KR20160084003A - Pharmaceutical composition for preventing or treating epithelial-mesenchymal transition related disease comprising red-ginseng extract - Google Patents
Pharmaceutical composition for preventing or treating epithelial-mesenchymal transition related disease comprising red-ginseng extract Download PDFInfo
- Publication number
- KR20160084003A KR20160084003A KR1020150000279A KR20150000279A KR20160084003A KR 20160084003 A KR20160084003 A KR 20160084003A KR 1020150000279 A KR1020150000279 A KR 1020150000279A KR 20150000279 A KR20150000279 A KR 20150000279A KR 20160084003 A KR20160084003 A KR 20160084003A
- Authority
- KR
- South Korea
- Prior art keywords
- red ginseng
- ginseng extract
- emt
- preventing
- pharmaceutical composition
- Prior art date
Links
- 235000002789 Panax ginseng Nutrition 0.000 title claims abstract description 98
- 230000007705 epithelial mesenchymal transition Effects 0.000 title claims abstract description 74
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 title claims abstract description 50
- 201000010099 disease Diseases 0.000 title claims abstract description 44
- 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 26
- 239000000203 mixture Substances 0.000 claims abstract description 24
- 235000013305 food Nutrition 0.000 claims abstract description 19
- 239000003814 drug Substances 0.000 claims abstract description 14
- 229940079593 drug Drugs 0.000 claims abstract description 12
- 230000000694 effects Effects 0.000 claims description 44
- 238000000034 method Methods 0.000 claims description 33
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 10
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 9
- 238000005194 fractionation Methods 0.000 claims description 8
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 8
- 206010016654 Fibrosis Diseases 0.000 claims description 7
- 230000004761 fibrosis Effects 0.000 claims description 7
- 239000003085 diluting agent Substances 0.000 claims description 6
- 239000004480 active ingredient Substances 0.000 claims description 5
- 239000002904 solvent Substances 0.000 claims description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 4
- 208000037819 metastatic cancer Diseases 0.000 claims description 3
- 208000011575 metastatic malignant neoplasm Diseases 0.000 claims description 3
- 238000004587 chromatography analysis Methods 0.000 claims description 2
- 239000012046 mixed solvent Substances 0.000 claims description 2
- 238000000108 ultra-filtration Methods 0.000 claims description 2
- 102000004495 STAT3 Transcription Factor Human genes 0.000 claims 1
- 108010017324 STAT3 Transcription Factor Proteins 0.000 claims 1
- 125000004432 carbon atom Chemical group C* 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- 230000001404 mediated effect Effects 0.000 claims 1
- 238000011161 development Methods 0.000 abstract description 8
- 230000002401 inhibitory effect Effects 0.000 abstract description 8
- 230000002159 abnormal effect Effects 0.000 abstract description 4
- 229940124597 therapeutic agent Drugs 0.000 abstract description 2
- 210000004027 cell Anatomy 0.000 description 47
- 230000014509 gene expression Effects 0.000 description 42
- UBQYURCVBFRUQT-UHFFFAOYSA-N N-benzoyl-Ferrioxamine B Chemical compound CC(=O)N(O)CCCCCNC(=O)CCC(=O)N(O)CCCCCNC(=O)CCC(=O)N(O)CCCCCN UBQYURCVBFRUQT-UHFFFAOYSA-N 0.000 description 37
- 229960000958 deferoxamine Drugs 0.000 description 37
- 206010009944 Colon cancer Diseases 0.000 description 29
- 206010028980 Neoplasm Diseases 0.000 description 22
- 201000011510 cancer Diseases 0.000 description 22
- 108020004999 messenger RNA Proteins 0.000 description 19
- 206010021143 Hypoxia Diseases 0.000 description 16
- 208000029742 colonic neoplasm Diseases 0.000 description 16
- 238000001262 western blot Methods 0.000 description 15
- 238000011282 treatment Methods 0.000 description 14
- 208000001333 Colorectal Neoplasms Diseases 0.000 description 13
- 101150047834 SNAI2 gene Proteins 0.000 description 13
- 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 description 13
- 239000000047 product Substances 0.000 description 13
- 241000237858 Gastropoda Species 0.000 description 12
- 101001046870 Homo sapiens Hypoxia-inducible factor 1-alpha Proteins 0.000 description 12
- 102100022875 Hypoxia-inducible factor 1-alpha Human genes 0.000 description 12
- 230000001146 hypoxic effect Effects 0.000 description 12
- 239000001301 oxygen Substances 0.000 description 12
- 229910052760 oxygen Inorganic materials 0.000 description 12
- 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 description 11
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 11
- 206010027476 Metastases Diseases 0.000 description 10
- 230000009401 metastasis Effects 0.000 description 10
- 108020004414 DNA Proteins 0.000 description 8
- 210000001519 tissue Anatomy 0.000 description 8
- 238000004458 analytical method Methods 0.000 description 7
- 230000018109 developmental process Effects 0.000 description 7
- 230000001965 increasing effect Effects 0.000 description 7
- 230000008569 process Effects 0.000 description 7
- 102000000905 Cadherin Human genes 0.000 description 6
- 108050007957 Cadherin Proteins 0.000 description 6
- 230000003247 decreasing effect Effects 0.000 description 6
- 238000009472 formulation Methods 0.000 description 6
- 210000002901 mesenchymal stem cell Anatomy 0.000 description 6
- 210000004748 cultured cell Anatomy 0.000 description 5
- 230000007954 hypoxia Effects 0.000 description 5
- 241000208340 Araliaceae Species 0.000 description 4
- 102100031181 Glyceraldehyde-3-phosphate dehydrogenase Human genes 0.000 description 4
- 235000005035 Panax pseudoginseng ssp. pseudoginseng Nutrition 0.000 description 4
- 235000003140 Panax quinquefolius Nutrition 0.000 description 4
- 239000002246 antineoplastic agent Substances 0.000 description 4
- 235000009508 confectionery Nutrition 0.000 description 4
- 230000013020 embryo development Effects 0.000 description 4
- 235000008434 ginseng Nutrition 0.000 description 4
- 108020004445 glyceraldehyde-3-phosphate dehydrogenase Proteins 0.000 description 4
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
- 239000000843 powder Substances 0.000 description 4
- 230000035755 proliferation Effects 0.000 description 4
- 210000000130 stem cell Anatomy 0.000 description 4
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 102100035071 Vimentin Human genes 0.000 description 3
- 108010065472 Vimentin Proteins 0.000 description 3
- 229940041181 antineoplastic drug Drugs 0.000 description 3
- 239000002775 capsule Substances 0.000 description 3
- 230000004069 differentiation Effects 0.000 description 3
- 101150042537 dld1 gene Proteins 0.000 description 3
- 239000000839 emulsion Substances 0.000 description 3
- 239000000945 filler Substances 0.000 description 3
- 229930182494 ginsenoside Natural products 0.000 description 3
- 239000008187 granular material Substances 0.000 description 3
- 230000006698 induction Effects 0.000 description 3
- 210000001161 mammalian embryo Anatomy 0.000 description 3
- 239000003550 marker Substances 0.000 description 3
- 230000007246 mechanism Effects 0.000 description 3
- 229930014626 natural product Natural products 0.000 description 3
- 235000012149 noodles Nutrition 0.000 description 3
- -1 olive oil Chemical compound 0.000 description 3
- 235000015277 pork Nutrition 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 230000002265 prevention Effects 0.000 description 3
- 235000021067 refined food Nutrition 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- 239000003826 tablet Substances 0.000 description 3
- 210000005048 vimentin Anatomy 0.000 description 3
- YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 2
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 2
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 2
- 244000144730 Amygdalus persica Species 0.000 description 2
- NLZUEZXRPGMBCV-UHFFFAOYSA-N Butylhydroxytoluene Chemical compound CC1=CC(C(C)(C)C)=C(O)C(C(C)(C)C)=C1 NLZUEZXRPGMBCV-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
- 241000283153 Cetacea Species 0.000 description 2
- 241000287828 Gallus gallus Species 0.000 description 2
- 108010010803 Gelatin Proteins 0.000 description 2
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
- 235000006040 Prunus persica var persica Nutrition 0.000 description 2
- 229920002472 Starch Polymers 0.000 description 2
- 229930006000 Sucrose Natural products 0.000 description 2
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 239000013543 active substance Substances 0.000 description 2
- 230000001093 anti-cancer Effects 0.000 description 2
- 235000015278 beef Nutrition 0.000 description 2
- 235000013361 beverage Nutrition 0.000 description 2
- 239000007844 bleaching agent Substances 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 235000014121 butter Nutrition 0.000 description 2
- 239000011575 calcium Substances 0.000 description 2
- 235000013339 cereals Nutrition 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 235000013330 chicken meat Nutrition 0.000 description 2
- 239000011651 chromium Substances 0.000 description 2
- 239000003086 colorant Substances 0.000 description 2
- 239000002299 complementary DNA Substances 0.000 description 2
- 239000010949 copper Substances 0.000 description 2
- 230000007423 decrease Effects 0.000 description 2
- 210000004443 dendritic cell Anatomy 0.000 description 2
- 239000000645 desinfectant Substances 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 230000032692 embryo implantation Effects 0.000 description 2
- 239000003995 emulsifying agent Substances 0.000 description 2
- 210000002919 epithelial cell Anatomy 0.000 description 2
- 210000000981 epithelium Anatomy 0.000 description 2
- 235000021107 fermented food Nutrition 0.000 description 2
- 230000008175 fetal development Effects 0.000 description 2
- 210000003754 fetus Anatomy 0.000 description 2
- 239000006260 foam Substances 0.000 description 2
- 235000003599 food sweetener Nutrition 0.000 description 2
- 235000013376 functional food Nutrition 0.000 description 2
- 229920000159 gelatin Polymers 0.000 description 2
- 239000008273 gelatin Substances 0.000 description 2
- 235000019322 gelatine Nutrition 0.000 description 2
- 235000011852 gelatine desserts Nutrition 0.000 description 2
- 235000020710 ginseng extract Nutrition 0.000 description 2
- 230000036541 health Effects 0.000 description 2
- 230000009067 heart development Effects 0.000 description 2
- 210000003494 hepatocyte Anatomy 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 239000003112 inhibitor Substances 0.000 description 2
- 208000028867 ischemia Diseases 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- 210000001542 lens epithelial cell Anatomy 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 239000011777 magnesium Substances 0.000 description 2
- 235000019359 magnesium stearate Nutrition 0.000 description 2
- 239000011572 manganese Substances 0.000 description 2
- 235000013336 milk Nutrition 0.000 description 2
- 239000008267 milk Substances 0.000 description 2
- 210000004080 milk Anatomy 0.000 description 2
- 235000013923 monosodium glutamate Nutrition 0.000 description 2
- 230000002107 myocardial effect Effects 0.000 description 2
- 210000000056 organ Anatomy 0.000 description 2
- 235000013324 preserved food Nutrition 0.000 description 2
- 238000012545 processing Methods 0.000 description 2
- 108090000623 proteins and genes Proteins 0.000 description 2
- 238000003753 real-time PCR Methods 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
- 230000012488 skeletal system development Effects 0.000 description 2
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 2
- GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 2
- 239000008107 starch Substances 0.000 description 2
- 235000019698 starch Nutrition 0.000 description 2
- 239000005720 sucrose Substances 0.000 description 2
- 239000000829 suppository Substances 0.000 description 2
- 239000000375 suspending agent Substances 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 239000003765 sweetening agent Substances 0.000 description 2
- 230000005062 synaptic transmission Effects 0.000 description 2
- 239000006188 syrup Substances 0.000 description 2
- 235000020357 syrup Nutrition 0.000 description 2
- 239000000454 talc Substances 0.000 description 2
- 229910052623 talc Inorganic materials 0.000 description 2
- 235000012222 talc Nutrition 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 230000017423 tissue regeneration Effects 0.000 description 2
- 210000005239 tubule Anatomy 0.000 description 2
- 239000000080 wetting agent Substances 0.000 description 2
- 230000029663 wound healing Effects 0.000 description 2
- VRYALKFFQXWPIH-RANCGNPWSA-N (3r,4s,5r)-3,4,5,6-tetrahydroxy-2-tritiohexanal Chemical compound O=CC([3H])[C@@H](O)[C@H](O)[C@H](O)CO VRYALKFFQXWPIH-RANCGNPWSA-N 0.000 description 1
- CHHHXKFHOYLYRE-UHFFFAOYSA-M 2,4-Hexadienoic acid, potassium salt (1:1), (2E,4E)- Chemical compound [K+].CC=CC=CC([O-])=O CHHHXKFHOYLYRE-UHFFFAOYSA-M 0.000 description 1
- VZSRBBMJRBPUNF-UHFFFAOYSA-N 2-(2,3-dihydro-1H-inden-2-ylamino)-N-[3-oxo-3-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)propyl]pyrimidine-5-carboxamide Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)C(=O)NCCC(N1CC2=C(CC1)NN=N2)=O VZSRBBMJRBPUNF-UHFFFAOYSA-N 0.000 description 1
- YLZOPXRUQYQQID-UHFFFAOYSA-N 3-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)-1-[4-[2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidin-5-yl]piperazin-1-yl]propan-1-one Chemical compound N1N=NC=2CN(CCC=21)CCC(=O)N1CCN(CC1)C=1C=NC(=NC=1)NCC1=CC(=CC=C1)OC(F)(F)F YLZOPXRUQYQQID-UHFFFAOYSA-N 0.000 description 1
- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 description 1
- FHVDTGUDJYJELY-UHFFFAOYSA-N 6-{[2-carboxy-4,5-dihydroxy-6-(phosphanyloxy)oxan-3-yl]oxy}-4,5-dihydroxy-3-phosphanyloxane-2-carboxylic acid Chemical compound O1C(C(O)=O)C(P)C(O)C(O)C1OC1C(C(O)=O)OC(OP)C(O)C1O FHVDTGUDJYJELY-UHFFFAOYSA-N 0.000 description 1
- 102100022900 Actin, cytoplasmic 1 Human genes 0.000 description 1
- 241000251468 Actinopterygii Species 0.000 description 1
- 108010085238 Actins Proteins 0.000 description 1
- 241001116389 Aloe Species 0.000 description 1
- 244000099147 Ananas comosus Species 0.000 description 1
- 235000007119 Ananas comosus Nutrition 0.000 description 1
- 206010005042 Bladder fibrosis Diseases 0.000 description 1
- 208000003174 Brain Neoplasms Diseases 0.000 description 1
- 206010006187 Breast cancer Diseases 0.000 description 1
- 208000026310 Breast neoplasm Diseases 0.000 description 1
- 102100032912 CD44 antigen Human genes 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- ZKQDCIXGCQPQNV-UHFFFAOYSA-N Calcium hypochlorite Chemical compound [Ca+2].Cl[O-].Cl[O-] ZKQDCIXGCQPQNV-UHFFFAOYSA-N 0.000 description 1
- 206010008342 Cervix carcinoma Diseases 0.000 description 1
- VYZAMTAEIAYCRO-UHFFFAOYSA-N Chromium Chemical compound [Cr] VYZAMTAEIAYCRO-UHFFFAOYSA-N 0.000 description 1
- 241001149724 Cololabis adocetus Species 0.000 description 1
- 208000035473 Communicable disease Diseases 0.000 description 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
- 241001137251 Corvidae Species 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- FBPFZTCFMRRESA-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
- 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
- FEWJPZIEWOKRBE-LWMBPPNESA-M D-tartrate(1-) Chemical compound OC(=O)[C@@H](O)[C@H](O)C([O-])=O FEWJPZIEWOKRBE-LWMBPPNESA-M 0.000 description 1
- 244000000626 Daucus carota Species 0.000 description 1
- 235000002767 Daucus carota Nutrition 0.000 description 1
- 206010012335 Dependence Diseases 0.000 description 1
- 102100031814 EGF-containing fibulin-like extracellular matrix protein 1 Human genes 0.000 description 1
- 101710176517 EGF-containing fibulin-like extracellular matrix protein 1 Proteins 0.000 description 1
- LVGKNOAMLMIIKO-UHFFFAOYSA-N Elaidinsaeure-aethylester Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC LVGKNOAMLMIIKO-UHFFFAOYSA-N 0.000 description 1
- 239000004386 Erythritol Substances 0.000 description 1
- UNXHWFMMPAWVPI-UHFFFAOYSA-N Erythritol Natural products OCC(O)C(O)CO UNXHWFMMPAWVPI-UHFFFAOYSA-N 0.000 description 1
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 1
- 239000004606 Fillers/Extenders Substances 0.000 description 1
- 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
- 206010019668 Hepatic fibrosis Diseases 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 101000868273 Homo sapiens CD44 antigen Proteins 0.000 description 1
- 208000013016 Hypoglycemia Diseases 0.000 description 1
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 1
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 1
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 1
- QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 description 1
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 1
- 240000007472 Leucaena leucocephala Species 0.000 description 1
- 235000010643 Leucaena leucocephala Nutrition 0.000 description 1
- 108060001084 Luciferase Proteins 0.000 description 1
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 244000070406 Malus silvestris Species 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- PWHULOQIROXLJO-UHFFFAOYSA-N Manganese Chemical compound [Mn] PWHULOQIROXLJO-UHFFFAOYSA-N 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- PKVZBNCYEICAQP-UHFFFAOYSA-N Mecamylamine hydrochloride Chemical compound Cl.C1CC2C(C)(C)C(NC)(C)C1C2 PKVZBNCYEICAQP-UHFFFAOYSA-N 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- 244000294411 Mirabilis expansa Species 0.000 description 1
- 235000015429 Mirabilis expansa Nutrition 0.000 description 1
- NIPNSKYNPDTRPC-UHFFFAOYSA-N N-[2-oxo-2-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)ethyl]-2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidine-5-carboxamide Chemical compound O=C(CNC(=O)C=1C=NC(=NC=1)NCC1=CC(=CC=C1)OC(F)(F)F)N1CC2=C(CC1)NN=N2 NIPNSKYNPDTRPC-UHFFFAOYSA-N 0.000 description 1
- AFCARXCZXQIEQB-UHFFFAOYSA-N N-[3-oxo-3-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)propyl]-2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidine-5-carboxamide Chemical compound O=C(CCNC(=O)C=1C=NC(=NC=1)NCC1=CC(=CC=C1)OC(F)(F)F)N1CC2=C(CC1)NN=N2 AFCARXCZXQIEQB-UHFFFAOYSA-N 0.000 description 1
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 1
- 206010061902 Pancreatic neoplasm Diseases 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 241000220324 Pyrus Species 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 108700005075 Regulator Genes Proteins 0.000 description 1
- 241000269821 Scombridae Species 0.000 description 1
- 239000004288 Sodium dehydroacetate Substances 0.000 description 1
- 239000005708 Sodium hypochlorite Substances 0.000 description 1
- 208000005718 Stomach Neoplasms Diseases 0.000 description 1
- 244000299461 Theobroma cacao Species 0.000 description 1
- 235000005764 Theobroma cacao ssp. cacao Nutrition 0.000 description 1
- 235000005767 Theobroma cacao ssp. sphaerocarpum Nutrition 0.000 description 1
- 108091023040 Transcription factor Proteins 0.000 description 1
- 102000040945 Transcription factor Human genes 0.000 description 1
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 1
- 208000006105 Uterine Cervical Neoplasms Diseases 0.000 description 1
- 208000002495 Uterine Neoplasms Diseases 0.000 description 1
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 1
- 241000219094 Vitaceae Species 0.000 description 1
- TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 description 1
- 240000008042 Zea mays Species 0.000 description 1
- 235000005824 Zea mays ssp. parviglumis Nutrition 0.000 description 1
- 235000002017 Zea mays subsp mays Nutrition 0.000 description 1
- BDKZHNJTLHOSDW-UHFFFAOYSA-N [Na].CC(O)=O Chemical compound [Na].CC(O)=O BDKZHNJTLHOSDW-UHFFFAOYSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 229940072056 alginate Drugs 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 235000011399 aloe vera Nutrition 0.000 description 1
- 229940024606 amino acid Drugs 0.000 description 1
- 235000001014 amino acid Nutrition 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 230000033115 angiogenesis Effects 0.000 description 1
- 230000002421 anti-septic effect Effects 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 235000006708 antioxidants Nutrition 0.000 description 1
- 229940064004 antiseptic throat preparations Drugs 0.000 description 1
- 235000021016 apples Nutrition 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 235000013405 beer Nutrition 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 229960002685 biotin Drugs 0.000 description 1
- 235000020958 biotin Nutrition 0.000 description 1
- 239000011616 biotin Substances 0.000 description 1
- 235000015895 biscuits Nutrition 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 235000008429 bread Nutrition 0.000 description 1
- 235000001046 cacaotero Nutrition 0.000 description 1
- 235000012970 cakes Nutrition 0.000 description 1
- 235000001465 calcium Nutrition 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 229910000019 calcium carbonate Inorganic materials 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 229910000389 calcium phosphate Inorganic materials 0.000 description 1
- 235000011010 calcium phosphates Nutrition 0.000 description 1
- 239000000378 calcium silicate Substances 0.000 description 1
- 229910052918 calcium silicate Inorganic materials 0.000 description 1
- 235000012241 calcium silicate Nutrition 0.000 description 1
- OYACROKNLOSFPA-UHFFFAOYSA-N calcium;dioxido(oxo)silane Chemical compound [Ca+2].[O-][Si]([O-])=O OYACROKNLOSFPA-UHFFFAOYSA-N 0.000 description 1
- 235000014171 carbonated beverage Nutrition 0.000 description 1
- 231100000504 carcinogenesis Toxicity 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 239000013592 cell lysate Substances 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 235000010980 cellulose Nutrition 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 201000010881 cervical cancer Diseases 0.000 description 1
- 235000013351 cheese Nutrition 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 229910052804 chromium Inorganic materials 0.000 description 1
- 235000020971 citrus fruits Nutrition 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 235000008504 concentrate Nutrition 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 235000005822 corn Nutrition 0.000 description 1
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 1
- 235000018417 cysteine Nutrition 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 239000003599 detergent Substances 0.000 description 1
- 239000008121 dextrose Substances 0.000 description 1
- 235000021186 dishes Nutrition 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- PXEDJBXQKAGXNJ-QTNFYWBSSA-L disodium L-glutamate Chemical compound [Na+].[Na+].[O-]C(=O)[C@@H](N)CCC([O-])=O PXEDJBXQKAGXNJ-QTNFYWBSSA-L 0.000 description 1
- 239000003651 drinking water Substances 0.000 description 1
- 235000020188 drinking water Nutrition 0.000 description 1
- 229940126534 drug product Drugs 0.000 description 1
- 230000001819 effect on gene Effects 0.000 description 1
- 229920001971 elastomer Polymers 0.000 description 1
- 210000002308 embryonic cell Anatomy 0.000 description 1
- 239000008393 encapsulating agent Substances 0.000 description 1
- UNXHWFMMPAWVPI-ZXZARUISSA-N erythritol Chemical compound OC[C@H](O)[C@H](O)CO UNXHWFMMPAWVPI-ZXZARUISSA-N 0.000 description 1
- 235000019414 erythritol Nutrition 0.000 description 1
- 229940009714 erythritol Drugs 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- LVGKNOAMLMIIKO-QXMHVHEDSA-N ethyl oleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC LVGKNOAMLMIIKO-QXMHVHEDSA-N 0.000 description 1
- 229940093471 ethyl oleate Drugs 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- 235000019688 fish Nutrition 0.000 description 1
- 229940014144 folate Drugs 0.000 description 1
- OVBPIULPVIDEAO-LBPRGKRZSA-N folic acid Chemical compound C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 OVBPIULPVIDEAO-LBPRGKRZSA-N 0.000 description 1
- 235000019152 folic acid Nutrition 0.000 description 1
- 239000011724 folic acid Substances 0.000 description 1
- 235000013373 food additive Nutrition 0.000 description 1
- 239000002778 food additive Substances 0.000 description 1
- 235000011194 food seasoning agent Nutrition 0.000 description 1
- 239000003205 fragrance Substances 0.000 description 1
- 235000019990 fruit wine Nutrition 0.000 description 1
- 235000011389 fruit/vegetable juice Nutrition 0.000 description 1
- 210000004211 gastric acid Anatomy 0.000 description 1
- 206010017758 gastric cancer Diseases 0.000 description 1
- 229930182470 glycoside Natural products 0.000 description 1
- 150000002338 glycosides Chemical class 0.000 description 1
- 235000021021 grapes Nutrition 0.000 description 1
- 201000008298 histiocytosis Diseases 0.000 description 1
- 230000002218 hypoglycaemic effect Effects 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 239000002917 insecticide Substances 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 235000015110 jellies Nutrition 0.000 description 1
- 150000002596 lactones Chemical class 0.000 description 1
- VMPHSYLJUKZBJJ-UHFFFAOYSA-N lauric acid triglyceride Natural products CCCCCCCCCCCC(=O)OCC(OC(=O)CCCCCCCCCCC)COC(=O)CCCCCCCCCCC VMPHSYLJUKZBJJ-UHFFFAOYSA-N 0.000 description 1
- 229940057995 liquid paraffin Drugs 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 201000007270 liver cancer Diseases 0.000 description 1
- 208000014018 liver neoplasm Diseases 0.000 description 1
- 244000144972 livestock Species 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 201000005202 lung cancer Diseases 0.000 description 1
- 208000020816 lung neoplasm Diseases 0.000 description 1
- 235000020640 mackerel Nutrition 0.000 description 1
- 229960003511 macrogol Drugs 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 description 1
- 239000000845 maltitol Substances 0.000 description 1
- 235000010449 maltitol Nutrition 0.000 description 1
- VQHSOMBJVWLPSR-WUJBLJFYSA-N maltitol Chemical compound OC[C@H](O)[C@@H](O)[C@@H]([C@H](O)CO)O[C@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O VQHSOMBJVWLPSR-WUJBLJFYSA-N 0.000 description 1
- 229940035436 maltitol Drugs 0.000 description 1
- 229910052748 manganese Inorganic materials 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
- 230000007721 medicinal effect Effects 0.000 description 1
- 229940126601 medicinal product Drugs 0.000 description 1
- HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 239000002480 mineral oil Substances 0.000 description 1
- 235000010446 mineral oil Nutrition 0.000 description 1
- 235000013536 miso Nutrition 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- LPUQAYUQRXPFSQ-DFWYDOINSA-M monosodium L-glutamate Chemical compound [Na+].[O-]C(=O)[C@@H](N)CCC(O)=O LPUQAYUQRXPFSQ-DFWYDOINSA-M 0.000 description 1
- 208000015122 neurodegenerative disease Diseases 0.000 description 1
- 229960003512 nicotinic acid Drugs 0.000 description 1
- 235000001968 nicotinic acid Nutrition 0.000 description 1
- 239000011664 nicotinic acid Substances 0.000 description 1
- 239000012457 nonaqueous media Substances 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 235000008390 olive oil Nutrition 0.000 description 1
- 239000004006 olive oil Substances 0.000 description 1
- 201000005443 oral cavity cancer Diseases 0.000 description 1
- 238000004806 packaging method and process Methods 0.000 description 1
- 201000002528 pancreatic cancer Diseases 0.000 description 1
- 208000008443 pancreatic carcinoma Diseases 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
- 238000007911 parenteral administration Methods 0.000 description 1
- 235000021017 pears Nutrition 0.000 description 1
- 210000005259 peripheral blood Anatomy 0.000 description 1
- 239000011886 peripheral blood Substances 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 239000002831 pharmacologic agent Substances 0.000 description 1
- 235000015108 pies Nutrition 0.000 description 1
- 239000000049 pigment Substances 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229920000136 polysorbate Polymers 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 229940050271 potassium alum Drugs 0.000 description 1
- GNHOJBNSNUXZQA-UHFFFAOYSA-J potassium aluminium sulfate dodecahydrate Chemical compound O.O.O.O.O.O.O.O.O.O.O.O.[Al+3].[K+].[O-]S([O-])(=O)=O.[O-]S([O-])(=O)=O GNHOJBNSNUXZQA-UHFFFAOYSA-J 0.000 description 1
- 239000004302 potassium sorbate Substances 0.000 description 1
- 235000010241 potassium sorbate Nutrition 0.000 description 1
- 229940069338 potassium sorbate Drugs 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002250 progressing effect Effects 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 1
- 229960003415 propylparaben Drugs 0.000 description 1
- 208000005069 pulmonary fibrosis Diseases 0.000 description 1
- 239000012264 purified product Substances 0.000 description 1
- 239000001397 quillaja saponaria molina bark Substances 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 201000002793 renal fibrosis Diseases 0.000 description 1
- 235000019992 sake Nutrition 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
- 229930182490 saponin Natural products 0.000 description 1
- 150000007949 saponins Chemical class 0.000 description 1
- 235000013580 sausages Nutrition 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 235000020083 shōchū Nutrition 0.000 description 1
- 239000000344 soap Substances 0.000 description 1
- WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 description 1
- 239000004299 sodium benzoate Substances 0.000 description 1
- 235000010234 sodium benzoate Nutrition 0.000 description 1
- 229960003885 sodium benzoate Drugs 0.000 description 1
- 235000019259 sodium dehydroacetate Nutrition 0.000 description 1
- 229940079839 sodium dehydroacetate Drugs 0.000 description 1
- 229940073490 sodium glutamate Drugs 0.000 description 1
- SUKJFIGYRHOWBL-UHFFFAOYSA-N sodium hypochlorite Chemical compound [Na+].Cl[O-] SUKJFIGYRHOWBL-UHFFFAOYSA-N 0.000 description 1
- 235000010288 sodium nitrite Nutrition 0.000 description 1
- 235000010265 sodium sulphite Nutrition 0.000 description 1
- DSOWAKKSGYUMTF-GZOLSCHFSA-M sodium;(1e)-1-(6-methyl-2,4-dioxopyran-3-ylidene)ethanolate Chemical compound [Na+].C\C([O-])=C1/C(=O)OC(C)=CC1=O DSOWAKKSGYUMTF-GZOLSCHFSA-M 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 235000010356 sorbitol Nutrition 0.000 description 1
- 235000014347 soups Nutrition 0.000 description 1
- 235000013555 soy sauce Nutrition 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 201000011549 stomach cancer Diseases 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000002511 suppository base Substances 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 230000008961 swelling Effects 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- JBQYATWDVHIOAR-UHFFFAOYSA-N tellanylidenegermanium Chemical compound [Te]=[Ge] JBQYATWDVHIOAR-UHFFFAOYSA-N 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 235000015193 tomato juice Nutrition 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 230000007704 transition Effects 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
- 206010046766 uterine cancer Diseases 0.000 description 1
- 239000004474 valine Substances 0.000 description 1
- MWOOGOJBHIARFG-UHFFFAOYSA-N vanillin Chemical compound COC1=CC(C=O)=CC=C1O MWOOGOJBHIARFG-UHFFFAOYSA-N 0.000 description 1
- FGQOOHJZONJGDT-UHFFFAOYSA-N vanillin Natural products COC1=CC(O)=CC(C=O)=C1 FGQOOHJZONJGDT-UHFFFAOYSA-N 0.000 description 1
- 235000012141 vanillin Nutrition 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 235000019155 vitamin A Nutrition 0.000 description 1
- 239000011719 vitamin A Substances 0.000 description 1
- 235000015041 whisky Nutrition 0.000 description 1
- 239000000811 xylitol Substances 0.000 description 1
- 235000010447 xylitol Nutrition 0.000 description 1
- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 description 1
- 229960002675 xylitol Drugs 0.000 description 1
- 235000013618 yogurt Nutrition 0.000 description 1
Images
Classifications
-
- 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)
- A61K36/25—Araliaceae (Ginseng family), e.g. ivy, aralia, schefflera or tetrapanax
- A61K36/258—Panax (ginseng)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/04—Antineoplastic agents specific for metastasis
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2200/00—Function of food ingredients
- A23V2200/30—Foods, ingredients or supplements having a functional effect on health
Abstract
The present invention relates to a pharmaceutical composition, a quasi-drug, and a food composition for preventing or treating epithelial-mesenchymal transition-related diseases including red ginseng extract or fractions thereof capable of inhibiting epithelial-mesenchymal transition (EMT) . The use of the pharmaceutical composition of the present invention can safely prevent or treat diseases caused by abnormal EMT in the adult body, and thus can be widely used for the development of therapeutic agents for various diseases caused by EMT.
Description
The present invention relates to a pharmaceutical composition for the prevention or treatment of epithelial-mesenchymal transition-related diseases including red ginseng extract. More particularly, the present invention relates to a pharmaceutical composition for inhibiting epithelial-mesenchymal transition (EMT) The present invention also relates to pharmaceutical compositions, quasi-drugs and food compositions for preventing or treating epithelial-mesenchymal transition-related diseases comprising red ginseng extract or fractions thereof.
Mesenchymal stem cells are known to be present in adult as well as embryonic cells, which can be differentiated into various tissue cells. Recently, studies on such stem cells have been actively conducted. These mesenchymal stem cells can be converted into epithelial cells by a unique process called epithelial-mesenchymal transition (EMT) / mesenchymal-epithelial transition (MET) It is known that EMT is not only a process that is essential for the formation of various tissues or organs of a fetus by the differentiation process at the development stage but also a process that is essentially performed in processes such as wound healing and tissue regeneration in the adult have. There are three known effects of EMT in vivo. First, it is involved in embryo implantation, embryogenesis, embryogenesis, neurotransmission, heart, and skeletal development in normal fetal development. In general, it occurs in the stage of development of the embryo. Second, it induces fibrosis of tissues in the renal tubules, lens epithelial cells, hepatocytes, dendritic cells, myocardial cells and the like. Third, it plays an important role in the metastasis of cancer, the generation of cancer stem cells, and the induction of tolerance to anticancer drugs, and it occurs in cancer-related diseases such as cancer metastasis. Particularly, since the above-mentioned third type is found in cancer-related diseases, it is expected that when the EMT process is inhibited at the onset of the cancer disease, the onset of the disease can be prevented or treated early, It is progressing. For example, WO2009-067429 discloses a method of treating cancer by blocking EMT using a monoclonal antibody that binds to? 2 and blocks the binding of? 2 to Notch1, Korean Patent Publication No. 2013-0015669 discloses a method of treating cancer Discloses a method for inhibiting proliferation, differentiation, or metastasis of cancer stem cells by inhibiting EMT using 2-Deoxy-D-glucose, Korean Patent Laid-Open Publication No. 2014-0062724 Korean Patent Laid-Open Publication No. 2014-0089234 discloses a method for suppressing EMT by inhibiting EMT using fibulin-3 protein, and Korean Patent Laid-Open Publication No. 2014-0089234 discloses a method for inhibiting the expression of a CD44 promoter and a luciferase gene operably linked thereto Discloses a method of screening a drug for EMT inhibition using a recombinant vector for EMT monitoring. However, most of the methods thus far developed are directed to a method for preventing or treating cancer metastasis, proliferation, etc. by inhibiting EMT by using a specific compound, and it is disadvantageous in that it is accompanied by mild or serious side effects similar to other anticancer drugs The development of safer EMT inhibitors is required.
On the other hand, red ginseng has been used as a medicinal product derived from natural products prepared by drying ginseng containing various pharmacologically active ingredients such as saponin, and has been used for treatment of various symptoms from whales in Korea and other Far East Asian countries. Recently, research on various ginsenosides contained in ginseng or red ginseng has been conducted. As a result, ginsenosides contained in ginseng or red ginseng have been identified as glycosides. In particular, in the case of red ginseng, Rg3 Of ginsenosides were found to be significantly higher than that of ginseng. The red ginseng is known to exhibit excellent anticancer activity that inhibits the development, proliferation and metastasis of cancer cells. Studies on the specific action mechanism exhibiting such anticancer activity have also been actively conducted, and some action mechanisms have been clarified. However, The mechanism was not known at all.
Under these circumstances, the inventors of the present invention have made intensive researches on various natural products in order to develop a formulation that can inhibit EMT more safely and effectively, and as a result, the extract of red ginseng can effectively inhibit EMT, Prevention or treatment of cancer, and completed the present invention.
It is an object of the present invention to provide a pharmaceutical composition for preventing or treating epithelial-mesenchymal transition-related diseases including red ginseng extract or fractions thereof capable of inhibiting epithelial-mesenchymal transition (EMT) .
Another object of the present invention is to provide a quasi-drug for preventing or treating EMT-related diseases including the red ginseng extract or fractions thereof.
It is another object of the present invention to provide a food composition for preventing or ameliorating an EMT-related disease comprising the red ginseng extract or a fraction thereof.
The present inventors have focused on red ginseng while carrying out various studies on various natural products in order to develop a formulation which can safely and effectively inhibit EMT. The red ginseng is known to exhibit the effects of preventing, treating, alleviating, and improving various diseases in a herbal or folk remedy from whales. In particular, it has an effect of preventing or treating cancer, proliferation and metastasis of various cancer diseases . The present inventors tried to confirm whether or not the red ginseng extract can inhibit the progression of EMT, which is a cause of degenerative diseases such as various tissue fibrosis, in addition to the above-mentioned cancer diseases. As a result, it was found that the red ginseng extract inhibits the expression of ischemia-related genes in hypoxic conditions that can induce the progression of EMT, and inhibits the expression of cadherin, which is an indicator for confirming the progression of EMT, And Slug gene expression, increase the expression of the CAD headrin, and decrease the expression level of virimentin, a marker of mesenchymal stem cells.
Therefore, the present inventors confirmed that the red ginseng extract can inhibit the progression of EMT induced by hypoxia, and the effect of such red ginseng extract has not been reported in the prior art, and was first identified by the present inventors.
In one aspect, the present invention provides a pharmaceutical composition for preventing or treating epithelial-mesenchymal transition (EMT) -related diseases comprising red ginseng extract or a fraction thereof.
The term "epithelial-mesenchymal transition (EMT)" of the present invention means the transformation of epithelial cells into mesenchymal stem cells in the embryo or adult body. The EMT is not only a process that is essentially performed to form various tissues or organs of the fetus by the differentiation process in the development stage, but is also known to be an essential process performed in processes such as wound healing and tissue regeneration in the adult. There are three known effects of EMT in vivo. First, it is involved in embryo implantation, embryogenesis, embryogenesis, neurotransmission, heart, and skeletal development in normal fetal development. In general, it occurs in the stage of development of the embryo. Second, it induces fibrosis of tissues in the renal tubules, lens epithelial cells, hepatocytes, dendritic cells, myocardial cells and the like. Third, it plays an important role in the metastasis of cancer, the generation of cancer stem cells, and the induction of tolerance to anticancer drugs, and it occurs in cancer-related diseases such as cancer metastasis.
The term " epithelial-mesenchymal transition (EMT) -related disease "of the present invention means a disease caused by abnormal induction of the EMT to convert normal epithelium into mesenchymal stem cells.
In the present invention, the EMT-related diseases include, but are not limited to, histiocytosis or metastatic cancer diseases caused by abnormal EMT, and more preferably, hepatic fibrosis, pulmonary fibrosis, Various fibrosis such as fibrosis, oral mucosal fibrosis, bladder fibrosis, renal fibrosis; Or a metastatic cancer disease caused by metastasis of breast cancer, lung cancer, colon cancer, brain cancer, liver cancer, oral cavity cancer, uterine cancer, cervical cancer, pancreatic cancer, stomach cancer and the like.
The term "red ginseng extract" of the present invention means an extract obtained by extracting red ginseng. For the purpose of the present invention, red ginseng extract is preferably selected from the group consisting of ethyl acetate, water, (Methanol, ethanol, butanol, etc.) or a mixed solvent thereof, more preferably a solvent such as ethyl acetate, ethanol or the like, most preferably ethanol as a solvent, but is not limited thereto The resultant product includes all of the extract, the diluted solution or concentrate of the extract, the dried product obtained by drying the extract, or the adjusted product or the purified product.
The term "fraction " of the present invention means a product obtained by a fractionation method for separating a specific component or a specific group from a mixture containing various constituents. In the present invention, the red ginseng extract may preferably be obtained by fractionation by various methods such as a solvent fractionation method, an ultrafiltration fractionation method, and a chromatography fractionation method.
According to one embodiment of the present invention, red ginseng extract inhibits the expression of an ischemia-related gene that is induced to develop in a hypoxic state capable of inducing the progression of EMT (FIG. 1) (Fig. 2) inhibits the expression of Snail and Slug genes, which are regulatory genes for suppressing the expression of horseradin (Fig. 2), thereby increasing the expression of CAD-headrin and decreasing the level of expression of visemen, a marker of mesenchymal stem cells (Fig. 3).
The pharmaceutical compositions of the present invention may further comprise suitable carriers, excipients or diluents conventionally used in the manufacture of pharmaceutical compositions. Specifically, the pharmaceutical composition may be formulated in the form of powders, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols and the like, oral preparations, suppositories and sterilized injection solutions according to a conventional method . In the present invention, the carrier, excipient and diluent which may be contained in the pharmaceutical composition include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia rubber, alginate, gelatin, calcium phosphate, Calcium silicate, cellulose, methylcellulose, microcrystalline cellulose, polyvinylpyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil. In the case of formulation, a diluent or excipient such as a filler, an extender, a binder, a wetting agent, a disintegrant, or a surfactant is usually used. Solid formulations for oral administration include tablets, pills, powders, granules, capsules and the like, which may contain at least one excipient such as starch, calcium carbonate, Sucrose, lactose, gelatin and the like. In addition to simple excipients, lubricants such as magnesium stearate and talc are also used. Liquid preparations for oral use may include various excipients such as wetting agents, sweetening agents, fragrances, preservatives, etc. in addition to water and liquid paraffin, which are simple diluents commonly used in suspension agents, solutions, emulsions and syrups have. Formulations for parenteral administration include sterilized aqueous solutions, non-aqueous solutions, suspensions, emulsions, freeze-dried preparations, and suppositories. Examples of the suspending agent include propylene glycol, polyethylene glycol, vegetable oil such as olive oil, injectable ester such as ethyl oleate, and the like. Examples of the suppository base include witepsol, macrogol, tween 61, cacao butter, laurin, glycerogelatin and the like.
The content of the red ginseng extract or its fraction contained in the pharmaceutical composition for preventing or treating EMT-related diseases of the present invention is not particularly limited, but is preferably 0.0001 to 50% by weight, more preferably 0.01 to 50% by weight, May be contained in an amount of 20% by weight.
The pharmaceutical composition of the present invention can be administered in a pharmaceutically effective amount. The term "pharmaceutically effective amount " of the present invention means a therapeutic or prophylactic treatment of a disease at a reasonable benefit / risk ratio applicable to medical treatment or prevention And the effective dose level refers to the level of the disease to be treated, the severity of the disease, the activity of the drug, the age, body weight, health, sex, sensitivity of the patient to the drug, Duration, duration of administration, factors involved in combination with or contemporaneously with the composition of the present invention, and other factors well known in the medical arts. The pharmaceutical composition of the present invention can be administered alone or in combination with known anti-cancer agents. It is important to take into account all of the above factors and administer an amount that will achieve the maximum effect in the least amount without side effects.
The dosage of the pharmaceutical composition of the present invention can be determined by those skilled in the art in consideration of the purpose of use, the degree of addiction to the disease, the age, body weight, sex, history, or kind of the substance used as the active ingredient. For example, the pharmaceutical composition of the present invention may be administered at about 0.1 ng to about 100 mg / kg, preferably 1 ng to about 10 mg / kg, per adult, and the frequency of administration of the composition of the present invention is particularly It is not limited, but it can be administered once a day or divided into several doses. The dose is not intended to limit the scope of the invention in any way.
In another aspect of the present invention, there is provided a method for treating an EMT-related disease, comprising administering the pharmaceutical composition to a subject other than a human suffering from an EMT-related disease in a pharmaceutically effective amount do.
The term "individual" of the present invention includes, but is not limited to, mammals including, but not limited to, rats, livestock,
In the method for treating an EMT-related disease of the present invention, the EMT-related disease to be treated is the same as described above.
In the method of treating an EMT-related disease of the present invention, the administration route of the pharmaceutical composition may be administered through any ordinary route as long as it can reach the target tissue. The pharmaceutical composition of the present invention is not particularly limited, but may be administered by intraperitoneal administration, intravenous administration, intramuscular administration, subcutaneous administration, intradermal administration, oral administration, intranasal administration, intrapulmonary administration, rectal administration and the like ≪ / RTI > However, since the red ginseng extract or its fractions may be denatured by gastric acid when orally administered, the oral composition should be formulated so as to coat the active agent or protect it from decomposition at the top. In addition, the composition may be administered by any device capable of transferring the active agent to the target cell.
As another embodiment for achieving the above object, the present invention provides a quasi-drug composition for preventing or treating EMT-related diseases comprising the red ginseng extract or its fractions as an active ingredient.
The term "quasi-drug product" used in the present invention means products that are less active than drugs, among the products used for diagnosing, treating, improving, alleviating, treating or preventing diseases of human or animal. For example, The quasi-quasi-drug means a product that is used for the treatment of diseases of humans and animals, except for the products used for medicines, which are slightly or not directly acting on the human body, , And sterilization and insecticides to prevent infectious diseases. The type and formulations of the quasi-drug composition of the present invention are not particularly limited, but may be disinfectant cleaner, shower foam, gagrin, wet tissue, detergent soap, hand wash, humidifier filler, mask, ointment or filter filler.
In another aspect of the present invention, there is provided a food composition for preventing or ameliorating an EMT-related disease comprising the red ginseng extract or a fraction thereof.
Since the red ginseng extract has been used for a long time as a medicinal or food resource and its safety has been proved, the red ginseng extract or its fractions can be prepared in the form of food which can be common but can prevent or improve EMT related diseases . At this time, the content of the red ginseng extract or its fraction contained in the food is not particularly limited, but may be in the range of 0.001 to 10% by weight, more preferably 0.1 to 1% by weight based on the total weight of the food composition. When the food is a beverage, it may be contained in a proportion of 1 to 10 g, preferably 2 to 7 g based on 100 ml. In addition, the composition may contain additional ingredients which are commonly used in food compositions and which can improve odor, taste, vision and the like. For example, vitamins A, C, D, E, B1, B2, B6, B12, niacin, biotin, folate, panthotenic acid and the like. In addition, it may include minerals such as zinc (Zn), iron (Fe), calcium (Ca), chromium (Cr), magnesium (Mg), manganese (Mn) and copper (Cu) It may also include amino acids such as lysine, tryptophan, cysteine, valine, and the like. In addition, it is also possible to use antiseptics (such as potassium sorbate, sodium benzoate, salicylic acid, and sodium dehydroacetate), disinfectants (such as bleaching powder and highly bleached white powder, sodium hypochlorite), antioxidants (butylhydroxyanilide (BHA), butylhydroxytoluene BHT), etc.), coloring agents (such as tar pigments), coloring agents (such as sodium nitrite and sodium acetic acid), bleaching agents (sodium sulfite), seasoning (such as MSG sodium glutamate), sweeteners (such as hypoglycemia, , Food additives such as flavorings (vanillin, lactones, etc.), swelling agents (alum, potassium hydrogen D-tartrate), emulsifiers, emulsifiers, thickeners, encapsulating agents, gum bases, foam inhibitors, ) Can be added. The additives are selected according to the type of food and used in an appropriate amount.
Meanwhile, a food composition containing the red ginseng extract or its fractions can be used to produce a functional food for preventing or ameliorating an EMT-related disease.
As a specific example, the food composition can be used to produce processed foods that can prevent or improve EMT-related diseases. Such processed foods include, for example, confectionery, drinks, liquor, fermented foods, canned foods, processed milk products, processed marine foods, noodles and the like. The sweets include biscuits, pies, cakes, breads, candies, jellies, gums, cereals (including dinner utensils such as cereal flakes). Drinks include drinking water, carbonated beverages, functional ionic beverages, juices (such as apples, pears, grapes, aloes, citrus fruits, peaches, carrots, tomato juices, etc.) and sikhye. The mainstream includes sake, whiskey, shochu, beer, liquor, and fruit wine. Fermented foods include soy sauce, miso, and kochujang. Canned products include canned products (eg, tuna, mackerel, saury, canned fish, etc.), canned products (canned beef, pork, chicken, turkey canned food) and canned products (corn, peach and canned pineapple). Milk processed foods include cheese, butter, yogurt and the like. Meat-processed foods include pork cutlet, beef cutlet, chicken cutlet, sausage. Sweet and sour pork, nuggets, and nubani. And noodles such as sealed packaging raw noodles. In addition, the composition may be used in retort food, soup and the like.
The term "functional food " of the present invention is the same term as " food for special health use (FoSHU) ", and includes medical and medical effects The food may be prepared in various forms such as tablets, capsules, powders, granules, liquids, rings and the like in order to obtain a useful effect for preventing or improving diseases caused by active oxygen.
The use of the pharmaceutical composition of the present invention can safely prevent or treat diseases caused by abnormal EMT in the adult body, and thus can be widely used for the development of therapeutic agents for various diseases caused by EMT.
FIG. 1A is a Western blot analysis image showing the effect of red ginseng extract on the expression of HIF-1α protein under hypoxic or normal oxygen conditions in a colon cancer cell line (HCT116). FIG.
FIG. 1B is a Western blot analysis image showing the effect of red ginseng extract on the expression of HIF-1α protein under hypoxic or normal oxygen conditions in a colon cancer cell line (HT29).
FIG. 1C is a western blot analysis image showing the effect of red ginseng extract on the expression of HIF-1α protein under the condition of treating DFO in colon cancer cell line (HCT116). FIG.
FIG. 1D is a graph showing the effect of red ginseng extract on the mRNA level of VEGF in the presence of DFO treated with a colorectal cancer cell line (HCT116), wherein DFO + 1RG is an experimental group treated with 1 mg / , And DFO + 2RG represents an experimental group treated with 2 mg / ml of red ginseng extract.
FIG. 1E is a graph showing the effect of red ginseng extract on the mRNA level of VEGF in the treatment of DFO in colorectal cancer cell line (HT29). DFO + 1RG is an experimental group treated with 1 mg / ml of red ginseng extract , And DFO + 2RG represents an experimental group treated with 2 mg / ml of red ginseng extract.
FIG. 2A is a graph showing the results of analysis of the effect of red ginseng extract on the mRNA level of snail under the condition of treating DFO with colorectal cancer cell line (HCT116).
FIG. 2B is a graph showing the results of analysis of the effect of red ginseng extract on snail mRNA levels under conditions of DFO treatment of colorectal cancer cell line (HT29).
FIG. 2C is a graph showing the results of analysis of the effect of red ginseng extract on the mRNA level of Slug under the condition of treating DFO with colon cancer cell line (HCT116). FIG.
FIG. 2d is a graph showing the results of analysis of the effect of red ginseng extract on the mRNA level of Slug under conditions in which DFO was treated in colon cancer cell line (HT29).
FIG. 3A is a western blot analysis image showing the effect of red ginseng extract on the expression level of the cadherin in a condition in which the colorectal cancer cell line (HCT116) was treated with DFO.
FIG. 3B is a Western blot analysis image showing the effect of red ginseng extract on the expression level of CADHERN under the condition of treating DOLF with a colorectal cancer cell line (DLD1).
FIG. 3c is a Western blot analysis image showing the effect of red ginseng extract on the expression level of Vimentin in the condition of treatment with DFO in colon cancer cell line (HT29).
Hereinafter, the present invention will be described in more detail with reference to examples. However, these examples are for illustrative purposes only, and the scope of the present invention is not limited to these examples.
Example
One:
At hypoxic
Effect of red ginseng extract on induced gene expression
When cancer cells proliferate at a high rate, the oxygen supply is not smooth, and angiogenesis of peripheral blood vessels occurs. Nonetheless, hypoxia appears in the center of cancer cells as oxygen supply decreases. It is known that such hypoxic environment acts as an important cause of cancer cell metastasis and therapeutic resistance. Therefore, the effect of red ginseng extract on the hypoxia-induced HIF-1α protein and VEGF expression level was investigated.
Example 1-1: Expression level of HIF-1α protein in colon cancer cell line cultured in hypoxic condition Effect of Korean red ginseng extract
The colon cancer cell line (HCT116 or HT29) was inoculated into a culture vessel at 1 × 10 6 cells, treated with various concentrations of red ginseng extract (0, 0.5, 1 or 2 mg / For 24 hours (HCT116) or 48 hours (HT29). After completion of the cultivation, the wastes of each cultured cell were subjected to Western blot analysis using an anti-HIF-1α antibody (FIGS. 1A and 1B). At this time, as a control group, cells cultured while supplying normal oxygen (21%) without using red ginseng were used.
FIG. 1A is a Western blot image showing the effect of red ginseng extract on the expression of HIF-1α protein under hypoxic or normal oxygen conditions in a colon cancer cell line (HCT116). FIG. This is a western blot analysis showing the effect of red ginseng extract on the expression of HIF-1α protein under hypoxic or normal oxygen conditions. As shown in FIGS. 1A and 1B, it was confirmed that the expression level of HIF-1α protein decreased as the concentration of red ginseng extract treated in a low-oxygen state was increased.
Example 1-2: Expression level of HIF-1α protein in DFO (deferoxamine) -treated colon cancer cell line Effect of Korean red ginseng extract
Colon cancer cell line (HCT116) was inoculated into a culture vessel at a density of 1 × 10 6 cells, and a 200 μM DFO (Deferoxamine), which is a hypoxic condition-simulating agent, and red ginseng of various concentrations (0, 0.01, 0.1 or 1 mg / The extract was treated and incubated for 48 hours. After completion of the cultivation, the wastes of each cultured cell were subjected to Western blot analysis using an anti-HIF-1α antibody (FIG. 1C). At this time, as a control group, cells cultured while supplying normal oxygen (21%) without using red ginseng were used.
FIG. 1C is a western blot analysis image showing the effect of red ginseng extract on the expression of HIF-1α protein under the condition of treating DFO in colon cancer cell line (HCT116). FIG. As shown in FIG. 1C, it was confirmed that the expression level of HIF-1α protein decreased as the concentration of red ginseng extract treated with DFO increased.
Example 1-3: Expression level of VEGF in DFO (Deferoxamine) -treated colorectal cancer cell line Effect of Korean red ginseng extract
Colorectal cancer cell line (HCT116 or HT29) to 1
VEGF F: 5'-ATC TTC AAG CCA TCC TGT GTG C-3 '(SEQ ID NO: 1)
VEGF R: 5'-CAA GGC CCA CAG GGA TTT TC-3 '(SEQ ID NO: 2)
GAPDH F: 5'-AGG TCG GAG TCA ACG GAT TTG G-3 '(SEQ ID NO: 3)
GAPDH R: 5'-ACA GTC TTC TGG GTG GCA GTG ATG-3 '(SEQ ID NO: 4)
FIG. 1D is a graph showing the results of analysis of the effect of red ginseng extract on the mRNA level of VEGF in a condition in which DFO was treated with a colorectal cancer cell line (HCT116). FIG. DFO + 1RG was treated with 1 mg / ml of red ginseng extract and DFO + 2RG was treated with 2 mg / ml of red ginseng extract. Treated group. As shown in FIGS. 1d and 1e, when the DFO was treated alone, the mRNA level of VEGF was rapidly increased. However, when the red ginseng extract was treated, the mRNA level of VEGF was decreased depending on the treatment concentration of red ginseng extract Respectively.
Therefore, the results of Examples 1-1 to 1-3 above indicate that the red ginseng extract inhibits hypoxia-induced HIF-1α protein and VEGF expression.
Example
2: Red ginseng extract has epithelium -
Liver
The effect on the expression of the conversion marker
In order to evaluate the effect of red ginseng extract on epithelial-mesenchymal transition (EMT) induced by cancer cells under hypoxic condition, Snail and Slug, which are transcription factors that increase expression level during epithelial-mesenchymal transition, The effect of red ginseng extract on the expression levels of E-caherin and Vimentin in which the expression level is regulated was examined.
Example
2-1:
Hypoxia
The red ginseng extract
Snail
And
Slug
Effect on gene expression level
Colorectal cancer cell line (HCT116 or HT29) to 1
Snail F: 5'-CCC CAACTCG GAA GCC TAA CT-3 '(SEQ ID NO: 5)
Snail R: 5'-GCT GGA AGG TAA ACT CTG GAT TAG A-3 '(SEQ ID NO: 6)
Slug F: 5'-ACG CCC AGC TAC CCA ATG-3 '(SEQ ID NO: 7)
Slug R: 5'-CGC CCC AAA GAT GAG GAG TA-3 '(SEQ ID NO: 8)
FIG. 2A is a graph showing the results of analysis of the effect of red ginseng extract on mRNA level of snail under the condition that DFO was treated with a colorectal cancer cell line (HCT116). FIG. 2B is a graph showing the effect of DFO treatment on colorectal cancer cell line FIG. 2C is a graph showing the effect of red ginseng extract on the mRNA level of snails. FIG. 2C is a graph showing the effect of red ginseng extract on slug mRNA levels in DFO-treated colon cancer cell line (HCT116) And FIG. 2d is a graph showing the results of analysis of the effect of red ginseng extract on the mRNA level of Slug under the condition of treating DFO in the colon cancer cell line (HT29). As shown in FIGS. 2A to 2D, when the DFO was treated alone, mRNA levels of Snail and Slug were rapidly increased. However, when the red ginseng extract was treated, the mRNA levels of Snail and Slug were dependent on the treatment concentration of red ginseng extract .
Example
2-2:
Under hypoxic conditions
Red ginseng extract
Cadherin
(E-
caherin
) And visentin (
Vimentin
Effect on expression level
Colon cancer cell lines (HCT116, DLD1 or HT29) were inoculated into culture dishes at 1 × 10 6 cells, treated with 50 μM DFO and various concentrations of red ginseng (0, 0.5, 1 or 2 mg / (HCT116), 6 days (DLD1) or 3 days (HT29). After completion of the culture, a western blot analysis using an anti-cadherin antibody or an anti-Vimentin antibody was performed on each of the cultured cell lysates (Figs. 3A to 3C). At this time, as a control group, cells cultured without DFO treatment were used and β-actin was used as an internal control group.
FIG. 3 (a) is a Western blot analysis photograph showing the effect of red ginseng extract on the expression level of camphorin on the condition that DFO was treated with a colorectal cancer cell line (HCT116) FIG. 3c is a photograph of Western blot analysis showing the effect of red ginseng extract on the expression level of cadherin. FIG. 3c is a graph showing the effect of red ginseng extract on the expression level of virgin Western blot analysis showing the effect on the expression level. As shown in FIGS. 3A to 3C, when DFO alone was treated, the level of expression of the cadherin decreased, but when the red ginseng extract was treated, the expression level of the cadherin was increased depending on the treatment concentration of the red ginseng extract And DFO alone increased the expression level of visentin. However, when the red ginseng extract was treated, the expression level of visentin decreased depending on the treatment concentration of red ginseng extract.
Thus, the results of Examples 2-1 and 2-2 above show that red ginseng extract inhibits epithelial-mesenchymal transition.
<110> GIL MEDICAL CENTER Gachon University of Industry-Academic cooperation Foundation <120> Pharmaceutical composition for or treating epithelial-mesenchymal transition related red-ginseng extract <130> KPA141073-KR <160> 8 <170> Kopatentin 2.0 <210> 1 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> primer <400> 1 atcttcaagc catcctgtgt gc 22 <210> 2 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> primer <400> 2 caaggcccac agggattttc 20 <210> 3 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> primer <400> 3 aggtcggagt caacggattt gg 22 <210> 4 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> primer <400> 4 acagtcttct gggtggcagt gatg 24 <210> 5 <211> 21 <212> DNA <213> Artificial Sequence <220> <223> primer <400> 5 ccccaactcg gaagcctaac t 21 <210> 6 <211> 25 <212> DNA <213> Artificial Sequence <220> <223> primer <400> 6 gctggaaggt aaactctgga ttaga 25 <210> 7 <211> 18 <212> DNA <213> Artificial Sequence <220> <223> primer <400> 7 acgcccagct acccaatg 18 <210> 8 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> primer <400> 8 cgccccaaag atgaggagta 20
Claims (9)
Wherein the red ginseng extract is obtained by extracting red ginseng or a pulverized product thereof with ethyl acetate, water, an alcohol having 1 to 6 carbon atoms, or a mixed solvent thereof.
Wherein the fraction is a fraction obtained by applying the red ginseng extract to a method selected from the group consisting of a solvent fractionation method, an ultrafiltration fractionation method, a chromatography fractionation method, and a combination thereof.
Wherein said EMT related disease is tissue fibrosis or metastatic cancer disease.
Lt; RTI ID = 0.0 > pharmaceutically < / RTI > acceptable carrier, excipient or diluent.
A pharmaceutical composition, which further comprises a pharmaceutically acceptable carrier, excipient or diluent.
Wherein said pharmaceutical composition inhibits the progression of EMT and thus has the effect of preventing or treating STAT3 mediated diseases.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| KR1020150000279A KR20160084003A (en) | 2015-01-02 | 2015-01-02 | Pharmaceutical composition for preventing or treating epithelial-mesenchymal transition related disease comprising red-ginseng extract |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| KR1020150000279A KR20160084003A (en) | 2015-01-02 | 2015-01-02 | Pharmaceutical composition for preventing or treating epithelial-mesenchymal transition related disease comprising red-ginseng extract |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| KR20160084003A true KR20160084003A (en) | 2016-07-13 |
Family
ID=56505439
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR1020150000279A KR20160084003A (en) | 2015-01-02 | 2015-01-02 | Pharmaceutical composition for preventing or treating epithelial-mesenchymal transition related disease comprising red-ginseng extract |
Country Status (1)
| Country | Link |
|---|---|
| KR (1) | KR20160084003A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20200026572A (en) * | 2018-09-03 | 2020-03-11 | 연세대학교 산학협력단 | A pharmaceutical composition for functional recovery of cord blood endothelial progenitor cells and treat of preeclampsia by Ginseng including Rg3 |
-
2015
- 2015-01-02 KR KR1020150000279A patent/KR20160084003A/en not_active Application Discontinuation
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20200026572A (en) * | 2018-09-03 | 2020-03-11 | 연세대학교 산학협력단 | A pharmaceutical composition for functional recovery of cord blood endothelial progenitor cells and treat of preeclampsia by Ginseng including Rg3 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| KR101867184B1 (en) | Lipid nanoparticle complex containing curcumin comprising ginsenosides | |
| KR101645464B1 (en) | Composition for anti-obesity comprising extract from young barley leaves | |
| KR101880542B1 (en) | Pharmaceutical composition for treating cancer comprising lactate metallic salts | |
| WO2003006037A1 (en) | Remedies | |
| JP2019031527A (en) | Pharmaceutical composition for preventing or treating gleevec-resistant leukemia containing ginsenoside f1 or ginsenoside rg3 as an active ingredient | |
| KR101722547B1 (en) | Anti-cancer adjuvant comprising panaxadiols compound | |
| KR20160084003A (en) | Pharmaceutical composition for preventing or treating epithelial-mesenchymal transition related disease comprising red-ginseng extract | |
| KR101787954B1 (en) | Pharmaceutical composition for treating and inhibiting metastasis of glioblastoma comprising protopanaxadiols compound | |
| JP7089044B2 (en) | Composition for the prevention or treatment of osteoporosis | |
| KR101394807B1 (en) | Pharmaceutical composition for preventing or treating inflammatory bowel disease comprising Lillium brownii F.E. extract | |
| JP6386173B2 (en) | Composition for preventing or treating vascular leakage syndrome | |
| JP2016079163A (en) | Composition for treating tumor, and production method thereof | |
| JP2016531844A (en) | Composition for promoting erythroid cell differentiation or proliferation containing a monoacetyldiacylglycerol compound as an active ingredient | |
| EP2939672A1 (en) | Igf-1 production promoter | |
| WO2023249075A1 (en) | Prophylactic or therapeutic agent for non-alcoholic steatohepatitis-derived hepatocarcinoma | |
| JP6253235B2 (en) | Neurite outgrowth inducer and use thereof | |
| JP4228371B2 (en) | Apoptosis-inducing substance contained in carotenoid-containing potato, anticancer agent having potato-derived gastric cancer cell growth inhibitory action or gastric cancer development inhibitory action | |
| KR20170057474A (en) | Pharmaceutical composition for treating and inhibiting metastasis of glioblastoma comprising protopanaxadiols compound | |
| KR101830480B1 (en) | Pharmaceutical composition for preventing or treating hypertriglyceridemia comprising methyl linolenate | |
| JP6583787B2 (en) | Food, nausea / vomiting inhibitor and quasi drug | |
| KR101340675B1 (en) | Pharmaceutical composition comprising tangeretin for preventing or treating cardiovascular diseases | |
| KR20190017206A (en) | Composition for preventing or treating bone disease comprising mollugin and BMP-2 | |
| KR20200031737A (en) | Pharmaceutical composition for prevention or treatment of bone disease containing parthenocissus tricuspidata extract and method for preparing parthenocissus tricuspidata extract | |
| KR20200031736A (en) | Composition containing resveratrol extracted from peanut sprout and method for extracting resveratrol | |
| KR20150087814A (en) | Pharmaceutical composition for treating bone disease comprising extract of wood-cultivated ginseng |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A201 | Request for examination | ||
| E902 | Notification of reason for refusal | ||
| E601 | Decision to refuse application |