JP6510017B1 - 神経細胞死抑制剤及び神経細胞死抑制用食品組成物 - Google Patents
神経細胞死抑制剤及び神経細胞死抑制用食品組成物 Download PDFInfo
- Publication number
- JP6510017B1 JP6510017B1 JP2017226399A JP2017226399A JP6510017B1 JP 6510017 B1 JP6510017 B1 JP 6510017B1 JP 2017226399 A JP2017226399 A JP 2017226399A JP 2017226399 A JP2017226399 A JP 2017226399A JP 6510017 B1 JP6510017 B1 JP 6510017B1
- Authority
- JP
- Japan
- Prior art keywords
- cell death
- extract
- nerve cell
- present
- lotus
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
- 230000030833 cell death Effects 0.000 title claims abstract description 31
- 235000013305 food Nutrition 0.000 title claims abstract description 12
- 239000000203 mixture Substances 0.000 title claims abstract description 11
- 239000003112 inhibitor Substances 0.000 title claims abstract description 10
- 230000001629 suppression Effects 0.000 title claims abstract description 4
- 210000003061 neural cell Anatomy 0.000 title claims abstract 4
- 240000002853 Nelumbo nucifera Species 0.000 claims abstract description 43
- 235000006508 Nelumbo nucifera Nutrition 0.000 claims abstract description 34
- 210000002569 neuron Anatomy 0.000 claims abstract description 34
- 235000006510 Nelumbo pentapetala Nutrition 0.000 claims abstract description 21
- 239000004575 stone Substances 0.000 claims abstract description 16
- 239000012259 ether extract Substances 0.000 claims description 7
- 239000000284 extract Substances 0.000 abstract description 39
- 238000000605 extraction Methods 0.000 abstract description 12
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 abstract description 6
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 abstract description 6
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 abstract description 6
- 239000003960 organic solvent Substances 0.000 abstract description 6
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 abstract description 4
- LCGLNKUTAGEVQW-UHFFFAOYSA-N Dimethyl ether Chemical compound COC LCGLNKUTAGEVQW-UHFFFAOYSA-N 0.000 abstract description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 abstract description 4
- 239000002904 solvent Substances 0.000 abstract description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 abstract description 4
- 239000002547 new drug Substances 0.000 abstract description 2
- VZFRNCSOCOPNDB-UHFFFAOYSA-N domoic acid Natural products OC(=O)C(C)C=CC=C(C)C1CNC(C(O)=O)C1CC(O)=O VZFRNCSOCOPNDB-UHFFFAOYSA-N 0.000 description 21
- VZFRNCSOCOPNDB-AJKFJWDBSA-N domoic acid Chemical compound OC(=O)[C@@H](C)\C=C\C=C(/C)[C@H]1CN[C@H](C(O)=O)[C@H]1CC(O)=O VZFRNCSOCOPNDB-AJKFJWDBSA-N 0.000 description 21
- VZFRNCSOCOPNDB-OXYNIABMSA-N isodomoic acid D Natural products CC(C=C/C=C(/C)C1CNC(C1CC(=O)O)C(=O)O)C(=O)O VZFRNCSOCOPNDB-OXYNIABMSA-N 0.000 description 21
- 210000004027 cell Anatomy 0.000 description 17
- 239000003814 drug Substances 0.000 description 15
- 241000700159 Rattus Species 0.000 description 12
- 230000000052 comparative effect Effects 0.000 description 11
- 229940079593 drug Drugs 0.000 description 10
- 206010012289 Dementia Diseases 0.000 description 9
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 8
- 230000016273 neuron death Effects 0.000 description 8
- 230000006907 apoptotic process Effects 0.000 description 7
- 210000004556 brain Anatomy 0.000 description 7
- 239000000243 solution Substances 0.000 description 6
- 239000007787 solid Substances 0.000 description 5
- 238000009825 accumulation Methods 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 4
- 210000001947 dentate gyrus Anatomy 0.000 description 4
- 238000011161 development Methods 0.000 description 4
- 201000010099 disease Diseases 0.000 description 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 4
- 235000019441 ethanol Nutrition 0.000 description 4
- 230000002401 inhibitory effect Effects 0.000 description 4
- 238000000034 method Methods 0.000 description 4
- 230000001936 parietal effect Effects 0.000 description 4
- 239000006188 syrup Substances 0.000 description 4
- 235000020357 syrup Nutrition 0.000 description 4
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- 102000009091 Amyloidogenic Proteins Human genes 0.000 description 3
- 108010048112 Amyloidogenic Proteins Proteins 0.000 description 3
- 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 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- 241000196324 Embryophyta Species 0.000 description 3
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical class OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 3
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical class OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 230000018109 developmental process Effects 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 210000001353 entorhinal cortex Anatomy 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- 238000002347 injection Methods 0.000 description 3
- 239000000546 pharmaceutical excipient Substances 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 239000000600 sorbitol Substances 0.000 description 3
- 235000010356 sorbitol Nutrition 0.000 description 3
- 239000003826 tablet Substances 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- 229940126585 therapeutic drug Drugs 0.000 description 3
- 231100000691 up-and-down procedure Toxicity 0.000 description 3
- 244000215068 Acacia senegal Species 0.000 description 2
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 2
- 102100033215 DNA nucleotidylexotransferase Human genes 0.000 description 2
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- 229920000084 Gum arabic Polymers 0.000 description 2
- WZUVPPKBWHMQCE-UHFFFAOYSA-N Haematoxylin Chemical compound C12=CC(O)=C(O)C=C2CC2(O)C1C1=CC=C(O)C(O)=C1OC2 WZUVPPKBWHMQCE-UHFFFAOYSA-N 0.000 description 2
- 102000000079 Kainic Acid Receptors Human genes 0.000 description 2
- 108010069902 Kainic Acid Receptors Proteins 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 239000000205 acacia gum Substances 0.000 description 2
- 235000010489 acacia gum Nutrition 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 235000003704 aspartic acid Nutrition 0.000 description 2
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Chemical class OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 2
- 210000005013 brain tissue Anatomy 0.000 description 2
- 239000011575 calcium Substances 0.000 description 2
- 229910052791 calcium Inorganic materials 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 230000034994 death Effects 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 description 2
- 230000002964 excitative effect Effects 0.000 description 2
- 235000019197 fats Nutrition 0.000 description 2
- 229920000159 gelatin Polymers 0.000 description 2
- 235000019322 gelatine Nutrition 0.000 description 2
- 235000013922 glutamic acid Nutrition 0.000 description 2
- 239000004220 glutamic acid Substances 0.000 description 2
- 239000008187 granular material Substances 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 210000004498 neuroglial cell Anatomy 0.000 description 2
- 239000002858 neurotransmitter agent Substances 0.000 description 2
- 239000012188 paraffin wax Substances 0.000 description 2
- 230000003449 preventive effect Effects 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 102000013498 tau Proteins Human genes 0.000 description 2
- 108010026424 tau Proteins Proteins 0.000 description 2
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 2
- 229940124597 therapeutic agent Drugs 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 238000013042 tunel staining Methods 0.000 description 2
- 239000003981 vehicle Substances 0.000 description 2
- 235000013618 yogurt Nutrition 0.000 description 2
- MGRVRXRGTBOSHW-UHFFFAOYSA-N (aminomethyl)phosphonic acid Chemical compound NCP(O)(O)=O MGRVRXRGTBOSHW-UHFFFAOYSA-N 0.000 description 1
- ZORQXIQZAOLNGE-UHFFFAOYSA-N 1,1-difluorocyclohexane Chemical compound FC1(F)CCCCC1 ZORQXIQZAOLNGE-UHFFFAOYSA-N 0.000 description 1
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 1
- 102000003678 AMPA Receptors Human genes 0.000 description 1
- 108090000078 AMPA Receptors Proteins 0.000 description 1
- 230000002407 ATP formation Effects 0.000 description 1
- 235000019489 Almond oil Nutrition 0.000 description 1
- 208000024827 Alzheimer disease Diseases 0.000 description 1
- 206010002091 Anaesthesia Diseases 0.000 description 1
- 241000416162 Astragalus gummifer Species 0.000 description 1
- 244000025254 Cannabis sativa Species 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 239000004215 Carbon black (E152) Substances 0.000 description 1
- 102000004039 Caspase-9 Human genes 0.000 description 1
- 108090000566 Caspase-9 Proteins 0.000 description 1
- 229920002261 Corn starch Polymers 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
- 108010008286 DNA nucleotidylexotransferase Proteins 0.000 description 1
- 102000013138 Drug Receptors Human genes 0.000 description 1
- 108010065556 Drug Receptors Proteins 0.000 description 1
- JOYRKODLDBILNP-UHFFFAOYSA-N Ethyl urethane Chemical compound CCOC(N)=O JOYRKODLDBILNP-UHFFFAOYSA-N 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 239000001828 Gelatine Substances 0.000 description 1
- 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 1
- 239000004471 Glycine Substances 0.000 description 1
- 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 1
- 241001465754 Metazoa Species 0.000 description 1
- 102000004868 N-Methyl-D-Aspartate Receptors Human genes 0.000 description 1
- 108090001041 N-Methyl-D-Aspartate Receptors Proteins 0.000 description 1
- HOKKHZGPKSLGJE-GSVOUGTGSA-N N-Methyl-D-aspartic acid Chemical compound CN[C@@H](C(O)=O)CC(O)=O HOKKHZGPKSLGJE-GSVOUGTGSA-N 0.000 description 1
- 229930040373 Paraformaldehyde Natural products 0.000 description 1
- 208000018737 Parkinson disease Diseases 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 241001278097 Salix alba Species 0.000 description 1
- 241000304446 Sinocrassula Species 0.000 description 1
- 241000326250 Sinocrassula densirosulata Species 0.000 description 1
- 241000304445 Sinocrassula indica Species 0.000 description 1
- 241000304460 Sinocrassula yunnanensis Species 0.000 description 1
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
- 229920001615 Tragacanth Polymers 0.000 description 1
- 210000000683 abdominal cavity Anatomy 0.000 description 1
- 230000005856 abnormality Effects 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 239000008168 almond oil Substances 0.000 description 1
- 230000037005 anaesthesia Effects 0.000 description 1
- 229940125687 antiparasitic agent Drugs 0.000 description 1
- 239000003096 antiparasitic agent Substances 0.000 description 1
- 229940009098 aspartate Drugs 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000005540 biological transmission Effects 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 229910000389 calcium phosphate Inorganic materials 0.000 description 1
- 235000011010 calcium phosphates Nutrition 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 230000011712 cell development Effects 0.000 description 1
- 210000003855 cell nucleus Anatomy 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 239000003240 coconut oil Substances 0.000 description 1
- 235000019864 coconut oil Nutrition 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 235000009508 confectionery Nutrition 0.000 description 1
- 239000000039 congener Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 235000014510 cooky Nutrition 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 229960003638 dopamine Drugs 0.000 description 1
- 238000009509 drug development Methods 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 description 1
- 230000010222 extracellular calcium influx Effects 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 210000001061 forehead Anatomy 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 230000010030 glucose lowering effect Effects 0.000 description 1
- 229930195712 glutamate Natural products 0.000 description 1
- 235000011187 glycerol Nutrition 0.000 description 1
- 235000013402 health food Nutrition 0.000 description 1
- 238000007490 hematoxylin and eosin (H&E) staining Methods 0.000 description 1
- 210000001320 hippocampus Anatomy 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- 125000001841 imino group Chemical group [H]N=* 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 230000010365 information processing Effects 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 239000007928 intraperitoneal injection Substances 0.000 description 1
- 238000004255 ion exchange chromatography Methods 0.000 description 1
- 235000015110 jellies Nutrition 0.000 description 1
- 238000002372 labelling Methods 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 235000010445 lecithin Nutrition 0.000 description 1
- 239000000787 lecithin Substances 0.000 description 1
- 229940067606 lecithin Drugs 0.000 description 1
- 239000012669 liquid formulation Substances 0.000 description 1
- 239000012263 liquid product Substances 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 210000001259 mesencephalon Anatomy 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
- 239000004292 methyl p-hydroxybenzoate Substances 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 230000002438 mitochondrial effect Effects 0.000 description 1
- 239000012046 mixed solvent Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 210000000653 nervous system Anatomy 0.000 description 1
- 230000004770 neurodegeneration Effects 0.000 description 1
- 208000015122 neurodegenerative disease Diseases 0.000 description 1
- 230000019581 neuron apoptotic process Effects 0.000 description 1
- 210000004940 nucleus Anatomy 0.000 description 1
- 235000016709 nutrition Nutrition 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 229920002866 paraformaldehyde Polymers 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 239000002304 perfume Substances 0.000 description 1
- 230000010412 perfusion Effects 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 229920001592 potato starch Polymers 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 1
- 239000004405 propyl p-hydroxybenzoate Substances 0.000 description 1
- 235000013772 propylene glycol Nutrition 0.000 description 1
- QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 235000019685 rice crackers Nutrition 0.000 description 1
- 210000003625 skull Anatomy 0.000 description 1
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
- 235000014214 soft drink Nutrition 0.000 description 1
- 235000010199 sorbic acid Nutrition 0.000 description 1
- 239000004334 sorbic acid Substances 0.000 description 1
- 229940075582 sorbic acid Drugs 0.000 description 1
- 239000001593 sorbitan monooleate Substances 0.000 description 1
- 235000011069 sorbitan monooleate Nutrition 0.000 description 1
- 229940035049 sorbitan monooleate Drugs 0.000 description 1
- 235000014347 soups Nutrition 0.000 description 1
- -1 specifically Substances 0.000 description 1
- 230000002269 spontaneous effect Effects 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 210000003523 substantia nigra Anatomy 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000013616 tea Nutrition 0.000 description 1
- 231100000027 toxicology Toxicity 0.000 description 1
- 239000000196 tragacanth Substances 0.000 description 1
- 235000010487 tragacanth Nutrition 0.000 description 1
- 229940116362 tragacanth Drugs 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
Landscapes
- Medicines Containing Plant Substances (AREA)
- Coloring Foods And Improving Nutritive Qualities (AREA)
Abstract
Description
これらの食品の製造工程において、あるいは最終製品に、石蓮花の抽出物を添加して、神経細胞死抑制用食品組成物とすることができる。
(実施例1)
・石蓮花の抽出
石蓮花は予め乾燥試料をエーテル抽出し、エバポレーターにて乾燥した後、エタノールに溶解して保存した。
上記石蓮花抽出物のエタノール溶液を、無麻酔にてドウモイ酸脳内注射の前日及び当日3時間前に(合計2回)定められた用量を腹腔内投与した。用量決定は、石蓮花用量希釈段階の前処置にてup-and-down 法により50% 有効量を算出し、石蓮花の用量はエーテル抽出物0.5mg/kg B.W.とした。なお、試験を行ったラットの個体数は10例以上とした。
ドウモイ酸で処理したラットは、翌日に4%パラホルムアルデヒド溶液で全身を灌流固定して、パラフィン包埋し、パラフィンブロックを薄切した。切片の厚さは1μmである。切片をグラスプレパラートに載せて固定し、ヘマトキシリン・エオジン染色を行った。別のプレパラートではアポトーシス検出キット(和光:コード293-71501、TdT-mediated uUTP backend labeling 3’-OH terminal transferase手法)に従った。発色はPOD conjugated antibodyを浸漬させて、ウォッシュ後、DABで発色させた。アポトーシスは細胞核が茶褐色に発色することで容易に判別できる。さらにヘマトキシリン染色を軽く行い、アポトーシスになっていない細胞の核は、青暗色である。
比較例1では石蓮花抽出物の替りに生理食塩水を腹腔内投与した。その他の処置については実施例1と同様であり、説明を省略する。
ラットの脳組織の水平断面図を図1に示す。また、ドウモイ酸を脳内に注入した後の各部位における光学顕微鏡写真を図2〜図6に示す。
図2の左側写真に示すように、比較例1(すなわち生理食塩水を投与したcontrol)では、側頭部前野に位置するParietal cortexにおいて、Tunel陽性細胞が束をなして密集しており、その大部分は、比較的小さい細胞であった。中には陰性細胞は少し散見された。以上のことから、石蓮花抽出物を投与しなかった比較例1においては、ドウモイ酸によって神経細胞死が顕著に引き起こされることが分かった。これに対して、図2の右側写真に示すように、石蓮花抽出物を投与した実施例1では、そのようなTunel陽性細胞はほとんど観察されず、神経細胞死の抑制効果が顕著に認められた。
いっぽう、比較例1では海馬帯におけるHillおよびCA4に隣接する歯状回では、大きな細胞と小さな細胞がともにTunel染色陽性の細胞が認められ、小さな細胞が集まっている部位の大きな細胞が強く陽性に染まっていた(図3及び図4参照)。これらの結果から、ドウモイ酸による神経細胞死が顕著に認められた。これに対して、石蓮花抽出物を事前投与した実施例1では、小さな陽性細胞はほとんど見られず、大きな細胞がわずかに陽性になっている程度であって、神経細胞死の抑制効果が顕著に認められた。
また、Entorhinal cortex及びPRhでは、比較例1においてTunel染色陽性の細胞は小さな細胞に限って認められた。一方、石蓮花抽出物を事前投与した実施例1では、このような小さな細胞についても陽性になることが抑制されていることが分かった。これらの小さな細胞は神経細胞と思われるが、神経膠細胞も石蓮花抽出物によってTunel染色が陰性化し、ドウモイ酸によって引き起こされるアポトーシス細胞死を石蓮花が強く抑制することが示された。
石蓮花の有効用量を調べた結果を表1に示す。この表に基づきup-and-down法によって50%有効用量を求めた結果、0.15mg/kg B.W.と算出された。上記の神経細胞死抑制効果試験は、すべて1 mg/kg B.W.を用いたものであり、50%有効量の約10倍であるため、ラット全例で十分な有効性を示したと考えられる。
Claims (2)
- 石蓮花のエーテル抽出物を含有する神経細胞死抑制剤。
- 石蓮花のエーテル抽出物を含有することを特徴とする神経細胞死抑制用食品組成物。
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2017226399A JP6510017B1 (ja) | 2017-11-27 | 2017-11-27 | 神経細胞死抑制剤及び神経細胞死抑制用食品組成物 |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2017226399A JP6510017B1 (ja) | 2017-11-27 | 2017-11-27 | 神経細胞死抑制剤及び神経細胞死抑制用食品組成物 |
Publications (2)
Publication Number | Publication Date |
---|---|
JP6510017B1 true JP6510017B1 (ja) | 2019-05-08 |
JP2019094302A JP2019094302A (ja) | 2019-06-20 |
Family
ID=66429857
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2017226399A Active JP6510017B1 (ja) | 2017-11-27 | 2017-11-27 | 神経細胞死抑制剤及び神経細胞死抑制用食品組成物 |
Country Status (1)
Country | Link |
---|---|
JP (1) | JP6510017B1 (ja) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN114984079A (zh) * | 2022-05-20 | 2022-09-02 | 丁庆 | 石莲花醚提取物在抑制神经细胞死亡制剂及食品上的应用 |
-
2017
- 2017-11-27 JP JP2017226399A patent/JP6510017B1/ja active Active
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN114984079A (zh) * | 2022-05-20 | 2022-09-02 | 丁庆 | 石莲花醚提取物在抑制神经细胞死亡制剂及食品上的应用 |
Also Published As
Publication number | Publication date |
---|---|
JP2019094302A (ja) | 2019-06-20 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
KR101126117B1 (ko) | 한방 약제 조성물, 그의 제조 방법 및 용도 | |
Bellampalli et al. | Betulinic acid, derived from the desert lavender Hyptis emoryi, attenuates paclitaxel-, HIV-, and nerve injury–associated peripheral sensory neuropathy via block of N-and T-type calcium channels | |
CN102548571A (zh) | 用于预防和治疗脑部疾病和疾病状态的组合物和方法 | |
JP2014205724A (ja) | 脳梗塞の予防及び治療用医薬品の製造におけるl−ブチルフタリドの使用 | |
CN102688501A (zh) | 原花青素b2磷脂复合物及其制备方法和用途 | |
KR101807953B1 (ko) | 고수 추출물을 유효성분으로 하는 치매 예방 또는 치료용 약학적 조성물 | |
JP6510017B1 (ja) | 神経細胞死抑制剤及び神経細胞死抑制用食品組成物 | |
CN101590065A (zh) | 西伯利亚远志糖A1、西伯利亚远志糖A5和tenuifoliside A在制备治疗抑郁症产品中的应用 | |
CN102935100A (zh) | 一种大花罗布麻叶总黄酮的制备方法和用途 | |
ES2873601T3 (es) | Formulaciones de honokiol y magnolol con estabilidad incrementada y absorción mejorada y procedimientos de uso de las mismas | |
ES2904263T3 (es) | Composiciones que comprenden triterpenoides para el tratamiento de la enfermedad de Alzheimer y la enfermedad de Parkinson | |
TW201615204A (zh) | 含有肉蓯蓉及銀杏萃取物之有助提升個體記憶之組成物 | |
CN103735761B (zh) | 一种防治阿尔茨海默病的药物组合物及其制备方法 | |
KR101029699B1 (ko) | 생약추출물을 유효성분으로 함유하는 알쯔하이머 치매 치료 및 예방용 조성물 | |
CN107405372A (zh) | 乳香胶的分离级分用于治疗视神经病变的用途 | |
US20180110816A1 (en) | Process For Producing A Fluid Soluble Cannabis Base Product | |
RU2408384C2 (ru) | Китайский лекарственный состав, способ его получения и применение | |
JP6670531B1 (ja) | 神経細胞死抑制剤及び神経細胞死抑制用食品組成物 | |
JP2012214500A (ja) | 漢方薬組成物ならびにこれらの調製方法および使用 | |
CN109432267B (zh) | 一种治疗阿尔茨海默病的中药组合物及其制备方法和应用 | |
Cobos et al. | Anti-inflammatory and antinociceptive properties of the extracts from the leaves of Porophyllum tagetoides and Annona reticulata | |
JP4698167B2 (ja) | アルツハイマー病予防・治療剤 | |
CN104130232B (zh) | 一种egcg的提纯方法及获得的egcg和药物组合物 | |
EP2845589B1 (en) | Composition for the prevention and treatment of migraine or neuropathic pain | |
KR102453757B1 (ko) | 황새냉이 추출물 또는 이의 분획물을 포함하는 당뇨병의 예방 또는 치료용 조성물 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20180409 |
|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20180409 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20190104 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20190222 |
|
TRDD | Decision of grant or rejection written | ||
A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20190402 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20190403 |
|
R150 | Certificate of patent or registration of utility model |
Ref document number: 6510017 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |