a particle size of 60 mesh.
검정콩, 검정깨, 들깨도 공지의 방법으로 쪄서 건조시킨 것을 배전한 후 분쇄기로 입도 60 메쉬의 분말로 제조하였다.Black soybeans, black sesame seeds, and perilla seeds were steamed and dried by a conventional method, and then they were prepared into powder having a particle size of 60 mesh by a pulverizer.
본 발명의 실시예 <1-2>의 추출물을 진공 농축기에서 감압농축하고, 분무, 열풍건조기로 건조하여 얻은 건조물을 분쇄기로 입도 60 메쉬로 분쇄하여 건조분말을 얻었다.The extract of Example <1-2> of the present invention was concentrated under reduced pressure in a vacuum concentrator, and the dried product obtained by drying with a sprayer and a hot air dryer was pulverized with a particle size of 60 mesh to obtain a dry powder.
상기에서 제조한 곡물류, 종실류 및 계지 추출물의 건조분말을 다음의 비율로 배합하여 제조하였다.It was prepared by combining the dry powder of the grains, seeds and cinnamon extract prepared in the following ratio.
곡물류(현미 30 중량부, 율무 15 중량부, 보리 20 중량부),Cereals (30 parts by weight brown rice, 15 parts by weight brittle, 20 parts by weight of barley),
종실류(들깨 7 중량부, 검정콩 8 중량부, 검정깨 7 중량부),Seeds (7 parts by weight of perilla, 8 parts by weight of black beans, 7 parts by weight of black sesame seeds)
실시예 <1-2> 추출물의 건조분말(3 중량부),Example <1-2> dry powder of the extract (3 parts by weight),
영지(0.5 중량부),(0.5 part by weight),
지황(0.5 중량부)Foxglove (0.5 part by weight)
<< 제제예Formulation example 3> : 음료의 제조 3>: Manufacture of beverage
1. 건강음료의 제조1. Manufacture of health drinks
실시예 <1-2>의 추출물 1000 ㎎ 1000 mg of extract of Example <1-2>
구연산 1000 ㎎ Citric acid 1000 mg
올리고당 100 g 100 g oligosaccharides
매실농축액 2 g Plum concentrate 2 g
타우린 1 g 1 g of taurine
정제수를 가하여 전체 900 ㎖ Add 900 ml of purified water
통상의 건강음료 제조방법에 따라 상기의 성분을 혼합한 다음, 약 1시간 동안 85℃에서 교반 가열한 후, 만들어진 용액을 여과하여 멸균된 2 ℓ용기에 취득하여 밀봉 멸균한 뒤 냉장 보관한 다음 본 발명의 건강음료 조성물 제조에 사용한다. After mixing the above components according to the conventional healthy beverage manufacturing method, and stirred and heated at 85 ℃ for about 1 hour, the resulting solution is filtered and obtained in a sterilized 2 L container, sealed sterilization and then refrigerated and stored Used to prepare the healthy beverage composition of the invention.
상기 조성비는 비교적 기호 음료에 적합한 성분을 바람직한 실시예로 혼합 조성하였지만, 수요계층, 수요국가, 사용 용도 등 지역적, 민족적 기호도에 따라서 그 배합비를 임의로 변형 실시하여도 무방하다.Although the composition ratio is a composition suitable for a preferred beverage in a preferred embodiment, the composition ratio may be arbitrarily modified according to regional and ethnic preferences such as demand hierarchy, demand country, and intended use.
2. 야채쥬스의 제조2. Preparation of Vegetable Juice
본 발명의 실시예 <1-2>의 추출물 5 g을 토마토 또는 당근 쥬스 1,000 ㎖에 가하여 건강 증진용 야채쥬스를 제조하였다.5 g of the extract of Example <1-2> of the present invention was added to 1,000 ml of tomato or carrot juice to prepare a vegetable juice for health promotion.
3. 과일쥬스의 제조3. Preparation of Fruit Juice
본 발명의 실시예 <1-2>의 추출물 1 g을 사과 또는 포도 쥬스 1,000㎖ 에 가하여 건강 증진용 과일쥬스를 제조하였다.1 g of the extract of Example <1-2> of the present invention was added to 1,000 ml of apple or grape juice to prepare a fruit juice for health promotion.
도 1은 6-OHDA 투여(30 mg/kg, i.p.) 후, 흑질에서 TH 양성 도파민성 신경세포(TH-ir neuron)의 생존율에 대한 트랜스-신남알데하이드의 효과를 나타내는 그래프이다: 1 is a graph showing the effect of trans-cinnaaldehyde on survival of TH-positive dopaminergic neurons (TH-ir neuron) in black matter after 6-OHDA administration (30 mg / kg, i.p.):
*** p < 0.001 (대조군에 비해); ## p < 0.01 6-OHDA (처리군에 비해). *** p <0.001 (relative to control); ## p <0.01 6-OHDA (relative to treatment group).
도 2는 6-OHDA에 의해 유발된 흑질에서 TH 양성 도파민성 신경세포(TH-ir neuron) 죽음에 대한 트랜스-신남알데하이드의 효과를 알아보기 위해, 면역조직화학염색을 이용하여 도파민성 신경세포를 형태학적으로 관찰한 결과를 나타내는 그림이다: Figure 2 shows the effect of trans-cinnamaldehyde on TH-ir neuron death in black matter induced by 6-OHDA, using immunohistochemical staining for dopaminergic neurons. Here is a pictorial representation of the morphological observations:
A: 식염수(30 mg/kg, i.p.)를 투여;A: administered saline (30 mg / kg, i.p.);
B: 트랜스-신남알데하이드를 투여(30 mg/kg, i.p.);B: trans-cinnamaldehyde administered (30 mg / kg, i.p.);
C: 6-OHDA를 투여(60 ug); 및C: 6-OHDA administered (60 ug); And
D: 6-OHDA 및 트랜스-신남알데하이드를 함께 투여.D: 6-OHDA and trans-cinnaaldehyde were administered together.
도 3은 6-OHDA에 의해 유발된 선조체의 TH 양성 도파민 섬유(dopaminergic fiber) 손실에 대한 트랜스-신남알데하이드의 효과를 알아보기 위해, 면역조직화학염색을 이용하여 도파민 섬유를 형태학적으로 관찰한 결과를 나타내는 그림이다: FIG. 3 shows the results of morphological observation of dopamine fibers using immunohistochemical staining to determine the effect of trans-cinnaaldehyde on TH-positive dopaminergic fiber loss of striatum induced by 6-OHDA. The figure shows:
A: A: 식염수(30 mg/kg, i.p.)를 투여;A: A: saline (30 mg / kg, i.p.);
B: 트랜스-신남알데하이드를 투여(30 mg/kg, i.p.);B: trans-cinnamaldehyde administered (30 mg / kg, i.p.);
C: 6-OHDA를 투여(60 ug); 및C: 6-OHDA administered (60 ug); And
D: 6-OHDA 및 트랜스-신남알데하이드를 함께 투여.D: 6-OHDA and trans-cinnaaldehyde were administered together.
Claims (15)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| KR1020080116692A KR101051085B1 (en) | 2008-11-24 | 2008-11-24 | Parkinson's disease prevention and treatment composition containing cinnamon extract, fractions thereof or trans-cinnaaldehyde isolated from cinnamon as an active ingredient |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| KR1020080116692A KR101051085B1 (en) | 2008-11-24 | 2008-11-24 | Parkinson's disease prevention and treatment composition containing cinnamon extract, fractions thereof or trans-cinnaaldehyde isolated from cinnamon as an active ingredient |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| KR20100058032A KR20100058032A (en) | 2010-06-03 |
| KR101051085B1 true KR101051085B1 (en) | 2011-07-21 |
Family
ID=42359734
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR1020080116692A KR101051085B1 (en) | 2008-11-24 | 2008-11-24 | Parkinson's disease prevention and treatment composition containing cinnamon extract, fractions thereof or trans-cinnaaldehyde isolated from cinnamon as an active ingredient |
Country Status (1)
| Country | Link |
|---|---|
| KR (1) | KR101051085B1 (en) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2018038292A1 (en) * | 2016-08-25 | 2018-03-01 | 경희대학교 산학협력단 | Pharmaceutical composition containing cinnamomum camphora extract as active ingredient for the prevention and treatment of neurological diseases |
| CN106474191A (en) * | 2016-12-13 | 2017-03-08 | 宜春学院 | Cinnamomum cassia extract and preparation method and its application in treatment of Parkinson disease |
| CN108283662A (en) * | 2018-04-23 | 2018-07-17 | 陕西新药技术开发中心 | It is a kind of to treat neurasthenic cassia tree bark oil dripping pill and preparation method thereof |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20060094395A (en) * | 2005-02-24 | 2006-08-29 | 충북대학교 산학협력단 | Pharmaceutical composition comprising cinnamaldehyde derivatives for treating and preventing inflammatory disease |
| US20070116779A1 (en) | 2005-11-23 | 2007-05-24 | Elizabeth Mazzio | Comprehensive nutraceutical agent for treatment/ prevention of Parkinson's disease |
| JP2008509199A (en) | 2004-08-12 | 2008-03-27 | グリューネンタール・ゲゼルシャフト・ミット・ベシュレンクテル・ハフツング | Para-alkyl substituted N- (4-hydroxy-3-methoxybenzyl) -cinnamic amides and their use for preparing pharmaceuticals |
-
2008
- 2008-11-24 KR KR1020080116692A patent/KR101051085B1/en not_active IP Right Cessation
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2008509199A (en) | 2004-08-12 | 2008-03-27 | グリューネンタール・ゲゼルシャフト・ミット・ベシュレンクテル・ハフツング | Para-alkyl substituted N- (4-hydroxy-3-methoxybenzyl) -cinnamic amides and their use for preparing pharmaceuticals |
| KR20060094395A (en) * | 2005-02-24 | 2006-08-29 | 충북대학교 산학협력단 | Pharmaceutical composition comprising cinnamaldehyde derivatives for treating and preventing inflammatory disease |
| US20070116779A1 (en) | 2005-11-23 | 2007-05-24 | Elizabeth Mazzio | Comprehensive nutraceutical agent for treatment/ prevention of Parkinson's disease |
Also Published As
| Publication number | Publication date |
|---|---|
| KR20100058032A (en) | 2010-06-03 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| KR101115500B1 (en) | A composition for the prevention and treatment of inflammatory disease comprising the mixture of extract of Notopterygium incisum and Saposhnikovia divaricata as an effective ingredient | |
| KR101805801B1 (en) | Pharmaceutical composition for prevention or treatment of Parkinson's disease comprising tilianin | |
| KR101051085B1 (en) | Parkinson's disease prevention and treatment composition containing cinnamon extract, fractions thereof or trans-cinnaaldehyde isolated from cinnamon as an active ingredient | |
| KR101236233B1 (en) | Pharmaceutical compositions and health functional foods compositions for the improvement of liver functions containing the extract of Youngia denticulata, fraction of thereof or compound isolated therefrom as an active ingredient | |
| KR101391308B1 (en) | Composition comprising the extracts and fractions of Gymnaster koraiensis for prevention or treatment of retinal diseases | |
| KR20110093474A (en) | Composition for composition for prevention or treatment of rotavirus infection comprising glycyrrhiza uralensis | |
| KR20130011111A (en) | Pharmaceutical compositions for preventing or treating inflammatory diseases comprising phytosterol compound | |
| KR101453455B1 (en) | Pharmaceutical composition or healthy food composition containing Oenanthe javanica extract, fractions thereof or isolated flavonoidic compounds for antioxidant and antiobesity activity | |
| KR101039145B1 (en) | A composition containing extract of typha angustata for preventing and treating circulatory diseases | |
| KR102272425B1 (en) | Composition for preventing or treating Sjogren's syndrome comprising Adenophrae Radix | |
| KR100778373B1 (en) | therapeutic agent comprising Mantidis ootheca extracts, N-acetyldopamine or biphenol compounds isolated from the same for prevention and treatment of cardiovascular disease | |
| KR20120060002A (en) | A composition for prevention and treatment of dementia or Parkinson's disease comprising extracts of Morus alba or Lycium chinense, or mixture thereof as an active ingredient | |
| KR101503792B1 (en) | Neuroprotective composition comprising extract or fractions of Vaccinium uliginosum as an active ingredient | |
| KR101954891B1 (en) | A composition for treating or improving hepatic fibrosis comprising Seahorse extract | |
| KR101077916B1 (en) | Pharmaceutical compositions for prevention and treatment of obesity comprising extract of eremochloa ophiuroides as an active ingredient | |
| KR101165337B1 (en) | Compositions for prevention and treatment of cerebral edema containing the extracts of sesame seed as an active ingredient | |
| KR20090129016A (en) | Pharmaceutical compositions for prevention and treatment of viral diseases containing rodiola extracts, fractions, the isolated flavonoid compounds therefrom, derivatives compounds thereof or the pharmaceutically acceptable salts as an active ingredient | |
| KR20130070616A (en) | A composition for prevention and treatment of dementia or parkinson's disease comprising extracts of morus alba or lycium chinense, or mixture thereof as an active ingredient | |
| KR20190093849A (en) | Composition comprising extract of Gymnema sylvestre or compound isolated from thereof for preventing or treating of diabetes mellitus | |
| KR102117560B1 (en) | Pharmaceutical composition for the prevention or treatment of cancer comprising khellactone or pharmaceutically acceptable salts thereof as an active ingredient | |
| KR101164908B1 (en) | The composition for the treatment of cancers or inhibition of metastasis containing the extracts or fractions of Asparagus cochinchinensis as active ingredient | |
| KR102600557B1 (en) | A composition having anti-inflammation activity comprising compounds isolated from the fraction of the Podocarpus macrophyllus extracts as an active ingredient | |
| KR20190103665A (en) | Food composition for improving or preventing obesity containing extract of saururus chinensis | |
| KR101404036B1 (en) | Extract of Crepidiastrum denticulatum for prevention or treatment of retinal diseases | |
| US8785503B2 (en) | Biphenyl compound or pharmaceutically acceptable salt thereof, method for preparing novel biphenyl compound or pharmaceutically acceptable salt thereof, and pharmaceutical composition containing same as active ingredient for preventing or treating diabetes complications |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A201 | Request for examination | ||
| E902 | Notification of reason for refusal | ||
| AMND | Amendment | ||
| E601 | Decision to refuse application | ||
| AMND | Amendment | ||
| J201 | Request for trial against refusal decision | ||
| B701 | Decision to grant | ||
| GRNT | Written decision to grant | ||
| FPAY | Annual fee payment |
Payment date: 20140711 Year of fee payment: 4 |
|
| FPAY | Annual fee payment |
Payment date: 20150615 Year of fee payment: 5 |
|
| LAPS | Lapse due to unpaid annual fee |