CN110368391B - 三萜化合物在制备降血糖相关产品中的用途 - Google Patents
三萜化合物在制备降血糖相关产品中的用途 Download PDFInfo
- Publication number
- CN110368391B CN110368391B CN201910543612.8A CN201910543612A CN110368391B CN 110368391 B CN110368391 B CN 110368391B CN 201910543612 A CN201910543612 A CN 201910543612A CN 110368391 B CN110368391 B CN 110368391B
- Authority
- CN
- China
- Prior art keywords
- preparation
- blood sugar
- compound
- alpha
- formula
- 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.)
- Active
Links
- 235000000346 sugar Nutrition 0.000 title abstract description 24
- 238000002360 preparation method Methods 0.000 title abstract description 23
- 239000008280 blood Substances 0.000 title abstract description 13
- 210000004369 blood Anatomy 0.000 title abstract description 13
- 230000009467 reduction Effects 0.000 title abstract description 10
- -1 triterpene compound Chemical class 0.000 title description 12
- 150000001875 compounds Chemical class 0.000 claims abstract description 28
- 235000003145 Hippophae rhamnoides Nutrition 0.000 claims abstract description 21
- 240000000950 Hippophae rhamnoides Species 0.000 claims abstract description 3
- 229940077274 Alpha glucosidase inhibitor Drugs 0.000 claims description 6
- 239000003888 alpha glucosidase inhibitor Substances 0.000 claims description 6
- 239000003814 drug Substances 0.000 claims description 5
- 239000003472 antidiabetic agent Substances 0.000 claims 1
- 230000005764 inhibitory process Effects 0.000 abstract description 19
- 102100024295 Maltase-glucoamylase Human genes 0.000 abstract description 16
- 108010028144 alpha-Glucosidases Proteins 0.000 abstract description 16
- 230000000694 effects Effects 0.000 abstract description 13
- 238000011161 development Methods 0.000 abstract description 3
- 238000011160 research Methods 0.000 abstract description 2
- 241000229143 Hippophae Species 0.000 description 19
- XUFXOAAUWZOOIT-SXARVLRPSA-N (2R,3R,4R,5S,6R)-5-[[(2R,3R,4R,5S,6R)-5-[[(2R,3R,4S,5S,6R)-3,4-dihydroxy-6-methyl-5-[[(1S,4R,5S,6S)-4,5,6-trihydroxy-3-(hydroxymethyl)-1-cyclohex-2-enyl]amino]-2-oxanyl]oxy]-3,4-dihydroxy-6-(hydroxymethyl)-2-oxanyl]oxy]-6-(hydroxymethyl)oxane-2,3,4-triol Chemical compound O([C@H]1O[C@H](CO)[C@H]([C@@H]([C@H]1O)O)O[C@H]1O[C@@H]([C@H]([C@H](O)[C@H]1O)N[C@@H]1[C@@H]([C@@H](O)[C@H](O)C(CO)=C1)O)C)[C@@H]1[C@@H](CO)O[C@@H](O)[C@H](O)[C@H]1O XUFXOAAUWZOOIT-SXARVLRPSA-N 0.000 description 11
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 11
- 229960002632 acarbose Drugs 0.000 description 11
- XUFXOAAUWZOOIT-UHFFFAOYSA-N acarviostatin I01 Natural products OC1C(O)C(NC2C(C(O)C(O)C(CO)=C2)O)C(C)OC1OC(C(C1O)O)C(CO)OC1OC1C(CO)OC(O)C(O)C1O XUFXOAAUWZOOIT-UHFFFAOYSA-N 0.000 description 11
- JPQFUHCOKXIWBB-ZCRGAIPPSA-N isoobtusol Natural products CC1(C)[C@@H](Br)[C@@H](O)CC(=C)[C@@]11C[C@H](Cl)[C@@](C)(Br)CC1 JPQFUHCOKXIWBB-ZCRGAIPPSA-N 0.000 description 11
- MJYXNLJVQSSJFM-UHFFFAOYSA-N obtusol Natural products C1CC(O)C(C)(C)C2CCC3(C)C4(CO)CCC5(C)CCC(C)C(C)C5C4=CCC3C21C MJYXNLJVQSSJFM-UHFFFAOYSA-N 0.000 description 11
- 229930182470 glycoside Natural products 0.000 description 10
- 239000003112 inhibitor Substances 0.000 description 10
- JPQFUHCOKXIWBB-FWZIUSJTSA-N obtusol Chemical compound CC1(C)[C@H](Br)[C@H](O)CC(=C)[C@]11C[C@@H](Cl)[C@](C)(Br)CC1 JPQFUHCOKXIWBB-FWZIUSJTSA-N 0.000 description 10
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 9
- 239000000243 solution Substances 0.000 description 9
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 8
- 239000003153 chemical reaction reagent Substances 0.000 description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 8
- 238000002474 experimental method Methods 0.000 description 7
- 150000002338 glycosides Chemical class 0.000 description 7
- 239000011734 sodium Substances 0.000 description 6
- 102000004190 Enzymes Human genes 0.000 description 5
- 108090000790 Enzymes Proteins 0.000 description 5
- 238000002835 absorbance Methods 0.000 description 5
- 235000013399 edible fruits Nutrition 0.000 description 5
- 238000005303 weighing Methods 0.000 description 5
- ZZZCUOFIHGPKAK-UHFFFAOYSA-N D-erythro-ascorbic acid Natural products OCC1OC(=O)C(O)=C1O ZZZCUOFIHGPKAK-UHFFFAOYSA-N 0.000 description 4
- 229930003268 Vitamin C Natural products 0.000 description 4
- 238000006243 chemical reaction Methods 0.000 description 4
- 238000001514 detection method Methods 0.000 description 4
- 150000002148 esters Chemical class 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- 238000004811 liquid chromatography Methods 0.000 description 4
- 239000000203 mixture Substances 0.000 description 4
- 239000008055 phosphate buffer solution Substances 0.000 description 4
- 235000019154 vitamin C Nutrition 0.000 description 4
- 239000011718 vitamin C Substances 0.000 description 4
- HIXDQWDOVZUNNA-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)-5-hydroxy-7-methoxychromen-4-one Chemical compound C=1C(OC)=CC(O)=C(C(C=2)=O)C=1OC=2C1=CC=C(OC)C(OC)=C1 HIXDQWDOVZUNNA-UHFFFAOYSA-N 0.000 description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- 235000019441 ethanol Nutrition 0.000 description 3
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 3
- 238000000605 extraction Methods 0.000 description 3
- 238000010829 isocratic elution Methods 0.000 description 3
- 238000002156 mixing Methods 0.000 description 3
- 239000010413 mother solution Substances 0.000 description 3
- 239000003208 petroleum Substances 0.000 description 3
- 238000004366 reverse phase liquid chromatography Methods 0.000 description 3
- BTJIUGUIPKRLHP-UHFFFAOYSA-N 4-nitrophenol Chemical compound OC1=CC=C([N+]([O-])=O)C=C1 BTJIUGUIPKRLHP-UHFFFAOYSA-N 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
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- 239000013543 active substance Substances 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 238000003556 assay Methods 0.000 description 2
- 238000004587 chromatography analysis Methods 0.000 description 2
- 238000007865 diluting Methods 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 235000013305 food Nutrition 0.000 description 2
- 235000011389 fruit/vegetable juice Nutrition 0.000 description 2
- 239000008103 glucose Substances 0.000 description 2
- 230000036541 health Effects 0.000 description 2
- 230000002218 hypoglycaemic effect Effects 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- OKKJLVBELUTLKV-VMNATFBRSA-N methanol-d1 Chemical compound [2H]OC OKKJLVBELUTLKV-VMNATFBRSA-N 0.000 description 2
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical group CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 239000000376 reactant Substances 0.000 description 2
- 239000012064 sodium phosphate buffer Substances 0.000 description 2
- 239000002689 soil Substances 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- WCGUUGGRBIKTOS-GPOJBZKASA-N (3beta)-3-hydroxyurs-12-en-28-oic acid Chemical compound C1C[C@H](O)C(C)(C)[C@@H]2CC[C@@]3(C)[C@]4(C)CC[C@@]5(C(O)=O)CC[C@@H](C)[C@H](C)[C@H]5C4=CC[C@@H]3[C@]21C WCGUUGGRBIKTOS-GPOJBZKASA-N 0.000 description 1
- HBOQXIRUPVQLKX-UHFFFAOYSA-N 2,3-di(octadeca-9,12-dienoyloxy)propyl octadeca-9,12-dienoate Chemical compound CCCCCC=CCC=CCCCCCCCC(=O)OCC(OC(=O)CCCCCCCC=CCC=CCCCCC)COC(=O)CCCCCCCC=CCC=CCCCCC HBOQXIRUPVQLKX-UHFFFAOYSA-N 0.000 description 1
- MIJYXULNPSFWEK-GTOFXWBISA-N 3beta-hydroxyolean-12-en-28-oic acid Chemical compound C1C[C@H](O)C(C)(C)[C@@H]2CC[C@@]3(C)[C@]4(C)CC[C@@]5(C(O)=O)CCC(C)(C)C[C@H]5C4=CC[C@@H]3[C@]21C MIJYXULNPSFWEK-GTOFXWBISA-N 0.000 description 1
- IFBHRQDFSNCLOZ-IIRVCBMXSA-N 4-nitrophenyl-α-d-galactoside Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@@H]1OC1=CC=C([N+]([O-])=O)C=C1 IFBHRQDFSNCLOZ-IIRVCBMXSA-N 0.000 description 1
- 244000298697 Actinidia deliciosa Species 0.000 description 1
- 235000009436 Actinidia deliciosa Nutrition 0.000 description 1
- 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 1
- 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 1
- 238000002965 ELISA Methods 0.000 description 1
- 241001117772 Elaeagnaceae Species 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- JKLISIRFYWXLQG-UHFFFAOYSA-N Epioleonolsaeure Natural products C1CC(O)C(C)(C)C2CCC3(C)C4(C)CCC5(C(O)=O)CCC(C)(C)CC5C4CCC3C21C JKLISIRFYWXLQG-UHFFFAOYSA-N 0.000 description 1
- 102000004366 Glucosidases Human genes 0.000 description 1
- 108010056771 Glucosidases Proteins 0.000 description 1
- 102000005744 Glycoside Hydrolases Human genes 0.000 description 1
- 108010031186 Glycoside Hydrolases Proteins 0.000 description 1
- 235000003935 Hippophae Nutrition 0.000 description 1
- YBRJHZPWOMJYKQ-UHFFFAOYSA-N Oleanolic acid Natural products CC1(C)CC2C3=CCC4C5(C)CCC(O)C(C)(C)C5CCC4(C)C3(C)CCC2(C1)C(=O)O YBRJHZPWOMJYKQ-UHFFFAOYSA-N 0.000 description 1
- MIJYXULNPSFWEK-UHFFFAOYSA-N Oleanolinsaeure Natural products C1CC(O)C(C)(C)C2CCC3(C)C4(C)CCC5(C(O)=O)CCC(C)(C)CC5C4=CCC3C21C MIJYXULNPSFWEK-UHFFFAOYSA-N 0.000 description 1
- OUUQCZGPVNCOIJ-UHFFFAOYSA-M Superoxide Chemical compound [O-][O] OUUQCZGPVNCOIJ-UHFFFAOYSA-M 0.000 description 1
- GAMYVSCDDLXAQW-AOIWZFSPSA-N Thermopsosid Natural products O(C)c1c(O)ccc(C=2Oc3c(c(O)cc(O[C@H]4[C@H](O)[C@@H](O)[C@H](O)[C@H](CO)O4)c3)C(=O)C=2)c1 GAMYVSCDDLXAQW-AOIWZFSPSA-N 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 239000007853 buffer solution Substances 0.000 description 1
- 235000021258 carbohydrate absorption Nutrition 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 150000004665 fatty acids Chemical class 0.000 description 1
- 229930003944 flavone Natural products 0.000 description 1
- 150000002212 flavone derivatives Chemical class 0.000 description 1
- 235000011949 flavones Nutrition 0.000 description 1
- 235000015203 fruit juice Nutrition 0.000 description 1
- 229930182478 glucoside Natural products 0.000 description 1
- 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 1
- 230000003301 hydrolyzing effect Effects 0.000 description 1
- 201000001421 hyperglycemia Diseases 0.000 description 1
- 238000002372 labelling Methods 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 230000037353 metabolic pathway Effects 0.000 description 1
- 238000000034 method Methods 0.000 description 1
- 239000012452 mother liquor Substances 0.000 description 1
- 238000003953 normal phase liquid chromatography Methods 0.000 description 1
- 235000016709 nutrition Nutrition 0.000 description 1
- 230000035764 nutrition Effects 0.000 description 1
- 229940100243 oleanolic acid Drugs 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- HZLWUYJLOIAQFC-UHFFFAOYSA-N prosapogenin PS-A Natural products C12CC(C)(C)CCC2(C(O)=O)CCC(C2(CCC3C4(C)C)C)(C)C1=CCC2C3(C)CCC4OC1OCC(O)C(O)C1O HZLWUYJLOIAQFC-UHFFFAOYSA-N 0.000 description 1
- 239000008213 purified water Substances 0.000 description 1
- 239000011435 rock Substances 0.000 description 1
- 239000004576 sand Substances 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 239000011550 stock solution Substances 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 235000013619 trace mineral Nutrition 0.000 description 1
- 239000011573 trace mineral Substances 0.000 description 1
- 150000003648 triterpenes Chemical class 0.000 description 1
- 229940096998 ursolic acid Drugs 0.000 description 1
- PLSAJKYPRJGMHO-UHFFFAOYSA-N ursolic acid Natural products CC1CCC2(CCC3(C)C(C=CC4C5(C)CCC(O)C(C)(C)C5CCC34C)C2C1C)C(=O)O PLSAJKYPRJGMHO-UHFFFAOYSA-N 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
- 239000011782 vitamin Substances 0.000 description 1
- 235000013343 vitamin Nutrition 0.000 description 1
- 229940088594 vitamin Drugs 0.000 description 1
- VHBFFQKBGNRLFZ-UHFFFAOYSA-N vitamin p Natural products O1C2=CC=CC=C2C(=O)C=C1C1=CC=CC=C1 VHBFFQKBGNRLFZ-UHFFFAOYSA-N 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 239000002699 waste material Substances 0.000 description 1
Images
Classifications
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
- A23L33/105—Plant extracts, their artificial duplicates or their derivatives
-
- 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
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
-
- 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
- A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Diabetes (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Endocrinology (AREA)
- General Chemical & Material Sciences (AREA)
- Epidemiology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Emergency Medicine (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Botany (AREA)
- Mycology (AREA)
- Nutrition Science (AREA)
- Food Science & Technology (AREA)
- Polymers & Plastics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Description
技术领域
本发明涉及沙棘中有效物质的提取领域,特别是涉及沙棘三萜提取物及其提取方法。
背景技术
沙棘(拉丁学名:Hippophae rhamnoides Linn.),是一种胡颓子科、沙棘属落叶性灌木,其特性是耐旱、抗风沙,可以在盐碱化土地上生存,因此被广泛用于水土保持。中国西北部大量种植沙棘,用于沙漠绿化。
沙棘果实营养丰富,据测定其果实中含有多种维生素、脂肪酸、微量元素、亚油素、沙棘黄酮、超氧化物等活性物质和人体所需的各种氨基酸。其中维生素C含量极高,每100克果汁中,维生素C含量可达到825~1100毫克,是猕猴桃的2~3倍,素有维生素C之王的美称。现被广泛应用于沙棘果汁、沙棘原浆液的生产,在生产过程中,需要去皮,去掉的沙棘果皮往往当作废料丢弃,或生产成干粉当作饲料,价格非常低廉。
现在已经被报道过沙棘果皮中含有熊果酸和齐墩果酸两种三萜酸,它们具有保肝护肝、降低血糖和抗皮肤氧化等功效,还有望在沙棘果皮中开发更多的活性物质,这对于沙棘的综合开发利用具有重要意义。
发明内容
本发明的目的在于提供一种三萜化合物在制备降血糖相关产品中的用途。
本发明提供式I所示化合物,或其与糖结合成的苷类、酯类化合物中的至少一种,在制备降血糖相关产品中的用途,
式I所示化合物与糖结合成的苷类、酯类化合物,是指式I所示化合物作为苷元与糖缩合形成的糖苷类化合物,或与糖缩合形成的糖苷类化合物。式I所示化合物通常以游离形式或以与糖结合成苷或酯的形式存在于植物体内,其与对应的糖苷类化合物和糖酯类化合物具有相同的多方面的生化活性。经实验验证,式I所示化合物具有α-葡萄糖苷酶的活性抑制效果。葡萄糖苷酶是糖苷水解酶大家族中的一大类酶,主要功能为水解葡萄糖苷键,释放出葡萄糖作为产物,是生物体糖代谢途径中不可或缺的一类酶。式I所示化合物可抑制α-葡萄糖苷酶以延缓碳水化合物的吸收,降低餐后高血糖,从而可用于降血糖产品的制备中。
进一步地,所述产品为需要具有降血糖功效的任何产品,可以是药物、保健品或日常副食品。
优选地,所述药物为α-葡萄糖苷酶抑制剂。
本发明提供式I所示化合物在制备α-葡萄糖苷酶抑制剂中的用途,所述三萜化合物中至少包括式I化合物,或其与糖结合成的苷类、酯类化合物中的至少一种。
本发明提供一种降血糖产品,含有式I所示化合物,或其与糖结合成的苷类、酯类化合物中的至少一种。
进一步地,所述产品为需要具有降血糖功效的任何产品,可以是药物、保健品活日常辅食品。
本发明提供一种α-葡萄糖苷酶抑制剂,其中含有式I所示化合物,或其与糖结合成的苷类、酯类化合物中的至少一种。
本发明提供一种组合物,包括式I所示化合物,或其与糖结合成的苷类、酯类化合物中的至少一种。
本发明提供上述组合物在制备降血糖相关产品中的用途。
本发明提供上述组合物在制备α-葡萄糖苷酶抑制剂中的用途。
与现有技术相比,本发明具有以下有效果:
本发明提供一种沙棘提取物中分离的化合物的新用途,通过实验验证,该化合物具有抑制抑制α-葡萄糖苷酶活性的效果,可作为α-葡萄糖苷酶抑制剂或抑制剂的主要功效成分,可应用于降血糖相关产品的制备中,为沙棘的综合开发利用以及降血糖方面的研究提供了新方向。
附图说明
图1为正相液相色谱分析图谱;
图2为正相色谱制备图谱;
图3为反相液相色谱分析图谱;
图4为反相色谱制备图谱;
图5为制备后的液相色谱分析液图谱。
图6不同浓度的阿卡波糖抑制曲线;
图7不同浓度ObtusolObtusol的抑制剂的抑制曲线。
具体实施方式
下面通过具体实施方式和相关实验对本发明做进一步说明。
实施例1制备ObtusolObtusol
1.制备浸膏
取沙棘果渣5kg,95%乙醇在中药煎药机中进行提取,每次2h,料液比为1:10kg/L,共提取3次,合并3次提取液减压浓缩后得到浸膏约500g。
2.制备化合物
主要仪器和试剂
仪器:安捷伦1260系列高效液相色谱仪,配备G1311C四元梯度泵、G1329B自动进样器、G1316A柱温箱、G1315D检测器。
试剂:分析和制备级乙腈均来自云南新蓝景化学工业有限公司,色谱用水为娃哈哈纯净水。
2.1将浸膏与硅胶进行拌样后,以石油醚和不同比例的石油醚与乙酸乙酯进行冲柱,其中石油醚和乙酸乙酯比例分别为9:1,8:2,7:3,6:4,5:5,4:6,3:7,2:8,1:9,经过硅胶柱点板确定石油醚:乙酸乙酯7:3中的馏分部位为三萜酸含量较高的部位,将7:3馏分中4~13部分(是指每500mL收集一瓶,取第4瓶~第13瓶的馏分)进行正相色谱分析和制备。
2.2液相色谱分析方法建立
将7:3馏分中4~13部分在XAmide(4.6×250mm,5μm)分析柱上进行分析,色谱条件如下:流动相:A为乙醇,B为正己烷;等度洗脱条件:0~45min,4%A,96%B;流速:1mL/min;柱温:30℃;检测波长:203nm,进样量为10μL。
2.3正相色谱制备
将7:3馏分中4~13部分在XAmide(20mm×250mm,5μm)制备柱上进行正相色谱制备。制备时进样量为1mL,流速:19mL/min,其它条件与XAmide分析柱分析条件相同。组分收集:3~3.8min为F~1;3.9~4.6min为F~2;6.2~8min为F~3;8.5~10min为F~4;10~14min为F~5;14~19min为F~6;20~23min为F~7;23~25min为F~8;25~30min为F~9;30~35min为F~10;35~37min为F~11。
2.4反相色谱制备
将F~6(7:3馏分中4~13部分经正相色谱制备后得到的第6个馏分)在Kromasil100~5~C18(4.6×250mm,5μm)分析柱上进行分析后,在Kromasil 100~5~C18(21.2×250mm,5μm)制备柱上进行反相色谱制备,之后以同样的液相条件在Kromasil 100~5~C18(4.6×250mm,5μm)分析柱上进行分析。
色谱分析条件为:流动相:A:水,B:乙腈;等度洗脱条件:0~40min,20%A,80%B;分析流速:1mL/min;检测波长:203nm;柱温:30℃。本分析条件也是化合物定性定量检测的液相色谱条件。
色谱制备条件为:流动相:A:水,B:乙腈;等度洗脱条件:0~40min,20%A,80%B;流速:21mL/min;检测波长:203nm;柱温:30℃;
对制备的组分进行液相色谱分析,结果见图5,色谱峰纯度为96.8%。对获得的化合物进行NMR鉴定:
该化合物的NMR信息如下:Obtusol化合物,分子式:C30H50O2,白色粉末,1H NMR(600MHz,MeOD)δ5.14(1H,t,J=3.6Hz,H-12),3.56,3.03(2H,(a)d,J=11.0Hz;(b)d,J=11.0Hz,H-27),3.16(1H,dd,J=11.4,4.8Hz,H-3),1.95(1H,m,H-18),1.94(2H,m,H-16),1.91(2H,m,H-11),1.62(2H,m,H-21),1.61(1H,m,H-19),1.57(2H,m,H-22),1.55(2H,m,H-1),1.41(2H,m,H-7),1.39(2H,m,H-6),1.32(1H,m,H-9),1.25(2H,m,H-2),1.23(2H,m,H-15),1.12(3H,s,H-28),1.03(3H,s,H-26),1.0(1H,m,H-20),0.98(3H,s,H-23),0.97(3H,s,H-24),0.93(3H,d,J=6.6Hz,H-30),0.81(3H,d,J=6.6Hz,H-29),0.78(3H,s,H-25),0.76(2H,dd,J=12.0,1.2Hz,H-5).
13C NMR(151MHz,MeOD)δ140.21(s,C-13),126.32(s,C-12),79.68(s,C-3),70.20(s,C-27),56.68(s,C-18),55.64(s,C-5),49.57(s,C-9),49.00,43.18(s,C-17),41.29(s,C-8),40.86(s,C-19),40.74(s,C-4),40.14(s,C-1),39.86(s,C-14),39.17(s,C-20),37.99(s,C-10),36.61(s,C-22),34.04(s,C-7),31.82(s,C-15),28.73(s,C-2),27.92(s,C-23),27.11(s,C-21),24.45(s,C-11),24.13(s,C-30),23.86(s,C-16),21.78(s,C-29),19.46(s,C-6),17.93(s,C-28),17.34(s,C-24),16.37(s,C-25),16.22(s,C-26).
该化合物分子式:C30H50O2
分子量:442.3811
结构式为
实验1:本发明所述化合物的α-葡萄糖苷酶抑制实验
一、仪器与试剂
NaH2PO4·2H2O(天津市大茂化学试剂厂);
Na2HPO4·12H2O(天津市大茂化学试剂厂);
无水Na2CO3(天津市河东区红岩试剂厂);
无水乙醇(天津市凯通化学试剂有限公司);
酵母α-葡萄糖苷酶(美国sigma公司,100UN);
pNPG(阿拉丁试剂(上海)有限公司);
阿卡波糖(上海源叶科技有限公司);
酶标仪(BioTek公司,型号:EPOCH2);
恒温振荡器(THOMMO SHAKER,型号:BE-9010)。
二、实验方法
1、试剂的配制
(1)甲液的配制:NaH2PO4·2H2O称取15.603g,定容至500mL,4℃,棕色瓶保存,备用。
(2)乙液的配制:Na2HPO4·12H2O称取35.822g,定容至500mL,4℃,棕色瓶保存,备用。
(3)0.1M磷酸缓冲液的配置:量取甲液51mL,乙液49mL,加入100mL水,混匀,得pH值6.8的磷酸缓冲液,4℃,棕色瓶保存,备用。
(4)酵母α-葡萄糖苷酶:将100U/ml酶原液用磷酸缓冲液(pH 6.8)稀释为20U/mL的酶溶液,冷冻备用,使用前用磷酸缓冲液(pH 6.8)稀释为1U/mL,备用。
(5)底物pNPG配制:精密称取0.3766g pNPG,加入适量的磷酸钠缓冲液中溶解,再定容至50mL,配制成25mmol/L母液,使用前用磷酸钠缓冲液配制成0.5mmol/L,备用。
(6)阿卡波糖抑制剂配制:精密称取13.9mg阿卡波糖,用DMSO定容至1mL,配制成13.9mg/mL,备用。
(7)0.1mol/L的Na2CO3配制:称取1.06g Na2CO3于烧杯中,加入适量蒸馏水溶解,并定容到100mL,4℃下保存,备用。
2、抑制剂的制备
精密称取2.5mg Obtusol至离心管中,用1mL无水乙醇溶解后作为母液,需要使用时再稀释至适当的浓度,即得系列不同浓度Obtusol的抑制剂。
3、Obtusol对α-葡萄糖苷酶的活性抑制效果实验
原理:对硝基苯-α-D-葡萄糖苷(pNPG)经α-葡萄糖苷酶水解可产生对硝基苯酚,其在405nm呈特异性吸收,因此可以通过检测对硝基苯酚的生成量检测α-葡萄糖苷酶的活性。
实验分为空白组、对照组、样品空白组和样品组,制备方法:各反应物按表1中剂量在96孔板中进行加样,每组3个平行,将抑制剂、乙醇、缓冲液和酶溶液混合均匀,在恒温振荡器中37℃保温10min,结束后,取出,加入50μL 0.5mmol/L pNPG溶液,充分混匀,于37℃水浴反应20min,结束后加入50μL 0.1mol/L的Na2CO3溶液中止反应,即得各试验组(空白组、对照组、样品空白组和样品组)。
由于PNPG在α-葡萄糖苷酶的作用下能水解产生葡萄糖和PNP,PNP在405nm处有最大吸收,使用酶标仪测定其吸光度,根据公式便可计算出各样品α-葡萄糖苷酶的抑制率及IC 50值。
表1各反应物添加计量和顺序(单位:μL)
阿卡波糖不同浓度与不同浓度Obtusol的抑制剂的抑制率见表2、表3,在分别对两组数据绘制拟合曲线,如图1、图2所示,以浓度为横坐标,抑制率为纵坐标,不同浓度的阿卡波糖抑制曲线见图1,不同浓度Obtusol的抑制剂的抑制曲线见图2。再由拟合的曲线得到曲线方程:
不同浓度的阿卡波糖抑制曲线方程为:y=0.3639x+0.0767,R2=0.9926。
不同浓度Obtusol的抑制剂的抑制曲线方程为:y=19.107x+0.0546,R2=0.9963。
通过上述两个曲线方程即可分别求得阿卡波糖和Obtusol对α-葡萄糖苷酶50%的抑制率时的浓度,求得阿卡波糖对α-葡萄糖苷酶的半抑制浓度IC 50值为1.1632mg/mL,Obtusol对α-葡萄糖苷酶的半抑制浓度IC 50值为0.0233mg/mL。
表2阿卡波糖不同浓度的抑制率(n=3)
浓度(mg/mL) | 抑制率(%) | RSD |
0.07 | 9.82 | 14.32% |
0.139 | 13.22 | 18.68% |
0.278 | 19.11 | 8.53% |
0.556 | 25.79 | 7.79% |
1.112 | 48.82 | 2.72% |
IC50值为1.1632mg/mL
表3不同浓度Obtusol的抑制剂的抑制率(n=3)
浓度(mg/mL) | 抑制率(%) | RSD |
0.05 | 100.54% | 1.67% |
0.025 | 55.29% | 7.99% |
0.0125 | 27.59% | 12.82% |
0.00625 | 15.01% | 7.23% |
0.003125 | 13.97% | 5.81% |
IC50值为0.0233mg/mL
可见,本发明所述化合物具有显著的α-葡萄糖苷酶的活性抑制效果,并且其IC50远低于阿卡波糖。
Claims (1)
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201910543612.8A CN110368391B (zh) | 2019-06-21 | 2019-06-21 | 三萜化合物在制备降血糖相关产品中的用途 |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201910543612.8A CN110368391B (zh) | 2019-06-21 | 2019-06-21 | 三萜化合物在制备降血糖相关产品中的用途 |
Publications (2)
Publication Number | Publication Date |
---|---|
CN110368391A CN110368391A (zh) | 2019-10-25 |
CN110368391B true CN110368391B (zh) | 2022-11-08 |
Family
ID=68249150
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN201910543612.8A Active CN110368391B (zh) | 2019-06-21 | 2019-06-21 | 三萜化合物在制备降血糖相关产品中的用途 |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN110368391B (zh) |
Families Citing this family (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN111789873B (zh) * | 2020-08-04 | 2022-05-27 | 中国科学院西北高原生物研究所 | 高含量沙棘三萜酸提取物的提取方法 |
CN111939183A (zh) * | 2020-08-05 | 2020-11-17 | 中国科学院西北高原生物研究所 | 一种超声提取的沙棘提取物及其提取方法和用途 |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN105919096A (zh) * | 2016-05-16 | 2016-09-07 | 西藏康德生物科技有限公司 | 一种保健食品组合物及其制剂和用途 |
CN108851071A (zh) * | 2018-09-17 | 2018-11-23 | 青海清华博众生物技术有限公司 | 沙棘vp营养组合物及其制备方法和应用 |
CN109805373A (zh) * | 2019-01-18 | 2019-05-28 | 青岛科技大学 | 一种具有辅助降血糖、降血脂作用的功能性食品及其制备方法 |
Family Cites Families (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN109111496B (zh) * | 2018-10-23 | 2020-06-02 | 青海清华博众生物技术有限公司 | 沙棘中三萜酸的提取纯化方法和三萜酸及三萜皂苷和应用 |
CN109673695A (zh) * | 2019-01-18 | 2019-04-26 | 青岛科技大学 | 一种俄色叶沙棘功能性食品及其制备方法 |
CN110407906B (zh) * | 2019-06-21 | 2022-01-07 | 中国科学院西北高原生物研究所 | 从沙棘提取物中分离和制备三萜化合物的方法 |
CN110441410B (zh) * | 2019-06-21 | 2022-08-23 | 中国科学院西北高原生物研究所 | 沙棘提取物中化合物的色谱分析检测方法 |
CN113663043B (zh) * | 2021-08-24 | 2022-05-20 | 广东工业大学 | 一种具有α-葡萄糖苷酶抑制作用的组合物及其制备方法和应用 |
-
2019
- 2019-06-21 CN CN201910543612.8A patent/CN110368391B/zh active Active
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN105919096A (zh) * | 2016-05-16 | 2016-09-07 | 西藏康德生物科技有限公司 | 一种保健食品组合物及其制剂和用途 |
CN108851071A (zh) * | 2018-09-17 | 2018-11-23 | 青海清华博众生物技术有限公司 | 沙棘vp营养组合物及其制备方法和应用 |
CN109805373A (zh) * | 2019-01-18 | 2019-05-28 | 青岛科技大学 | 一种具有辅助降血糖、降血脂作用的功能性食品及其制备方法 |
Non-Patent Citations (3)
Title |
---|
沙棘中的营养成分与生物活性物质研究进展;丁小林,等;《中国食物与营养》;20080928(第09期);第57-59页 * |
沙棘功能性食品开发探讨;胡建忠;《国际沙棘研究与开发》;20071215;第05卷(第04期);第16-20页 * |
沙棘叶多酚提取物抗氧化及体外降血糖活性研究;柳梅,等;《天然产物研究与开发》;20170615;第29卷(第06期);第1013-1019页 * |
Also Published As
Publication number | Publication date |
---|---|
CN110368391A (zh) | 2019-10-25 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN110407906B (zh) | 从沙棘提取物中分离和制备三萜化合物的方法 | |
Dini et al. | Saponins in Ipomoea batatas tubers: Isolation, characterization, quantification and antioxidant properties | |
Munafo Jr et al. | Isolation and structural determination of steroidal glycosides from the bulbs of easter lily (Lilium longiflorum Thunb.) | |
CN110441410B (zh) | 沙棘提取物中化合物的色谱分析检测方法 | |
CN101736050B (zh) | 一种牛蒡子苷元的制备方法 | |
Chen et al. | Identification of flavonol glycosides in American cranberry fruit | |
CN110368391B (zh) | 三萜化合物在制备降血糖相关产品中的用途 | |
Lendl et al. | Phenolic and terpenoid compounds from Chione venosa (sw.) urban var. venosa (Bois Bandé) | |
Zhang et al. | Polyacetyleneginsenoside-Ro, a novel triterpene saponin from Panax ginseng | |
CN105017353B (zh) | 金银花中环烯醚萜苷类化合物及其制备方法和用途 | |
Xu et al. | LC-MS guided isolation of gracilistones A and B, a pair of diastereomeric sesquiterpenoids with an unusual tetrahydrofuran-fused tricyclic skeleton from Acanthopanax gracilistylus and their potential anti-inflammatory activities | |
CN106727598B (zh) | 阔叶丰花草三萜化合物的制备方法及其在制备糖苷酶抑制剂药物中的应用 | |
El Sayed et al. | New calogenin pregnane glycoside derivative from Huernia saudi-arabica and its lipase and α-glucosidase inhibitory activities | |
Liu et al. | Purification and quantification of ginsenoside Rb3 and Rc from crude extracts of caudexes and leaves of Panax notoginseng | |
Lu et al. | Spirostanol saponins from Ypsilandra parviflora induce platelet aggregation | |
CN112028959A (zh) | 无柄灵芝中具有抗糖尿病活性的三萜化合物的制备方法及应用 | |
CN112125944A (zh) | 无柄灵芝中具有α葡萄糖苷酶抑制活性的三萜化合物的制备方法及应用 | |
CN108912049B (zh) | 从高乌头中提取的二萜类生物碱化合物及制备方法和应用 | |
Li et al. | New nor-oleanane triterpenoids from the fruits of Stauntonia brachyanthera with potential anti-inflammation activity | |
Peng et al. | Three novel pterosin dimers form Pteris obtusiloba | |
CN116425817A (zh) | 一种从瑶药六方藤中提取多种单体化合物的方法 | |
Xiao et al. | Acyl atractyligenin and carboxyatractyligenin glycosides from Antennaria rosea subsp. confinis | |
CN106265681B (zh) | 一种三萜化合物在制备糖苷酶抑制剂药物中的应用 | |
CN101830880B (zh) | 一种从落叶松加工剩余物粗提物中分离纯化紫杉叶素的方法 | |
CN101830997B (zh) | 一种东北铁线莲三萜皂苷对照品的制备方法 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
PB01 | Publication | ||
PB01 | Publication | ||
SE01 | Entry into force of request for substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
GR01 | Patent grant | ||
GR01 | Patent grant | ||
TR01 | Transfer of patent right |
Effective date of registration: 20230922 Address after: Room 1218-19, Building 3, No. 1366 Hongfeng Road, Huzhou Economic and Technological Development Zone, Huzhou City, Zhejiang Province, 313098 Patentee after: Zhonghe baosang Biotechnology Co.,Ltd. Address before: 810008 No. 59 Xiguan Street, Xining, Qinghai Patentee before: Northwest Institute of Plateau Biology, Chinese Academy of Sciences |
|
TR01 | Transfer of patent right |