KR102009219B1 - A composition for preventing or improving obesity or obesity-related disease comprising gentiopicroside - Google Patents
A composition for preventing or improving obesity or obesity-related disease comprising gentiopicroside Download PDFInfo
- Publication number
- KR102009219B1 KR102009219B1 KR1020180005589A KR20180005589A KR102009219B1 KR 102009219 B1 KR102009219 B1 KR 102009219B1 KR 1020180005589 A KR1020180005589 A KR 1020180005589A KR 20180005589 A KR20180005589 A KR 20180005589A KR 102009219 B1 KR102009219 B1 KR 102009219B1
- Authority
- KR
- South Korea
- Prior art keywords
- obesity
- genthiopicroside
- acid
- composition
- differentiation
- Prior art date
Links
- 208000008589 Obesity Diseases 0.000 title claims abstract description 53
- 235000020824 obesity Nutrition 0.000 title claims abstract description 53
- 239000000203 mixture Substances 0.000 title claims abstract description 35
- DUAGQYUORDTXOR-GPQRQXLASA-N Gentiopicrin Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1O[C@H]1[C@H](C=C)C2=CCOC(=O)C2=CO1 DUAGQYUORDTXOR-GPQRQXLASA-N 0.000 title claims abstract description 12
- DUAGQYUORDTXOR-WULZUDSJSA-N Gentiopicrin Natural products O([C@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1)[C@H]1[C@@H](C=C)C=2C(C(=O)OCC=2)=CO1 DUAGQYUORDTXOR-WULZUDSJSA-N 0.000 title claims abstract description 12
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 title description 32
- 201000010099 disease Diseases 0.000 title description 31
- 230000002265 prevention Effects 0.000 claims abstract description 10
- 230000006872 improvement Effects 0.000 claims abstract description 7
- 150000003839 salts Chemical class 0.000 claims description 30
- 235000013305 food Nutrition 0.000 claims description 22
- 239000004480 active ingredient Substances 0.000 claims description 19
- 238000011282 treatment Methods 0.000 claims description 16
- 239000008194 pharmaceutical composition Substances 0.000 claims description 12
- 230000004069 differentiation Effects 0.000 abstract description 34
- 230000000694 effects Effects 0.000 abstract description 33
- 230000014509 gene expression Effects 0.000 abstract description 24
- 108090000623 proteins and genes Proteins 0.000 abstract description 16
- 150000002632 lipids Chemical class 0.000 abstract description 15
- 230000007935 neutral effect Effects 0.000 abstract description 9
- 238000009825 accumulation Methods 0.000 abstract description 6
- 230000002222 downregulating effect Effects 0.000 abstract description 2
- 210000001789 adipocyte Anatomy 0.000 description 36
- 210000004027 cell Anatomy 0.000 description 26
- 230000002441 reversible effect Effects 0.000 description 19
- 108020004414 DNA Proteins 0.000 description 18
- 238000000034 method Methods 0.000 description 14
- 235000019197 fats Nutrition 0.000 description 13
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 12
- 102000040945 Transcription factor Human genes 0.000 description 12
- 108091023040 Transcription factor Proteins 0.000 description 12
- 230000015572 biosynthetic process Effects 0.000 description 11
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 11
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
- 239000002253 acid Substances 0.000 description 9
- 238000005259 measurement Methods 0.000 description 9
- 238000012360 testing method Methods 0.000 description 9
- 235000014113 dietary fatty acids Nutrition 0.000 description 8
- 238000002474 experimental method Methods 0.000 description 8
- 239000000194 fatty acid Substances 0.000 description 8
- 229930195729 fatty acid Natural products 0.000 description 8
- 150000004665 fatty acids Chemical class 0.000 description 8
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 8
- -1 ρ-toluenesulfone Chemical compound 0.000 description 8
- 239000003814 drug Substances 0.000 description 7
- 230000002401 inhibitory effect Effects 0.000 description 7
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- 101150018889 FABP4 gene Proteins 0.000 description 6
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- NPGIHFRTRXVWOY-UHFFFAOYSA-N Oil red O Chemical compound Cc1ccc(C)c(c1)N=Nc1cc(C)c(cc1C)N=Nc1c(O)ccc2ccccc12 NPGIHFRTRXVWOY-UHFFFAOYSA-N 0.000 description 6
- 230000004663 cell proliferation Effects 0.000 description 6
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
- 238000000605 extraction Methods 0.000 description 6
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 6
- 239000000546 pharmaceutical excipient Substances 0.000 description 6
- 239000000243 solution Substances 0.000 description 6
- 239000002904 solvent Substances 0.000 description 6
- 238000010186 staining Methods 0.000 description 6
- 238000003786 synthesis reaction Methods 0.000 description 6
- IOOMXAQUNPWDLL-UHFFFAOYSA-N 2-[6-(diethylamino)-3-(diethyliminiumyl)-3h-xanthen-9-yl]-5-sulfobenzene-1-sulfonate Chemical compound C=12C=CC(=[N+](CC)CC)C=C2OC2=CC(N(CC)CC)=CC=C2C=1C1=CC=C(S(O)(=O)=O)C=C1S([O-])(=O)=O IOOMXAQUNPWDLL-UHFFFAOYSA-N 0.000 description 5
- 101150061453 Cebpa gene Proteins 0.000 description 5
- 101150102653 Dgat2 gene Proteins 0.000 description 5
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 5
- 101150003888 FASN gene Proteins 0.000 description 5
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 5
- 208000001145 Metabolic Syndrome Diseases 0.000 description 5
- 108010016731 PPAR gamma Proteins 0.000 description 5
- 101150023417 PPARG gene Proteins 0.000 description 5
- 102100038825 Peroxisome proliferator-activated receptor gamma Human genes 0.000 description 5
- 101150097713 SCD1 gene Proteins 0.000 description 5
- 101150044214 Srebf1 gene Proteins 0.000 description 5
- 201000000690 abdominal obesity-metabolic syndrome Diseases 0.000 description 5
- 238000010521 absorption reaction Methods 0.000 description 5
- 230000035508 accumulation Effects 0.000 description 5
- 229940079593 drug Drugs 0.000 description 5
- 239000012091 fetal bovine serum Substances 0.000 description 5
- 239000000796 flavoring agent Substances 0.000 description 5
- 230000001965 increasing effect Effects 0.000 description 5
- 230000006698 induction Effects 0.000 description 5
- 230000006372 lipid accumulation Effects 0.000 description 5
- 208000030159 metabolic disease Diseases 0.000 description 5
- 208000001072 type 2 diabetes mellitus Diseases 0.000 description 5
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- 208000031226 Hyperlipidaemia Diseases 0.000 description 4
- 238000011529 RT qPCR Methods 0.000 description 4
- 150000001875 compounds Chemical class 0.000 description 4
- 238000011161 development Methods 0.000 description 4
- 230000018109 developmental process Effects 0.000 description 4
- 150000001982 diacylglycerols Chemical class 0.000 description 4
- 239000003085 diluting agent Substances 0.000 description 4
- 239000012153 distilled water Substances 0.000 description 4
- 230000005764 inhibitory process Effects 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- 230000008569 process Effects 0.000 description 4
- 230000002829 reductive effect Effects 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- 239000006228 supernatant Substances 0.000 description 4
- 208000024891 symptom Diseases 0.000 description 4
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- 102100034033 Alpha-adducin Human genes 0.000 description 3
- 102100026189 Beta-galactosidase Human genes 0.000 description 3
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 3
- 208000024172 Cardiovascular disease Diseases 0.000 description 3
- 108020004635 Complementary DNA Proteins 0.000 description 3
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 3
- 102000004190 Enzymes Human genes 0.000 description 3
- 108090000790 Enzymes Proteins 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- 208000004930 Fatty Liver Diseases 0.000 description 3
- 102100030431 Fatty acid-binding protein, adipocyte Human genes 0.000 description 3
- 206010019708 Hepatic steatosis Diseases 0.000 description 3
- 101000799076 Homo sapiens Alpha-adducin Proteins 0.000 description 3
- 102000004877 Insulin Human genes 0.000 description 3
- 108090001061 Insulin Proteins 0.000 description 3
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 3
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
- 102000003728 Peroxisome Proliferator-Activated Receptors Human genes 0.000 description 3
- 108090000029 Peroxisome Proliferator-Activated Receptors Proteins 0.000 description 3
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 101000629598 Rattus norvegicus Sterol regulatory element-binding protein 1 Proteins 0.000 description 3
- 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 3
- 229930006000 Sucrose Natural products 0.000 description 3
- 238000002835 absorbance Methods 0.000 description 3
- 230000009471 action Effects 0.000 description 3
- 239000000654 additive Substances 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- 238000010804 cDNA synthesis Methods 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 239000002299 complementary DNA Substances 0.000 description 3
- 208000010706 fatty liver disease Diseases 0.000 description 3
- 235000013355 food flavoring agent Nutrition 0.000 description 3
- 238000009472 formulation Methods 0.000 description 3
- 238000002347 injection Methods 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- 229940125396 insulin Drugs 0.000 description 3
- 230000007246 mechanism Effects 0.000 description 3
- 239000002609 medium Substances 0.000 description 3
- 150000007524 organic acids Chemical class 0.000 description 3
- 238000007911 parenteral administration Methods 0.000 description 3
- 102000005962 receptors Human genes 0.000 description 3
- 108020003175 receptors Proteins 0.000 description 3
- 238000000926 separation method Methods 0.000 description 3
- 231100000240 steatosis hepatitis Toxicity 0.000 description 3
- 239000005720 sucrose Substances 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- YNJBWRMUSHSURL-UHFFFAOYSA-N trichloroacetic acid Chemical compound OC(=O)C(Cl)(Cl)Cl YNJBWRMUSHSURL-UHFFFAOYSA-N 0.000 description 3
- PUPZLCDOIYMWBV-UHFFFAOYSA-N (+/-)-1,3-Butanediol Chemical compound CC(O)CCO PUPZLCDOIYMWBV-UHFFFAOYSA-N 0.000 description 2
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 2
- 102000057234 Acyl transferases Human genes 0.000 description 2
- 108700016155 Acyl transferases Proteins 0.000 description 2
- 102100022089 Acyl-[acyl-carrier-protein] hydrolase Human genes 0.000 description 2
- 102000014777 Adipokines Human genes 0.000 description 2
- 108010078606 Adipokines Proteins 0.000 description 2
- 102000011690 Adiponectin Human genes 0.000 description 2
- 108010076365 Adiponectin Proteins 0.000 description 2
- 201000001320 Atherosclerosis Diseases 0.000 description 2
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- 102000014914 Carrier Proteins Human genes 0.000 description 2
- 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 2
- 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 2
- RGHNJXZEOKUKBD-SQOUGZDYSA-N D-gluconic acid Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O RGHNJXZEOKUKBD-SQOUGZDYSA-N 0.000 description 2
- 102000002148 Diacylglycerol O-acyltransferase Human genes 0.000 description 2
- 108010001348 Diacylglycerol O-acyltransferase Proteins 0.000 description 2
- 239000004386 Erythritol Substances 0.000 description 2
- UNXHWFMMPAWVPI-UHFFFAOYSA-N Erythritol Natural products OCC(O)C(O)CO UNXHWFMMPAWVPI-UHFFFAOYSA-N 0.000 description 2
- 108010039731 Fatty Acid Synthases Proteins 0.000 description 2
- 108050003772 Fatty acid-binding protein 4 Proteins 0.000 description 2
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- IAJILQKETJEXLJ-UHFFFAOYSA-N Galacturonsaeure Natural products O=CC(O)C(O)C(O)C(O)C(O)=O IAJILQKETJEXLJ-UHFFFAOYSA-N 0.000 description 2
- 108010010803 Gelatin Proteins 0.000 description 2
- 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 2
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 2
- 108010092277 Leptin Proteins 0.000 description 2
- 102000016267 Leptin Human genes 0.000 description 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
- 229920002472 Starch Polymers 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 2
- 244000299461 Theobroma cacao Species 0.000 description 2
- TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 description 2
- 230000000996 additive effect Effects 0.000 description 2
- 230000002293 adipogenic effect Effects 0.000 description 2
- 239000000478 adipokine Substances 0.000 description 2
- 230000011759 adipose tissue development Effects 0.000 description 2
- 235000010443 alginic acid Nutrition 0.000 description 2
- 229920000615 alginic acid Polymers 0.000 description 2
- 229910052783 alkali metal Inorganic materials 0.000 description 2
- 150000001340 alkali metals Chemical class 0.000 description 2
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 2
- 230000003321 amplification Effects 0.000 description 2
- 239000003125 aqueous solvent Substances 0.000 description 2
- 208000011775 arteriosclerosis disease Diseases 0.000 description 2
- 208000015337 arteriosclerotic cardiovascular disease Diseases 0.000 description 2
- 235000003704 aspartic acid Nutrition 0.000 description 2
- 239000002585 base Substances 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- 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 2
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 2
- 235000013361 beverage Nutrition 0.000 description 2
- 108091008324 binding proteins Proteins 0.000 description 2
- 230000004071 biological effect Effects 0.000 description 2
- 229940098773 bovine serum albumin Drugs 0.000 description 2
- 235000014121 butter Nutrition 0.000 description 2
- 235000019577 caloric intake Nutrition 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 150000001720 carbohydrates Chemical class 0.000 description 2
- 235000014633 carbohydrates Nutrition 0.000 description 2
- 229910002091 carbon monoxide Inorganic materials 0.000 description 2
- 239000005516 coenzyme A Substances 0.000 description 2
- 229940093530 coenzyme a Drugs 0.000 description 2
- 235000009508 confectionery Nutrition 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- UREBDLICKHMUKA-CXSFZGCWSA-N dexamethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O UREBDLICKHMUKA-CXSFZGCWSA-N 0.000 description 2
- 229960003957 dexamethasone Drugs 0.000 description 2
- 206010012601 diabetes mellitus Diseases 0.000 description 2
- 235000005911 diet Nutrition 0.000 description 2
- FFYPMLJYZAEMQB-UHFFFAOYSA-N diethyl pyrocarbonate Chemical compound CCOC(=O)OC(=O)OCC FFYPMLJYZAEMQB-UHFFFAOYSA-N 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
- 230000003828 downregulation Effects 0.000 description 2
- 239000000839 emulsion Substances 0.000 description 2
- 239000003623 enhancer Substances 0.000 description 2
- UNXHWFMMPAWVPI-ZXZARUISSA-N erythritol Chemical compound OC[C@H](O)[C@H](O)CO UNXHWFMMPAWVPI-ZXZARUISSA-N 0.000 description 2
- 235000019414 erythritol Nutrition 0.000 description 2
- 229940009714 erythritol Drugs 0.000 description 2
- 239000000284 extract Substances 0.000 description 2
- 235000019634 flavors Nutrition 0.000 description 2
- 235000013373 food additive Nutrition 0.000 description 2
- 239000002778 food additive Substances 0.000 description 2
- 235000015203 fruit juice 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
- 229960001031 glucose Drugs 0.000 description 2
- 235000011187 glycerol Nutrition 0.000 description 2
- 239000008187 granular material Substances 0.000 description 2
- 230000036541 health Effects 0.000 description 2
- 208000019622 heart disease Diseases 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- NRYBAZVQPHGZNS-ZSOCWYAHSA-N leptin Chemical compound O=C([C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)CNC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](N)CC(C)C)CCSC)N1CCC[C@H]1C(=O)NCC(=O)N[C@@H](CS)C(O)=O NRYBAZVQPHGZNS-ZSOCWYAHSA-N 0.000 description 2
- 229940039781 leptin Drugs 0.000 description 2
- 230000003520 lipogenic effect Effects 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 description 2
- 230000004060 metabolic process Effects 0.000 description 2
- 229910052751 metal Inorganic materials 0.000 description 2
- 239000002184 metal Substances 0.000 description 2
- 150000007522 mineralic acids Chemical class 0.000 description 2
- 238000003199 nucleic acid amplification method Methods 0.000 description 2
- 210000000056 organ Anatomy 0.000 description 2
- 235000005985 organic acids Nutrition 0.000 description 2
- AHLBNYSZXLDEJQ-FWEHEUNISA-N orlistat Chemical compound CCCCCCCCCCC[C@H](OC(=O)[C@H](CC(C)C)NC=O)C[C@@H]1OC(=O)[C@H]1CCCCCC AHLBNYSZXLDEJQ-FWEHEUNISA-N 0.000 description 2
- 239000006187 pill Substances 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 210000000229 preadipocyte Anatomy 0.000 description 2
- 239000003755 preservative agent Substances 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 230000001737 promoting effect Effects 0.000 description 2
- 235000018102 proteins Nutrition 0.000 description 2
- 102000004169 proteins and genes Human genes 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- UNAANXDKBXWMLN-UHFFFAOYSA-N sibutramine Chemical compound C=1C=C(Cl)C=CC=1C1(C(N(C)C)CC(C)C)CCC1 UNAANXDKBXWMLN-UHFFFAOYSA-N 0.000 description 2
- SQGYOTSLMSWVJD-UHFFFAOYSA-N silver(1+) nitrate Chemical compound [Ag+].[O-]N(=O)=O SQGYOTSLMSWVJD-UHFFFAOYSA-N 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- GGCZERPQGJTIQP-UHFFFAOYSA-N sodium;9,10-dioxoanthracene-2-sulfonic acid Chemical compound [Na+].C1=CC=C2C(=O)C3=CC(S(=O)(=O)O)=CC=C3C(=O)C2=C1 GGCZERPQGJTIQP-UHFFFAOYSA-N 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 235000010356 sorbitol Nutrition 0.000 description 2
- 239000000600 sorbitol Substances 0.000 description 2
- 229960002920 sorbitol Drugs 0.000 description 2
- 239000008107 starch Substances 0.000 description 2
- 235000019698 starch Nutrition 0.000 description 2
- SIARJEKBADXQJG-LFZQUHGESA-N stearoyl-CoA Chemical compound O[C@@H]1[C@H](OP(O)(O)=O)[C@@H](COP(O)(=O)OP(O)(=O)OCC(C)(C)[C@@H](O)C(=O)NCCC(=O)NCCSC(=O)CCCCCCCCCCCCCCCCC)O[C@H]1N1C2=NC=NC(N)=C2N=C1 SIARJEKBADXQJG-LFZQUHGESA-N 0.000 description 2
- 239000000829 suppository Substances 0.000 description 2
- 239000003826 tablet Substances 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
- 239000011975 tartaric acid Substances 0.000 description 2
- 235000002906 tartaric acid Nutrition 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- 150000003626 triacylglycerols Chemical class 0.000 description 2
- DCXXMTOCNZCJGO-UHFFFAOYSA-N tristearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(OC(=O)CCCCCCCCCCCCCCCCC)COC(=O)CCCCCCCCCCCCCCCCC DCXXMTOCNZCJGO-UHFFFAOYSA-N 0.000 description 2
- 235000013343 vitamin Nutrition 0.000 description 2
- 239000011782 vitamin Substances 0.000 description 2
- 229930003231 vitamin Natural products 0.000 description 2
- 229940088594 vitamin Drugs 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- 239000000080 wetting agent Substances 0.000 description 2
- 229940002552 xenical Drugs 0.000 description 2
- 239000000811 xylitol Substances 0.000 description 2
- 235000010447 xylitol Nutrition 0.000 description 2
- 229960002675 xylitol Drugs 0.000 description 2
- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 description 2
- 229940058015 1,3-butylene glycol Drugs 0.000 description 1
- RTBFRGCFXZNCOE-UHFFFAOYSA-N 1-methylsulfonylpiperidin-4-one Chemical compound CS(=O)(=O)N1CCC(=O)CC1 RTBFRGCFXZNCOE-UHFFFAOYSA-N 0.000 description 1
- OWEGMIWEEQEYGQ-UHFFFAOYSA-N 100676-05-9 Natural products OC1C(O)C(O)C(CO)OC1OCC1C(O)C(O)C(O)C(OC2C(OC(O)C(O)C2O)CO)O1 OWEGMIWEEQEYGQ-UHFFFAOYSA-N 0.000 description 1
- XNWFRZJHXBZDAG-UHFFFAOYSA-N 2-METHOXYETHANOL Chemical compound COCCO XNWFRZJHXBZDAG-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
- JEFDYHWPYRIMCZ-UHFFFAOYSA-N 8-(3-methylbutyl)-3,7-dihydropurine-2,6-dione Chemical compound N1C(=O)NC(=O)C2=C1N=C(CCC(C)C)N2 JEFDYHWPYRIMCZ-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 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 1
- 108010011485 Aspartame Proteins 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- 210000003771 C cell Anatomy 0.000 description 1
- 101710186200 CCAAT/enhancer-binding protein Proteins 0.000 description 1
- 102100034808 CCAAT/enhancer-binding protein alpha Human genes 0.000 description 1
- 101710168309 CCAAT/enhancer-binding protein alpha Proteins 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- 241000283707 Capra Species 0.000 description 1
- PTHCMJGKKRQCBF-UHFFFAOYSA-N Cellulose, microcrystalline Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC)C(CO)O1 PTHCMJGKKRQCBF-UHFFFAOYSA-N 0.000 description 1
- 241000282693 Cercopithecidae Species 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- 229920000858 Cyclodextrin Polymers 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- RGHNJXZEOKUKBD-UHFFFAOYSA-N D-gluconic acid Natural products OCC(O)C(O)C(O)C(O)C(O)=O RGHNJXZEOKUKBD-UHFFFAOYSA-N 0.000 description 1
- 101100447432 Danio rerio gapdh-2 gene Proteins 0.000 description 1
- 239000004375 Dextrin Substances 0.000 description 1
- 229920001353 Dextrin Polymers 0.000 description 1
- 238000002965 ELISA Methods 0.000 description 1
- LVGKNOAMLMIIKO-UHFFFAOYSA-N Elaidinsaeure-aethylester Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC LVGKNOAMLMIIKO-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
- 229930091371 Fructose Natural products 0.000 description 1
- 239000005715 Fructose Substances 0.000 description 1
- RFSUNEUAIZKAJO-ARQDHWQXSA-N Fructose Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O RFSUNEUAIZKAJO-ARQDHWQXSA-N 0.000 description 1
- 101100226596 Gallus gallus FABP gene Proteins 0.000 description 1
- 101150112014 Gapdh gene Proteins 0.000 description 1
- 241001071795 Gentiana Species 0.000 description 1
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 1
- 101001062864 Homo sapiens Fatty acid-binding protein, adipocyte Proteins 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- 206010020880 Hypertrophy Diseases 0.000 description 1
- 206010022489 Insulin Resistance Diseases 0.000 description 1
- 208000031773 Insulin resistance syndrome Diseases 0.000 description 1
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 240000007472 Leucaena leucocephala Species 0.000 description 1
- 235000010643 Leucaena leucocephala Nutrition 0.000 description 1
- 102000004882 Lipase Human genes 0.000 description 1
- 108090001060 Lipase Proteins 0.000 description 1
- 108010013563 Lipoprotein Lipase Proteins 0.000 description 1
- 102100022119 Lipoprotein lipase Human genes 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 208000002720 Malnutrition Diseases 0.000 description 1
- GUBGYTABKSRVRQ-PICCSMPSSA-N Maltose Natural products O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@@H](CO)OC(O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-PICCSMPSSA-N 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 208000012902 Nervous system disease Diseases 0.000 description 1
- 208000025966 Neurological disease Diseases 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- QACUPNAKIPYZAW-RMQWDSPGSA-N O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)OC(O)[C@H](O)[C@H]1O.O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)OC(O)[C@H](O)[C@H]1O 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)OC(O)[C@H](O)[C@H]1O.O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)OC(O)[C@H](O)[C@H]1O QACUPNAKIPYZAW-RMQWDSPGSA-N 0.000 description 1
- 238000009004 PCR Kit Methods 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 229920002230 Pectic acid Polymers 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- 102000007156 Resistin Human genes 0.000 description 1
- 108010047909 Resistin Proteins 0.000 description 1
- 108091027981 Response element Proteins 0.000 description 1
- 108010074436 Sterol Regulatory Element Binding Protein 1 Proteins 0.000 description 1
- 108010020396 Sterol Regulatory Element Binding Proteins Proteins 0.000 description 1
- 102000009822 Sterol Regulatory Element Binding Proteins Human genes 0.000 description 1
- 102100026839 Sterol regulatory element-binding protein 1 Human genes 0.000 description 1
- 244000228451 Stevia rebaudiana Species 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
- 241000282887 Suidae Species 0.000 description 1
- 101000629599 Sus scrofa Sterol regulatory element-binding protein 1 Proteins 0.000 description 1
- 244000269722 Thea sinensis Species 0.000 description 1
- 235000005764 Theobroma cacao ssp. cacao Nutrition 0.000 description 1
- 235000005767 Theobroma cacao ssp. sphaerocarpum Nutrition 0.000 description 1
- 239000007983 Tris buffer Substances 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 238000001467 acupuncture Methods 0.000 description 1
- 210000000577 adipose tissue Anatomy 0.000 description 1
- 235000013334 alcoholic beverage Nutrition 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- IAJILQKETJEXLJ-RSJOWCBRSA-N aldehydo-D-galacturonic acid Chemical compound O=C[C@H](O)[C@@H](O)[C@@H](O)[C@H](O)C(O)=O IAJILQKETJEXLJ-RSJOWCBRSA-N 0.000 description 1
- IAJILQKETJEXLJ-QTBDOELSSA-N aldehydo-D-glucuronic acid Chemical compound O=C[C@H](O)[C@@H](O)[C@H](O)[C@H](O)C(O)=O IAJILQKETJEXLJ-QTBDOELSSA-N 0.000 description 1
- 229940072056 alginate Drugs 0.000 description 1
- 239000000783 alginic acid Substances 0.000 description 1
- 229960001126 alginic acid Drugs 0.000 description 1
- 150000004781 alginic acids Chemical class 0.000 description 1
- 150000008044 alkali metal hydroxides Chemical class 0.000 description 1
- 229910001860 alkaline earth metal hydroxide Inorganic materials 0.000 description 1
- SHGAZHPCJJPHSC-YCNIQYBTSA-N all-trans-retinoic acid Chemical compound OC(=O)\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C SHGAZHPCJJPHSC-YCNIQYBTSA-N 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- JFCQEDHGNNZCLN-UHFFFAOYSA-N anhydrous glutaric acid Natural products OC(=O)CCCC(O)=O JFCQEDHGNNZCLN-UHFFFAOYSA-N 0.000 description 1
- 239000000883 anti-obesity agent Substances 0.000 description 1
- 239000002543 antimycotic Substances 0.000 description 1
- 230000036528 appetite Effects 0.000 description 1
- 235000019789 appetite Nutrition 0.000 description 1
- 239000002830 appetite depressant Substances 0.000 description 1
- 239000011260 aqueous acid Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 239000000605 aspartame Substances 0.000 description 1
- 235000010357 aspartame Nutrition 0.000 description 1
- IAOZJIPTCAWIRG-QWRGUYRKSA-N aspartame Chemical compound OC(=O)C[C@H](N)C(=O)N[C@H](C(=O)OC)CC1=CC=CC=C1 IAOZJIPTCAWIRG-QWRGUYRKSA-N 0.000 description 1
- 229960003438 aspartame Drugs 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- GUBGYTABKSRVRQ-QUYVBRFLSA-N beta-maltose Chemical compound OC[C@H]1O[C@H](O[C@H]2[C@H](O)[C@@H](O)[C@H](O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@@H]1O GUBGYTABKSRVRQ-QUYVBRFLSA-N 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 235000008429 bread Nutrition 0.000 description 1
- 235000019437 butane-1,3-diol Nutrition 0.000 description 1
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
- 235000001046 cacaotero Nutrition 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 235000001465 calcium Nutrition 0.000 description 1
- 239000011575 calcium Substances 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
- 159000000007 calcium salts Chemical class 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
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 235000014171 carbonated beverage Nutrition 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical compound OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 230000024245 cell differentiation Effects 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
- 238000005119 centrifugation Methods 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 235000019219 chocolate Nutrition 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 235000015165 citric acid Nutrition 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 230000002596 correlated effect Effects 0.000 description 1
- 230000000875 corresponding effect Effects 0.000 description 1
- 230000003013 cytotoxicity Effects 0.000 description 1
- 231100000135 cytotoxicity Toxicity 0.000 description 1
- 235000013365 dairy product Nutrition 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000001934 delay Effects 0.000 description 1
- 238000009795 derivation Methods 0.000 description 1
- 235000019425 dextrin Nutrition 0.000 description 1
- 239000008121 dextrose Substances 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- 230000000378 dietary effect Effects 0.000 description 1
- 239000000539 dimer Substances 0.000 description 1
- 150000002016 disaccharides Chemical class 0.000 description 1
- 208000016097 disease of metabolism Diseases 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 238000009509 drug development Methods 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 230000002526 effect on cardiovascular system Effects 0.000 description 1
- 229920001971 elastomer Polymers 0.000 description 1
- 239000003792 electrolyte Substances 0.000 description 1
- 239000012149 elution buffer Substances 0.000 description 1
- 230000002124 endocrine Effects 0.000 description 1
- 238000004146 energy storage Methods 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
- 238000001704 evaporation Methods 0.000 description 1
- 230000029142 excretion Effects 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 239000003205 fragrance Substances 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 235000011087 fumaric acid Nutrition 0.000 description 1
- 239000000174 gluconic acid Substances 0.000 description 1
- 235000012208 gluconic acid Nutrition 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 229940097043 glucuronic acid Drugs 0.000 description 1
- 235000013922 glutamic acid Nutrition 0.000 description 1
- 239000004220 glutamic acid Substances 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- 235000013402 health food Nutrition 0.000 description 1
- 230000013632 homeostatic process Effects 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-M hydrogensulfate Chemical compound OS([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 description 1
- 229940071870 hydroiodic acid Drugs 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 206010020718 hyperplasia Diseases 0.000 description 1
- 210000003016 hypothalamus Anatomy 0.000 description 1
- 235000015243 ice cream Nutrition 0.000 description 1
- 230000001976 improved effect Effects 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 239000007928 intraperitoneal injection Substances 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 229960001375 lactose Drugs 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
- 230000004130 lipolysis Effects 0.000 description 1
- 229940057995 liquid paraffin Drugs 0.000 description 1
- 230000004807 localization Effects 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 229960003511 macrogol Drugs 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 230000001071 malnutrition Effects 0.000 description 1
- 235000000824 malnutrition Nutrition 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
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 229960001855 mannitol Drugs 0.000 description 1
- 235000013372 meat Nutrition 0.000 description 1
- 108020004999 messenger RNA Proteins 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 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
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 239000002480 mineral oil Substances 0.000 description 1
- 235000010446 mineral oil Nutrition 0.000 description 1
- 239000012046 mixed solvent Substances 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 150000002772 monosaccharides Chemical class 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 239000002858 neurotransmitter agent Substances 0.000 description 1
- 239000002547 new drug Substances 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 231100000956 nontoxicity Toxicity 0.000 description 1
- 235000012149 noodles Nutrition 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- 208000015380 nutritional deficiency disease Diseases 0.000 description 1
- 235000008390 olive oil Nutrition 0.000 description 1
- 239000004006 olive oil Substances 0.000 description 1
- 238000001543 one-way ANOVA Methods 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 230000008520 organization Effects 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- LCLHHZYHLXDRQG-ZNKJPWOQSA-N pectic acid Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)O[C@H](C(O)=O)[C@@H]1OC1[C@H](O)[C@@H](O)[C@@H](OC2[C@@H]([C@@H](O)[C@@H](O)[C@H](O2)C(O)=O)O)[C@@H](C(O)=O)O1 LCLHHZYHLXDRQG-ZNKJPWOQSA-N 0.000 description 1
- 239000003614 peroxisome proliferator Substances 0.000 description 1
- 238000002135 phase contrast microscopy Methods 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 235000013550 pizza Nutrition 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 239000010318 polygalacturonic acid Substances 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 150000004804 polysaccharides Chemical class 0.000 description 1
- 229920000136 polysorbate Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 159000000001 potassium salts Chemical class 0.000 description 1
- 230000001376 precipitating effect Effects 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 230000002062 proliferating effect Effects 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 1
- 229960003415 propylparaben Drugs 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 238000011002 quantification Methods 0.000 description 1
- 238000004445 quantitative analysis Methods 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- HELXLJCILKEWJH-NCGAPWICSA-N rebaudioside A Chemical compound O([C@H]1[C@H](O)[C@@H](CO)O[C@H]([C@@H]1O[C@H]1[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O1)O)O[C@]12C(=C)C[C@@]3(C1)CC[C@@H]1[C@@](C)(CCC[C@]1([C@@H]3CC2)C)C(=O)O[C@H]1[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O1)O)[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O HELXLJCILKEWJH-NCGAPWICSA-N 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000016438 regulation of fat cell differentiation Effects 0.000 description 1
- 230000037425 regulation of transcription Effects 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 230000008844 regulatory mechanism Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 208000023504 respiratory system disease Diseases 0.000 description 1
- 229930002330 retinoic acid Natural products 0.000 description 1
- 235000019204 saccharin Nutrition 0.000 description 1
- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
- 229940081974 saccharin Drugs 0.000 description 1
- 239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 1
- 235000013580 sausages Nutrition 0.000 description 1
- HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical compound O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 0.000 description 1
- 230000003248 secreting effect Effects 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 229910001961 silver nitrate Inorganic materials 0.000 description 1
- 235000011888 snacks Nutrition 0.000 description 1
- 235000014347 soups Nutrition 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 229940032147 starch Drugs 0.000 description 1
- 102000028561 sterol response element binding proteins Human genes 0.000 description 1
- 108091009326 sterol response element binding proteins Proteins 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 229960004793 sucrose Drugs 0.000 description 1
- 150000005846 sugar alcohols Chemical class 0.000 description 1
- 229910021653 sulphate ion Inorganic materials 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 238000013518 transcription Methods 0.000 description 1
- 230000035897 transcription Effects 0.000 description 1
- 229960001727 tretinoin Drugs 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 235000013311 vegetables Nutrition 0.000 description 1
- 150000003722 vitamin derivatives Chemical class 0.000 description 1
- 230000004580 weight loss Effects 0.000 description 1
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
- A61K31/7048—Compounds having saccharide radicals and heterocyclic rings having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin, digitoxin or digoxin
-
- 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
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
- A23L33/125—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives containing carbohydrate syrups; containing sugars; containing sugar alcohols; containing starch hydrolysates
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/04—Anorexiants; Antiobesity agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2200/00—Function of food ingredients
- A23V2200/30—Foods, ingredients or supplements having a functional effect on health
- A23V2200/328—Foods, ingredients or supplements having a functional effect on health having effect on glycaemic control and diabetes
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2200/00—Function of food ingredients
- A23V2200/30—Foods, ingredients or supplements having a functional effect on health
- A23V2200/332—Promoters of weight control and weight loss
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Diabetes (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Food Science & Technology (AREA)
- Molecular Biology (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Mycology (AREA)
- Polymers & Plastics (AREA)
- Nutrition Science (AREA)
- Emergency Medicine (AREA)
- Endocrinology (AREA)
- Child & Adolescent Psychology (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
본 발명은 젠티오피크로사이드(gentiopicroside)를 포함하는 비만의 예방 또는 개선용 조성물에 관한 것으로, 본 발명에 따른 젠티오피크로사이드는 지방합성 관련 유전자의 발현을 하향 조절함으로써 전구지방세포의 지방세포로의 분화시 분화를 억제하는 효과를 가지며, 중성지질의 축적을 억제하는 효과가 우수하다. 따라서, 본 발명에 따른 젠티오피크로사이드는 비만을 예방, 개선 또는 치료하는데에 유용하게 사용될 수 있다.The present invention relates to a composition for the prevention or improvement of obesity comprising geniopicroside (gentiopicroside), the genthiopicroside according to the present invention is to control the fat tax of profat cells by down-regulating the expression of fat-related genes It has the effect of suppressing differentiation during the differentiation of captives and the effect of suppressing the accumulation of neutral lipids. Therefore, the genthiopicroside according to the present invention can be usefully used to prevent, ameliorate or treat obesity.
Description
본 발명은 젠티오피크로사이드(gentiopicroside)를 포함하는 비만의 예방 또는 개선용 조성물에 관한 것으로, 보다 상세하게는 젠티오피크로사이드, 또는 이의 약학적 또는 식품학적으로 허용가능한 염을 유효성분으로 포함하는 비만의 예방 또는 개선용 약학적 또는 식품 조성물에 관한 것이다. The present invention relates to a composition for the prevention or improvement of obesity comprising gentiopicroside, and more particularly, to gentiopicroside, or a pharmaceutically or pharmaceutically acceptable salt thereof as an active ingredient. It relates to a pharmaceutical or food composition for preventing or improving obesity comprising.
인류가 풍요로운 사회로 점점 발전해 감에 따라 비만이 심각한 질병 중의 하나로 등장하게 되었고 이에 세계보건기구(WHO)는 비만을 치료해야 할 질병의 대상이라고 선언하였다. 비만은 열량의 섭취와 소비의 불균형으로 발생되는 대사성 질환이며, 형태학적으로 볼 때 체내 지방 세포의 크기 증가(hypertrophy) 또는 수의 증가(hyperplasia)에 의해 초래된다. 비만은 서구사회에서 가장 흔한 영양장애일 뿐만 아니라, 최근 우리나라에서도 경제발전에 의한 식생활의 향상과 생활 방식의 서구화로 비만의 빈도가 급속히 증가하는 추세에 있어서 그 치료와 예방에 대한 중요성이 크게 부각되고 있다. 비만은 심리적으로 개인을 위축시킬 뿐만 아니라 사회적으로도 여러 가지 성인병의 발병 위험을 증가시키는 중요한 요인이다. 비만이 2형 당뇨병, 고혈압, 고지혈증, 심질환 등 여러 가지 성인병의 유병율 증가와 직접적인 관련이 있다고 알려져 있으며(Cell 87:377, 1999), 비만과 관련된 질환들을 함께 묶어서 대사증후군(metabolic syndrome) 또는 인슐린 저항성 증후군(insulin resistance syndrome)이라고 하며, 이들이 동맥경화증 및 심혈관질환의 원인으로 밝혀지고 있다. 이처럼 비만이 다양한 대사성 질환의 발병률을 증가시키고 실제 체중감소가 이러한 질환의 발병률을 현격히 감소시킨다는 사실로부터 지방을 많이 함유하는 지방세포가 이러한 현상을 매개할 것이라고 유추해 볼 수 있다.As mankind has developed into a prosperous society, obesity has emerged as one of the serious diseases, and the World Health Organization (WHO) has declared it the object of the disease to be treated. Obesity is a metabolic disease caused by an imbalance between calorie intake and consumption and is morphologically caused by hypertrophy or hyperplasia of fat cells in the body. Obesity is not only the most common malnutrition in Western society, but the importance of treatment and prevention has been highlighted in recent years in Korea, as the frequency of obesity is rapidly increasing due to the improvement of dietary life and the westernization of lifestyle. have. Obesity is an important factor that not only psychologically diminishes individuals but also increases the risk of developing various adult diseases. Obesity is known to be directly related to the increased prevalence of various adult diseases, such as
과거에는 지방 조직은 과다한 에너지를 트리글리세롤(triacylglycerol)의 형태로 저장하고 필요할 때 방출하는 에너지 저장 기관으로만 생각되었으나, 최근에는 지방 조직이 아디포넥틴(adiponectin), 렙틴(leptin) 및 레지스틴(resistin) 등 여러 가지 아디포카인(adipokine)들을 분비하여 에너지의 항상성(homeostasis)을 조절하는 중요한 내분비 기관으로 받아들여지고 있다(Trends Endocrinol Metab 13:18, 2002). 따라서 지방 세포의 증식과 지방세포에서 분비되는 물질들에 대한 이해와 그 생체 내 조절 메카니즘에 대한 규명이 비만 및 그로 인한 여러 가지 질병들을 이해하고 효과적인 치료제를 개발할 수 있는 밑거름이 될 것으로 여겨지고 있고 이에 따라 지방세포 분화 조절에 관한 연구가 활발히 진행되고 있으며, 비만 환자에서의 증가한 지방세포의 유래와 관련하여 체내의 전구지방세포(preadipocytes)로부터 분화된다는 것이 가장 주된 기전으로 받아들여지고 있다. In the past, adipose tissue was only thought of as an energy storage organ that stores excess energy in the form of triglyceryl (triacylglycerol) and releases it when needed, but recently, adiponectin, leptin, and resistin Various adipokines are accepted as important endocrine organs that regulate the homeostasis of energy (Trends Endocrinol Metab 13:18, 2002). Therefore, understanding of the proliferation of fat cells and the substances secreted from fat cells and their in vivo regulation mechanisms are expected to be the foundation for understanding obesity and various diseases and developing effective treatments. Studies on the regulation of adipocyte differentiation are being actively conducted, and the main mechanism is that differentiation from preadipocytes in the body is associated with increased adipocyte derivation in obese patients.
전구지방세포의 지방세포로의 분화 과정은 3T3-L1과 같은 세포를 이용하여 연구되어 왔으며, 여러 종류의 전사인자(transcription factor)들, 특히 지방화에 관여하는 것으로 알려진 전사인자, C/EBPs(CCAAT enhancer binding proteins), PPARs(Peroxisome proliferator activated receptor)와 ADD1/SREBPs(Adipocyte determination and differentiation dependent factor1/sterol response element binding proteins) 등이 시간의 차이에 따라 발현하며 그 과정을 조절한다는 것이 알려져 있다(Bart A Jessen et al., Gene, 299, pp95-100, 2002; Darlington et al., J . Biol. Chem., 273, pp30057-30060, 1998; Brun R.P et al., Curr. Opin.Cell. Biol., 8, pp826-832, 1996). MDI(isobutylmethylxanthin, dexamethasone and insulin)와 같은 호르몬의 자극이 주어질 때, C/EBP β와 δ가 가장 먼저, 일시적으로 발현되며, 지방세포로의 분화를 개시하게 한다(Reusch J. E et al., Mol. Cell. Biol., 20, pp1008-1020, 2000). 이는 계속해서 C/EBP α와 PPARγ의 발현증가를 유도하게 된다(James M. N. et al., J. Nutr., 130, pp3122S-3126S, 2000). PPARγ는 특히 지방세포 분화에 중요한 전사인자로 알려져 있으며, 레티논산 X 수용체(retinoic acid X receptor) 단백질(RXR)과 이합체(dimer)를 형성한 뒤, 다양한 지방세포 유전자의 프로모터(promoter)에 존재하는 PPRE(peroxisome proliferator response elements)에 결합한다 (Tontonoz P.E et al., Genes Dev., 8, pp1224-1234, 1994 ; Hwang, C. S et al., Cell Dev. Biol., 13, pp873-877). PPARγ와 C/EBP α의 상호 작용이 성숙한 지방세포로의 분화에 매우 결정적인데, 이러한 전사인자들 및 지방세포 조절 인자들에 의해 지방세포로의 분화가 촉진되고, aP2(adipocyte fatty acid binding protein 2)와 같은 지방세포 특이적 단백질 및 Fas(fatty acid synthase)와 같은 지방 대사 효소의 발현량이 증가한다. 더불어 ADD1/SREBPs는 지방 대사에도 중요한 역할을 하지만, 또한 분화과정에도 관여하는 것으로 알려졌다. 미성숙 지방세포에서 ADD1/SREBP1c가 발현되는 것은 PPARγ의 활성화에 기여하는 것으로 여겨진다(Rosen E.D. et al., Annu. Rev. Cell Dev. Biol., 16, pp145-171, 2000; Osborn T.F., J. Biol. Chem., 275, pp32379-32382, 2000). 분화과정을 마친 지방세포만이 지방산(fatty acid)을 합성하고 중성지질(triglycerides)을 저장하게 된다. 따라서, 현재 연구 동향은 비만 및 지질 관련 대사성 질환을 예방 또는 치료하기 위한 방법으로서, 지방세포 분화에 관한 대사과정을 저해할 수 있는 물질을 탐색하는데 초점이 맞추어져 있다. 즉, 비만의 발생 기전에 의거하여 지방세포 조절을 통해 비만을 치료하려는 시도가 이루어지고 있으며, 이것은 지방 합성을 억제하거나 지방 분해 및 산화를 촉진하여 지방 양을 감소시키려는 것과 지방세포 분화를 억제하여 지방세포 수를 감소시키려는 것으로, 이들 과정을 매개하거나 조절하는 것으로 알려진 전사인자들이나 단백질 그리고 지방세포 분비 물질들(adipokines)을 새로운 비만치료제 개발의 표적으로 떠오르게 하였다. 실제로 지방세포 분화 전사인자인 PPAR(Peroxisome proliferator activated receptor) 패밀리, 지방세포 분비 물질인 렙틴(leptin) 및 아디포넥틴 (adiponectin) 등은 많은 새로운 약제 개발의 표적이 되고 있다.The process of differentiation of pro-adipocytes into adipocytes has been studied using cells such as 3T3-L1, and several transcription factors, especially transcription factors known to be involved in localization, C / EBPs (CCAAT enhancers). It is known that binding proteins, PPARs (Peroxisome proliferator activated receptor) and ADD1 / SREBPs (Adipocyte determination and differentiation dependent factor1 / sterol response element binding proteins) are expressed over time and regulate the process (Bart A Jessen). et al., Gene, 299, pp95-100, 2002; Darlington et al., J. Biol. Chem., 273, pp30057-30060, 1998; Brun RP et al., Curr. Opin. Cell. Biol., 8 , pp826-832, 1996). Given the stimulation of hormones such as isobutylmethylxanthin, dexamethasone and insulin (MDI), C / EBP β and δ are the first, transiently expressed, to initiate differentiation into adipocytes (Reusch J. E et al., Mol Cell Biol., 20, pp 1008-1020, 2000). This continues to lead to increased expression of C / EBPa and PPARγ (James M. N. et al., J. Nutr., 130, pp 3122S-3126S, 2000). PPARγ is a particularly important transcription factor for adipocyte differentiation, and forms dimers with the retinoic acid X receptor protein (RXR), which is present in the promoters of various adipocyte genes. Binds to peroxisome proliferator response elements (Tontonoz PE et al., Genes Dev., 8, pp1224-1234, 1994; Hwang, C. S et al., Cell Dev. Biol., 13, pp873-877) . The interaction of PPARγ with C / EBP α is critical for differentiation into mature adipocytes. These transcription factors and adipocyte modulators promote the differentiation of adipocytes into adipocytes, and with ap2 (adipocyte fatty acid binding protein 2) Expression levels of fat cell specific proteins such as fat fat enzymes such as fat acid synthase (FAS) are increased. In addition, ADD1 / SREBPs play an important role in fat metabolism, but are also known to be involved in the differentiation process. Expression of ADD1 / SREBP1c in immature adipocytes is believed to contribute to the activation of PPARγ (Rosen ED et al., Annu. Rev. Cell Dev. Biol., 16, pp 145-171, 2000; Osborn TF, J. Biol Chem., 275, pp 32379-32382, 2000). Only the differentiated fat cells synthesize fatty acids and store triglycerides. Therefore, current research trends are focused on the discovery of substances that can inhibit metabolic processes related to adipocyte differentiation as a method for preventing or treating obesity and lipid-related metabolic diseases. In other words, attempts have been made to treat obesity through the regulation of fat cells based on the mechanism of the development of obesity, which aims to reduce fat synthesis by inhibiting fat synthesis or promoting fat breakdown and oxidation, and inhibiting fat cell differentiation. To reduce cell numbers, transcription factors, proteins and adipokines, known to mediate or regulate these processes, have emerged as targets for the development of new anti-obesity drugs. Indeed, the PPAR family of adipocyte differentiation transcription factors, leptin and adiponectin, adipocyte secreting substances, have been targeted for many new drug developments.
현재까지 알려진 비만치료제로는 제니칼(Xenical, 로슈제약회사, 스위스), 리덕틸([0004] Reductil, 에보트사, 미국), 엑소리제(Exolise, 아토파마, 프랑스) 등으로 크게 식욕억제제, 에너지소비 촉진제, 지방흡수억제제로 분류되며, 대부분의 비만치료제는 시상하부와 관련된 신경전달물질을 조절함으로써 식욕을 억제하는 식욕억제제이다. 그러나 종래의 치료제들은 심장질환, 호흡기질환, 신경계질환 등의 부작용과 함께 그 효능의 지속성도 낮아, 더욱 개선된 비만치료제의 개발이 필요하고 또한, 현재 개발되고 있는 제품도 부작용 없이 만족할 만한 치료 효과를 가지는 치료제는 거의 없어 새로운 비만치료제의 개발이 요구되고 있다.Known obesity treatments so far include Xenical (Xenical, Roche Pharmaceuticals, Switzerland), Reductil (Reductil, Evot, USA), Exorise (Exolise, Atopama, France), etc. In addition, most obesity drugs are appetite suppressants that suppress appetite by regulating neurotransmitters related to the hypothalamus. However, the conventional treatments have low side effects such as heart disease, respiratory disease, and neurological disease, and thus have low continuity. Therefore, the development of improved obesity drugs is needed, and the currently developed products have satisfactory treatment effects without side effects. Since there are few therapeutic agents, development of new obesity agents is required.
따라서, 본 발명에서 해결하고자 하는 기술적 과제는 비만 또는 비만 관련 질환에 대한 예방 또는 치료 효능을 가지는 새로운 물질을 제공하기 위한 것이다.Accordingly, the technical problem to be solved in the present invention is to provide a new material having a prophylactic or therapeutic effect on obesity or obesity-related diseases.
상기한 기술적 과제를 해결하기 위하여, 본 발명에서는 젠티오피크로사이드(gentiopicroside) 또는 이의 약학적으로 허용가능한 염을 유효성분으로 포함하는 비만 또는 비만 관련 질환의 예방 또는 치료용 약학적 조성물을 제공한다.In order to solve the above technical problem, the present invention provides a pharmaceutical composition for the prevention or treatment of obesity or obesity-related diseases comprising gentiopicroside or a pharmaceutically acceptable salt thereof as an active ingredient. .
본 발명의 하나의 구현예에 따르면, 본 발명에서는 젠티오피크로사이드(gentiopicroside) 또는 이의 식품학적으로 허용가능한 염을 유효성분으로 포함하는 비만 또는 비만 관련 질환의 예방 또는 개선용 식품 조성물을 제공한다.According to one embodiment of the present invention, the present invention provides a food composition for the prevention or improvement of obesity or obesity-related diseases comprising gentiopicroside or a food acceptable salt thereof as an active ingredient. .
본 발명에서 사용되는 용어 "약학적으로 허용가능한" 및 "식품학적으로 허용가능한" 이란 생물체를 자극하지 않고 투여 활성 물질의 생물학적 활성 및 특성을 저해하지 않는 것을 의미한다.As used herein, the terms "pharmaceutically acceptable" and "food acceptable" mean that they do not stimulate the organism and do not inhibit the biological activity and properties of the administered active substance.
본 발명에서 사용되는 용어 "예방"은 본 발명의 조성물의 투여로 특정 질환 예를 들어, 비만 또는 비만 관련 질환의 증상을 억제시키거나 진행을 지연시키는 모든 행위를 의미한다.As used herein, the term "prevention" refers to any action that inhibits the symptoms or delays the progression of a particular disease, such as obesity or obesity-related disease, by administration of a composition of the invention.
본 발명에서 사용되는 용어 "치료"는 본 발명의 조성물의 투여로 특정 질환 예를 들어, 비만 또는 비만 관련 질환의 증상을 호전 또는 이롭게 변경시키는 모든 행위를 의미한다.As used herein, the term "treatment" refers to any action that improves or beneficially alters the symptoms of a particular disease, such as obesity or an obesity related disease, by administration of a composition of the present invention.
본 발명에서 사용되는 용어 "개선"은 치료되는 상태와 관련된 파라미터, 예를 들면 증상의 정도를 적어도 감소시키는 모든 행위를 의미한다.The term "improvement" as used herein refers to any action that at least reduces the parameters associated with the condition being treated, for example, the extent of symptoms.
본 발명에서 사용되는 용어 "투여"는 임의의 적절한 방법으로 개체에 소정의 본 발명의 조성물을 제공하는 것을 의미한다. 이때, 개체는 본 발명의 조성물을 투여하여 특정 질환의 증상이 호전될 수 있는 질환을 가진 인간, 원숭이, 개, 염소, 돼지 또는 쥐 등 모든 동물을 의미한다.As used herein, the term "administration" means providing a subject with a composition of the present invention in any suitable manner. At this time, the subject refers to all animals, such as humans, monkeys, dogs, goats, pigs or mice having a disease that can improve the symptoms of a particular disease by administering the composition of the present invention.
본 발명에서 사용되는 용어 "약학적으로 유효한 양"은 의학적 치료에 적용 가능한 합리적인 수혜 또는 위험 비율로 질환을 치료하기에 충분한 양을 의미하며, 이는 개체의 질환의 종류, 중증도, 약물의 활성, 약물에 대한 민감도, 투여 시간, 투여 경로 및 배출비율, 치료기간, 동시에 사용되는 약물을 포함한 요소 및 기타 의학 분야에 잘 알려진 요소에 따라 결정될 수 있다.As used herein, the term “pharmaceutically effective amount” means an amount sufficient to treat a disease at a reasonable benefit or risk ratio applicable to medical treatment, which means the type of disease, the severity, the activity of the drug, the drug Sensitivity to, time of administration, route of administration and rate of administration, duration of treatment, factors including drug used concurrently, and other factors well known in the medical arts.
본 발명의 조성물의 유효성분인 젠티오피크로사이드(gentiopicroside)는 젠티오피크린(gentiopicrin)이라고도 명명되며, 분자식 C16H20O9으로 표현되는 화합물로서 이를 함유하는 물질, 예를 들어 용담과(Gentianaceae)에 속하는 진교(Gentianae Macrophyllae Radix)로부터 분리되거나 화학적으로 합성될 수 있으며, 하기 화학식 1의 구조식을 가진다.Genthiopicroside, an active ingredient of the composition of the present invention, is also called gentiopicrin, and is a compound represented by the molecular formula C 16 H 20 O 9 , containing a substance, for example, gentian ( Gentianae ) can be isolated or chemically synthesized from Gentianae Macrophyllae Radix, and has the structure of Formula 1.
본 발명에 있어서, 상기 젠티오피크로사이드를 진교로부터 분리하는 경우, 당업계에서 통상적으로 사용되는 추출용매를 사용하여 추출할 수 있는데, 추출용매는 예를 들어, (a) 물, (b) 탄소수 1-4의 무수 또는 함수 저급 알코올(메탄올, 에탄올, 프로판올, 부탄올 등), (c) 상기 저급 알코올과 물과의 혼합용매, (d) 아세톤, (e) 에틸 아세테이트, (f) 클로로포름, 또는 (g) 1,3-부틸렌글리콜을 사용할 수 있다. 한편, 본 발명의 젠티오피크로사이드는 상기한 추출용매 뿐만 아니라, 다른 추출용매를 이용하여도 실질적으로 동일한 효과를 나타내는 추출물이 얻어질 수 있다는 것은 당업자에게 자명한 것이다.In the present invention, in the case of separating the genthiopicroside from the orthogonal, it can be extracted using an extraction solvent commonly used in the art, the extraction solvent is, for example, (a) water, (b) Anhydrous or hydrous lower alcohol having 1 to 4 carbon atoms (methanol, ethanol, propanol, butanol, etc.), (c) a mixed solvent of the lower alcohol with water, (d) acetone, (e) ethyl acetate, (f) chloroform, Or (g) 1,3-butylene glycol can be used. On the other hand, it will be apparent to those skilled in the art that the genthiopicroside of the present invention can be obtained in addition to the above-described extraction solvents, and extracts having substantially the same effect using other extraction solvents.
또한, 상기 젠티오피크로사이드는 상기 추출용매에 의하여 추출하는 방법 이외에 통상적인 분리 및 정제과정을 거쳐서도 수득할 수 있다. 예컨대, 다양한 크로마토그래피(크기, 전하, 소수성 또는 친화성에 따른 분리를 위해 제작된 것)에 의한 분리 등, 추가적으로 실시된 다양한 정제방법을 통해 얻어진 분획을 통하여서도 젠티오피크로사이드를 수득할 수 있다.In addition, the genthiopicroside can be obtained through a conventional separation and purification in addition to the extraction by the extraction solvent. Genthiopicrosides can also be obtained through fractions obtained through various purification methods additionally carried out, for example by separation by various chromatography (manufactured for separation according to size, charge, hydrophobicity or affinity). .
본 발명의 하나의 구현예에 따르면, 본 발명은 젠티오피크로사이드의 신규 용도에 관한 것으로서, 젠티오피크로사이드 또는 이의 약학적 또는 식품학적으로 허용가능한 염을 유효성분으로 포함하는 비만 또는 비만 관련 질환의 예방, 개선 또는 치료용 조성물을 제공한다.According to one embodiment of the present invention, the present invention relates to a novel use of genthiopicroside, wherein obesity or obesity comprising genthiopicroside or a pharmaceutically or pharmaceutically acceptable salt thereof as an active ingredient Provided are compositions for the prevention, amelioration or treatment of related diseases.
본 발명에 따른 젠티오피크로사이드 또는 이의 약학적 또는 식품학적으로 허용가능한 염은 비만 또는 비만 관련 질환을 예방, 개선 또는 치료하기 위한 유효성분으로 사용할 수 있다. 상기 비만 관련 질환은 비만에 의해 유발되거나 비만과 상관관계가 높은 질환이라면 그 종류가 크게 제한되지 않으며, 예를 들어 지방간, 제2형 당뇨, 고지혈증, 심혈관 질환, 동맥경화증 및 지질 관련 대사증후군에서 선택되는 어느 하나일 수 있다. 또한, 상기 지질 관련 대사증후군은 당뇨, 비만 등 여러 가지 대사성 질환이 한 사람에게 동시에 나타나는 질환을 의미한다.Genthiopicroside according to the present invention or a pharmaceutically or food acceptable salt thereof can be used as an active ingredient for preventing, ameliorating or treating obesity or obesity-related diseases. The obesity-related diseases are not limited in kind as long as they are caused by obesity or are highly correlated with obesity, for example, selected from fatty liver,
본 발명의 젠티오피크로사이드 또는 이의 약학적 또는 식품학적으로 허용가능한 염을 유효성분으로 포함하는 조성물은 사용 목적 내지 양상에 따라 약학 조성물, 식품 첨가제, 식품 조성물(특히 기능성 식품 조성물), 또는 사료 첨가제 등으로 구체화될 수 있고, 조성물 내에서 젠티오피크로사이드의 함량도 조성물의 구체적인 형태, 사용 목적 내지 양상에 따라 다양한 범위에서 조정될 수 있다.The composition comprising the genothiopicroside of the present invention or a pharmaceutically or food acceptable salt thereof as an active ingredient may be a pharmaceutical composition, a food additive, a food composition (particularly a functional food composition), or a feed, depending on the purpose of use and aspects It may be embodied as an additive or the like, and the content of genthiopicroside in the composition may also be adjusted in various ranges according to the specific form of the composition, the purpose of use, and the aspect.
본 발명에 있어서, 상기 젠티오피크로사이드의 약학적으로 또는 식품학적으로 허용가능한 염은 히드록시기의 나트륨, 칼슘 및 칼륨염이 포함되며, 아미노기의 기타 약학적으로 허용 가능한 염으로는 이드로브로마이드, 황산염, 수소 황산염, 인산염, 이수소 인산염, 아세테이트, 숙시네이트, 시트레이트, 타르트레이트, 락테이트, 만텔레이트, 메탄설포네이트 및 ρ-톨루엔설포네이트 염이 있으며, 당업계에서 알려진 염의 제조방법이나 제조과정을 통하여 제조될 수 있으나, 이에 제한되지 않는다.In the present invention, the pharmaceutically or food acceptable salts of the genthiopicroside include sodium, calcium and potassium salts of the hydroxy group, and other pharmaceutically acceptable salts of the amino group include ibrobromide, sulfate , Hydrogen sulphate, phosphate, dihydrogen phosphate, acetate, succinate, citrate, tartrate, lactate, mantellate, methanesulfonate and ρ-toluenesulfonate salts. It may be prepared through, but is not limited thereto.
또한, 약학적으로 허용가능한 유리산(free acid)에 의해 형성되는 산부가염이 유용하다. 산부가염은 통상의 방법, 예를 들면 화합물을 과량의 산 수용액에 용해시키고, 이 염을 메탄올, 에탄올, 아세톤 또는 아세토니트릴과 같은 수혼화성 유기용매를 사용하여 침전시켜 제조한다. 동 몰량의 화합물 및 물 중의 산 또는 알코올(예, 글리콜 모노메틸에테르)을 가열하고 이어서 상기 혼합물을 증발시켜 건조시키거나, 또는 석출된 염을 흡인 여과시킬 수 있다. Also useful are acid addition salts formed by pharmaceutically acceptable free acid. Acid addition salts are prepared by conventional methods, for example by dissolving a compound in an excess of aqueous acid solution and precipitating the salt using a water miscible organic solvent such as methanol, ethanol, acetone or acetonitrile. Equivalent molar amounts of the compound and acid or alcohol (eg, glycol monomethyl ether) in water can be heated and the mixture can then be evaporated to dryness or the precipitated salts can be suction filtered.
이 때, 유리산으로는 유기산과 무기산을 사용할 수 있으며, 무기산으로는 염산, 인산, 황산, 질산, 주석산 등을 사용할 수 있고, 유기산으로는 메탄술폰산, ρ-톨로엔술폰한, 아세트산, 트리플루오르아세트산, 시트르산, 말레인산, 숙신산, 옥살산, 벤조산, 타르타르산, 푸마르산, 만데르산, 프로피온산, 구연산, 젖산, 글리콜산, 글로콘산, 갈락투론산, 글루탐산, 글루타르산, 글루쿠론산, 아스파르트산, 아스코르빈산, 카본산, 바닐릭산, 히드로 아이오딕산 등을 사용할 수 있다. In this case, organic acids and inorganic acids may be used as the free acid, and hydrochloric acid, phosphoric acid, sulfuric acid, nitric acid, tartaric acid, and the like may be used as the inorganic acid, and methanesulfonic acid, ρ-toluenesulfone, acetic acid, and trifluorine may be used as the organic acid. Acetic acid, citric acid, maleic acid, succinic acid, oxalic acid, benzoic acid, tartaric acid, fumaric acid, manderic acid, propionic acid, citric acid, lactic acid, glycolic acid, gluconic acid, galacturonic acid, glutamic acid, glutaric acid, glucuronic acid, aspartic acid, aspartic acid Corbic acid, carbonic acid, vanic acid, hydroiodic acid and the like can be used.
또한, 염기를 사용하여 약학적으로 허용가능한 금속염을 만들 수 있다. 알칼리 금속 또는 알칼리토 금속염은, 예를 들면 화합물을 과량의 알칼리 금속 수산화물 또는 알칼리토 금속 수산화물 용액 중에 용해하고, 비용해 화합물 염을 여과한 후 여액을 증발, 건조시켜 얻는다. 이 때, 금속염으로는 특히, 나트륨, 칼륨 또는 칼슘염을 제조하는 것이 제약상 적합하며, 이에 대응하는 은염은 알칼리 금속 또는 알칼리토 금속염을 적당한 은염(예, 질산은)과 반응시켜 얻는다.Bases can also be used to make pharmaceutically acceptable metal salts. An alkali metal or alkaline earth metal salt is obtained by, for example, dissolving a compound in an excess alkali metal hydroxide or alkaline earth metal hydroxide solution, filtering the insoluble compound salt, and then evaporating and drying the filtrate. At this time, as the metal salt, it is particularly suitable to prepare sodium, potassium or calcium salt, and the corresponding silver salt is obtained by reacting an alkali metal or alkaline earth metal salt with a suitable silver salt (for example, silver nitrate).
본 발명의 하나의 실시양태에 따르면, 상기 젠티오피크로사이드 또는 이의 약학적 또는 식품학적으로 허용가능한 염은 전구지방세포의 지방세포로의 분화시 분화 관련 전사인자인 페록시솜 증식체 활성화 수용체 감마(peroxisome proliferator activated receptor gamma, Pparg)와 CCAAT/인핸서 결합 단백질 알파(enhancer binding protein alpha, Cebpa)뿐만 아니라 지방형성의 조절자인 스테롤 조절인자 결합 전사인자(sterol regulatory element binding transcription factor 1, Srebf1)의 유전자 및 지질흡수관련 유전자인 단백질 리파제(Lpl) 및 지방산 결합 단백질 4(Fabp4)의 발현을 하향 조절하여 분화를 억제하거나 중성지질의 축적을 억제할 수 있다. According to one embodiment of the present invention, said genthiopicroside or a pharmaceutically or food-acceptable salt thereof is a peroxysomal proliferator activating receptor gamma, which is a differentiation-related transcription factor in the differentiation of profat cells into adipocytes. not only peroxisome proliferator activated receptor gamma ( Pparg ) and CCAAT / enhancer binding protein alpha ( Cebpa ) but also sterol regulatory element binding transcription factor 1 ( Srebf1 ), a regulator of lipoogenesis . And down-regulation of the expression of protein lipase ( Lpl ) and fatty acid binding protein 4 ( Fabp4 ), which are lipid absorption-related genes, may inhibit differentiation or inhibit accumulation of neutral lipids .
본 발명의 하나의 실시양태에 따르면, 상기 젠티오피크로사이드 또는 이의 약학적 또는 식품학적으로 허용가능한 염은 지방산생성을 조절하는 유전자인 지방산 합성효소(Fasn)와 스테아로일-코엔자임 A 델타-9 디세츄라제(stearol-Coenzyme A desaturase) 1(Scd1)뿐만 아니라 디아실글리세롤(diacylglycerol)에 지방산을 붙여 트리아실글리세롤(triacylglycerol)로 만드는 효소로 중성지방 합성의 최종단계를 촉매하는 디아실글리세롤 O-아실트랜스퍼라제(diacylglycerol O-acyltransferase) 2(Dgat2)의 유전자 발현을 하향 조절하여 지방의 합성 및 축적을 억제할 수 있다. According to one embodiment of the invention, the genothiopicroside or a pharmaceutically or food acceptable salt thereof is a fatty acid synthase ( Fasn ) and a stearoyl-coenzyme A delta- which are genes that regulate fatty acid production. 9 Diacylglycerol O, which catalyzes the final stage of triglyceride synthesis with enzymes that attach fatty acids to diacylglycerol as well as sterolol-Coenzyme A desaturase 1 ( Scd1 ). Downregulation of gene expression of acyltransferase (diacylglycerol O-acyltransferase) 2 ( Dgat2 ) can inhibit the synthesis and accumulation of fat.
따라서, 본 발명의 젠티오피크로사이드 또는 이의 약학적 또는 식품학적으로 허용가능한 염은 비만을 예방, 개선 또는 치료하기 위한 유효성분으로 사용될 수 있고, 더 나아가 지방간, 제2형 당뇨, 고지혈증, 심혈관 질환, 동맥경화증 및 지질 관련 대사증후군으로 이루어진 군에서 선택되는 비만 관련 질환을 예방, 개선 또는 치료하기 위한 유효성분으로 사용될 수 있다. 상기 지질 관련 대사증후군은 당뇨, 비만 등 여러 가지 대사성 질환이 한 사람에게 동시에 나타나는 질환을 의미한다.Therefore, the genothiopicroside of the present invention or a pharmaceutically or food acceptable salt thereof can be used as an active ingredient for preventing, improving or treating obesity, and furthermore, fatty liver,
본 발명의 젠티오피크로사이드 또는 이의 약학적 또는 식품학적으로 허용가능한 염을 유효성분으로 포함하는 조성물은 사용 목적 내지 양상에 따라 약학 조성물, 식품 첨가제, 식품 조성물(특히 기능성 식품 조성물), 또는 사료 첨가제 등으로 구체화될 수 있고, 조성물 내에서 상기 유효성분의 함량도 조성물의 구체적인 형태, 사용 목적 내지 양상에 따라 다양한 범위에서 조정될 수 있다.The composition comprising the genothiopicroside of the present invention or a pharmaceutically or food acceptable salt thereof as an active ingredient may be a pharmaceutical composition, a food additive, a food composition (particularly a functional food composition), or a feed, depending on the purpose of use and aspects It may be embodied as an additive and the like, and the content of the active ingredient in the composition may be adjusted in various ranges according to the specific form of the composition, the purpose of use, and the aspect.
본 발명에 따른 젠티오피크로사이드 또는 이의 약학적으로 허용 가능한 염을 유효성분으로 포함하는 약학 조성물에서 상기 유효성분의 함량은 크게 제한되지 않으며, 예를 들어 조성물 총 중량을 기준으로 0.001 내지 50 중량%, 바람직하게는 0.01 내지 30 중량%, 보다 바람직하게는 0.01 내지 10 중량%의 함량으로 포함될 수 있다. 상기 젠티오피크로사이드 또는 이의 약학적으로 허용 가능한 염의 함량이 0.001 중량% 미만일 경우 지방분해억제 및 생성방지 효과가 미약하고, 50 중량%를 초과하는 경우 함량 증가에 따른 효과 증가가 비례적이지 않아 비효율적일 수 있으며, 제형상의 안정성이 확보되지 않는 문제가 있다. In the pharmaceutical composition comprising genthiopicroside according to the present invention or a pharmaceutically acceptable salt thereof as an active ingredient, the content of the active ingredient is not particularly limited, for example, 0.001 to 50 wt.% Based on the total weight of the composition. %, Preferably 0.01 to 30% by weight, more preferably 0.01 to 10% by weight. If the content of the genothiopiroside or the pharmaceutically acceptable salt thereof is less than 0.001% by weight, the effect of inhibiting lipolysis and formation is weak, and when the content exceeds 50% by weight, the increase in effect due to the increase in content is not proportional. It may be inefficient, and there is a problem in that formulation stability is not secured.
또한, 본 발명에 따른 약학 조성물은 젠티오피크로사이드 또는 이의 약학적으로 허용 가능한 염 외에 약학적으로 허용가능한 담체, 부형제 또는 희석제와 같은 첨가제를 더 포함할 수 있다. 본 발명의 약학 조성물에 포함될 수 있는 담체, 부형제 및 희석제로는 락토즈, 덱스트로즈, 수크로스, 솔비톨, 만니톨, 자일리톨, 에리스리톨, 말티톨, 전분, 아카시아 고무, 알지네이트, 젤라틴, 칼슘 포스페이트, 칼슘 실리케이트, 셀룰로즈, 메틸 셀룰로즈, 미정질 셀룰로스, 폴리비닐 피롤리돈, 물, 메틸히드록시 벤조에이트, 프로필히드록시벤조에이트, 탈크, 마그네슘 스테아레이트 및 광물유를 들 수 있다. In addition, the pharmaceutical composition according to the present invention may further include additives such as pharmaceutically acceptable carriers, excipients or diluents in addition to genthiopicroside or a pharmaceutically acceptable salt thereof. Carriers, excipients and diluents that may be included in the pharmaceutical compositions of the present invention include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia rubber, alginate, gelatin, calcium phosphate, calcium silicate , Cellulose, methyl cellulose, microcrystalline cellulose, polyvinyl pyrrolidone, water, methyl hydroxy benzoate, propyl hydroxy benzoate, talc, magnesium stearate and mineral oil.
또한, 본 발명의 비만 또는 비만 관련 질환의 예방 또는 치료용 약학 조성물은 젠티오피크로사이드의 약학적으로 허용 가능한 염 외에 비만 또는 비만 관련 질환의 예방 또는 치료 효과를 갖는 공지의 유효성분을 1종 이상 더 함유할 수 있다. In addition, the pharmaceutical composition for the prevention or treatment of obesity or obesity-related diseases of the present invention includes one known effective ingredient having the effect of preventing or treating obesity or obesity-related diseases in addition to the pharmaceutically acceptable salt of genthiopicroside. It may contain more.
본 발명의 약학 조성물은 통상의 방법에 의해 경구 투여를 위한 제형 또는 비경구 투여를 위한 제형으로 제제화될 수 있고, 제제화할 경우 보통 사용하는 충진제, 증량제, 결합제, 습윤제, 붕해제, 계면활성제 등의 희석제 또는 부형제를 사용하여 조제될 수 있다. 경구 투여를 위한 고형 제제에는 정제, 환제, 산제, 과립제, 캡슐제 등이 포함되며, 이러한 고형 제제는 유효성분에 적어도 하나 이상의 부형제 예를 들면, 전분, 칼슘카보네이트(Calcium carbonate), 수크로스(Sucrose), 락토오스(Lactose) 또는 젤라틴 등을 섞어 조제될 수 있다. 또한, 단순한 부형제 이외에 마그네슘 스티레이트 탈크 같은 윤활제들도 사용될 수 있다. 경구 투여를 위한 액상 제제로는 현탁제, 내용액제, 유제 및 시럽제 등이 해당되는데 흔히 사용되는 단순희석제인 물, 리퀴드 파라핀 이외에 여러 가지 부형제, 예를 들면 습윤제, 감미제, 방향제, 보존제 등이 포함될 수 있다. 비경구 투여를 위한 제제에는 멸균된 수용액, 비수성용제, 현탁제, 유제, 동결건조제제, 좌제가 포함될 수 있다. 비수성 용제, 현탁용제로는 프로필렌글리콜(Propylene glycol), 폴리에틸렌 글리콜, 올리브 오일과 같은 식물성 기름, 에틸올레이트와 같은 주사 가능한 에스테르 등이 사용될 수 있다. 좌제의 기제로는 위텝솔(witepsol), 마크로골, 트윈(tween) 61, 카카오지, 라우린지, 글리세로제라틴 등이 사용될 수 있다. 더 나아가 당 분야의 적정한 방법으로 또는 Remington's Pharmaceutical Science(최근판), Mack Publishing Company, Easton PA에 개시되어 있는 방법을 이용하여 각 질환에 따라 또는 성분에 따라 바람직하게 제제화할 수 있다. The pharmaceutical composition of the present invention may be formulated into a formulation for oral administration or a parenteral administration by a conventional method, and when formulated, such as fillers, extenders, binders, wetting agents, disintegrating agents, surfactants, etc. Diluents or excipients may be used. Solid preparations for oral administration include tablets, pills, powders, granules, capsules, and the like, and such solid preparations contain at least one excipient such as starch, calcium carbonate, sucrose in active ingredients. ), Lactose (Lactose) or gelatin can be prepared by mixing. In addition to simple excipients, lubricants such as magnesium styrate talc may also be used. Liquid preparations for oral administration include suspensions, solutions, emulsions, and syrups, and various excipients such as wetting agents, sweeteners, fragrances, and preservatives, in addition to commonly used simple diluents, water and liquid paraffin. have. Formulations for parenteral administration may include sterile aqueous solutions, non-aqueous solvents, suspensions, emulsions, lyophilized preparations, suppositories. As the non-aqueous solvent and the suspension solvent, propylene glycol, polyethylene glycol, vegetable oil such as olive oil, injectable ester such as ethyl oleate, and the like can be used. As the base of the suppository, witepsol, macrogol, tween 61, cacao butter, laurin butter, glycerogelatin and the like can be used. Furthermore, it may be preferably formulated according to each disease or component by an appropriate method in the art or using a method disclosed in Remington's Pharmaceutical Science (Recent Edition), Mack Publishing Company, Easton PA.
본 발명의 약학 조성물은 목적하는 방법에 따라 인간을 포함한 포유류에 경구 투여되거나 비경구 투여될 수 있으며, 비경구 투여 방식으로는 피부 외용, 복강내주사, 직장내주사, 피하주사, 정맥주사, 근육내 주사 또는 흉부내 주사 주입방식 등이 있다. 본 발명의 약학 조성물의 투여량은 약학적으로 유효한 양이라면 크게 제한되지 않으며, 환자의 체중, 연령, 성별, 건강상태, 식이, 투여시간, 투여방법, 배설율 및 질환의 중증도에 따라 그 범위가 다양하다.The pharmaceutical composition of the present invention can be administered orally or parenterally to mammals including humans according to a desired method, and parenteral administration methods include external skin, intraperitoneal injection, rectal injection, subcutaneous injection, intravenous injection, muscle Intra-injection or intrathoracic injection; The dosage of the pharmaceutical composition of the present invention is not particularly limited as long as it is a pharmaceutically effective amount, and the range thereof depends on the weight, age, sex, health condition, diet, time of administration, method of administration, excretion rate and severity of the disease. Varies.
본 발명의 약학 조성물의 통상적인 1일 투여량은 크게 제한되지 않으나 바람직하게는 유효성분인 젠티오피크로사이드 또는 이의 약학적으로 허용 가능한 염을 기준으로 할 때 0.1 내지 3000 ㎎/㎏이고, 더 바람직하게는 1 내지 2000 ㎎/㎏이며, 하루 1회 또는 수회로 나누어 투여될 수 있다.Typical daily dosages of the pharmaceutical compositions of the present invention are not particularly limited but are preferably 0.1 to 3000 mg / kg, based on the active ingredient genthiopicroside or a pharmaceutically acceptable salt thereof, and more Preferably it is 1-2000 mg / kg, and can be administered once a day or divided into several times.
또한, 본 발명의 젠티오피크로사이드 또는 이의 식품학적으로 허용 가능한 염을 유효성분으로 포함하는 식품 조성물은 환제, 분말, 과립, 침제, 정제, 캡슐, 또는 액제 등의 형태를 포함하며, 구체적인 식품의 예로는 육류, 소시지, 빵, 초콜릿, 캔디류, 스넥류, 과자류, 피자, 라면, 기타 면류, 껌류, 아이스크림류를 포함한 낙농제품, 각종 스프, 음료수, 차, 기능수, 드링크제, 알코올음료 및 비타민 복합제 등이 있으며, 통상적인 의미에서의 건강식품을 모두 포함한다. In addition, the food composition comprising the genothiopicroside of the present invention or a food-acceptable salt thereof as an active ingredient includes the form of pills, powders, granules, acupuncture, tablets, capsules, or liquids, and specific foods Examples include dairy products, including meat, sausages, bread, chocolate, candy, snacks, confectionery, pizza, ramen, other noodles, gums, ice cream, various soups, drinks, tea, functional water, drinks, alcoholic beverages and vitamin complexes. And the like, and include all health foods in the conventional sense.
본 발명의 식품 조성물에서 젠티오피크로사이드 또는 이의 식품학적으로 허용 가능한 염과 같은 유효성분의 함량은 조성물 총 중량을 기준으로 0.001 내지 50 중량%, 바람직하게는 0.01 내지 30 중량%, 보다 바람직하게는 0.01 내지 10 중량%의 함량이나, 이에 한정되는 것은 아니다. In the food composition of the present invention, the content of the active ingredient, such as genthiopicroside or a food acceptable salt thereof, is 0.001 to 50% by weight, preferably 0.01 to 30% by weight, more preferably based on the total weight of the composition. Is an amount of 0.01 to 10% by weight, but is not limited thereto.
본 발명의 식품 조성물은 젠티오피크로사이드 또는 이의 식품학적으로 허용 가능한 염 외에 여러 가지 향미제 또는 천연 탄수화물 등을 추가 성분으로서 함유할 수 있다. 또한, 본 발명의 식품 조성물은 여러 가지 영양제, 비타민, 전해질, 풍미제, 착색제, 펙트산 및 그의 염, 알긴산 및 그의 염, 유기산, 보호성 콜로이드 증점제, pH 조절제, 안정화제, 방부제, 글리세린, 알코올, 탄산음료에 사용되는 탄산화제 등을 함유할 수 있다. 그 밖에 본 발명의 식품 조성물은 천연 과일주스, 과일주스 음료 및 야채 음료의 제조를 위한 과육을 함유할 수 있다. 이러한 성분들은 독립적으로 또는 혼합하여 사용할 수 있다. 상술한 천연 탄수화물은 포도당, 과당과 같은 모노사카라이드, 말토스, 슈크로스와 같은 디사카라이드, 및 덱스트린, 사이클로덱스트린과 같은 폴리사카라이드, 자일리톨, 소르비톨, 에리트리톨 등의 당알코올이다. 향미제로는 타우마틴, 스테비아 추출물과 같은 천연 향미제나 사카린, 아스파르탐과 같은 합성 향미제 등을 사용할 수 있다.The food composition of the present invention may contain various flavors, natural carbohydrates, and the like as additional components in addition to genthiopicroside or a food acceptable salt thereof. In addition, the food composition of the present invention is a variety of nutrients, vitamins, electrolytes, flavors, colorants, pectic acid and salts thereof, alginic acid and salts thereof, organic acids, protective colloidal thickeners, pH regulators, stabilizers, preservatives, glycerin, alcohols And carbonation agents used in carbonated beverages. In addition, the food composition of the present invention may contain a flesh for preparing natural fruit juice, fruit juice beverage and vegetable beverage. These components can be used independently or in combination. The above-mentioned natural carbohydrates are glucose, monosaccharides such as fructose, disaccharides such as maltose and sucrose, and polysaccharides such as dextrin and cyclodextrin, sugar alcohols such as xylitol, sorbitol and erythritol. As the flavoring agent, natural flavoring agents such as taumartin, stevia extract, synthetic flavoring agents such as saccharin, aspartame, etc. may be used.
이와 같이, 본 발명에 따른 젠티오피크로사이드는 지방합성 관련 유전자의 발현을 하향 조절함으로써 전구지방세포의 지방세포로의 분화시 분화를 억제하는 효과를 가지며, 중성지질의 축적을 억제하는 효과가 우수하다. 따라서, 본 발명에 따른 젠티오피크로사이드는 비만, 지방간, 제2형 당뇨, 고지혈증, 심혈관 질환, 동맥경화증 및 지질 관련 같은 질환을 예방, 개선 또는 치료하는데에 유용하게 사용될 수 있다.As such, the genthiopicroside according to the present invention has an effect of inhibiting the differentiation of pro-adipocytes into adipocytes by down-regulating the expression of fat synthesis-related genes, and is excellent in inhibiting accumulation of neutral lipids. . Therefore, the genothiopicroside according to the present invention can be usefully used to prevent, ameliorate or treat diseases such as obesity, fatty liver,
도 1은 젠티오피크로사이드가 세포증식에 미치는 영향을 나타낸 것이다.
도 2는 젠티오피크로사이드가 지방세포 분화억제에 미치는 영향을 나타낸 것이다.
도 3은 젠티오피크로사이드가 중성지질 축적에 미치는 영향을 나타낸 것이다.
도 4는 젠티오피크로사이드가 지방세포분화 인자(adipogenic factor)와 지방생성(lipogenic) 전사인자의 유전자 발현에 미치는 영향을 나타낸 것이다.
도 5는 젠티오피크로사이드가 지질흡수관련 유전자 발현에 미치는 영향을 나타낸 것이다.
도 6은 젠티오피크로사이드가 지방생합성관련 유전자 발현에 미치는 영향을 나타낸 것이다. 1 shows the effect of genthiopicroside on cell proliferation.
2 shows the effect of genthiopicroside on the inhibition of adipocyte differentiation.
Figure 3 shows the effect of genthiopicroside on neutral lipid accumulation.
Figure 4 shows the effect of genthiopicroside on the gene expression of adipogenic factors and lipogenic transcription factors.
Figure 5 shows the effect of genthiopicroside on lipid absorption-related gene expression.
Figure 6 shows the effect of genthiopicroside on the gene expression related to fat biosynthesis.
이하, 본 발명의 이해를 돕기 위하여 실시예 등을 들어 상세하게 설명하기로 한다. 그러나, 본 발명에 따른 실시예들은 여러 가지 다른 형태로 변형될 수 있으며, 본 발명의 범위가 하기 실시예들에 한정되는 것으로 해석되어서는 안 된다. 본 발명의 실시예들은 당업계에서 평균적인 지식을 가진 자에게 본 발명을 보다 완전하게 설명하기 위해 제공되는 것이다. Hereinafter, examples and the like will be described in detail to help understand the present invention. However, embodiments according to the present invention can be modified in many different forms, the scope of the invention should not be construed as limited to the following examples. Embodiments of the present invention are provided to more fully describe the present invention to those skilled in the art.
실험재료 및 방법Experimental Materials and Methods
(1) 3T3-L1 지방세포의 배양 및 분화(1) Culture and Differentiation of 3T3-L1 Adipocytes
실험에 사용한 3T3-L1 지방전구세포(pre-adipocyte cell)는 미국 생물자원센터(American Type Culture Collection, Manassas, VA, USA)로부터 구입하여 사용하였으며, 둘베코 개질화된 이글스 배지(Dulbecco's modified Eagle's medium, DMEM, Gibco, Grand Island, NY, USA)에 10% 소태아 혈청(FBS, Gibco)과 1% antibiotics-antimycotic(Gibco)을 첨가하여 5% CO2가 존재하는 37℃ 세포 배양기에서 2-3일에 한 번씩 계대 배양하면서 실험에 사용하였다.The 3T3-L1 pre-adipocyte cells used in the experiment were purchased from the American Biotechnology Center (American Type Culture Collection, Manassas, VA, USA), and used in Dulbecco's modified Eagle's medium. , DMEM, Gibco, Grand Island, NY, USA) added in 10% fetal bovine serum (FBS, Gibco) and 1% antibiotics-antimycotic (Gibco) 2-3 in a 37 ° C cell incubator with 5% CO 2 It was used for the experiment while subcultured once a day.
(2) 3T3-L1 지방전구세포의 분화유도(2) Induction of differentiation of 3T3-L1 adipocytes
3T3-L1 세포는 2X104 cells/well 농도로 6 well plate에 분주 후 세포밀도가 100%가 될 때까지 10% NBCS을 포함한 DMEM으로 배양하였다. 다음 2일 후(day 0), 10% FBS를 포함한 DMEM에 10 μg/mL 인슐린(Sigma-Aldrich, Saint Louis, MO, USA), 0.25 μM 덱사메타손(Sigma-Aldrich), 및 0.5 mM 3-아이소부틸-1-메틸잔틴(Sigma-Aldrich)이 첨가된 분화 유도 배지로 교체하여 2일간 처리하였다. 2일 후(day 2) 10% FBS를 포함한 새 배지에 10 μg/mL 인슐린이 첨가된 성숙 촉진 배지로 교체하여 배양한 후 2일 간격으로 10% FBS를 포함한 DMEM으로 교체하였다. 분화유도과정 중에 젠티오피크로사이드(gentiopicroside)의 분화억제 효능 확인하기 위해 분화 유도 0일부터 8일간 젠티오피크로사이드를 5 및 10 μM의 농도로 처리하였고, 중성지질 축적 함량 및 유전자 발현을 확인하기 위해 동일한 농도로 처리ㅇ확인하였다. 3T3-L1 cells were inoculated in 6 well plates at a concentration of 2X10 4 cells / well and incubated with DMEM containing 10% NBCS until the cell density reached 100%. After 2 days (day 0), 10 μg / mL insulin (Sigma-Aldrich, Saint Louis, MO, USA), 0.25 μM dexamethasone (Sigma-Aldrich), and 0.5 mM 3-isobutyl in DMEM containing 10% FBS Treatment was carried out for 2 days by replacing with differentiation induction medium to which -1-methylxanthine (Sigma-Aldrich) was added. After 2 days (day 2) to the new medium containing 10% FBS was replaced with the growth promoting medium added 10 μg / mL insulin and incubated with DMEM containing 10% FBS every two days. In order to confirm the differentiation inhibitory effect of gentiopicroside during the differentiation induction process, gentiopicroside was treated at concentrations of 5 and 10 μM for 0 to 8 days of differentiation induction, and neutral lipid accumulation content and gene expression were examined. Treatment was confirmed at the same concentration to confirm.
(3) 3T3-L1 세포를 이용한 세포증식 측정(3) Measurement of cell proliferation using 3T3-L1 cells
시료의 세포독성은 Papazisis 등(2006)의 방법에 준한 술포로다민(sulforhodamine) B(SRB) 분석을 하였다. 즉 SRB 분석은 단층으로 자란 3T3-L1 세포를 0.25% 트립신-에틸렌 다이아민 테트라아세트산(trypsin-EDTA, Gibco)을 처리하여 단일 세포로 만든 후 최종 농도가 3X103 cells/well 되도록 96 well 플레이트에 분주하여 37℃, 5% CO2 인큐베이터에서 48시간 배양하였다. 배양 후 plate에 세포의 부착을 확인하고 젠티오피크로사이드를 농도별(1, 5, 10, 50, 100μM)로 각각 첨가하여 48시간 반응시켰다. 반응이 종료된 후 plate의 상층액을 버리고 차가운 12% 트리클로로아세트산(TCA)을 50 μL 첨가하고, 4℃에서 1시간 동안 세포를 고정시켰다. TCA를 버린 후 증류수로 well을 세척하고, 0.4% SRB 용액을 50 μL 첨가하여 30분 동안 염색하였다. 염색이 종료된 후 1% 아세트산으로 well을 세척한 후 차가운 10 mM 트리스 완충액 100 μL를 첨가하여 SRB를 녹였다. 상등액 50 μL를 새로운 96 well 플레이트에 옮겨 마이크로플레이트 리더(Molecular Devices, Sunnyvale, CA, USA)를 사용하여 540 nm에서 흡광도를 측정하였다.Cytotoxicity of the samples was analyzed by sulforhodamine B (SRB) analysis according to Papazisis et al. (2006). In other words, SRB analysis was carried out to treat single-layered 3T3-L1 cells with 0.25% trypsin-ethylenediamine tetraacetic acid (trypsin-EDTA, Gibco) into single cells, and then divided into 96-well plates to give a final concentration of 3X10 3 cells / well And incubated for 48 hours at 37 ℃, 5% CO 2 incubator. After incubation, the adhesion of the cells to the plate was confirmed, and the thiothiocyclosides were added by concentration (1, 5, 10, 50, 100 μM) and reacted for 48 hours. After the reaction was completed, the supernatant of the plate was discarded, 50 μL of cold 12% trichloroacetic acid (TCA) was added, and the cells were fixed at 4 ° C. for 1 hour. After discarding TCA, the wells were washed with distilled water, and stained for 30 minutes by adding 50 μL of 0.4% SRB solution. After staining, the wells were washed with 1% acetic acid, and then 100 μL of cold 10 mM Tris buffer was added to dissolve the SRB. 50 μL of the supernatant was transferred to a new 96 well plate and the absorbance was measured at 540 nm using a microplate reader (Molecular Devices, Sunnyvale, Calif., USA).
(4) Oil Red O 염색 및 정량(4) Oil Red O Staining and Quantification
분화된 3T3-L1 세포를 PBS로 세척한 후 10% 포르말린으로 1시간 동안 고정하여 증류수로 세척한 다음 Oil Red O 용액을 처리하여 실온에서 15분 염색하였다. 염색 후 Oil Red O 용액을 제거하고 증류수로 3회 세척한 다음 염색된 세포를 위상차 현미경을 이용하여 관찰하였다. 또한 정량적 분석을 위하여 Oil Red O 염색 성분을 100% 아이소프로판올로 용출시켜 회수한 후 ELISA 리더로 540 nm에서 흡광도를 측정하였다.Differentiated 3T3-L1 cells were washed with PBS, fixed with 10% formalin for 1 hour, washed with distilled water, and treated with Oil Red O solution for 15 minutes at room temperature. After staining, the Oil Red O solution was removed, washed three times with distilled water, and the stained cells were observed using a phase contrast microscope. For quantitative analysis, Oil Red O staining was recovered by eluting with 100% isopropanol and absorbance was measured at 540 nm with an ELISA reader.
(5) 트리글리세라이드(TG) 함량 측정(5) Triglyceride (TG) content measurement
분화된 3T3-L1 세포를 PBS로 세척한 후 트립신-EDTA를 이용하여 세포를 떼어내어 1,200 rpm, 5분간 원심분리한 후 PBS로 2회 세척한 다음, 세포 용리 완충액을 이용하여 세포를 용리시킨 후 10,000 rpm, 5분간 원심 분리한 상층액을 TG 함량 측정에 사용하였다. TG 함량은 키트(Asan Pharmaceutical Co., Ltd., Seoul, Korea)를 사용하여 측정하였고, 단백질 함량은 소혈청 알부민(BSA)을 표준으로 하는 Bradford(1976)의 방법을 사용하여 측정하였다.After washing the differentiated 3T3-L1 cells with PBS, the cells were removed using trypsin-EDTA, centrifuged at 1,200 rpm for 5 minutes, washed twice with PBS, and then eluted with the cell elution buffer. The supernatant centrifuged at 10,000 rpm for 5 minutes was used for the TG content measurement. TG content was measured using a kit (Asan Pharmaceutical Co., Ltd., Seoul, Korea), and protein content was measured using the method of Bradford (1976) based on bovine serum albumin (BSA).
(6) 유전자 발현 측정(6) gene expression measurement
세포를 키운 세포 배양 플레이트의 well 마다 PBS로 세척한 뒤 트리졸 시약(Invitrogen, Grand Island, NY, USA) 1 mL을 첨가하여 상온에서 5-10분간 세포를 균질화하였고, 이를 각각 마이크로튜브로 옮긴 후 클로로포름 200 μL를 첨가하여 15,000 rpm, 4℃에서 20분간 원심분리하였다. 그 다음 상기 상층액을 취해 동량의 아이소프로판올을 첨가한 후 15,000 rpm, 4℃에 20분간 원심분리하여 RNA를 침전시켰다. 침전된 RNA는 75% 에탄올로 3회 세척하여 건조시킨 후 디에틸 피로카보네이트(DEPC) 처리 증류수에 녹여 분석 시까지 -70℃에 보관하였다. ReverTra Ace qPCR RT 마스터 믹스(Toyobo, Osaka, Japan)를 사용하여 상보적(complementary) DNA(cDNA)를 합성하고 실시간 정량적 PCR(RT-qPCR) 수행 시 주형(template)으로 사용하였다. cDNA에 각각의 프라이머를 넣고 SYBR green PCR kit(Qiagen Gmbh, Hilden, Germany)와 CFX96 실시간 시스템(Bio-rad, USA)을 이용하여 RT-qPCR법으로 표적 유전자의 발현을 조사하였다. 증폭된 산물은 2-△△Ct 방법을 이용하여 정량하였으며, Gapdh의 발현량으로 보정하였다. 증폭에 사용된 유전자 프라이머 서열은 하기 표 1에 나타내었다.After washing with PBS for each well of the cell culture plate in which the cells were grown, 1 mL of trizol reagent (Invitrogen, Grand Island, NY, USA) was added to homogenize the cells for 5-10 minutes at room temperature, and each was transferred to a microtube. 200 μL of chloroform was added and centrifuged at 15,000 rpm, 4 ° C. for 20 minutes. Then, the supernatant was taken and an equal amount of isopropanol was added, followed by centrifugation at 15,000 rpm and 4 ° C. for 20 minutes to precipitate RNA. The precipitated RNA was washed three times with 75% ethanol, dried, and then dissolved in diethyl pyrocarbonate (DEPC) -treated distilled water and stored at -70 ° C until analysis. Complementary DNA (cDNA) was synthesized using ReverTra Ace qPCR RT master mix (Toyobo, Osaka, Japan) and used as a template when performing real-time quantitative PCR (RT-qPCR). Each primer was put in cDNA and the expression of target gene was examined by RT-qPCR using SYBR green PCR kit (Qiagen Gmbh, Hilden, Germany) and CFX96 real-time system (Bio-rad, USA). The amplification product was 2 - was quantified using a △△ Ct method was calibrated with the expression level of Gapdh. Gene primer sequences used for amplification are shown in Table 1 below.
(7) 통계처리(7) Statistical Processing
실험결과는 컴퓨터 통계 프로그램 중의 하나인 SPSS package program을 이용하여 평균 ± 표준오차로 표시하였다. 각 군간 평균차이에 대한 유의성 검정은 one-way ANOVA를 실시하고 다 군간 차이는 던칸의 다중범위 테스트에 의해 p < 0.05 이상의 수준에서 사후검정을 실시하였다.The experimental results were expressed as mean ± standard error using the SPSS package program, one of computer statistics programs. The significance test for the mean difference between groups was one-way ANOVA, and the difference between the groups was post-test at the level of p <0.05 or more by Duncan's multi-range test.
<실시예 1> 젠티오피크로사이드의 세포증식 측정Example 1 Measurement of Cell Proliferation of Genthiopicroside
전구지방세포에 젠티오피크로사이드를 농도별로 처리하고 48시간 후, 세포증식에 미치는 영향을 살펴보았다. After 48 hours of genopicroside treatment in the proliferative cells, the effects on cell proliferation were examined.
도 1은 젠티오피크로사이드가 세포증식에 미치는 영향을 나타낸 것이다. 결과 값은 6회 실험한 결과를 평균 ± 표준오차로 표기하였다. 대조군에 대한 젠티오피크로사이드의 유의성은 던칸의 다중범위 테스트에 의해 p < 0.05 이상의 수준에서 사후검정을 실시하였다. 도 1에서 보듯이, 48시간 후 젠티오피크로사이드는 50 μM이상의 농도에서 세포증식이 유의적으로 억제 되었으며, 10 μM이하에서 독성이 나타나지 않았다.1 shows the effect of genthiopicroside on cell proliferation. The results were expressed as the mean ± standard error of the six experiments. Significance of genthiopicroside relative to the control group was post-tested at a level of p <0.05 or higher by Duncan's multirange test. As shown in FIG. 1, after 48 hours, genthiopicroside significantly inhibited cell proliferation at a concentration of 50 μM or more, and showed no toxicity below 10 μM.
<실시예 2> 젠티오피크로사이드의 지방세포 분화억제 효과 측정Example 2 Determination of the Adipocyte Differentiation Inhibitory Effect of Genthiopicroside
젠티오피크로사이드가 지방세포분화억제에 미치는 영향을 살펴보았다. 8일간 분화를 유도한 후 Oil Red O 염색하여 분화된 지방세포 생성 정도를 위상차 현미경으로 관찰한 결과, 분화 대조군에 비하여 5 μM과 10 μM 농도의 젠티오피크로사이드에서 분화된 지방세포가 유의적으로 감소되었다.The effects of genthiopicroside on the inhibition of adipocyte differentiation were examined. Induction of differentiation for 8 days, followed by phase contrast microscopy of oil red O staining, showed significant differentiation of adipocytes differentiated at 5 and 10 μM genthiopicrosides compared to the control group. Was reduced.
도 2는 젠티오피크로사이드가 지방세포 분화억제에 미치는 영향을 나타낸 것이다. 결과 값은 6회 실험한 결과를 평균 ± 표준오차로 표기하였다. 대조군에 대한 젠티오피크로사이드의 유의성은 던칸의 다중범위 테스트에 의해 p < 0.05 이상의 수준에서 사후검정을 실시하였다.2 shows the effect of genthiopicroside on the inhibition of adipocyte differentiation. The results were expressed as the mean ± standard error of the six experiments. Significance of genthiopicroside relative to the control group was post-tested at a level of p <0.05 or higher by Duncan's multirange test.
도 2에서 보듯이, 분화를 유도한 후 Oil Red O 염색하여 분화된 지방세포 생성 정도를 100% 아이소프로판올로 융해시킨 후 이를 흡광도 540 nm에서 정량화 한 결과, 분화 대조군에 비하여 5 μM과 10 μM 농도의 젠티오피크로사이드에서 분화세포가 감소하였다.As shown in FIG. 2, after inducing differentiation, oil red O staining was used to melt differentiated adipocytes with 100% isopropanol and quantify it at absorbance at 540 nm. As a result, 5 μM and 10 μM concentrations were compared with the control group. Differentiated cells were decreased in genthiopicroside.
<실시예 3> 젠티오피크로사이드의 중성지질 축적억제 효과 측정Example 3 Measurement of Neutral Lipid Accumulation Inhibition Effect of Genthiopicroside
젠티오피크로사이드가 중성지질 축적에 미치는 영향을 살펴보았다. 도 3은 젠티오피크로사이드가 중성지질 축적에 미치는 영향을 나타낸 것이다. 결과 값은 6회 실험한 결과를 평균 ± 표준오차로 표기하였다. 대조군에 대한 젠티오피크로사이드의 유의성은 던칸의 다중범위 테스트에 의해 p < 0.05 이상의 수준에서 사후검정을 실시하였다. The effect of genthiopicroside on neutral lipid accumulation was examined. Figure 3 shows the effect of genthiopicroside on neutral lipid accumulation. The results were expressed as the mean ± standard error of the six experiments. Significance of genthiopicroside relative to the control group was post-tested at a level of p <0.05 or higher by Duncan's multirange test.
도 3에서 보듯이, 젠티오피크로사이드를 5 μM과 10 μM 농도로 처리하였을 때, 분화 대조군에 비하여 유의적으로 중성지질 축적이 감소하였다.As shown in FIG. 3, when treated with 5 μM and 10 μM concentrations of genthiopicroside, triglyceride accumulation was significantly reduced compared to the differentiation control group.
<실시예 4> 젠티오피크로사이드가 지방세포분화 및 지방생성 관련 전사인자의 유전자 발현에 미치는 영향 측정Example 4 Measurement of the Effect of Genothiopicroside on Gene Expression of Adipocyte Differentiation and Adipogenesis-related Transcription Factors
젠티오피크로사이드가 지방세포분화 및 지방생성에 관여하는 전사인자 조절에 미치는 영향을 살펴보았다. The effects of genthiopicroside on the regulation of transcription factors involved in adipocyte differentiation and adipogenesis were examined.
도 4는 젠티오피크로사이드가 지방세포분화 인자(adipogenic factor)와 지방생성(lipogenic) 전사인자의 유전자 발현에 미치는 영향을 나타낸 것이다. 결과 값은 6회 실험한 결과를 평균 ± 표준오차로 표기하였다. 대조군에 대한 젠티오피크로사이드의 유의성은 던칸의 다중범위 테스트에 의해 p < 0.05 이상의 수준에서 사후검정을 실시하였다. Figure 4 shows the effect of genthiopicroside on the gene expression of adipogenic factors and lipogenic transcription factors. The results were expressed as the mean ± standard error of the six experiments. Significance of genthiopicroside relative to the control group was post-tested at a level of p <0.05 or higher by Duncan's multirange test.
젠티오피크로사이드를 5 μM과 10 μM 농도로 처리하였을 때, 분화 대조군에 비해 중기분화 관련 전사인자인 페록시솜 증식체 활성화 수용체 감마(peroxisome proliferator activated receptor gamma, Pparg)와 CCAAT/인핸서 결합 단백질 알파(enhancer binding protein alpha, Cebpa)뿐만 아니라 지방형성의 조절자 중 하나인 스테롤 조절인자 결합 전사인자 (sterol regulatory element binding transcription factor 1, Srebf1)의 유전자 발현을 낮추었다.When treated with 5 and 10 μM concentrations of genthiopicroside , the perixisome proliferator activated receptor gamma ( Pparg ) and CCAAT / enhancer binding proteins, which are transcription-related transcription factors, were compared to the differentiation controls. Not only alpha (enhancer binding protein alpha, Cebpa ) but also sterol regulatory element binding transcription factor ( Srebf1 ), one of the regulators of lipoogenesis , reduced gene expression.
<실시예 5> 젠티오피크로사이드가 지질흡수관련 유전자 발현에 미치는 영향 측정Example 5 Measurement of the Effect of Genthiopicroside on Lipid Absorption Related Gene Expression
젠티오피크로사이드가 지질흡수에 관여하는 유전자에 미치는 영향을 살펴보았다. 도 5는 젠티오피크로사이드가 지질흡수관련 유전자 발현에 미치는 영향을 나타낸 것이다. 결과 값은 6회 실험한 결과를 평균 ± 표준오차로 표기하였다. 대조군에 대한 젠티오피크로사이드의 유의성은 던칸의 다중범위 테스트에 의해 p < 0.05 이상의 수준에서 사후검정을 실시하였다. 혈액의 중성지질은 지질단백질 리파제(Lpl)의 조절 하에 지방산과 글리세롤로 분해되고 지방산 결합 단백질 4(Fabp4)는 지방세포내로 지방산 흡수를 촉진시킨다. FABP는 중성지방 개선의 기전 연구의 바이로마커로 사용되고 있다.We examined the effects of genthiopicroside on genes involved in lipid absorption. Figure 5 shows the effect of genthiopicroside on lipid absorption-related gene expression. The results were expressed as the mean ± standard error of the six experiments. Significance of genthiopicroside relative to the control group was post-tested at a level of p <0.05 or higher by Duncan's multirange test. Neutral lipids in the blood are broken down into fatty acids and glycerol under the control of lipoprotein lipase ( Lpl ) and fatty acid binding protein 4 ( Fabp4 ) promotes fatty acid uptake into adipocytes. FABP has been used as a viromarker in the mechanism study of triglyceride improvement.
도 5에서 보듯이, Lpl과 Fabp4의 mRNA 발현은 젠티오피크로사이드의 5 μM과 10 μM 농도에서 분화대조군에 비해 유의적으로 감소하였다.As shown in Figure 5, mRNA expression of Lpl and Fabp4 was significantly reduced compared to the control group at 5 μM and 10 μM concentrations of genthiopicroside .
<실시예 6> 젠티오피크로사이드가 지방생합성관련 유전자 발현에 미치는 영향 측정Example 6 Measurement of the Effect of Genthiopicroside on the Gene Expression Related to Adipose Biosynthesis
젠티오피크로사이드 처리에 의한 지방생합성에 관여하는 유전자에 미치는 영향을 살펴보았다. 도 6은 젠티오피크로사이드가 지방생합성관련 유전자 발현에 미치는 영향을 나타낸 것이다. 결과 값은 6회 실험한 결과를 평균 ± 표준오차로 표기하였다. 대조군에 대한 젠티오피크로사이드의 유의성은 던칸의 다중범위 테스트에 의해 p < 0.05 이상의 수준에서 사후검정을 실시하였다. The effects on the genes involved in fat biosynthesis by genthiopicroside treatment were examined. Figure 6 shows the effect of genthiopicroside on the gene expression related to fat biosynthesis. The results were expressed as the mean ± standard error of the six experiments. Significance of genthiopicroside relative to the control group was post-tested at a level of p <0.05 or higher by Duncan's multirange test.
도 6에서 보듯이, 젠티오피크로사이드를 5 μM와 10 μM 농도로 처리하였을 때, 분화 대조군에 비해 지방산생성을 조절하는 유전자인 지방산 합성효소(Fasn)와 스테아로일-코엔자임 A 델타-9 디세츄라제(stearol-Coenzyme A desaturase) 1(Scd1)을 비롯하여 디아실글리세롤(diacylglycerol)에 지방산을 붙여 트리아실글리세롤(triacylglycerol)로 만드는 효소로 중성지방 합성의 최종단계를 촉매하는 디아실글리세롤 O-아실트랜스퍼라제(diacylglycerol O-acyltransferase) 2(Dgat2)의 유전자 발현은 농도 의존적으로 억제되었다.As shown in Figure 6, when treated with a concentration of 5 μM and 10 μM genthiopicroside , fatty acid synthase ( Fasn ) and stearoyl-coenzyme A delta-9, a gene that controls fatty acid production compared to the differentiation control Diacylglycerol O- which catalyzes the final stage of triglyceride synthesis with enzymes that make fatty acid to triacylglycerol by attaching fatty acid to diacylglycerol, including sterol-Coenzyme A desaturase 1 ( Scd1 ). Gene expression of acyltransferase (diacylglycerol O-acyltransferase) 2 ( Dgat2 ) was inhibited concentration dependently.
이러한 결과로부터 분화과정에 관여하는 유전자의 발현수준의 감소와 중성지질의 축적이 감소하는 것으로 보아 젠티오피크로사이드는 비만을 예방하고 치료할 수 있는 것으로 판단된다.From these results, the reduction in the expression level of genes involved in the differentiation process and the decrease in the accumulation of triglycerides, it is considered that genthiopicroside can prevent and treat obesity.
<110> Industry-academic cooperation foundation of sunchon national university <120> A composition for preventing or improving obesity or obesity-related disease comprising gentiopicroside <130> PA-170284 <160> 18 <170> KoPatentIn 3.0 <210> 1 <211> 21 <212> DNA <213> Artificial Sequence <220> <223> Actb forward primer <400> 1 gatcagcaag caggagtacg a 21 <210> 2 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> Actb reverse primer <400> 2 ggtgtaaaac gcagctcagt aac 23 <210> 3 <211> 19 <212> DNA <213> Artificial Sequence <220> <223> Cebpa forward primer <400> 3 gcgcaagagc cgagataaa 19 <210> 4 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> Cebpa reverse primer <400> 4 ggtgaggaca cagactcaaa tc 22 <210> 5 <211> 25 <212> DNA <213> Artificial Sequence <220> <223> Dgat2 forward primer <400> 5 ctggctgata gctgtgctct acttc 25 <210> 6 <211> 21 <212> DNA <213> Artificial Sequence <220> <223> Dgat2 reverse primer <400> 6 tgcgatctcc tgccaccttt c 21 <210> 7 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Fabp4 forward primer <400> 7 tttggtcacc atccggtcag 20 <210> 8 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Fabp4 reverse primer <400> 8 cccgccatct agggttatga 20 <210> 9 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Fasn forward primer <400> 9 agccttccat ctcctgtcat catc 24 <210> 10 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Fasn reverse primer <400> 10 cgctcctcgc ttgtcgtctg 20 <210> 11 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Lpl forward primer <400> 11 agcccttgct aggagaaagc 20 <210> 12 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Lpl reverse primer <400> 12 ataatgggga tgccggtgac 20 <210> 13 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Pparg forward primer <400> 13 tcgctgatgc actgcctatg 20 <210> 14 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Pparg reverse primer <400> 14 gagaggtcca cagagctgat 20 <210> 15 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Scd1 forward primer <400> 15 ttcttcatcg actgcatggc 20 <210> 16 <211> 21 <212> DNA <213> Artificial Sequence <220> <223> Scd1 reverse primer <400> 16 actcagaagc ccaaagctca g 21 <210> 17 <211> 18 <212> DNA <213> Artificial Sequence <220> <223> Srebf1 forward primer <400> 17 aacctcatcc gccacctg 18 <210> 18 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Srebf1 reverse primer <400> 18 tggtagacaa cagccgcatc 20 <110> Industry-academic cooperation foundation of sunchon national university <120> A composition for preventing or improving obesity or obesity-related disease comprising gentiopicroside <130> PA-170284 <160> 18 <170> KoPatentIn 3.0 <210> 1 <211> 21 <212> DNA <213> Artificial Sequence <220> <223> Actb forward primer <400> 1 gatcagcaag caggagtacg a 21 <210> 2 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> Actb reverse primer <400> 2 ggtgtaaaac gcagctcagt aac 23 <210> 3 <211> 19 <212> DNA <213> Artificial Sequence <220> <223> Cebpa forward primer <400> 3 gcgcaagagc cgagataaa 19 <210> 4 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> Cebpa reverse primer <400> 4 ggtgaggaca cagactcaaa tc 22 <210> 5 <211> 25 <212> DNA <213> Artificial Sequence <220> <223> Dgat2 forward primer <400> 5 ctggctgata gctgtgctct acttc 25 <210> 6 <211> 21 <212> DNA <213> Artificial Sequence <220> <223> Dgat2 reverse primer <400> 6 tgcgatctcc tgccaccttt c 21 <210> 7 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Fabp4 forward primer <400> 7 tttggtcacc atccggtcag 20 <210> 8 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Fabp4 reverse primer <400> 8 cccgccatct agggttatga 20 <210> 9 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Fasn forward primer <400> 9 agccttccat ctcctgtcat catc 24 <210> 10 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Fasn reverse primer <400> 10 cgctcctcgc ttgtcgtctg 20 <210> 11 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Lpl forward primer <400> 11 agcccttgct aggagaaagc 20 <210> 12 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Lpl reverse primer <400> 12 ataatgggga tgccggtgac 20 <210> 13 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Pparg forward primer <400> 13 tcgctgatgc actgcctatg 20 <210> 14 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Pparg reverse primer <400> 14 gagaggtcca cagagctgat 20 <210> 15 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Scd1 forward primer <400> 15 ttcttcatcg actgcatggc 20 <210> 16 <211> 21 <212> DNA <213> Artificial Sequence <220> <223> Scd1 reverse primer <400> 16 actcagaagc ccaaagctca g 21 <210> 17 <211> 18 <212> DNA <213> Artificial Sequence <220> <223> Srebf1 forward primer <400> 17 aacctcatcc gccacctg 18 <210> 18 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Srebf1 reverse primer <400> 18 tggtagacaa cagccgcatc 20
Claims (4)
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
KR1020180005589A KR102009219B1 (en) | 2018-01-16 | 2018-01-16 | A composition for preventing or improving obesity or obesity-related disease comprising gentiopicroside |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
KR1020180005589A KR102009219B1 (en) | 2018-01-16 | 2018-01-16 | A composition for preventing or improving obesity or obesity-related disease comprising gentiopicroside |
Publications (2)
Publication Number | Publication Date |
---|---|
KR20190087149A KR20190087149A (en) | 2019-07-24 |
KR102009219B1 true KR102009219B1 (en) | 2019-08-09 |
Family
ID=67481104
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
KR1020180005589A KR102009219B1 (en) | 2018-01-16 | 2018-01-16 | A composition for preventing or improving obesity or obesity-related disease comprising gentiopicroside |
Country Status (1)
Country | Link |
---|---|
KR (1) | KR102009219B1 (en) |
Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN105012329A (en) * | 2015-07-27 | 2015-11-04 | 中南民族大学 | Drug for treatment of type II diabetes |
-
2018
- 2018-01-16 KR KR1020180005589A patent/KR102009219B1/en active IP Right Grant
Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN105012329A (en) * | 2015-07-27 | 2015-11-04 | 中南民族大学 | Drug for treatment of type II diabetes |
Non-Patent Citations (2)
Title |
---|
Biochem. Cell. Biol., 94, 270-278, 2016.* |
Euro. J. Drug Metabolism and Pharmacokinetics, 29(3), 199-203, 2004. |
Also Published As
Publication number | Publication date |
---|---|
KR20190087149A (en) | 2019-07-24 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
EP1481671B1 (en) | Compositions and foods for improving lipid metabolism | |
JP2006306800A (en) | Farnesoid x receptor activator | |
KR20140100117A (en) | Compositions comprising the extract of Alnus japonica or the compounds derived therefrom for inhibiting adipogenesis | |
KR20150097173A (en) | Composition of extracts of Arctium lappa or compounds isolated therefrom for preventing, improving or treating obesity or obesity-related disease | |
KR101567573B1 (en) | Composition comprising extracts of Codonopsis lanceolata or compounds isolated therefrom for preventing, improving or treating obesity or obesity-related disease | |
KR20160123130A (en) | Composition comprising Chrisanthemum indicum extract or fraction for treating, improving or preventing obesity or obesity-related disease | |
KR101557934B1 (en) | Composition comprising extracts of Codonopsis lanceolata or compounds isolated therefrom for preventing, improving or treating obesity or obesity-related disease | |
KR102009219B1 (en) | A composition for preventing or improving obesity or obesity-related disease comprising gentiopicroside | |
AU2004206156B2 (en) | Blood pressure-lowering agent, vascular flexibility-improving agent and foods having these functions imparted thereto | |
EP4174166A1 (en) | Novel faecalibacterium prausnitzii strain eb-fpdk9 and use thereof | |
KR102017282B1 (en) | Composition comprising extract of processed ginseng for stimulating of myogenesis | |
KR20210000294A (en) | Pharmaceutical composition comprising the extract of Phlomis umbrosa Turczaninow as an effective ingredient for preventing or treating of obesity | |
KR20120048203A (en) | Composition for prevention and treatment of obesity and metabolic diseases comprising benzyl isothiocyanate | |
KR20140039809A (en) | Composition comprising soyasaponin aa for preventing or treating obesity or lipid related metabolic disease | |
KR101756790B1 (en) | Pharmaceutical composition for preventing or treating obesity or obesity-related disorders comprising the mixture of ginsenoside Rg3(R) and Rg3(S) | |
KR101448116B1 (en) | Composition comprising DDMP group soyasaponin for preventing or treating obesity or lipid related metabolic disease | |
KR102694496B1 (en) | Composition for preventing or treating obesity including microsporine-like amino acid as an effective ingredient | |
KR102283093B1 (en) | Composition for prevention and treatment of metabolic diseases including ginger extract | |
US20230106742A1 (en) | Composition for inducing browning, containing milk exosomes | |
KR20190106587A (en) | Pharmaceutical composition comprising the extract of Phlomis umbrosa Turczaninow for preventing or treating of obesity | |
KR102129707B1 (en) | A pharmaceutical composition for the treatment of metabolic disease and Anti-obesity, which mainly contains Emodin derivatives | |
KR102563745B1 (en) | Pharmaceutical composition for preventing or treating obesity having garcinia cambogia extract and health functional food having the same | |
KR101476738B1 (en) | Agent for improving insulin resistance | |
KR101799793B1 (en) | Novel Isonitramine Compound and Composition for Preventing or Treating Metabolic Disease Comprising the Same | |
KR20190125068A (en) | A composition for preventing or improving obesity or obesity-related disease comprising 6'-O-acetyl mangiferin |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A201 | Request for examination | ||
E902 | Notification of reason for refusal | ||
E701 | Decision to grant or registration of patent right | ||
GRNT | Written decision to grant |