CN101502547A - Application of notoginseng extract in preparing medicament for preventing and treating parkinsonism - Google Patents
Application of notoginseng extract in preparing medicament for preventing and treating parkinsonism Download PDFInfo
- Publication number
- CN101502547A CN101502547A CNA2009100941875A CN200910094187A CN101502547A CN 101502547 A CN101502547 A CN 101502547A CN A2009100941875 A CNA2009100941875 A CN A2009100941875A CN 200910094187 A CN200910094187 A CN 200910094187A CN 101502547 A CN101502547 A CN 101502547A
- Authority
- CN
- China
- Prior art keywords
- notoginseng
- saponins
- cell
- thioredoxin
- triol saponins
- 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
- 239000003814 drug Substances 0.000 title claims abstract description 20
- 241000180649 Panax notoginseng Species 0.000 title claims description 55
- 235000003143 Panax notoginseng Nutrition 0.000 title claims description 54
- 208000027089 Parkinsonian disease Diseases 0.000 title description 2
- 206010034010 Parkinsonism Diseases 0.000 title description 2
- -1 panaxtriol saponins Chemical class 0.000 claims abstract description 41
- 229930182490 saponin Natural products 0.000 claims abstract description 39
- 235000017709 saponins Nutrition 0.000 claims abstract description 39
- 108060008226 thioredoxin Proteins 0.000 claims abstract description 33
- 102000002933 Thioredoxin Human genes 0.000 claims abstract description 26
- 229940094937 thioredoxin Drugs 0.000 claims abstract description 25
- 208000018737 Parkinson disease Diseases 0.000 claims abstract description 11
- 230000001939 inductive effect Effects 0.000 claims abstract description 6
- 230000036542 oxidative stress Effects 0.000 claims abstract description 4
- 238000002360 preparation method Methods 0.000 claims abstract description 4
- 230000006378 damage Effects 0.000 claims abstract description 3
- 230000002265 prevention Effects 0.000 claims description 3
- 229930182494 ginsenoside Natural products 0.000 claims 1
- 229940089161 ginsenoside Drugs 0.000 claims 1
- 235000013402 health food Nutrition 0.000 claims 1
- 230000000694 effects Effects 0.000 abstract description 9
- FMGYKKMPNATWHP-UHFFFAOYSA-N Cyperquat Chemical compound C1=C[N+](C)=CC=C1C1=CC=CC=C1 FMGYKKMPNATWHP-UHFFFAOYSA-N 0.000 abstract description 4
- 229940079593 drug Drugs 0.000 abstract description 4
- 230000014509 gene expression Effects 0.000 abstract description 3
- 238000005516 engineering process Methods 0.000 abstract description 2
- 230000003834 intracellular effect Effects 0.000 abstract description 2
- 239000009277 Panax notoginseng extract Substances 0.000 abstract 1
- 208000027418 Wounds and injury Diseases 0.000 abstract 1
- 235000013305 food Nutrition 0.000 abstract 1
- 208000014674 injury Diseases 0.000 abstract 1
- 230000001681 protective effect Effects 0.000 abstract 1
- 210000004027 cell Anatomy 0.000 description 30
- 241000699670 Mus sp. Species 0.000 description 8
- 102100036407 Thioredoxin Human genes 0.000 description 7
- 238000000034 method Methods 0.000 description 7
- 108090000623 proteins and genes Proteins 0.000 description 7
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 6
- YBYRMVIVWMBXKQ-UHFFFAOYSA-N phenylmethanesulfonyl fluoride Chemical compound FS(=O)(=O)CC1=CC=CC=C1 YBYRMVIVWMBXKQ-UHFFFAOYSA-N 0.000 description 6
- 102000004169 proteins and genes Human genes 0.000 description 6
- 101710168651 Thioredoxin 1 Proteins 0.000 description 5
- 210000004556 brain Anatomy 0.000 description 4
- VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 description 4
- 238000002474 experimental method Methods 0.000 description 4
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- 239000012528 membrane Substances 0.000 description 4
- 229920002981 polyvinylidene fluoride Polymers 0.000 description 4
- 101710088194 Dehydrogenase Proteins 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 3
- 241000699666 Mus <mouse, genus> Species 0.000 description 3
- 229920001213 Polysorbate 20 Polymers 0.000 description 3
- 239000008280 blood Substances 0.000 description 3
- 210000004369 blood Anatomy 0.000 description 3
- 230000002490 cerebral effect Effects 0.000 description 3
- 230000007850 degeneration Effects 0.000 description 3
- 238000001514 detection method Methods 0.000 description 3
- 239000001963 growth medium Substances 0.000 description 3
- 210000001320 hippocampus Anatomy 0.000 description 3
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 3
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 3
- 238000004321 preservation Methods 0.000 description 3
- 230000008569 process Effects 0.000 description 3
- 238000012545 processing Methods 0.000 description 3
- 150000003254 radicals Chemical class 0.000 description 3
- 238000011160 research Methods 0.000 description 3
- 239000011780 sodium chloride Substances 0.000 description 3
- 210000001519 tissue Anatomy 0.000 description 3
- AVWQQPYHYQKEIZ-UHFFFAOYSA-K trisodium;2-dodecylbenzenesulfonate;3-dodecylbenzenesulfonate;4-dodecylbenzenesulfonate Chemical compound [Na+].[Na+].[Na+].CCCCCCCCCCCCC1=CC=C(S([O-])(=O)=O)C=C1.CCCCCCCCCCCCC1=CC=CC(S([O-])(=O)=O)=C1.CCCCCCCCCCCCC1=CC=CC=C1S([O-])(=O)=O AVWQQPYHYQKEIZ-UHFFFAOYSA-K 0.000 description 3
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 241000283707 Capra Species 0.000 description 2
- 208000030453 Drug-Related Side Effects and Adverse reaction Diseases 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- 108010025020 Nerve Growth Factor Proteins 0.000 description 2
- 102000015336 Nerve Growth Factor Human genes 0.000 description 2
- 206010029350 Neurotoxicity Diseases 0.000 description 2
- 206010042434 Sudden death Diseases 0.000 description 2
- 206010044221 Toxic encephalopathy Diseases 0.000 description 2
- 206010070863 Toxicity to various agents Diseases 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 230000008485 antagonism Effects 0.000 description 2
- 230000017531 blood circulation Effects 0.000 description 2
- 238000004113 cell culture Methods 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 239000012141 concentrate Substances 0.000 description 2
- 238000005336 cracking Methods 0.000 description 2
- 239000012895 dilution Substances 0.000 description 2
- 238000010790 dilution Methods 0.000 description 2
- 229960003638 dopamine Drugs 0.000 description 2
- 210000005064 dopaminergic neuron Anatomy 0.000 description 2
- 238000011010 flushing procedure Methods 0.000 description 2
- 230000012010 growth Effects 0.000 description 2
- 235000008216 herbs Nutrition 0.000 description 2
- 238000003119 immunoblot Methods 0.000 description 2
- 230000001965 increasing effect Effects 0.000 description 2
- 239000000411 inducer Substances 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000004310 lactic acid Substances 0.000 description 2
- 235000014655 lactic acid Nutrition 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 210000005036 nerve Anatomy 0.000 description 2
- 229940053128 nerve growth factor Drugs 0.000 description 2
- 208000015122 neurodegenerative disease Diseases 0.000 description 2
- 230000014511 neuron projection development Effects 0.000 description 2
- 230000007135 neurotoxicity Effects 0.000 description 2
- 231100000228 neurotoxicity Toxicity 0.000 description 2
- 230000003287 optical effect Effects 0.000 description 2
- 239000001301 oxygen Substances 0.000 description 2
- 229910052760 oxygen Inorganic materials 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- 238000000197 pyrolysis Methods 0.000 description 2
- 150000007949 saponins Chemical class 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- PLRACCBDVIHHLZ-UHFFFAOYSA-N 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine Chemical compound C1N(C)CCC(C=2C=CC=CC=2)=C1 PLRACCBDVIHHLZ-UHFFFAOYSA-N 0.000 description 1
- BRAJQLYTRXKQAW-UHFFFAOYSA-N 1-methyl-4-phenyl-2h-pyridine Chemical class C1=CN(C)CC=C1C1=CC=CC=C1 BRAJQLYTRXKQAW-UHFFFAOYSA-N 0.000 description 1
- HRPVXLWXLXDGHG-UHFFFAOYSA-N Acrylamide Chemical compound NC(=O)C=C HRPVXLWXLXDGHG-UHFFFAOYSA-N 0.000 description 1
- 229920000936 Agarose Polymers 0.000 description 1
- 108010039627 Aprotinin Proteins 0.000 description 1
- 108091007065 BIRCs Proteins 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 101100153083 Caenorhabditis elegans trx-1 gene Proteins 0.000 description 1
- 208000024172 Cardiovascular disease Diseases 0.000 description 1
- 235000016936 Dendrocalamus strictus Nutrition 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- KMHZPJNVPCAUMN-UHFFFAOYSA-N Erbon Chemical compound CC(Cl)(Cl)C(=O)OCCOC1=CC(Cl)=C(Cl)C=C1Cl KMHZPJNVPCAUMN-UHFFFAOYSA-N 0.000 description 1
- 241000206602 Eukaryota Species 0.000 description 1
- 101000852559 Homo sapiens Thioredoxin Proteins 0.000 description 1
- 206010021143 Hypoxia Diseases 0.000 description 1
- 102000055031 Inhibitor of Apoptosis Proteins Human genes 0.000 description 1
- 108010075639 MAP Kinase Kinase Kinase 5 Proteins 0.000 description 1
- 102100033127 Mitogen-activated protein kinase kinase kinase 5 Human genes 0.000 description 1
- 208000016285 Movement disease Diseases 0.000 description 1
- 241000699660 Mus musculus Species 0.000 description 1
- 101000835317 Mus musculus Thioredoxin Proteins 0.000 description 1
- 101001135571 Mus musculus Tyrosine-protein phosphatase non-receptor type 2 Proteins 0.000 description 1
- KWYHDKDOAIKMQN-UHFFFAOYSA-N N,N,N',N'-tetramethylethylenediamine Chemical compound CN(C)CCN(C)C KWYHDKDOAIKMQN-UHFFFAOYSA-N 0.000 description 1
- 206010029260 Neuroblastoma Diseases 0.000 description 1
- 235000002789 Panax ginseng Nutrition 0.000 description 1
- 244000131316 Panax pseudoginseng Species 0.000 description 1
- 235000003181 Panax pseudoginseng Nutrition 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
- 102000003992 Peroxidases Human genes 0.000 description 1
- 108091000080 Phosphotransferase Proteins 0.000 description 1
- 239000012979 RPMI medium Substances 0.000 description 1
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
- 239000004141 Sodium laurylsulphate Substances 0.000 description 1
- 101150008292 TXNDC2 gene Proteins 0.000 description 1
- 101710168624 Thioredoxin 2 Proteins 0.000 description 1
- 102000013090 Thioredoxin-Disulfide Reductase Human genes 0.000 description 1
- 108010079911 Thioredoxin-disulfide reductase Proteins 0.000 description 1
- XSTXAVWGXDQKEL-UHFFFAOYSA-N Trichloroethylene Chemical compound ClC=C(Cl)Cl XSTXAVWGXDQKEL-UHFFFAOYSA-N 0.000 description 1
- 239000007983 Tris buffer Substances 0.000 description 1
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 1
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 230000001919 adrenal effect Effects 0.000 description 1
- VREFGVBLTWBCJP-UHFFFAOYSA-N alprazolam Chemical compound C12=CC(Cl)=CC=C2N2C(C)=NN=C2CN=C1C1=CC=CC=C1 VREFGVBLTWBCJP-UHFFFAOYSA-N 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 230000006909 anti-apoptosis Effects 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 230000003064 anti-oxidating effect Effects 0.000 description 1
- 230000000648 anti-parkinson Effects 0.000 description 1
- 230000002785 anti-thrombosis Effects 0.000 description 1
- 239000003146 anticoagulant agent Substances 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 235000006708 antioxidants Nutrition 0.000 description 1
- 239000000939 antiparkinson agent Substances 0.000 description 1
- 230000006907 apoptotic process Effects 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 229960004405 aprotinin Drugs 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 210000005013 brain tissue Anatomy 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 230000019522 cellular metabolic process Effects 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 210000003710 cerebral cortex Anatomy 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000004140 cleaning Methods 0.000 description 1
- ZPUCINDJVBIVPJ-LJISPDSOSA-N cocaine Chemical compound O([C@H]1C[C@@H]2CC[C@@H](N2C)[C@H]1C(=O)OC)C(=O)C1=CC=CC=C1 ZPUCINDJVBIVPJ-LJISPDSOSA-N 0.000 description 1
- NKLPQNGYXWVELD-UHFFFAOYSA-M coomassie brilliant blue Chemical compound [Na+].C1=CC(OCC)=CC=C1NC1=CC=C(C(=C2C=CC(C=C2)=[N+](CC)CC=2C=C(C=CC=2)S([O-])(=O)=O)C=2C=CC(=CC=2)N(CC)CC=2C=C(C=CC=2)S([O-])(=O)=O)C=C1 NKLPQNGYXWVELD-UHFFFAOYSA-M 0.000 description 1
- 210000003618 cortical neuron Anatomy 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 238000004042 decolorization Methods 0.000 description 1
- 238000004925 denaturation Methods 0.000 description 1
- 230000036425 denaturation Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 239000003651 drinking water Substances 0.000 description 1
- 235000020188 drinking water Nutrition 0.000 description 1
- 230000005611 electricity Effects 0.000 description 1
- 238000001962 electrophoresis Methods 0.000 description 1
- 231100001129 embryonic lethality Toxicity 0.000 description 1
- 210000002472 endoplasmic reticulum Anatomy 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 238000007710 freezing Methods 0.000 description 1
- 230000008014 freezing Effects 0.000 description 1
- 238000001502 gel electrophoresis Methods 0.000 description 1
- 238000003306 harvesting Methods 0.000 description 1
- 102000056461 human TXN Human genes 0.000 description 1
- 230000007954 hypoxia Effects 0.000 description 1
- 230000036039 immunity Effects 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- ZPNFWUPYTFPOJU-LPYSRVMUSA-N iniprol Chemical compound C([C@H]1C(=O)NCC(=O)NCC(=O)N[C@H]2CSSC[C@H]3C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@H](C(N[C@H](C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=4C=CC(O)=CC=4)C(=O)N[C@@H](CC=4C=CC=CC=4)C(=O)N[C@@H](CC=4C=CC(O)=CC=4)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC=4C=CC=CC=4)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC2=O)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](CC=2C=CC=CC=2)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H]2N(CCC2)C(=O)[C@@H](N)CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N2[C@@H](CCC2)C(=O)N2[C@@H](CCC2)C(=O)N[C@@H](CC=2C=CC(O)=CC=2)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N2[C@@H](CCC2)C(=O)N3)C(=O)NCC(=O)NCC(=O)N[C@@H](C)C(O)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@H](C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@H](C(=O)N1)C(C)C)[C@@H](C)O)[C@@H](C)CC)=O)[C@@H](C)CC)C1=CC=C(O)C=C1 ZPNFWUPYTFPOJU-LPYSRVMUSA-N 0.000 description 1
- 238000011081 inoculation Methods 0.000 description 1
- 230000017306 interleukin-6 production Effects 0.000 description 1
- 239000007928 intraperitoneal injection Substances 0.000 description 1
- 238000011813 knockout mouse model Methods 0.000 description 1
- 239000012160 loading buffer Substances 0.000 description 1
- 206010025482 malaise Diseases 0.000 description 1
- 210000001161 mammalian embryo Anatomy 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 239000007758 minimum essential medium Substances 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 230000017074 necrotic cell death Effects 0.000 description 1
- 210000001577 neostriatum Anatomy 0.000 description 1
- 230000004770 neurodegeneration Effects 0.000 description 1
- 210000002569 neuron Anatomy 0.000 description 1
- 230000000324 neuroprotective effect Effects 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 230000008520 organization Effects 0.000 description 1
- 230000002018 overexpression Effects 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 230000033116 oxidation-reduction process Effects 0.000 description 1
- 102000002574 p38 Mitogen-Activated Protein Kinases Human genes 0.000 description 1
- 108010068338 p38 Mitogen-Activated Protein Kinases Proteins 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
- 230000007119 pathological manifestation Effects 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- 230000010412 perfusion Effects 0.000 description 1
- 108040007629 peroxidase activity proteins Proteins 0.000 description 1
- 102000020233 phosphotransferase Human genes 0.000 description 1
- 239000002574 poison Substances 0.000 description 1
- 231100000614 poison Toxicity 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 238000000751 protein extraction Methods 0.000 description 1
- 239000012474 protein marker Substances 0.000 description 1
- 150000003222 pyridines Chemical class 0.000 description 1
- 238000011002 quantification Methods 0.000 description 1
- 239000001397 quillaja saponaria molina bark Substances 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 238000007789 sealing Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 230000019491 signal transduction Effects 0.000 description 1
- 235000020183 skimmed milk Nutrition 0.000 description 1
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 1
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 229940041022 streptomycins Drugs 0.000 description 1
- 230000026683 transduction Effects 0.000 description 1
- 238000010361 transduction Methods 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 238000011830 transgenic mouse model Methods 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 239000012224 working solution Substances 0.000 description 1
Images
Landscapes
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
The invention relates to an application of a panax notoginseng extract in the preparation of drugs for preventing and treating Parkinson's disease. The invention relates to the field of pharmaceutical technology. The invention discloses that panaxtriol saponins have the effect of inducing the intracellular thioredoxin expression increase and proposes that the panaxtriol saponins have a protective effect for a 1-methyl-4-phenylpyridiniumion MPP<+>-induced Parkinson's disease cell model. The panaxtriol saponins can be also applied in the fields of drugs, medical and health-care foods and the like which are related to oxidative stress injury.
Description
Technical field
The present invention relates to medical technical field, exactly is the medical usage of Radix Notoginseng extract notoginseng triol saponins.
Background technology
(thioredoxin Trx) is a kind of small protein that is prevalent in prokaryote and the eukaryote to thioredoxin, and it forms the interior main oxidation-reduction system of cell with NAPDH and thioredoxin reductase.According to the difference of expressive site, thioredoxin is divided into 3 classes: Trx-1, Trx-2 and spTrx.Up to the present, the research of relevant Trx mostly concentrates on Trx-1 in the human diseases.TRX-1 is the necessary gene of organism, if the Trx-1 gene of knock-out mice optionally, mice then body early embryo causes death can not survive (Matsui M., Oshima M., Oshima H., Takaku K., Maruyama T., Yodoi J., andTaketo M.M.Early embryonic lethality caused by targeted disruption ofthe mouse thioredoxin gene.Dev.Biol.1996,178:179-185).Trx-1 is a kind of effective anti-oxidants in the cell, can protect cell, alleviate the damage due to the oxidative stress.Trx-1 can suppress the relevant apoptosis signal transduction approach of p38MAPK and apoptosis signal regulating kinase 1, strengthens anti-apoptosis capacity (Saito M., Nishitoh, the H. of cell, Fujii, M., Takeda, K., Tobiume, K., Sawada, Y., Kawabata, M., Miyazono, K., and Ichijyo, H.Mammalian thioredoxin is adirect inhibitor of apoptosis signal-regulating kinase (ASK) 1.EMBO, 1998,17:2596-2606; Hashimoto S., Matsumoto K., Gon Y., Furuichi S., MaruokaS., Takeshita I., Hirota K., Yodoi J., and Horie T.Thioredoxin negativelyregulates p38 MAP kinase activation and IL-6 production by tumor necrosisfactor-alpha.Biochem.Biophys.Res.Commun.1999,258:443-447.).Simultaneously, thioredoxin plays an important role in signal conduction that nerve growth factor is regulated and neurite-outgrowth, be an important candidate key element (Bai J. of nerve growth factor, Nakamura H., Kwon Y.W., HattoriI., Yamaguchi Y., Kim Y.C., Kondo N., Oka S., Ueda S., Masutani H., andYodoi J.Critical roles of thioredoxin in nerve growth factor-mediatedsignal transduction and neurite outgrowth in PC12cells.J.Neurosci, 2003,23:503-509.).Compare with control group mice, the life-span of thioredoxin high expressed mice has increased by 30% (Mitsui A, Hamuro J, Nakamura H, Kondo N, Hirabayashi Y, Ishizaki-Koizumi S, Hirakawa T, Inoue T, Yodoi J.Overexpression of humanthioredoxin in transgenic mice controls oxidative stress and life span.Antioxid Redox Signal.2002, (4): 693-6.).Along with going deep into of research, the effect of thioredoxin in neurodegenerative diseases more and more is subject to people's attention, and becomes the important target spot of nerve protection medicine.
Parkinson disease are the nervous system degenerative diseases that are common in middle-aged and elderly people, and its prevalence and sickness rate increase with the growth at age.Parkinsonian main pathological manifestations is the degeneration and necrosis (the Fahn S of dopaminergic neuron in the brain, Parkinsonism.In:J.B.Wyngaarden and L.H.Smith, Jr., Editors.Cecil ' s Textbook of Medicine, Saunders, Phi ladelphia, PA, 1998.2143-2147).The at present relevant pathogenetic theory of parkinson disease is a lot, and free radical theory is extensively approved by people.This theory is thought: along with the increase at age, central nervous system's oxidation resistance descends, the brain tissue cell metabolism produces too much reactive oxygen free radical, thereby cause the degeneration and the minimizing of dopaminergic neuron, and finally cause reduction (the Przedborski S of dopamine level in the excretory minimizing of dopamine and the striatum, Jackson-Lewis V.Experimental developments in movement disorders:updateon proposed free radical mechanisms.Curr Opin Neurol, 1998,11 (4): 335-9).Up to now, also there is not a kind of medicine can slow down, stop even reverse neuronic degeneration process in the parkinson disease clinically.Thioredoxin plays an important role in Parkinsonian control.Studies show that: the high expressed of thioredoxin, exogenous thioredoxin give or the thioredoxin inducer can protect cell to avoid parkinson drug toxicity 1-methyl-4-phenyl-1 effectively; 2; 3; 6 tetrahydrochysene yl pyridines (1-methyl-4-phenyl-1; 2,3,6-tetrahydropyridine; MPTP) or 1-methyl-4-phenylpyridinium ion (1-methyl-4-phenylpyridinium ion, MPP
+) effect (Bai J, Nakamura H, HattoriI, Tanito M, Yodoi J.Thioredoxin suppresses 1-methyl-4-phenylpyridiniuminduced neurotoxicity in rat PC12 cells.Neurosci Lett.2002; 321 (1-2): 81-4; Bai J, Nakamura H, Kwon YW, Tanito M, Ueda S, Tanaka T, Hattori I, BanS, Momoi T, Kitao Y, Ogawa S, Yodoi J.Does thioredoxin-1 preventmitochondria-and endoplasmic reticulum-mediated neurotoxicity of1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine? Antioxid Redox Signal.2007May; 9 (5): 603-8.).Therefore, many research worker all begin to be devoted to seek the curative effect height, side effect is little, can induce thioredoxin to express the medicine that increases and be used for control and treatment parkinson disease, and wherein treatment by Chinese herbs has obtained to pay close attention to widely.
Radix Notoginseng has another name called Radix Notoginseng, Panax pseudoginseng, is araliaceae ginseng plant Panax notoginseng (Burk) F.H.Chen rhizome, is the valuable ingredient of Chinese medicine of China's special product, mainly originates in ground such as Yunnan, Guangxi.Radix Notoginseng total arasaponins is the main active of Radix Notoginseng, and pharmacological action is extensive, as has pharmacological actions such as resisting fatigue, raising hypoxia-bearing capability, blood sugar lowering, blood circulation promoting and blood stasis dispelling, human body immunity improving function, removing free radical, antiinflammatory, antioxidation.Further studies show that Radix Notoginseng in recent years: the effective ingredient in the Radix Notoginseng total arasaponins be the notoginseng triol saponins (Protopanaxatriol-type saponins from panax notoginseng, PTS).The notoginseng triol saponins is the live part that separation and Extraction goes out from Radix Notoginseng based on notoginseng triol type saponin Rg1.Up to the present, the medical usage of relevant notoginseng triol saponins mainly concentrates on the activating blood circulation to dissipate blood stasis (antithrombotic) of cardiovascular disease and improves on the partial pressure of oxygen, and it is had the effect that the thioredoxin expression increases in the inducing cell, and the application on control and treatment parkinson disease does not but appear in the newspapers.
Summary of the invention
The present invention is intended to seek the thioredoxin inducer to be used for Parkinsonian control and treatment.
Radix Notoginseng is the high traditional rare medicinal herbs of medical value, uses historical existing more than 600 year.Thereby the increase of pointing out us whether can induce thioredoxin to express to the composition notoginseng triol saponins that derives from Radix Notoginseng is explored, to widen the medicinal field of Radix Notoginseng.The result shows: the notoginseng triol saponins in SH-SY5Y cell and PC12 cell, can induce the increase that thioredoxin expresses (Fig. 1, Fig. 2); The Kunming kind white mice of injection notoginseng triol saponins, in the neurocyte of its cerebral cortex and hippocampus, the expression of thioredoxin all occur increasing significantly (Fig. 3, Fig. 4); The pretreated PC12 cell of notoginseng triol saponins can be resisted parkinson and poison thing MPP
+Effect (Fig. 5, Fig. 6).The increase that this explanation notoginseng triol saponins can induce thioredoxin to express can be used for Parkinsonian control and treatment.
Because increase and the application in control and treatment parkinson disease thereof that the notoginseng triol saponins induces thioredoxin to express are inventor's discoveries first; therefore; no matter be that the notoginseng triol saponins uses the medicament of making as active component separately; still utilize the anti-parkinson activity of notoginseng triol saponins to be used the medicament of making, all within the protection domain of this patent with other active component.
The present invention has proved that by following embodiment the increase that the notoginseng triol saponins can induce thioredoxin to express also can be used for Parkinsonian control and treatment, but is not limited only to these examples of implementation.
Description of drawings
Fig. 1 is the influence of notoginseng triol saponins (PTS) to Trx content in the PC12 cell.
Fig. 2 is the influence of notoginseng triol saponins (PTS) to Trx content in the SH-SY5Y cell.
Fig. 3 is the influence of notoginseng triol saponins (PTS) to Trx content in the mouse brain cortical neuron.
Fig. 4 is the influence of notoginseng triol saponins (PTS) to Trx content in the mouse brain hippocampus neuron.
Fig. 5 is that notoginseng triol saponins (PTS) is to MPP
+The antagonism of inducing the PC12 cell proliferation to reduce.
Fig. 6 is that notoginseng triol saponins (PTS) is to MPP
+The antagonism of inducing the PC12 cytoactive to reduce.
The specific embodiment
The specific embodiment of the present invention is described below, and still content of the present invention is finished and is not limited to this.
1. animal and cell
Kunming kind white mice: male, 6～8 Zhou Zhouling.Available from unming Medical College, all white mice quiet environment are raised, the feed of freely drinking water.
The PC12 cell: rat adrenal chromaffin oncocyte, available from Kunming animal institute of the Chinese Academy of Sciences.
The SH-SY5Y cell: the human neuroblastoma cell, available from Kunming animal institute of the Chinese Academy of Sciences.
2. medicine and main agents
The notoginseng triol saponins is provided by Kunming Medicine Group Stock Co., Ltd; 1-methyl 4 phenylpyridines (1-methyl-4-phenylpyridinium ion, MPP
+), available from Sigma company; One anti-Anti-mouseTrx and Anti-human Trx are provided by the professor of the molten department of shallow lake well of Kyoto Univ Japan; Protein Marker is available from Fermentas company; RPMI Medium 1640 and Minimum Essential Medium are available from Invitrogen corporation; Quantification of protein test kit (BCA method) is available from Beyotime company; Chemiluminesent substrate is available from the brilliant U.S. of biology company; Pvdf membrane is available from Millipore company; TRIS Base is available from NOVON company; Acrylamide is available from Solarbio company; Sodium lauryl sulphate is available from xiamen sanland chemicals company limited; Agarose, Coomassie brilliant blue R-250, Aprotimin, PMSF and NP-40 are all available from Sanland-chem International InC; TEMED is available from HUALVYUAN BIOTECHNOLOGY; X-ray film is available from Chinese Lekai Film Group Co; Two anti-affinity purified antibody peroxidase labled goat anti-mouselgG (H+L) HSA liquid conjugate and affinity purified antibody peroxidaselabled goat anti-rabbit lgG (H+L) HSAliquid conjugate are available from U.S. Kirkegaard﹠amp; Laboratories.Four tetrazolium bromides (MTT), lactic dehydrogenase enzyme detection kit are available from U.S. Promega company.
3. main experimental apparatus
BHC-1300II A/B3 Biohazard Safety Equipment, SuZhou Antai Air Tech Co., Ltd. produces; The TDL-40B desk centrifuge, Anting Scientific Instrument Factory, Shanghai produces; TS-1 decolorization swinging table, golden numerous city Jie Ruier Electrical Appliances Co., Ltd produces; Electronic analysis sky chessboard, Beijing Sai Duolisi instrument system company limited is produced; Vortex mixer, its woods Bel instrument Manufacturing Co., Ltd of Haimen City produces; Electrophresis apparatus during the BYY-6C bistable, Beijing 61 Instr Ltd. produce; The biological inverted phase contrast microscope of TS100, Japanese NIKON company produces; DYCP-31D horizontal strip electrophoresis groove, Beijing 61 Instr Ltd. produce; The CO2 incubator, U.S. NBS company produces; Microplate reader, U.S. MD company produces; The J-25 centrifuge, U.S. Beckman company produces; BG-transBLOT shifts core, and Beijing Baijing Biotechnology Co.,Ltd. produces; XJX-IIX shadowgraph camera obscura, the Shanghai medical optical instrument factory of making a leapleap forward produces.
Embodiment 1: the increase that thioredoxin is expressed in the notoginseng triol saponins inducing cell
(1) cell strain is cultivated and notoginseng triol saponins stimulation process
PC12 cell and SH-SY5Y cell be with 1640 culture medium that contain 10% hyclone, 100U/mL penicillin and 100 μ g/mL streptomycins, carries out adhere-wall culture under 37 ℃, 5% CO2 and 95% humidity.Changed culture medium in every 2-3 days once, cell reaches about 70%～80% when merging, and goes down to posterity or is used for experiment.
In flat board, after the overnight incubation, notoginseng triol group saponins is handled cell with cell inoculation.Packet transaction is as follows: not dosing of matched group, experimental group add 250 μ g/ml respectively, 500 μ g/ml, the notoginseng triol saponins of 1000 μ g/ml.After the above-mentioned processing, place 37 ℃ and 5% CO2 incubator to cultivate 24 hours, collecting cell then, extract albumen: centrifugal 1000rpm * 10min harvesting adds 80 microlitre cell pyrolysis liquid (150mM NaCl respectively, 0.5% NP-40,10mM Tris-HCl, pH7.2,0.1mM PMSF, 2ug/mlaprotinin, 200ug/ml NaN
3), fully placing cracking 40min (middle vibration 2～3 times) down in ice bath behind the suspendible, 4 ℃ of centrifugal 15min of following 15000rpm change supernatant to new centrifuge tube ,-80 ℃ of preservations.
(2) notoginseng triol saponins administration and organize method of drawing material
8 of male cleaning level Kunming kind white mice are divided into matched group and administration group (notoginseng triol saponins 100mg/kg) at random.The matched group intraperitoneal injection of saline, the medicine of the above-mentioned dosage of administration group lumbar injection once a day, continuous 7 days, will be got respective organization after it sudden death on the 8th day.
Organize method of drawing material: after the mice sudden death, carry out perfusion, get mouse brain cortex cerebral tissue and hippocampus cerebral tissue then respectively with normal saline, behind the liquid nitrogen freezing ,-80 ℃ of preservations.
Protein extraction: with the homogenate under ice bath of each cerebral tissue, and add an amount of cell pyrolysis liquid (150mM NaCl, 0.5% NP-40,10mM Tris-HCl, pH 7.2,0.1mM PMSF, 2 μ g/ml aprotinin, 200 μ g/mlNaN
3), to transfer to then in the centrifuge tube, ice bath is placed cracking 30min (middle vibration 2～3 times) down, and 4 ℃ of centrifugal 15min of following 15000rpm change supernatant to new centrifuge tube ,-80 ℃ of preservations.
(3) immunoblotting
1. the mensuration of protein content
Use the BCA kit measurement: 10 μ l standard substance or sample to be tested are mixed with the 200ulWR working solution, hatch 30min, reaction tube temperature is cooled to room temperature for 37 ℃.Measure the 562nm optical density value, the drawing standard curve, and calculate protein concentration.
2. protein immunoblot
Total protein application of sample amount is 7 μ g, after 2 * sds gel sample loading buffer mixes, and 95 ℃ of thermal denaturation 5min, the SDS-PAGE gel electrophoresis with 15% is transferred to the protein band electricity consumption on the pvdf membrane after separating, and spends the night with 4 ℃ of sealings of 5% skim milk; Take out pvdf membrane, after the TPBS flushing that contains 0.1% Tween-20, add an anti-incubated at room 75min of 2000 times of dilutions; With the TPBS flushing that contains 0.1% Tween-20, add two anti-incubated at room 75min of 5000 times of dilutions; Wash with the TPBS that contains 0.1% Tween-20, pvdf membrane is immersed in the luminous substrate solution react 1min, the X-ray film exposure.
Embodiment 2: notoginseng triol saponins neuroprotective cell avoids parkinson drug toxicity MPP
+Effect
(1) experiment grouping and processing
The initial density of cell is 5 * 10
4Cell/well.According to the different experiments requirement, be divided into following each group: (1) blank group: in cell culture system, do not add any medicine; (2) MPP
+Processed group: in cell culture system, only add 1mmol/L MPP
+(3) notoginseng triol saponins pretreated group: after adding notoginseng triol saponins (500ug/ml) pretreatment 4h earlier, add the MPP of 1mmol/L again
+Above-mentioned respectively organize cell and continue to cultivate 24h after, by different experiments requirement processing cell.Each group is established 4 parallel controls.
(2) detection method
1. four tetrazolium bromides (MTT) test
Take out 96 porocyte culture plates to be measured, every hole adds MTT solution (5mg/ml) 10 μ l, continue to hatch 4 hours after, every hole adds the aqueous isopropanol of 100 μ l 0.04N hydrochloric acid, after the mixing piping and druming 20～30 times, measure absorbance at wavelength 570nm place with microplate reader.
2. lactic acid dehydrogenase (LDH) method for releasing
Culture medium and intracellular lactic acid dehydrogenase content are measured with the LDH detection kit, and the mensuration process is carried out according to its description.
Claims (5)
1, a kind of Radix Notoginseng extract is characterized in that being the notoginseng triol saponins, can express increase by the interior thioredoxin of inducing cell.
2, the described Radix Notoginseng extract of claim 1 is characterized in that the application of described notoginseng triol saponins in preparation prevention and treatment parkinson disease medicine.
3, Radix Notoginseng extract according to claim 1 is characterized in that the notoginseng triol saponins is applied to fields such as the medicine relevant with the oxidative stress damage, medical treatment, health food.
4, Radix Notoginseng extract according to claim 1 is characterized in that the notoginseng triol saponins uses separately the medicament made as active component or is used the medicament made in the preparation prevention and treat application in the parkinson disease medicine with other active component.
5, Radix Notoginseng extract according to claim 1 is characterized in that: ginsenoside Rg l content is 49%～70% in the notoginseng triol saponins.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA2009100941875A CN101502547A (en) | 2009-03-11 | 2009-03-11 | Application of notoginseng extract in preparing medicament for preventing and treating parkinsonism |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA2009100941875A CN101502547A (en) | 2009-03-11 | 2009-03-11 | Application of notoginseng extract in preparing medicament for preventing and treating parkinsonism |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN101502547A true CN101502547A (en) | 2009-08-12 |
Family
ID=40975008
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNA2009100941875A Pending CN101502547A (en) | 2009-03-11 | 2009-03-11 | Application of notoginseng extract in preparing medicament for preventing and treating parkinsonism |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN101502547A (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105816495A (en) * | 2015-01-07 | 2016-08-03 | 上海交通大学医学院 | Traditional Chinese medicine compound extract product and application thereof |
| CN112552254A (en) * | 2020-12-18 | 2021-03-26 | 沈阳药科大学 | Phenanthrene compound and preparation method and application thereof |
| WO2021249237A1 (en) * | 2020-06-08 | 2021-12-16 | 中国科学院昆明植物研究所 | Triepoxyhexahydrochromone a, and pharmaceutical composition and use thereof |
-
2009
- 2009-03-11 CN CNA2009100941875A patent/CN101502547A/en active Pending
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105816495A (en) * | 2015-01-07 | 2016-08-03 | 上海交通大学医学院 | Traditional Chinese medicine compound extract product and application thereof |
| WO2021249237A1 (en) * | 2020-06-08 | 2021-12-16 | 中国科学院昆明植物研究所 | Triepoxyhexahydrochromone a, and pharmaceutical composition and use thereof |
| CN112552254A (en) * | 2020-12-18 | 2021-03-26 | 沈阳药科大学 | Phenanthrene compound and preparation method and application thereof |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP7174102B2 (en) | Compositions and methods for improving mitochondrial function and treating neurodegenerative diseases and cognitive disorders | |
| Wang et al. | Emerging roles of Ganoderma lucidum in anti-aging | |
| Choy et al. | Natural products targeting ER stress pathway for the treatment of cardiovascular diseases | |
| Subash et al. | Diet rich in date palm fruits improves memory, learning and reduces beta amyloid in transgenic mouse model of Alzheimer's disease | |
| Ding et al. | Soybean isoflavone alleviates β-amyloid 1-42 induced inflammatory response to improve learning and memory ability by down regulation of Toll-like receptor 4 expression and nuclear factor-κB activity in rats | |
| TWI700278B (en) | NOX inhibitor and NFκB inhibitor containing methoxyflavonoids | |
| Cano et al. | Targeting pro-senescence mitogen activated protein kinase (Mapk) enzymes with bioactive natural compounds | |
| Wu et al. | North American ginseng protects the heart from ischemia and reperfusion injury via upregulation of endothelial nitric oxide synthase | |
| Kwon et al. | Morus alba accumulates reactive oxygen species to initiate apoptosis via FOXO-caspase 3-dependent pathway in neuroblastoma cells | |
| Lin et al. | Bioactive peptides attenuate cardiac apoptosis in spontaneously hypertensive rat hearts through activation of autophagy and mitochondrial biogenesis pathway | |
| Liu et al. | Pyrroloquinoline quinone protects against exercise‐induced fatigue and oxidative damage via improving mitochondrial function in mice | |
| Xu et al. | Luteolin Inhibits Angiotensin II‐Stimulated VSMC Proliferation and Migration through Downregulation of Akt Phosphorylation | |
| Li et al. | Berberine relieves insulin resistance via the cholinergic anti-inflammatory pathway in HepG2 cells | |
| KR20160041105A (en) | Composition for Prevention or TreaADEnt of Rheumatoid Arthritis Comprising extract suspension of Allomyrina dichotoma | |
| CN101502547A (en) | Application of notoginseng extract in preparing medicament for preventing and treating parkinsonism | |
| KR101208198B1 (en) | Pharmaceutical composition for treating or preventing Parkinson's disease comprising compound having inhibitory effect of LRRK2 kinase activity | |
| Wang et al. | Quercetin can improve spinal cord injury by regulating the mTOR signaling pathway | |
| KR20170129281A (en) | Platelet-derived growth factor-bb production promoter, and mesenchymal stem cell production accelerator, stem cell stabilizer and dermal regenerator comprising the same | |
| KR20180130268A (en) | Composition for preventing, alleviating and treating neurodegenerative diseases comprising Sargassum honeri extracts | |
| Chou et al. | Involvement of p38 MAPK in the Anticancer Activity of Cultivated Cordyceps militaris | |
| AL-Jumaily | Evaluation of anticancer activities of crude extracts of Apium graveolens L. seeds in two cell lines, RD and L20B in vitro | |
| KR20130026976A (en) | Composition for improving obesity and fatty liver using an extract of leaves of sasa quelpaertensis or p-coumaric acid | |
| KR20160101732A (en) | Composition for preventing, improving or treating brain diseases comprising extract of vitis labruscana or quercetin-3-o-glucuronide isolated from the extract | |
| KR101470241B1 (en) | Pharmaceutical composition for the prevention or treatment of depression | |
| Hwang | Effects of MOK, a pharmacopuncture medicine, on the TH1/TH2 immune response and antioxidation in Con A-stimulated primary mouse splenocytes |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C12 | Rejection of a patent application after its publication | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20090812 |