CN111388460A - 苏木酮a的抗衰老用途 - Google Patents
苏木酮a的抗衰老用途 Download PDFInfo
- Publication number
- CN111388460A CN111388460A CN202010025501.0A CN202010025501A CN111388460A CN 111388460 A CN111388460 A CN 111388460A CN 202010025501 A CN202010025501 A CN 202010025501A CN 111388460 A CN111388460 A CN 111388460A
- Authority
- CN
- China
- Prior art keywords
- hematoxylin
- aging
- nematodes
- group
- control group
- 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.)
- Pending
Links
- 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 title claims abstract description 76
- 230000003712 anti-aging effect Effects 0.000 title claims abstract description 28
- 239000003814 drug Substances 0.000 claims abstract description 32
- 229940079593 drug Drugs 0.000 claims abstract description 17
- 230000036541 health Effects 0.000 claims abstract description 9
- 238000002360 preparation method Methods 0.000 claims abstract description 6
- 241000244203 Caenorhabditis elegans Species 0.000 claims description 9
- 238000009472 formulation Methods 0.000 claims description 4
- 239000000203 mixture Substances 0.000 claims description 4
- 238000002347 injection Methods 0.000 claims description 3
- 239000007924 injection Substances 0.000 claims description 3
- 239000007788 liquid Substances 0.000 claims description 3
- 239000002775 capsule Substances 0.000 claims description 2
- 239000006071 cream Substances 0.000 claims description 2
- 239000008187 granular material Substances 0.000 claims description 2
- 239000002674 ointment Substances 0.000 claims description 2
- 239000006187 pill Substances 0.000 claims description 2
- 239000000843 powder Substances 0.000 claims description 2
- 239000000829 suppository Substances 0.000 claims description 2
- 230000002035 prolonged effect Effects 0.000 claims 1
- 238000009825 accumulation Methods 0.000 abstract description 11
- WZUVPPKBWHMQCE-XJKSGUPXSA-N (+)-haematoxylin Chemical compound C12=CC(O)=C(O)C=C2C[C@]2(O)[C@H]1C1=CC=C(O)C(O)=C1OC2 WZUVPPKBWHMQCE-XJKSGUPXSA-N 0.000 abstract description 10
- 230000032683 aging Effects 0.000 abstract description 8
- 108090000623 proteins and genes Proteins 0.000 abstract description 8
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 abstract description 4
- 239000001301 oxygen Substances 0.000 abstract description 4
- 229910052760 oxygen Inorganic materials 0.000 abstract description 4
- 239000004480 active ingredient Substances 0.000 abstract description 3
- 230000009286 beneficial effect Effects 0.000 abstract 1
- 241000244206 Nematoda Species 0.000 description 46
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 33
- 229940093265 berberine Drugs 0.000 description 17
- QISXPYZVZJBNDM-UHFFFAOYSA-N berberine Natural products COc1ccc2C=C3N(Cc2c1OC)C=Cc4cc5OCOc5cc34 QISXPYZVZJBNDM-UHFFFAOYSA-N 0.000 description 17
- 239000002904 solvent Substances 0.000 description 17
- HLUCICHZHWJHLL-UHFFFAOYSA-N hematein Chemical compound C12=CC=C(O)C(O)=C2OCC2(O)C1=C1C=C(O)C(=O)C=C1C2 HLUCICHZHWJHLL-UHFFFAOYSA-N 0.000 description 16
- 239000013641 positive control Substances 0.000 description 16
- YBHILYKTIRIUTE-UHFFFAOYSA-N berberine Chemical compound C1=C2CC[N+]3=CC4=C(OC)C(OC)=CC=C4C=C3C2=CC2=C1OCO2 YBHILYKTIRIUTE-UHFFFAOYSA-N 0.000 description 14
- 238000002474 experimental method Methods 0.000 description 11
- 239000011550 stock solution Substances 0.000 description 10
- 230000000694 effects Effects 0.000 description 8
- 238000012360 testing method Methods 0.000 description 7
- 230000009471 action Effects 0.000 description 6
- 239000003642 reactive oxygen metabolite Substances 0.000 description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- 241000282414 Homo sapiens Species 0.000 description 4
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 4
- 241001465754 Metazoa Species 0.000 description 4
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- 229920002472 Starch Polymers 0.000 description 4
- 230000005284 excitation Effects 0.000 description 4
- 230000012010 growth Effects 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- 238000000034 method Methods 0.000 description 4
- 230000009758 senescence Effects 0.000 description 4
- 239000008107 starch Substances 0.000 description 4
- 235000019698 starch Nutrition 0.000 description 4
- 241000209639 Biancaea sappan Species 0.000 description 3
- 101100447050 Caenorhabditis elegans daf-16 gene Proteins 0.000 description 3
- 235000015162 Caesalpinia sappan Nutrition 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 150000003836 berberines Chemical group 0.000 description 3
- 238000001543 one-way ANOVA Methods 0.000 description 3
- 230000001105 regulatory effect Effects 0.000 description 3
- 238000011160 research Methods 0.000 description 3
- 230000004083 survival effect Effects 0.000 description 3
- AXTGDCSMTYGJND-UHFFFAOYSA-N 1-dodecylazepan-2-one Chemical compound CCCCCCCCCCCCN1CCCCCC1=O AXTGDCSMTYGJND-UHFFFAOYSA-N 0.000 description 2
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- 241000196324 Embryophyta Species 0.000 description 2
- 208000002193 Pain Diseases 0.000 description 2
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
- 239000002202 Polyethylene glycol Substances 0.000 description 2
- 239000011543 agarose gel Substances 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 238000010171 animal model Methods 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- OSGAYBCDTDRGGQ-UHFFFAOYSA-L calcium sulfate Chemical compound [Ca+2].[O-]S([O-])(=O)=O OSGAYBCDTDRGGQ-UHFFFAOYSA-L 0.000 description 2
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 230000034994 death Effects 0.000 description 2
- 239000000796 flavoring agent Substances 0.000 description 2
- 238000000799 fluorescence microscopy Methods 0.000 description 2
- 235000013355 food flavoring agent Nutrition 0.000 description 2
- 239000011521 glass Substances 0.000 description 2
- 150000002576 ketones Chemical class 0.000 description 2
- RLSSMJSEOOYNOY-UHFFFAOYSA-N m-cresol Chemical compound CC1=CC=CC(O)=C1 RLSSMJSEOOYNOY-UHFFFAOYSA-N 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
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 2
- 235000019341 magnesium sulphate Nutrition 0.000 description 2
- 239000000178 monomer Substances 0.000 description 2
- 229910000402 monopotassium phosphate Inorganic materials 0.000 description 2
- 235000019796 monopotassium phosphate Nutrition 0.000 description 2
- 230000005937 nuclear translocation Effects 0.000 description 2
- PJNZPQUBCPKICU-UHFFFAOYSA-N phosphoric acid;potassium Chemical compound [K].OP(O)(O)=O PJNZPQUBCPKICU-UHFFFAOYSA-N 0.000 description 2
- 229920001223 polyethylene glycol Polymers 0.000 description 2
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
- 239000000523 sample Substances 0.000 description 2
- KVYZXXBTJHJISR-UHFFFAOYSA-N sappanone A Natural products C1OC2=CC(O)=CC=C2C(=O)C1=CC1=CC=C(O)C(O)=C1 KVYZXXBTJHJISR-UHFFFAOYSA-N 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 230000008961 swelling Effects 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 description 1
- FWBHETKCLVMNFS-UHFFFAOYSA-N 4',6-Diamino-2-phenylindol Chemical compound C1=CC(C(=N)N)=CC=C1C1=CC2=CC=C(C(N)=N)C=C2N1 FWBHETKCLVMNFS-UHFFFAOYSA-N 0.000 description 1
- LTYUPYUWXRTNFQ-UHFFFAOYSA-N 5,6-diamino-3',6'-dihydroxyspiro[2-benzofuran-3,9'-xanthene]-1-one Chemical compound C12=CC=C(O)C=C2OC2=CC(O)=CC=C2C11OC(=O)C2=C1C=C(N)C(N)=C2 LTYUPYUWXRTNFQ-UHFFFAOYSA-N 0.000 description 1
- LPEKGGXMPWTOCB-UHFFFAOYSA-N 8beta-(2,3-epoxy-2-methylbutyryloxy)-14-acetoxytithifolin Natural products COC(=O)C(C)O LPEKGGXMPWTOCB-UHFFFAOYSA-N 0.000 description 1
- 101150014742 AGE1 gene Proteins 0.000 description 1
- 229910002012 Aerosil® Inorganic materials 0.000 description 1
- 201000000736 Amenorrhea Diseases 0.000 description 1
- 206010001928 Amenorrhoea Diseases 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- 241000244202 Caenorhabditis Species 0.000 description 1
- 101100322915 Caenorhabditis elegans akt-1 gene Proteins 0.000 description 1
- 101100299500 Caenorhabditis elegans daf-18 gene Proteins 0.000 description 1
- 101100203566 Caenorhabditis elegans sod-3 gene Proteins 0.000 description 1
- 235000007627 Caesalpinia Nutrition 0.000 description 1
- 241000522234 Caesalpinia Species 0.000 description 1
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 1
- 229920002785 Croscarmellose sodium Polymers 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- 229920001353 Dextrin Polymers 0.000 description 1
- 239000004375 Dextrin Substances 0.000 description 1
- 208000005171 Dysmenorrhea Diseases 0.000 description 1
- 206010013935 Dysmenorrhoea Diseases 0.000 description 1
- 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 1
- 241000588724 Escherichia coli Species 0.000 description 1
- 239000001856 Ethyl cellulose Substances 0.000 description 1
- ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 description 1
- 241000220485 Fabaceae Species 0.000 description 1
- 229920002153 Hydroxypropyl cellulose Polymers 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
- 229930195725 Mannitol Natural products 0.000 description 1
- 229920000881 Modified starch Polymers 0.000 description 1
- 206010029240 Neuritis Diseases 0.000 description 1
- 101100259931 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) tba-1 gene Proteins 0.000 description 1
- 238000011529 RT qPCR Methods 0.000 description 1
- 101100533820 Rattus norvegicus Sod3 gene Proteins 0.000 description 1
- 101150082971 Sgk1 gene Proteins 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 229940124532 absorption promoter Drugs 0.000 description 1
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
- 150000004729 acetoacetic acid derivatives Chemical class 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000006978 adaptation Effects 0.000 description 1
- 208000037883 airway inflammation Diseases 0.000 description 1
- 125000001931 aliphatic group Chemical group 0.000 description 1
- 231100000540 amenorrhea Toxicity 0.000 description 1
- 150000003862 amino acid derivatives Chemical class 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 159000000032 aromatic acids Chemical class 0.000 description 1
- 238000005452 bending Methods 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 239000007853 buffer solution Substances 0.000 description 1
- 229910000019 calcium carbonate Inorganic materials 0.000 description 1
- 239000001110 calcium chloride Substances 0.000 description 1
- 229910001628 calcium chloride Inorganic materials 0.000 description 1
- FUFJGUQYACFECW-UHFFFAOYSA-L calcium hydrogenphosphate Chemical compound [Ca+2].OP([O-])([O-])=O FUFJGUQYACFECW-UHFFFAOYSA-L 0.000 description 1
- 159000000007 calcium salts Chemical class 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 235000012000 cholesterol Nutrition 0.000 description 1
- 239000002299 complementary DNA Substances 0.000 description 1
- 230000003750 conditioning effect Effects 0.000 description 1
- 235000009508 confectionery Nutrition 0.000 description 1
- 239000001767 crosslinked sodium carboxy methyl cellulose Substances 0.000 description 1
- 235000010947 crosslinked sodium carboxy methyl cellulose Nutrition 0.000 description 1
- 235000019425 dextrin Nutrition 0.000 description 1
- 235000019700 dicalcium phosphate Nutrition 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- HNPSIPDUKPIQMN-UHFFFAOYSA-N dioxosilane;oxo(oxoalumanyloxy)alumane Chemical compound O=[Si]=O.O=[Al]O[Al]=O HNPSIPDUKPIQMN-UHFFFAOYSA-N 0.000 description 1
- FPAFDBFIGPHWGO-UHFFFAOYSA-N dioxosilane;oxomagnesium;hydrate Chemical compound O.[Mg]=O.[Mg]=O.[Mg]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O FPAFDBFIGPHWGO-UHFFFAOYSA-N 0.000 description 1
- ZPWVASYFFYYZEW-UHFFFAOYSA-L dipotassium hydrogen phosphate Chemical compound [K+].[K+].OP([O-])([O-])=O ZPWVASYFFYYZEW-UHFFFAOYSA-L 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- ODQWQRRAPPTVAG-GZTJUZNOSA-N doxepin Chemical compound C1OC2=CC=CC=C2C(=C/CCN(C)C)/C2=CC=CC=C21 ODQWQRRAPPTVAG-GZTJUZNOSA-N 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 235000019325 ethyl cellulose Nutrition 0.000 description 1
- 229920001249 ethyl cellulose Polymers 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 230000003203 everyday effect Effects 0.000 description 1
- 239000000835 fiber Substances 0.000 description 1
- 239000007850 fluorescent dye Substances 0.000 description 1
- 210000002216 heart Anatomy 0.000 description 1
- 239000008172 hydrogenated vegetable oil Substances 0.000 description 1
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 1
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 1
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 1
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 1
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 229960003639 laurocapram Drugs 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 230000033001 locomotion Effects 0.000 description 1
- 238000001325 log-rank test Methods 0.000 description 1
- 229940031703 low substituted hydroxypropyl cellulose Drugs 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 229940037627 magnesium lauryl sulfate Drugs 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- HBNDBUATLJAUQM-UHFFFAOYSA-L magnesium;dodecyl sulfate Chemical compound [Mg+2].CCCCCCCCCCCCOS([O-])(=O)=O.CCCCCCCCCCCCOS([O-])(=O)=O HBNDBUATLJAUQM-UHFFFAOYSA-L 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 238000001819 mass spectrum Methods 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 229940057867 methyl lactate Drugs 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- 230000009456 molecular mechanism Effects 0.000 description 1
- 230000004899 motility Effects 0.000 description 1
- 230000004770 neurodegeneration Effects 0.000 description 1
- 208000015122 neurodegenerative disease Diseases 0.000 description 1
- 230000005311 nuclear magnetism Effects 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 235000019198 oils Nutrition 0.000 description 1
- 238000005457 optimization Methods 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 239000001508 potassium citrate Substances 0.000 description 1
- 229960002635 potassium citrate Drugs 0.000 description 1
- QEEAPRPFLLJWCF-UHFFFAOYSA-K potassium citrate (anhydrous) Chemical compound [K+].[K+].[K+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O QEEAPRPFLLJWCF-UHFFFAOYSA-K 0.000 description 1
- 235000011082 potassium citrates Nutrition 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 238000010839 reverse transcription Methods 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
- 230000019491 signal transduction Effects 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 210000000952 spleen Anatomy 0.000 description 1
- 238000007619 statistical method Methods 0.000 description 1
- 230000035882 stress Effects 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 230000001360 synchronised effect Effects 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 230000008736 traumatic injury Effects 0.000 description 1
- STCOOQWBFONSKY-UHFFFAOYSA-N tributyl phosphate Chemical compound CCCCOP(=O)(OCCCC)OCCCC STCOOQWBFONSKY-UHFFFAOYSA-N 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
- A61K31/352—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- 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)
- A61K36/48—Fabaceae or Leguminosae (Pea or Legume family); Caesalpiniaceae; Mimosaceae; Papilionaceae
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K49/00—Preparations for testing in vivo
- A61K49/0004—Screening or testing of compounds for diagnosis of disorders, assessment of conditions, e.g. renal clearance, gastric emptying, testing for diabetes, allergy, rheuma, pancreas functions
- A61K49/0008—Screening agents using (non-human) animal models or transgenic animal models or chimeric hosts, e.g. Alzheimer disease animal model, transgenic model for heart failure
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P39/00—General protective or antinoxious agents
- A61P39/06—Free radical scavengers or antioxidants
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Natural Medicines & Medicinal Plants (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Epidemiology (AREA)
- Medicinal Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Pharmacology & Pharmacy (AREA)
- Toxicology (AREA)
- Mycology (AREA)
- Food Science & Technology (AREA)
- Microbiology (AREA)
- Nutrition Science (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Polymers & Plastics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Alternative & Traditional Medicine (AREA)
- Biotechnology (AREA)
- Botany (AREA)
- Medical Informatics (AREA)
- Organic Chemistry (AREA)
- Biochemistry (AREA)
- Zoology (AREA)
- Biomedical Technology (AREA)
- Diabetes (AREA)
- Endocrinology (AREA)
- Gastroenterology & Hepatology (AREA)
- Pathology (AREA)
- Rheumatology (AREA)
- Urology & Nephrology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
本发明公开了中药有效成分苏木酮A在抗衰老及制备相关抗衰老药物和/或保健品的用途。苏木酮A可有效延缓衰老进程，降低脂褐素和活性氧蓄积，并调控相关基因的表达，有利于维持机体健康状态。
Description
技术领域
本发明涉及一种中药活性成分苏木酮A的抗衰老用途。
背景技术
衰老进程的影响因素复杂，涉及到器官、组织、细胞及分子等诸多层面。而中药是我国传统医学的宝贵财富，其中不乏记载有延缓衰老、调理身体机能的中药组方或单方，但中药组方药物繁多，单方成分亦十分复杂，同一种药材的不同产地、种植方式等均会影响其中的活性成分的和药效，药物单体提纯往往成本较高、产量少，很多情况下难以直接应用西药单体的评价方式，对中药成分进行抗衰老相关研究。
本专利应用秀丽隐杆线虫进行一种中药组分苏木酮A的抗衰老研究。线虫作为模式生物，在抗衰老研究方面有着其他实验动物所不具备的优点：作为一种整体动物，其基因与60％-80％的人类基因高度保守，多种衰老特征与人类类似，其实验结果可以对人类衰老进程起到重要的提示作用；其世代周期短、获取方便，短期内可培养获得大量线虫用于实验，样本量充足，实验结果可信；使用低等动物替代更高等的实验动物，更符合动物伦理和动物实验“替代、优化、节约”的原则。以往应用线虫评估外源化合物抗衰老作用的各项指标丰富全面，如自然寿命、脂褐素累积等都可以反应线虫的衰老程度。
苏木(Caesalpinia sappan L.)是一种豆科、云实属植物，其干燥心材可入药，味甘、咸，平，归心、肝、脾经，可以活血祛瘀，消肿止痛，用于跌打损伤，瘀滞肿痛，经闭痛经，产后瘀阻等。
苏木酮A是以苏木心材为原料，通过提取、分离、纯化和干燥后得到的化合物，具有抗神经炎、气道炎症等活性。专利号CN 107362160公开了苏木酮A在治疗神经退行性疾病中的应用。查阅相关资料可知，目前未见苏木酮A在抗衰老方面的相关报道，将苏木酮A作为抗衰老成分进行应用具有重大的现实意义。
苏木酮A的英文名字为：Sappanone A(SA)
分子式：C6H12O5
分子量：284.26
CAS登记号：102067-84-5
化学结构式：
发明内容
在上述背景下，本发明公开了苏木酮A的抗衰老作用，其目的在于提供苏木酮A在抗衰老药物和/或保健品制备方面的新用途。
为了实现上述发明目的，本发明采用了如下的技术方案。
苏木酮A在制备抗衰老药物和/或保健品中的应用。
作为优选方案，所述苏木酮A在抗衰老方面的应用还包括包含有苏木酮A的多药联合作用。
作为优选方案，所述抗衰老药物和/或保健品，可以是口服制剂，也可以是非口服制剂。
作为优选方案，所述口服制剂可以选自片剂、胶囊剂、滴丸剂、颗粒剂、粉剂、口腔膜剂和口服液中的一种或多种。
作为优选方案，所述非口服制剂可以选自注射剂、膏剂、霜剂和栓剂中的一种或多种。
本发明所述药学上可以接受的辅料，包括药学领域常规的溶剂(如水、乙醇、丙二醇、注射用油等)、稀释剂(如淀粉、糖粉、糊精、乳糖、预胶化淀粉、微晶纤维、无机钙盐(如硫酸钙、磷酸氢钙、药用碳酸钙等)、甘露醇等、植物油、聚乙二醇等)、粘合剂(如水、乙醇、淀粉浆、羧甲基纤维素钠、羟丙基纤维素、甲基纤维素和乙基纤维素、羟丙甲纤维素等)、崩解剂(如干淀粉、羧甲基淀粉钠、低取代羟丙基纤维素、交联聚乙烯吡咯烷酮、交联羧甲基纤维素钠等)、润滑剂(如硬脂酸镁、微粉硅胶、滑石粉、氢化植物油、聚乙二醇类、月桂醇硫酸镁等)、吸收促进剂(如表面活性剂、Azone(月桂氮卓酮)、EDTA、水杨酸、氨基酸乙胺衍生物、乙酰醋酸酯类、β-二羧酸酯、芳香族酸性化合物、脂肪族酸等)、防腐剂(如苯甲酸、羟丙丁酯、羟丙甲酯、苯酚、间甲酚等)、矫味剂(如蔗糖、甜菊素等)等。
药理试验表明，苏木酮A能够显著延长秀丽隐杆线虫的自然寿命，提高其活动能力及耐热能力，减少体内脂褐素和活性氧累积，并且作用效果强于本发明中所应用的阳性对照药物小檗碱。
本发明的优点是：在较低剂量作用下即能够观察到苏木酮A明显的抗衰老作用；可以形成一定规模的苏木种植基地，保障药材的来源和经济性。药用植物的市场认同性比较高，市场的接受度高，市场前景良好。
附图说明
结合以下附图，对本发明做进一步说明。
图1示出了实施例1中各组秀丽隐杆线虫的死亡曲线，其中SA为苏木酮A实验组，BBR为小檗碱阳性对照组，C为溶剂对照组。
图2示出了实施例1中各组秀丽隐杆线虫的平均寿命，其中SA为苏木酮A实验组，BBR为小檗碱阳性对照组，C为溶剂对照组。
图3示出了实施例2中各组秀丽隐杆线虫的20s内的头部摆动和身体弯曲次数，其中SA为苏木酮A实验组，BBR为小檗碱阳性对照组，C为溶剂对照组。
图4示出了实施例3中各组秀丽隐杆线虫的在荧光显微镜下的脂褐素累积情况，其中SA为苏木酮A实验组，BBR为小檗碱阳性对照组，C为溶剂对照组。
图5示出了实施例3中各组秀丽隐杆线虫的脂褐素自发荧光所呈现的平均荧光密度百分比，以溶剂对照组为100％计算。其中SA为苏木酮A实验组，BBR为小檗碱阳性对照组，C为溶剂对照组。
图6示出了实施例4中各组秀丽隐杆线虫的在荧光显微镜下的活性氧累积情况，其中SA为苏木酮A实验组，BBR为小檗碱阳性对照组，C为溶剂对照组。
图7示出了实施例4中各组秀丽隐杆线虫的活性氧结合荧光探针后所呈现的平均荧光密度百分比，以溶剂对照组为100％计算。其中SA为苏木酮A实验组，BBR为小檗碱阳性对照组，C为溶剂对照组。
图8示出了实施例5中各组秀丽隐杆线虫调控衰老相关基因的表达情况，以溶剂对照组为1计算。其中SA为苏木酮A实验组，BBR为小檗碱阳性对照组，C为溶剂对照组。
具体实施方式
以下内容是结合具体的优选实施方式对本发明所作的进一步详细说明，不能认定本发明的具体实施只局限于这些说明。对于本发明所属技术领域的普通技术人员来说，在不脱离本发明构思的前提下，还可以做出若干简单推演或替换，都应当视为属于本发明的保护范围。
实施例所用苏木酮A由本单位从苏木中提取，经质谱和核磁等波谱学分析，鉴定为苏木酮A。所用秀丽隐杆线虫购自美国明尼苏达大学线虫遗传学中心(CaenorhabditisGenetics Center，http：//www.cbs.umn.edu/CGC/)。其它的药品和试剂都能方便地市购。
实施例1：苏木酮A对秀丽隐杆线虫寿命的延长作用
1.1受试药物：
苏木酮A，溶解于DMSO，配制成40mM的储备液。
阳性对照(小檗碱)，溶解于DMSO，配制成50mM的储备液。
1.2实验方法：
采用同步化后的L4期线虫，20℃恒温液体体系培养(培养体系为含100mM氯化钠，5.74mM磷酸二氢钾、44mM磷酸氢二钾、10mM柠檬酸钾、3mM氯化钙、3μM硫酸镁、1.29μM胆固醇、适量灭活的OP50大肠杆菌的无菌水溶液)。溶剂对照组给予1％DMSO、阳性对照组给予100μM小檗碱、实验组分别给予2、50μM苏木酮A。给药至线虫死亡，每日记录其存活、死亡及丢失数目、得到各组平均寿命、并对数据进行生存分析。
1.3实验结果：
各组间生存时间差异可见表1。
表1 不同浓度苏木酮A作用下秀丽隐杆线虫的寿命
注：a)延长百分比计算公式为(处理组平均寿命-溶剂对照组平均寿命)/溶剂对照组平均寿命×100％。
b)P值应用Kaplan-Meier对数秩检验计算得出，*表示与溶剂对照组比较P＜0.05；**表示与溶剂对照组比较P＜0.01；
表1的数据结合图1，图2示出，苏木酮A使秀丽隐杆线虫衰老减缓，随着药物作用剂量的升高，线虫自然寿命显著延长，且50μM组延长寿命的效果略微强于阳性对照。
本实施例的结果说明苏木酮A可以延长秀丽隐杆线虫的自然寿命，且呈剂量依赖关系，提示苏木酮A能够延缓衰老进程；在50μM剂量作用下，其作用效果约与100μM小檗碱的抗衰老作用相当。
实施例2：苏木酮A对秀丽隐杆线虫运动能力的提高作用
2.1受试药物：
苏木酮A，溶解于DMSO，配制成40mM的储备液。
阳性对照(小檗碱)，溶解于DMSO，配制成50mM的储备液。
2.2实验方法：
线虫培养及药物浓度同实施例1。给药48h后，将线虫置于NGM(nematode growthmedium)平皿上，滴加60μl M9缓冲液(含1mM硫酸镁，5mM磷酸二氢钾，20mM磷酸氢二钠和20mM氯化钠的缓冲体系)，线虫适应1min后，体式显微镜下记录其20s内身体弯曲次数及头部摆动次数。每组20只线虫，实验重复三次，使用SPSS 20.0软件采用单因素方差分析方法统计各组差异。
2.3实验结果：
给药后线虫20s内头部摆动次数和身体弯曲次数如图3。苏木酮A不影响线虫头摆，但身体弯曲次数较对照组有显著提高。本实施例说明苏木酮A能够提高线虫的运动能力，健康状况得到改善，侧面反应其抗衰老作用。
实施例3：苏木酮A降低线虫体内脂褐素累积水平
自然界中很多生物都具有脂褐素随年龄增长而累积的特点，如人类衰老后产生的老年斑。脂褐素可以被荧光激发后产生自发荧光，其激发光波长落于DAPI的波长范围内(Ex/Em：300-400nm/410-510nm)，可方便地进行测量。
3.1受试药物：
苏木酮A，溶解于DMSO，配制成40mM的储备液。
阳性对照(小檗碱)，溶解于DMSO，配制成50mM的储备液。
3.2实验方法：
线虫培养及药物浓度同实施例1。给药5天后，将线虫置于铺有琼脂糖凝胶的载玻片上，使用0.4M叠氮钠麻醉线虫，在荧光显微镜405nm激发光波长下观察线虫体内脂褐素累积情况，并计算荧光密度。每组20只线虫，实验重复三次，使用SPSS 20.0软件采用单因素方差分析方法统计各组差异。
3.3实验结果：
各组线虫体内脂褐素水平样例如图4，图5为各组线虫平均荧光密度百分比。可见随着苏木酮A剂量的升高，线虫荧光密度降低，50μM组较对照组差异具有统计学意义。说明苏木酮A使线虫体内的脂褐素累积状况得到改善。本实施例说明苏木酮A减少了衰老特征代谢产物脂褐素的累积，具有抗衰老作用。
实施例4：苏木酮A降低线虫体内活性氧(reactive oxygen species，ROS)累积水平
4.1受试药物：
苏木酮A，溶解于DMSO，配制成40mM的储备液。
阳性对照(小檗碱)，溶解于DMSO，配制成50mM的储备液。
4.2实验方法：
线虫培养及药物浓度同实施例1。给药48h后，将线虫用DCFH-DA探针孵育后，置于铺有琼脂糖凝胶的载玻片上，使用0.4M叠氮钠麻醉线虫，在荧光显微镜488nm激发光波长下观察线虫体内ROS累积情况，并计算荧光密度。每组20只线虫，实验独立重复三次，使用SPSS20.0软件采用单因素方差分析方法统计各组差异。
4.3实验结果：
各组线虫体内ROS水平如图6，图7为各组线虫平均荧光密度。可见苏木酮A处理组线虫荧光较暗，随着苏木酮A剂量的升高，线虫荧光密度降低，且较对照组差异具有统计学意义，苏木酮A使线虫体内的ROS累积状况得到改善。本实施例说明苏木酮A减少了线虫体内的ROS，具有抗衰老作用。
实施例5：苏木酮A调节线虫衰老相关基因的表达
胰岛素/胰岛素样生长因子信号通路(Insulin/insulin-like growth factor-1signaling，IIS)是衰老调控的分子通路之一。DAF-2可以激活下游的AGE-1，进而激活PIP(Phosphatidylinositol-3，4，5-trisphosphate，磷脂酰肌醇-3，4，5-三磷酸肌醇)，促进AKT-1，2和SGK-1表达，抑制DAF-16的核转位。而DAF-16核转位后激活其下游SOD-3、CLT-1/2等基因，增强线虫抗逆性和抗衰老能力。
5.1受试药物：
苏木酮A，溶解于DMSO，配制成40mM的储备液。
阳性对照(小檗碱)，溶解于DMSO，配制成50mM的储备液。
5.2实验方法：
线虫培养同实施例1，苏木酮A给药剂量为50μM，小檗碱为100μM。给药48h后，采用TRlzol(Invitrogen，Carlsbad，CA，USA)提取线虫总RNA，使用反转录试剂盒(Takara，Kusatsu，Japan)反转录为cDNA，以tba-1为内参基因进行rt-qPCR。实验独立重复三次，使用2-ΔΔCt法进行统计分析。
5.3实验结果：
各组线虫待测基因表达情况如图8。苏木酮A作用后，线虫daf-2表达量下调，daf-16和daf-18表达量上调，且相对于对照组差异具有统计学意义。本实施例说明苏木酮A激活了抗衰老相关信号通路，解释了苏木酮A抗衰老作用的分子机制。
总之，本发明提供了苏木酮A作为抗衰老成分的新医药用途，从而为抗衰老药品或保健品的制备提供了新的选择。
Claims (7)
1.苏木酮A在制备抗衰老药物和/或保健品中的应用。
2.苏木酮A在制备延长寿命的药物和/或保健品中的应用。
3.苏木酮A在制备延长秀丽隐杆线虫寿命的药物中的应用。
4.根据权利要求1-3所述的应用，所述苏木酮A在抗衰老方面的应用还包括包含有苏木酮A的多药联合作用。
5.根据权利要求1-4所述应用，所述抗衰老药物和/或保健品，可以是口服制剂，也可以是非口服制剂。
6.根据权利要求1-5所述的应用，所述口服制剂可以选自片剂、胶囊剂、滴丸剂、颗粒剂、粉剂、口腔膜剂和口服液中的一种或多种。
7.根据权利要求1-6所述应用，所述非口服制剂可以选自注射剂、膏剂、霜剂和栓剂中的一种或多种。
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202010025501.0A CN111388460A (zh) | 2020-01-10 | 2020-01-10 | 苏木酮a的抗衰老用途 |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202010025501.0A CN111388460A (zh) | 2020-01-10 | 2020-01-10 | 苏木酮a的抗衰老用途 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN111388460A true CN111388460A (zh) | 2020-07-10 |
Family
ID=71410789
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202010025501.0A Pending CN111388460A (zh) | 2020-01-10 | 2020-01-10 | 苏木酮a的抗衰老用途 |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN111388460A (zh) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111671745A (zh) * | 2020-07-29 | 2020-09-18 | 北京大学 | 化合物在治疗溃疡性结肠炎药物制备中的应用 |
-
2020
- 2020-01-10 CN CN202010025501.0A patent/CN111388460A/zh active Pending
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111671745A (zh) * | 2020-07-29 | 2020-09-18 | 北京大学 | 化合物在治疗溃疡性结肠炎药物制备中的应用 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN102946877B (zh) | 乳突果及其分离的化合物在制备用于治疗神经疾病的药物中的用途 | |
| Khan et al. | Attenuation of neuropathic pain and neuroinflammatory responses by a pyranocoumarin derivative, anomalin in animal and cellular models | |
| Yang et al. | Effect of ginkgolide B on striatal extracellular amino acids in middle cerebral artery occluded rats | |
| Sripanidkulchai et al. | Anti-inflammatory effect of Streblus asper leaf extract in rats and its modulation on inflammation-associated genes expression in RAW 264.7 macrophage cells | |
| Zhang et al. | Procyanidin protects against 6-hydroxydopamine-induced dopaminergic neuron damage via the regulation of the PI3K/Akt signalling pathway | |
| JP5676881B2 (ja) | 認知障害改善剤 | |
| Chakrabarti et al. | MiR-7-1 potentiated estrogen receptor agonists for functional neuroprotection in VSC4. 1 motoneurons | |
| KR101721696B1 (ko) | 목단피, 백지 및 시호의 혼합 추출물 또는 이의 분획물을 유효성분으로 함유하는, 신경 퇴행성 질환의 치료 및 예방용 약학적 조성물 | |
| Bhattacharya et al. | Effect of Emblica officinalis tannoids on a rat model of tardive dyskinesia | |
| Alamdari et al. | Melatonin as a promising modulator of aging related neurodegenerative disorders: role of microRNAs | |
| CN111388460A (zh) | 苏木酮a的抗衰老用途 | |
| Bustamante et al. | Nicotinamide prevents the effect of perinatal asphyxia on dopamine release evaluated with in vivo microdialysis 3 months after birth | |
| KR101049041B1 (ko) | 항염증 및 면역억제 효과를 갖는 여뀌 메탄올 추출물 | |
| KR20100059302A (ko) | 목근피 추출물 함유 피부외용제 조성물 | |
| Ostock et al. | Striatal norepinephrine efflux in l-DOPA-induced dyskinesia | |
| JP2014152175A (ja) | カテプシンｋ抑制剤としてミリセチンの用途 | |
| KR20110023132A (ko) | 골관절염 치료 활성을 갖는 오가피, 해동피, 홍화씨 및 어성초의 생약 혼합 추출물 | |
| IL296758A (en) | Drug/compound for the treatment of the corona virus, inflammation caused by retroviruses and type c viral infection | |
| CN101856350A (zh) | 黄芩素在制备预防和治疗帕金森病药物中的应用 | |
| Wąsik et al. | 1-Benzyl-1, 2, 3, 4-tetrahydroisoquinoline, an endogenous parkinsonism-inducing toxin, strongly potentiates MAO-dependent dopamine oxidation and impairs dopamine release: ex vivo and in vivo neurochemical studies | |
| JP2021517886A (ja) | 口腔癌治療用の医薬の製造ためのジンセノサイドｍ１の使用 | |
| CN112791003B (zh) | 维甲酸受体激动剂化合物在化妆品组合物中的应用 | |
| CN112043700B (zh) | 盐酸去亚甲基四氢小檗碱在制备预防或治疗神经退行性疾病药物中的应用 | |
| CN112972490B (zh) | 透明质酸在用于制备预防或治疗铁死亡相关疾病的药物中的应用 | |
| KR100597612B1 (ko) | 항노화 활성이 우수한 현삼 추출물을 포함하는 식품 조성물 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination |