CN1993135A - Insulin secretion by anthocyanins and anthocyanidins - Google Patents
Insulin secretion by anthocyanins and anthocyanidins Download PDFInfo
- Publication number
- CN1993135A CN1993135A CN 200580025636 CN200580025636A CN1993135A CN 1993135 A CN1993135 A CN 1993135A CN 200580025636 CN200580025636 CN 200580025636 CN 200580025636 A CN200580025636 A CN 200580025636A CN 1993135 A CN1993135 A CN 1993135A
- Authority
- CN
- China
- Prior art keywords
- anthocyanin
- insulin
- anthocyanidin
- glucose
- glucosides
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 150000004636 anthocyanins Chemical class 0.000 title claims abstract description 62
- 229930002877 anthocyanin Natural products 0.000 title claims abstract description 60
- 235000010208 anthocyanin Nutrition 0.000 title claims abstract description 60
- 239000004410 anthocyanin Substances 0.000 title claims abstract description 60
- 230000003914 insulin secretion Effects 0.000 title claims abstract description 36
- 229930014669 anthocyanidin Natural products 0.000 title claims abstract description 34
- 235000008758 anthocyanidins Nutrition 0.000 title claims abstract description 34
- NWKFECICNXDNOQ-UHFFFAOYSA-N flavylium Chemical compound C1=CC=CC=C1C1=CC=C(C=CC=C2)C2=[O+]1 NWKFECICNXDNOQ-UHFFFAOYSA-N 0.000 title abstract 2
- 238000000034 method Methods 0.000 claims abstract description 19
- 238000001727 in vivo Methods 0.000 claims abstract 3
- 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 claims description 86
- 102000004877 Insulin Human genes 0.000 claims description 43
- 108090001061 Insulin Proteins 0.000 claims description 43
- 229940125396 insulin Drugs 0.000 claims description 43
- 150000001452 anthocyanidin derivatives Chemical class 0.000 claims description 33
- 239000000203 mixture Substances 0.000 claims description 27
- 235000013399 edible fruits Nutrition 0.000 claims description 24
- 210000004027 cell Anatomy 0.000 claims description 23
- 238000000746 purification Methods 0.000 claims description 9
- 235000013311 vegetables Nutrition 0.000 claims description 8
- ABVCUBUIXWJYSE-GQUPQBGVSA-O Callistephin Natural products O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1OC1=CC2=C(O)C=C(O)C=C2[O+]=C1C1=CC=C(O)C=C1 ABVCUBUIXWJYSE-GQUPQBGVSA-O 0.000 claims description 6
- 210000002237 B-cell of pancreatic islet Anatomy 0.000 claims description 5
- CAHGSEFWVUVGGL-UBNZBFALSA-N pelargonidin 3-O-beta-D-glucoside chloride Chemical compound [Cl-].O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1OC1=CC2=C(O)C=C(O)C=C2[O+]=C1C1=CC=C(O)C=C1 CAHGSEFWVUVGGL-UBNZBFALSA-N 0.000 claims 2
- 235000011389 fruit/vegetable juice Nutrition 0.000 claims 1
- 230000028327 secretion Effects 0.000 abstract description 5
- 230000004936 stimulating effect Effects 0.000 abstract description 2
- 241000124008 Mammalia Species 0.000 abstract 1
- 238000000338 in vitro Methods 0.000 abstract 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 51
- 239000008103 glucose Substances 0.000 description 51
- 206010012601 diabetes mellitus Diseases 0.000 description 14
- 241000209020 Cornus Species 0.000 description 13
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 12
- CAHGSEFWVUVGGL-QSLGVYCOSA-N Pelargonidin 3-galactoside Chemical compound [Cl-].O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1OC1=CC2=C(O)C=C(O)C=C2[O+]=C1C1=CC=C(O)C=C1 CAHGSEFWVUVGGL-QSLGVYCOSA-N 0.000 description 10
- 150000001875 compounds Chemical class 0.000 description 10
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
- 238000004458 analytical method Methods 0.000 description 9
- TWCMVXMQHSVIOJ-UHFFFAOYSA-N Aglycone of yadanzioside D Natural products COC(=O)C12OCC34C(CC5C(=CC(O)C(O)C5(C)C3C(O)C1O)C)OC(=O)C(OC(=O)C)C24 TWCMVXMQHSVIOJ-UHFFFAOYSA-N 0.000 description 8
- PLMKQQMDOMTZGG-UHFFFAOYSA-N Astrantiagenin E-methylester Natural products CC12CCC(O)C(C)(CO)C1CCC1(C)C2CC=C2C3CC(C)(C)CCC3(C(=O)OC)CCC21C PLMKQQMDOMTZGG-UHFFFAOYSA-N 0.000 description 8
- 210000000227 basophil cell of anterior lobe of hypophysis Anatomy 0.000 description 8
- PFOARMALXZGCHY-UHFFFAOYSA-N homoegonol Natural products C1=C(OC)C(OC)=CC=C1C1=CC2=CC(CCCO)=CC(OC)=C2O1 PFOARMALXZGCHY-UHFFFAOYSA-N 0.000 description 8
- 208000001072 type 2 diabetes mellitus Diseases 0.000 description 8
- JKHRCGUTYDNCLE-UHFFFAOYSA-O delphinidin Chemical compound [O+]=1C2=CC(O)=CC(O)=C2C=C(O)C=1C1=CC(O)=C(O)C(O)=C1 JKHRCGUTYDNCLE-UHFFFAOYSA-O 0.000 description 7
- 235000013305 food Nutrition 0.000 description 7
- GCPYCNBGGPHOBD-UHFFFAOYSA-N Delphinidin Natural products OC1=Cc2c(O)cc(O)cc2OC1=C3C=C(O)C(=O)C(=C3)O GCPYCNBGGPHOBD-UHFFFAOYSA-N 0.000 description 6
- 235000007242 delphinidin Nutrition 0.000 description 6
- 239000003814 drug Substances 0.000 description 6
- 230000000694 effects Effects 0.000 description 6
- HKUHOPQRJKPJCJ-UHFFFAOYSA-N pelargonidin Natural products OC1=Cc2c(O)cc(O)cc2OC1c1ccc(O)cc1 HKUHOPQRJKPJCJ-UHFFFAOYSA-N 0.000 description 6
- 235000006251 pelargonidin Nutrition 0.000 description 6
- AFOLOMGWVXKIQL-UHFFFAOYSA-O petunidin Chemical compound OC1=C(O)C(OC)=CC(C=2C(=CC=3C(O)=CC(O)=CC=3[O+]=2)O)=C1 AFOLOMGWVXKIQL-UHFFFAOYSA-O 0.000 description 6
- KQIKOUUKQBTQBE-UHFFFAOYSA-N 3,5,7-trihydroxy-2-(4-hydroxy-3,5-dimethoxyphenyl)-1lambda^{4}-chromen-1-ylium chloride Chemical compound [Cl-].COC1=C(O)C(OC)=CC(C=2C(=CC=3C(O)=CC(O)=CC=3[O+]=2)O)=C1 KQIKOUUKQBTQBE-UHFFFAOYSA-N 0.000 description 5
- 206010022489 Insulin Resistance Diseases 0.000 description 5
- 239000008280 blood Substances 0.000 description 5
- 210000004369 blood Anatomy 0.000 description 5
- 238000002474 experimental method Methods 0.000 description 5
- XVFMGWDSJLBXDZ-UHFFFAOYSA-O pelargonidin Chemical compound C1=CC(O)=CC=C1C(C(=C1)O)=[O+]C2=C1C(O)=CC(O)=C2 XVFMGWDSJLBXDZ-UHFFFAOYSA-O 0.000 description 5
- 229930015717 petunidin Natural products 0.000 description 5
- 235000006384 petunidin Nutrition 0.000 description 5
- 102000004169 proteins and genes Human genes 0.000 description 5
- 108090000623 proteins and genes Proteins 0.000 description 5
- 238000011160 research Methods 0.000 description 5
- 229940100389 Sulfonylurea Drugs 0.000 description 4
- 239000003472 antidiabetic agent Substances 0.000 description 4
- 239000003153 chemical reaction reagent Substances 0.000 description 4
- 235000005911 diet Nutrition 0.000 description 4
- 230000037213 diet Effects 0.000 description 4
- 229930182478 glucoside Natural products 0.000 description 4
- 150000008131 glucosides Chemical class 0.000 description 4
- 210000000496 pancreas Anatomy 0.000 description 4
- 238000003127 radioimmunoassay Methods 0.000 description 4
- 239000011347 resin Substances 0.000 description 4
- 229920005989 resin Polymers 0.000 description 4
- DAEPDZWVDSPTHF-UHFFFAOYSA-M sodium pyruvate Chemical compound [Na+].CC(=O)C([O-])=O DAEPDZWVDSPTHF-UHFFFAOYSA-M 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- 239000012980 RPMI-1640 medium Substances 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 150000002989 phenols Chemical class 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 2
- SWLAMJPTOQZTAE-UHFFFAOYSA-N 4-[2-[(5-chloro-2-methoxybenzoyl)amino]ethyl]benzoic acid Chemical class COC1=CC=C(Cl)C=C1C(=O)NCCC1=CC=C(C(O)=O)C=C1 SWLAMJPTOQZTAE-UHFFFAOYSA-N 0.000 description 2
- 241000196324 Embryophyta Species 0.000 description 2
- 102100023374 Forkhead box protein M1 Human genes 0.000 description 2
- 239000007995 HEPES buffer Substances 0.000 description 2
- 101000907578 Homo sapiens Forkhead box protein M1 Proteins 0.000 description 2
- 238000003820 Medium-pressure liquid chromatography Methods 0.000 description 2
- 208000008589 Obesity Diseases 0.000 description 2
- 241000473945 Theria <moth genus> Species 0.000 description 2
- 230000003178 anti-diabetic effect Effects 0.000 description 2
- 229940125708 antidiabetic agent Drugs 0.000 description 2
- 239000003963 antioxidant agent Substances 0.000 description 2
- 230000003078 antioxidant effect Effects 0.000 description 2
- 235000006708 antioxidants Nutrition 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- 235000012055 fruits and vegetables Nutrition 0.000 description 2
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 2
- 230000001939 inductive effect Effects 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- 210000004185 liver Anatomy 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 239000002609 medium Substances 0.000 description 2
- 229950004994 meglitinide Drugs 0.000 description 2
- 235000020824 obesity Nutrition 0.000 description 2
- 239000003538 oral antidiabetic agent Substances 0.000 description 2
- 229940127209 oral hypoglycaemic agent Drugs 0.000 description 2
- 230000003647 oxidation Effects 0.000 description 2
- 238000007254 oxidation reaction Methods 0.000 description 2
- 238000001556 precipitation Methods 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 229940054269 sodium pyruvate Drugs 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- DGVVWUTYPXICAM-UHFFFAOYSA-N β‐Mercaptoethanol Chemical compound OCCS DGVVWUTYPXICAM-UHFFFAOYSA-N 0.000 description 2
- GHKCSRZBNZQHKW-UHFFFAOYSA-N 1-sulfanylethanol Chemical class CC(O)S GHKCSRZBNZQHKW-UHFFFAOYSA-N 0.000 description 1
- 201000001320 Atherosclerosis Diseases 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- 208000024172 Cardiovascular disease Diseases 0.000 description 1
- 240000006766 Cornus mas Species 0.000 description 1
- 235000003363 Cornus mas Nutrition 0.000 description 1
- 229930091371 Fructose Natural products 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
- 239000005715 Fructose Substances 0.000 description 1
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 1
- 238000003231 Lowry assay Methods 0.000 description 1
- 238000009013 Lowry's assay Methods 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 101000905241 Mus musculus Heart- and neural crest derivatives-expressed protein 1 Proteins 0.000 description 1
- 101001031591 Mus musculus Heart- and neural crest derivatives-expressed protein 2 Proteins 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 229930182555 Penicillin Natural products 0.000 description 1
- 241000283984 Rodentia Species 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- BQCADISMDOOEFD-UHFFFAOYSA-N Silver Chemical compound [Ag] BQCADISMDOOEFD-UHFFFAOYSA-N 0.000 description 1
- 244000269722 Thea sinensis Species 0.000 description 1
- 240000001085 Trapa natans Species 0.000 description 1
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 description 1
- 235000009754 Vitis X bourquina Nutrition 0.000 description 1
- 235000012333 Vitis X labruscana Nutrition 0.000 description 1
- 240000006365 Vitis vinifera Species 0.000 description 1
- 235000014787 Vitis vinifera Nutrition 0.000 description 1
- 240000004482 Withania somnifera Species 0.000 description 1
- 235000001978 Withania somnifera Nutrition 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 230000036592 analgesia Effects 0.000 description 1
- 235000020052 applejack Nutrition 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 230000001363 autoimmune Effects 0.000 description 1
- 235000021028 berry Nutrition 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 235000013361 beverage Nutrition 0.000 description 1
- 230000000975 bioactive effect Effects 0.000 description 1
- 229940093797 bioflavonoids Drugs 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 239000007853 buffer solution Substances 0.000 description 1
- 210000000692 cap cell Anatomy 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 235000014633 carbohydrates Nutrition 0.000 description 1
- 201000011529 cardiovascular cancer Diseases 0.000 description 1
- 230000010261 cell growth Effects 0.000 description 1
- 229940125904 compound 1 Drugs 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 208000029078 coronary artery disease Diseases 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 230000006735 deficit Effects 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 230000001882 diuretic effect Effects 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 229930182479 fructoside Natural products 0.000 description 1
- 150000008195 galaktosides Chemical class 0.000 description 1
- 230000004153 glucose metabolism Effects 0.000 description 1
- 230000006377 glucose transport Effects 0.000 description 1
- 229960002743 glutamine Drugs 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 235000009200 high fat diet Nutrition 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 230000003301 hydrolyzing effect Effects 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 230000002218 hypoglycaemic effect Effects 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 238000002372 labelling Methods 0.000 description 1
- 230000037356 lipid metabolism Effects 0.000 description 1
- 229940126707 lipid peroxidation inhibitor Drugs 0.000 description 1
- 206010025482 malaise Diseases 0.000 description 1
- 229940126601 medicinal product Drugs 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 208000015122 neurodegenerative disease Diseases 0.000 description 1
- 235000016709 nutrition Nutrition 0.000 description 1
- 230000035764 nutrition Effects 0.000 description 1
- QYSGYZVSCZSLHT-UHFFFAOYSA-N octafluoropropane Chemical compound FC(F)(F)C(F)(F)C(F)(F)F QYSGYZVSCZSLHT-UHFFFAOYSA-N 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- -1 pelargonidin glucosides Chemical class 0.000 description 1
- 150000002960 penicillins Chemical class 0.000 description 1
- 150000002972 pentoses Chemical class 0.000 description 1
- XFDQJKDGGOEYPI-UHFFFAOYSA-O peonidin Chemical compound C1=C(O)C(OC)=CC(C=2C(=CC=3C(O)=CC(O)=CC=3[O+]=2)O)=C1 XFDQJKDGGOEYPI-UHFFFAOYSA-O 0.000 description 1
- 229930015721 peonidin Natural products 0.000 description 1
- 235000006404 peonidin Nutrition 0.000 description 1
- 239000000049 pigment Substances 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 239000002516 radical scavenger Substances 0.000 description 1
- 235000020095 red wine Nutrition 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 230000000630 rising effect Effects 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 239000004332 silver Substances 0.000 description 1
- 229910052709 silver Inorganic materials 0.000 description 1
- 210000002027 skeletal muscle Anatomy 0.000 description 1
- HELHAJAZNSDZJO-OLXYHTOASA-L sodium L-tartrate Chemical compound [Na+].[Na+].[O-]C(=O)[C@H](O)[C@@H](O)C([O-])=O HELHAJAZNSDZJO-OLXYHTOASA-L 0.000 description 1
- 239000001433 sodium tartrate Substances 0.000 description 1
- 229960002167 sodium tartrate Drugs 0.000 description 1
- 235000011004 sodium tartrates Nutrition 0.000 description 1
- 230000003068 static effect Effects 0.000 description 1
- 229960005322 streptomycin Drugs 0.000 description 1
- 229940041022 streptomycins Drugs 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 239000003643 water by type Substances 0.000 description 1
- 230000003442 weekly effect Effects 0.000 description 1
- 235000014101 wine Nutrition 0.000 description 1
- SASUFNRGCZMRFD-JCUIILOWSA-N withanolide D Chemical compound C1C(C)=C(C)C(=O)O[C@H]1[C@](C)(O)[C@@H]1[C@@]2(C)CC[C@@H]3[C@@]4(C)C(=O)C=C[C@H](O)[C@@]54O[C@@H]5C[C@H]3[C@@H]2CC1 SASUFNRGCZMRFD-JCUIILOWSA-N 0.000 description 1
Images
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines Containing Plant Substances (AREA)
- Coloring Foods And Improving Nutritive Qualities (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
A method for stimulating insulin secretion by anthocyanidins and anthocyanins is described. The secretion can be in vivo in mammals, including humans, or in vitro.
Description
The cross reference of related application
It is the priority of 60/591,806 temporary patent application that the application requires in the serial number that on July 29th, 2004 submitted to.
Government's rights and interests
The present invention is subjected to the subsidy of USDA fund No.2003-35504-13618.There is certain right in U.S. government to the present invention.
Background of invention
(1) invention field
The present invention relates to use anthocyanin, anthocyanidin or its mixture to increase the method that insulin produces in the cell.The invention still further relates to and be used for the compositions that this method increases the insulin generation.Described method and composition can be in the body or external.
(2) description of association area
The function of insulin is to keep the normal blood glucose level, this or by suppress glucose from liver output or by stimulating glucose absorption and metabolism (Ross, S.A., Deng, Chemistry and Biochemistry of diabetes.Chem.Rev.104 1255-1282 (2004)) and realize.The forfeiture inadequate or insulin action that insulin discharges in target tissue causes abnormal glucose and lipid metabolism.This just causes the rising of glucose level in the blood, i.e. Diabetes mellitus (Jovanovic, L. wait 2-type diabetes:The epidemicof new millennium.Ann.Clin.Lab.Sci.29 33-42 (1999)).There are two types diabetes, 1-type (insulin-dependent diabetes) and 2-type diabetes (non-insulin-dependent diabetes).1-type diabetes are destroyed by autoimmune by the pancreas beta cell and are caused, and the pancreas beta cell is the cell of excreting insulin, thereby causes insulin deficit.2-type diabetes are more general, and it is can not secrete the q.s insulin to overcome (Henquin, J.C, Diabetes 49 1751-1760 (2000)) that the insulin resistance set up by the h and E factor causes by beta cell.Insulin resistance is a kind of disease, and wherein insulin can not fully stimulate glucose transport in skeletal muscle and fat, can not fully suppress liver glucose and produce.Pathogenesis comprises that the insulin that stops beta cell secretion q.s is to overcome the periphery insulin resistance that will set up.Oral hypoglycemic directly stimulates insulin from the release of beta cell the medicine of sulfonylureas (for example based on), but, shown from the insulin of 2-diabetes mellitus type islet secretion can fully raise to overcome the periphery insulin resistance and to make blood glucose levels normal.Use is to control normal blood glucose level (Pfeiffer based on one of shortcoming of the medicine of sulfonylureas, A.F.H., Oral hypoglycemic agents:Sulfonylureas and meglitinides.InB.J.Goldstein, Deng, (Eds.), Test book of Type-2 Diabetes.MartinDunitz Ltd., London 77-85 page or leaf (2003)).These medicines also have adverse influence to beta cell excreting insulin ability, and cause weight to increase ((Pfeiffer, A.F.H., Oralhypoglycemic agents:Sulfonylureas and meglitinides.In B.J.Goldstein, Deng, (Eds.), Test book of Type-2 Diabetes.Martin DunitzLtd., London 77-85 page or leaf (2003)).Therefore, the control to the diet composition has the effect of regulating blood glucose levels or inducing pancreas beta cell generation insulin.
Few and the antioxidant of fat mass enriches the danger that can reduce obesity and insulin resistance (Blakely, S. is etc., J.Nutr.133 2838-2844 (2003)) in the diet consumption amount.Anthocyanin belongs to the polyhydric phenols of non-oxidizability, is present in the various F﹠B.The consumption figure of anthocyanin and several degenerative disease for example atherosclerosis, cardiovascular disease, cancer and risk of diabetes reduce relevant (Jayaprakasam, B., Deng, Potent lipid peroxidationinhibitors from Withania somnifera. " Tetrahedron 60 3109-3121 (2004)).These chemical compounds are well-known radical scavengers, are reported to effective chemical prevention material (Duthie, G.G. is etc., Nutr.Res.Rev.13 719-106 (2000)).For example by edible Fructus Fragariae Ananssae, Fructus Pruni pseudocerasi and red wine increase serum oxidation resistance (Kang, S.Y. is etc., Cane.Lett.194 13-19 (2003); Van Velden, D.P., etc., Ann.New YorkAcad.Sci.957 337-340 (2002); And Wang, H., etc., J.Nat.Prod.62294-296 (1999)).Nearest anthocyanin, the anthocyanidin 3-glucosides of studies show that reduces the inductive mice obesity of high fat diet (Tsuda, T. is etc., J.Nut.133 2125-2130 (2003)).Therefore, be present in natural pigment in the food owing to their safety, nutrition and therapeutic value attracts consumer (Espin, J.C is etc., J.Agri.Food Chem.481588-1592 (2000)).Because anthocyanin is extensively consumed, the other biologic activity of these chemical compounds will cause great interest.
Fructus Corni kind fruit is the abundant source of anthocyanin.The fruit of Eurasian Fructus Corni (Cornus masL.) is also called Eurasian Fructus Corni (European and Asiatic corneliancherry), is used for preparation (Millspaugh, CF., the In AmericanMedicinal plants of beverage in Europe; Dover Publications:New York, 282 (1974)).In conventional medicament is learned, the analgesia of known cornus fruit and diuretic activity (Kim, D.K., etc., Arch.Pharm.Res.21 787-789 (1998)).Cornus fruit still is one of main component of several anti-diabetic herbal medicinal products (Yamahara, J. is etc., Yakugaku Zasshi 101 86-90 (1981)) in Asian countries.We studies show that in early days that to Eurasian Fructus Corni and cornus fruit both all contain high-caliber anthocyanin (Seeram, N.P. is etc., J.Agri.Food chem..50 2519-2523 (2002)).
Purpose
Therefore the purpose of this invention is to provide increases the method and composition that insulin produces in external or the body.Further purpose will become clearer from following description and accompanying drawing.
Summary of the invention
The present invention relates to make the pancreatic cell of excreting insulin to increase the method for insulin secretion, comprise:
Be provided for anthocyanin or anthocyanidin or its mixture of pancreatic beta cell, increase when being used for making the secretion of insulin ratio not have anthocyanin.Anthocyanin preferably separates from fruit, vegetable with spending.Preferably in the method, anthocyanin is selected from following group: anthocyanidin-3-glucosides (Cyanidin-3-glycoside), delphinidin-3-glucosides (delphinidin-3-glycoside), callistephin (pelargonidin-3-glycoside) and composition thereof.Pancreatic cell can be for intravital.Pancreatic cell can be for external.Preferably in the method with anthocyanidin or anthocyanin or its mixture separation and purification.
The invention still further relates to anthocyanin or anthocyanidin or its mixture and be used to increase in the body insulin from the generation of pancreatic cell as dosage unit.
Preferably anthocyanin is from fruit, vegetable with isolating spending in compositions.Preferably anthocyanin is selected from group down in compositions: anthocyanidin-3-glucosides, delphinidin-3-glucosides, callistephin and composition thereof.Preferably anthocyanidin or anthocyanin or its mixture are separated and purification in compositions." glucosides " is meant any chemical compound that contains carbohydrate molecule (sugar), be meant any such natural product in plant especially, can be converted into sugar and non-sugar ingredient (aglycone) by hydrolytic rupture, and according to the special called after glucosides (glucose) of the sugar that contains, pentoside (pentose), fructoside (fructose) etc.
Anthocyanin causes fruit, vegetable and spends multiple bright color to comprise redness, blueness and purple, consumed as the diet polyhydric phenols.The fruit that contains anthocyanin is relevant with minimizing coronary heart disease, and is used for antidiabetic agent preparation.The present invention is presented at anthocyanin, anthocyanidin-3-glucosides (1), delphinidin-3-glucosides (2), anthocyanidin-3-galactoside (3) and pelargonidin-3-galactoside (4) in the external rodent pancreatic beta cell (INS-I 813/32); With anthocyanidin, anthocyanidin (5), delphinidin (delphinidin) (6), pelargonidin (7), enidin (8), and the ability that stimulates insulin secretion of petunidin (petunidin) (9).Described chemical compound 4 and the 10mM concentration of glucose in the presence of experimentize.4 and the 10mM concentration of glucose under in the experiment of anthocyanin and anthocyanidin, anthocyanidin-3-glucosides (1) and delphinidin-3-glucosides (2) is the most effective insulin succagoga.Pelargonidin-3-galactoside is one of main anthocyanin, and its aglycone pelargonidin causes insulin secretion to increase by 1.4 times under the 4mM concentration of glucose.Remaining anthocyanin tested and anthocyanidin 4 and the 10mM concentration of glucose under insulin is only had limit influence.
Description of drawings
Fig. 1 is the figure that shows anthocyanin 1-4 and anthocyanidin 5-9 structure.
Fig. 2 A be presented at 4 and the 10mM glucose exist down, the amount of every milligram of albumen insulin secretion that combined thing 1 and 2 causes, Fig. 2 B be presented at 4 and the 10mM glucose have down the amount of every milligram of albumen insulin secretion that combined thing 5 and 6 causes.Final DMSO concentration is 0.1% in analyzing the hole.The result is represented as the meansigma methods of three times or five times independent trialss, and each sample is carried out replicate analysis.Use the t-LSD that upchecks to determine the insulin secretion significance that causes by chemical compound 1,2,5 and 6
*(95% or p≤0.05) or
*(99% or p≤0.01).
Fig. 3 be presented at 4 and the 10mM concentration of glucose under cause the figure of insulin secretion by chemical compound 3,7-9.The amount of insulin secretion is to the milligram protein standardization.Final DMSO concentration is 0.1% in analyzing the hole.The result is represented as the meansigma methods of three independent trialss, and each sample is carried out replicate analysis.Use the t-LSD that upchecks to determine the insulin secretion significance that causes by chemical compound 3,7-9
*(95% or p≤0.05).
The description of preferred embodiment
Embodiment
Material and method
Chemicals.(Grand Island NY) obtains hyclone (FBS) and RPMI-1640 medium from Invitrogen.All organic solvents that use are as the ACS SILVER REAGENT.Be used to prepare HEPES, penicillin-streptomycin, glutamine, Sodium Pyruvate, 2 mercapto ethanol, insulin-EDTA, the BSA (bovine albumin of buffer; The RIA level), (St.Louis MO) buys from the Sigma-Aldrich chemical company for Folin-Ciolatues reagent and chemicals.(Laguna Hills CA) buys from Chromadex for the anthocyanidin that is used to analyze, anthocyanidin, delphinidin, pelargonidin, enidin and petunidin.
Anthocyanin.Delphinidin-3-glucosides (2) purification from cornus fruit.Anthocyanidin-3-galactoside (3) separates from Eurasian cornus fruit with pelargonidin-3-galactoside (4).Pure anthocyanidin-3-the glucosides (1) that is used for this research is from our stock at-20 ℃.
The separation of anthocyanin and purification.Cornus fruit is mixed with water (pH=3) and filter.Filtrate is passed through the XAD-16 penak in post, absorb resin water (17) cyclic washing of anthocyanin.Use acid MeOH (pH=3) eluting XAD-16 resin then, the solution that obtains is under reduced pressure concentrated obtain crude product anthocyanin part.This part is used MeOH: H by MPLC post (C18 silica gel)
2O (pH=3) purification under gradient condition.Use MeOH: H
2O (65: 35, v/v) solvent system eluting anthocyanin.The purity of chemical compound uses Capcell C18 analytical column to check under gradient condition by HPLC (Waters Corp.).The solvent that uses is A:TFA: H
2O (99.9: 0.1; V/v) and B:H
2O: CH
3CN: CH
3COOH: TFA (50.4: 48.5: 1.0: 0.1; V/v/v/v).Gradient under flow velocity 0.8ml/min at 26 minutes 20%B to 60%B, at 30 minutes to 20%B.Use the PDA detected peaks at 520nm.
Insulin secretion research.INS-1 832/13 cell (the Christopher doctor Newgard close friend by NC Duke university provides) (18) is being contained the 11.1mM glucose and is being supplemented with in the RPMI-1640 medium of 10%FBS (hyclone), 10mM HEPES, 100 U/ml penicillins, 100 μ g/ml streptomycins, 4mM glutamine, 1mM Sodium Pyruvate and 50 μ M 2 mercapto ethanols at 5%CO
237 ℃ of conventional down cultivations in the/air.Transfer sell weekly behind insulin-EDTA separately.For carrying out static secretion research, with cell with every hole 0.64 * 10
6The density of cell is put into 24 orifice plates, cultivates 24 hours.Then cell was cultivated in the RPMI-1640 that contains 4mM glucose and above-mentioned supplement 24 hours again.Then cell was cultivated twice 30 minutes in containing the Krebs Ringer Bicarbonate buffer (KRBB) of 4mM glucose and 0.1%BSA.Cell is washed fast with KRBB, contain 4 or the 10mM glucose contain or do not have in specified anthocyanin or the anthocyanidin and cultivated 60 minutes.Remove medium then for determining that insulin discharges.Then cell is used the PBS washed twice, be dissolved among the 1M NaOH.Then by Lowry assay determination intracellular protein concentration.Anthocyanin and anthocyanidin are dissolved in the required concentration of acquisition among the DMSO.The DMSO ultimate density is 0.1%.Pass through radioimmunoassay determination by emiocytosis to the insulin in the medium, to the total cell protein standardization.
Radioimmunoassay, RIA (RIA).(StCharles MO) buys the RIA test kit, analyzes according to the guidance of Producer from LINCO Research Inc..In brief, 0.1-10ng insulin standard product (100 μ l) are added in 12 * 75mm experiment tube.Similarly, will also join in the experiment tube from the sample (25 μ l) of insulin secretion research.To the analysis buffer that wherein adds equal portions (75 μ l).In each experiment tube, add then
125The insulin of I labelling (100 μ l).Chinese People's Anti-Japanese Military and Political College's Mus insulin antibody of 100 μ L equal portions is joined in the pipe, mix being incorporated in 4 ℃ of cultivations 24 hours, further cultivate 20 minutes with the insulin of precipitation at 4 ℃ with antibodies with the precipitation reagent of 1ml equal portions.Centrifuge tube uses gamma counter to measure radioactivity then.
The Lowry analysis of protein.Proteic amount is measured (Francis, J.A. is etc., Helv.Chim.Acta 87 317-326 (2004)) by the Lowry method in analyzing the hole.By with Lowry solution, CuSO
4.5H
2O (1%) and sodium tartrate (1%) are mixed with the Lowry analytical solution.In brief, protein sample (100 μ l) and Lowry mixture (1mL) are mixed in experiment tube (12 * 75).In these pipes, add Folin-Ciolatues reagent (100 μ l), mix and at room temperature cultivated 30 minutes.The optical density of resultant solution uses ultraviolet-uisible spectrophotometer at the 700nm reading.
Result and discussion
Cornus fruit be used to anti-diabetic prescriptions of Chinese medicine medicine for example " HachimiGan " (Yamahara, J., etc., Yakugaku Zasshi, 101 86-90 (1981)) in.Reported quantitatively (Seeram, N.P. etc., J.Agri.Food Chem.50 2519-2523 (2002)) of anthocyanin in cornus fruit recently.Cornus fruit studies show that the main bioactive ingredients in them is anthocyanidin, delphinidin and pelargonidin glucosides.Therefore, we use pancreatic beta cell to concentrate the insulin secretion ability of these anthocyanins of concern and their aglycone, to confirm the purposes of cornus fruit in the rumor antidiabetic agent preparation.Petunidin, enidin and peonidin aglycone are also included within this analysis, and be abundant because they are content in other fruit.
Anthocyanin is water-soluble chemical compound.Contain sugar, bioflavonoids and anthocyanin in the Eurasian cornus fruit aqueous solution extraction thing, therefore by the XAD-16 resin isolation.The anthocyanin part that eluting obtains from resin obtains pure anthocyanin by the MPLC purification.4,10 and the 16mM concentration of glucose under, measure by INS-1 832/13 grape cell sugar-induce the generation of insulin, find that insulin secretion reaches lag phase (data do not provide) under the 10mM concentration of glucose.At the concentration of glucose of 4mM level is the representative value (Christison, G.B. is etc., Med.Boil.Eng.Comp 31 284-290 (1993)) of people's normal glucose level.At the proteic insulin secretion of the every mg of cell under the 10mM glucose through relatively being more than 3 times of insulin secretion under the 4mM concentration of glucose.
Also with anthocyanin and anthocyanidin in cell growth medium 4 and the load of 10mM glucose under test.Anthocyanin and anthocyanidin are analyzed under 50 μ g/mL concentration at first.Anthocyanin, anthocyanidin 3-glucosides (1) show that increasing insulin secretion reaches 9ng/mg albumen (1.3 times) under the 4mM glucose, yet it strengthens 1.43 times of (119ng/mg albumen) (Fig. 2 A) of insulin secretion under the 10mM concentration of glucose.Delphinidin-3-glucosides (2) is the strongest active anthocyanin that tried, and shows insulin secretion 1.8-increase (49ng/mg albumen) doubly under the 4mM concentration of glucose.But it only demonstrates the doubly increase (Fig. 2 A) of (113ng) of 1.4-that insulin produces under the 10mM glucose.In this analysis 4 and the 10mM concentration of glucose under the insulin of emiocytosis be respectively every mg albumen 27 and 83ng insulin.Anthocyanin, anthocyanidin-3-galactoside (3) and pelargonidin-3-galactoside (4) do not increase insulin secretion under the 4mM concentration of glucose.But anthocyanidin-3-galactoside is presented at the increase (Fig. 3) of 17ng insulin/mg albumen (1.2 times) under the 10mM concentration of glucose.Because the sample restriction, pelargonidin-3-galactoside (4) is only tested once.
Anthocyanin anthocyanidin-3-glucosides (1) has been estimated the dose dependent insulin secretion under 5,10,50,100 and 250 μ g/mL concentration.The concentration of glucose that is used for this analysis is the 4mM level, and it is the representative value (Christison, G.B. is etc., Med.Boil.Eng.Comp.31 284-290 (1993)) of people's normal glucose level.Under this concentration, untreated emiocytosis 33ng insulin/mg albumen.By the emiocytosis insulin that anthocyanidin-3-glucosides (1) is handled under 5 μ g/mL is 46ng insulin/mg albumen.But insulin secretion does not have significant difference under chemical compound 1 concentration 10,50,100 and 250 μ g/mL.We do not have the delphinidin-3-glucosides of q.s to finish the dosage dependency analysis.
Anthocyanidin is analyzed under 50 μ g/mL concentration.The aglycone of anthocyanidin-3-glucosides, anthocyanidin (5) strengthen insulin secretion and reach 1.5 times (29ng/mg albumen) under the 4mM glucose, yet its secretes 88ng/mg albumen (Fig. 2 B) under the 10mM glucose.In this group analysis, untreated cell 4 and the 10mM glucose under secrete 19 and 83ng insulin/mg albumen respectively.Aglycone delphinidin (6) is presented at increases insulin secretion 6ng/mg albumen under the 4mM concentration of glucose, be not significant.Delphinidin does not show glucose-inductive insulin secretion (Fig. 2 B) under the 10mM glucose.Pelargonidin is a strongest active anthocyanidin, its 4 and the 10mM glucose under secrete 49 (1.4 times) and 91 (1.2 times) ng insulin/mg albumen (Fig. 3) respectively.Aglycone petunidin (9) increases insulin secretion 4ng insulin/mg albumen under the 4mM concentration of glucose.But for untreated cell, enidin (8) does not show increases the insulin secretion effect.
Report show the sickness rate that fruit and vegetable especially be rich in the consumption of the fruit of polyhydric phenols and vegetable and reduce 2-type diabetes (Anderson, R.A. is etc., J.Agric.Food Chem.507182-7186 (2002); Anderson, R.A., etc., J.Agric.Food Chem.52 65-70 (2004); And Landrault, N., etc., J.Agric.Food Chem.51 311-3188 (2003)).And the antioxidant protection pancreas beta cell in the also known diet is avoided the oxidation stress of glucose induction.Anthocyanin for example is that content is abundant in wine, applejack and the tea in fruit, vegetable and product processed; But, the ability of its reduction or prevent diabetes is also known little about it.Our results suggest anthocyanin and anthocyanidin all are the insulin succagoga.Delphinidin-3-glucosides the most effectively in them, with untreated cell comparison its 4 and the 10mM concentration of glucose under significantly induce insulin secretion.Although anthocyanidin-3-glucosides is more less than delphinidin-3-glycosidase activity under lower concentration of glucose, its activity is higher under higher concentration of glucose.In galactoside, pelargonidin-3-galactoside 4 and the 10mM concentration of glucose under do not induce insulin secretion, yet anthocyanidin-3-galactoside shows the significant insulin secretion effect that increases.The capability study of anthocyanin excreting insulin shows that by the order that increases be delphinidin-3-glucosides＞anthocyanidin-3-glucosides＞pelargonidin-3-galactoside.This shows in the excreting insulin ability of hydroxyl value at them in the anthocyanin B-ring and plays an important role.In the anthocyanidin that is tried, the pelargonidin activity is the highest under the 4mM glucose.Other aglycone 4 or the 10mM concentration of glucose under significantly do not increase insulin secretion.
This paper is exposed to first report that pancreatic beta cell causes insulin secretion by anthocyanin and anthocyanidin.Cornus fruit, Fructus Pruni pseudocerasi and berry that our results suggest contains these anthocyanins are used to prevent 2-type diabetes.And from fruit and vegetable, separate and the anthocyanin and the anthocyanidin of purification can be used for the treatment of 2-type diabetes.
The document of quoting
(1)Ross，S.A.；Gulve，E.A.；Wang，M.Chemistry?and?Biochemistry?of?diabetes.Chem.Rev.2004，104，1255-1282.
(2)Jovanovic，L.；Gondos，B.Type-2?diabetes：The?epidemic?of?new?millennium.Ann.Clin.Lab.Sci.1999，29，33-42.
(3)Henquin，J.C.Triggering?and?amplifying?pathways?of?regulation?of?insulin?secretionby?glucose.Diabetes?2000，49，1751-1760.
(4)Pfeiffer，A.F.H.Oral?hypoglycemic?agents：Sulfonylureas?and?meglitinides.In?B.J.Goldstein，D.Müller-Wieland(Eds.)，Text?book?of?Type-2?Diabetes.Martin?DunitzLtd.，London，2003，pp.77-85.
(5)Blakely，S.；Herbert，A.；Collins，M.；Jenkins，M.；Mitchell，G.；Grundel，E.；O′Neill，K.R.；Khachik，F.Lutein?interacts?with?ascorbic?acid?morefrequently?than?with?α-tocopherol?to?alter?biomarkers?of?oxidative?stress?in?female?Zucker?obese?rats.J.Nutr.2003，133，2838-2844.
(6)Jayaprakasam，B.；Strasburg，G.A.；Nair，M.G.Potent?lipid?peroxidation?inhibitorsfrom?Withania?somnifera.Tetrahedron?2004，60，3109-3121.
(7)Duthie，G.G.；Duthie，S.J.；Kyle，J.A.M.Plant?polyphenols?in?cancer?and?heartdisease：implications?as?nutritional?antioxidants.Nutr.Res.Rev.2000，13，79-106.
(8)Kang，S.Y.；Seeram，N.P.；Nair，M.G.；Bourquin，L.D.Tart?cberry?anthocyaninsinhibit?tumor?development?in?ApcMin?mice?and?reduce?proliferation?of?human?coloncancer?cells.Canc.Lett.2003，194，13-19.
(9)Van?Velden，D.P.；Mansvelt，E.P.G.；Fourie，E.；Rossouw，M.；Marais，A.D.Thecardioprotective?effect?of?wine?on?human?blood?chemistry.Ann.New?York?Acad.Sci.2002，957，337-340.
(10)Wang，H.；Nair，M.G.；Strasburg，G.M.；Chang，Y.C.；Booren，A.M.；Gray，I.J.；DeWitt，D.L.Antioxidant?and?antiinflammatory?activities?ofanthocyanins?and?theiraglycone，cyanidin，from?tart?cherries.J.Nat.Prod.1999，62，294-296.
(11)Tsuda，T.；Horio，F.；Uchida，K.；Aoki，H.；Osawa，T.Dietary?cyanidin?3-O-β-D-glucoside-rich?purple?com?color?prevents?obesity?and?ameliorates?hyperglycemia?inmice.J.Nut.2003，133，2125-2130.
(12)Espin，J.C.；Soler-Rivas，C.；Wichers.，H.J.；Garcia-Viguera，C.Anthocyanin-basednatural?colorants.A?new?source?of?antiradical?activity?for?foodstuff.J.Agri.FoodChem.2000，48，1588-1592.
(13)Millspaugh，C.F.In?American?Medicinal?Plants；Dover?Publications：New?York，1974；p?282.
(14)Kim，D.K.；Kwak，J.H.A?Furan?derivative?from?Cornus?officinalis.Arch.Pharm.Res.1998，21，787-789.
(15)Yamahara，J.；Mibu，H.；Sawada，T.；Fujimura，H.；Takino，S.；Yoshikawa，M.；Kitagawa，I.Biologically?active?principles?of?crude?drugs.Antidiabetic?principles?ofcomi?fructus?in?experimental?diabetes?induced?by?streptozotocin.Yakugaku?Zasshi1981，101，86-90.
(16)Seeram，N.P.；Schutzki，R.；Chandra，A.；Nair，M.G.Characterization，Quantification，and?Bioactivities?of?Anthocyanins?in?Cornus?Species.J.Agri.FoodChem.2002，50，2519-2523.
(17)Beckwith，A.G.；Zhang，Y.；Seeram，N.P.；Cameron，A.C.；Nair，M.G.Relationshipof?Light?Quantity?and?Anthocyanin?Production?in?Pennisetum?setaceum?Cvs.Rubrumand?Red?Riding?Hood.J.Agric.Food?Chem.2004，52，456-461.
(18)Hohmeier，H.E.；Mulder，H.；Chen，G.；Henkel-Rieger，R.；Prentki，M.；Newgard，C.B.Isolation?of?INS-1-derived?cell?lines?with?robust?ATP-sensitive?K+channel-dependent?and-independent?glucose-stimulated?insulin?secretion.Diabetes?2000，49，424-430.
(19)Francis，J.A.；Jayaprakasam，B.；Olson，L.K.；Nair，M.G.Insulin?secretagogues?fromMoringa?oleifera?with?cyclooxygenase?enzyme?and?lipid?peroxidation?inhibitoryactivities.Helv.Chim.Acta?2004，87，317-326.
(20)Christison，G.B.；MacKenzie，H.A.Laser?photoacoustic?determination?ofphysiological?glucose?concentrations?in?human?whole?blood.Med.Boil.Eng.Comp.1993，31，284-90.
(21)Anderson，R.A.；Polansky，M.M.Tea?Enhances?Insulin?Activity.J.Agric.FoodChem.2002，50，7182-7186.
(22)Anderson，R.A.；Broadhurst，C.L.；Polansky，M.M.；Schmidt，W.F.；Khan，A.；Flanagan，V.P.；Schoene，N.W.；Graves，D.J.Isolation?and?Characterization?of?Polyphenol?Type-A?Polymers?from?Cinnamon?with?Insulin-like?Biological?Activity.J.Agric.FoodChem.2004，52，65-70.
(23)Landrault，N.；Poucheret，P.；Azay，J.；Krosniak，M.；Gasc，F.；Jenin，C.；Cros，G.；Teissedre，P.Effect?of?a?Polyphenols-Enriched?Chardonnay?White?Wine?in?DiabeticRats.J.Agric.Food?Chem.2003，51，311-318.
Anthocyanin and anthocyanidin separate and production method in United States Patent (USP) 6,194,469; 6,423,365; 6,623,743; 6,676,978 and 6,656,914; And on February 27th, 2002 the U.S. Patent application S.N.10/084 that submits to, describe in 575, this paper is incorporated herein by reference its full content.
Previously described purpose only is to illustrate the present invention, and the present invention only is subjected to hereinafter appended Claim restriction.
Claims (11)
1. increase the method for insulin secretion of the pancreatic cell of excreting insulin, it comprises: provide anthocyanin or anthocyanidin or its mixture to pancreatic beta cell so that the insulin secretion increase of insulin secretion when not having anthocyanin.
2. the process of claim 1 wherein that anthocyanin is from fruit, vegetable with isolating spending.
3. the process of claim 1 wherein that anthocyanin is selected from: anthocyanidin-3-glucosides, delphinidin-3-glucosides, callistephin and composition thereof.
4. claim 1,2 or 3 any one methods, wherein pancreatic cell is in vivo.
5. claim 1,2 or 3 any one methods, wherein pancreatic cell is external.
6. as anthocyanin or anthocyanidin or its mixture of dosage unit, be used for increasing insulin in vivo and produce from pancreatic cell.
7. the compositions of claim 6, wherein anthocyanin separates from fruit, vegetable with spending.
8. the compositions of claim 6, wherein anthocyanin is selected from: anthocyanidin-3-glucosides, delphinidin-3-glucosides, callistephin and composition thereof.
9. the process of claim 1 wherein that anthocyanidin or anthocyanin or its mixture are separated and purification.
10. the compositions of claim 6, wherein anthocyanidin or anthocyanin or its mixture are separated and purification.
11. the process of claim 1 wherein that anthocyanin or anthocyanidin or its mixture are in the juice of fruit or vegetable.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US59180604P | 2004-07-29 | 2004-07-29 | |
| US60/591,806 | 2004-07-29 | ||
| US11/071,929 | 2005-03-04 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN1993135A true CN1993135A (en) | 2007-07-04 |
Family
ID=38185393
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 200580025636 Pending CN1993135A (en) | 2004-07-29 | 2005-06-21 | Insulin secretion by anthocyanins and anthocyanidins |
| CN200580025447.3A Expired - Fee Related CN1988912B (en) | 2004-07-29 | 2005-07-25 | Methods and compositions for the treatment of obesity, insulin related diseases and hypercholesterolemia |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN200580025447.3A Expired - Fee Related CN1988912B (en) | 2004-07-29 | 2005-07-25 | Methods and compositions for the treatment of obesity, insulin related diseases and hypercholesterolemia |
Country Status (2)
| Country | Link |
|---|---|
| CN (2) | CN1993135A (en) |
| ZA (2) | ZA200700249B (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104892700A (en) * | 2015-06-11 | 2015-09-09 | 威海紫光科技园有限公司 | Method for extracting anthocyanin from cherries |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2013115504A1 (en) * | 2012-01-30 | 2013-08-08 | 포항공과대학교 산학협력단 | Pharmaceutical composition for preventing or treating diabetes containing tenc1 expression or activity suppressor |
| WO2015163062A1 (en) * | 2014-04-23 | 2015-10-29 | 日本製紙株式会社 | Agent for preventing or ameliorating diabetes |
| CN109432112B (en) * | 2018-11-06 | 2020-09-22 | 江苏医药职业学院 | Application of delphinidin 3- [2- (xyloside) galactoside ] as active ingredient in preparation of blood fat reducing medicine |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4229439A (en) * | 1977-11-21 | 1980-10-21 | Societe De Recherches Industrielles (Sori) | Method of treatment of atheroma |
-
2005
- 2005-06-21 CN CN 200580025636 patent/CN1993135A/en active Pending
- 2005-07-25 CN CN200580025447.3A patent/CN1988912B/en not_active Expired - Fee Related
-
2007
- 2007-01-09 ZA ZA200700249A patent/ZA200700249B/en unknown
- 2007-01-23 ZA ZA200700640A patent/ZA200700640B/en unknown
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104892700A (en) * | 2015-06-11 | 2015-09-09 | 威海紫光科技园有限公司 | Method for extracting anthocyanin from cherries |
Also Published As
| Publication number | Publication date |
|---|---|
| CN1988912A (en) | 2007-06-27 |
| ZA200700640B (en) | 2008-09-25 |
| CN1988912B (en) | 2013-01-30 |
| ZA200700249B (en) | 2008-05-28 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| RU2359689C2 (en) | Ways and compositions for adiposity treatment, insulin-dependent diseases and hypercholesterinemia | |
| AU2015254309B2 (en) | Muscle atrophy inhibitor containing quercetin glycoside | |
| Marie-Magdeleine et al. | In vitro effects of Cassava (Manihot esculenta) leaf extracts on four development stages of Haemonchus contortus | |
| Marie-Magdeleine et al. | In vitro effects of Musa x paradisiaca extracts on four developmental stages of Haemonchus contortus | |
| AU2005301315B2 (en) | Insulin secretion by anthocyanins and anthocyanidins | |
| JP2001278792A (en) | Anti-allergic and anti-inflammatory agent, medicinal composition, quasi drug, cosmetic material, food and animal feed containing the same | |
| Calvin et al. | In vitro anthelmintic activity of aqueous extract of Crassocephalum crepidioides (Benth.) S. Moore on Haemonchus contortus. | |
| CN1993135A (en) | Insulin secretion by anthocyanins and anthocyanidins | |
| EP3406591A1 (en) | Dicaffeoyl-spermidine derivative glycoside and use thereof | |
| García-Hernández et al. | In vitro and in vivo anthelmintic properties of Caesalpinia coriaria fruits against Haemonchus contortus | |
| Zahner et al. | Effects of Bay 44-4400, a new cyclodepsipeptide, on developing stages of filariae (Acanthocheilonema viteae, Brugia malayi, Litomosoides sigmodontis) in the rodent Mastomys coucha | |
| Park et al. | Evaluation of genetic toxicity, acute and sub-chronic oral toxicity and systemic safety of Agrimonia pilosa and Rhus gall 50% ethanolic extract mixture (APRG64) in vitro and in vivo (rodent and non-rodent animal models) | |
| Lazarini et al. | The phytoactive constituents of Eugenia selloi BD Jacks (pitangatuba): Toxicity and elucidation of their anti-inflammatory mechanism (s) of action | |
| EP3406620B1 (en) | Dicaffeoyl-spermidine cyclic derivative and use thereof | |
| CN114948813A (en) | Anti-saccharification and anti-aging natural product composition, preparation method thereof and application thereof in oral beauty products | |
| Abubakar et al. | In vitro antidiabetic potentials of crude saponins extract from Leptodenia hastata and Adansonia digitata leaves | |
| Kim et al. | Effect of extraction conditions on radical scavenging and cholesterol metabolism regulating capacity of silkworm larvae. | |
| CN1169822C (en) | Quercetin derivative and its medicinal use | |
| Kolawole et al. | Effects of Russelia equisetiformis methanol and aqueous extracts on hepatic function indices | |
| JP5068736B2 (en) | Pharmaceutical substance and pharmaceutical composition for treatment and / or prevention of retinal pigment epithelial cell disease | |
| Prasetyo et al. | Anthelmintic effects of Podang mango (Mangifera indica) fruit peel waste extract through in vivo application on Indonesian Etawa goat production and health | |
| CN116115655B (en) | Application of pine bark extract in improving NAD (NAD) level | |
| CN115645431B (en) | Composition and application thereof | |
| RU2804478C2 (en) | Combination of rhodiola and astragalus for the treatment of neurodegenerative diseases | |
| EP2052728B1 (en) | Hypoglycemic composition containing component originating in the bark of tree belonging to the genus acacia |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C12 | Rejection of a patent application after its publication | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20070704 |