CN108685931A - Panaxsaponin composition with hypoglycemic activity and its application - Google Patents
Panaxsaponin composition with hypoglycemic activity and its application Download PDFInfo
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- CN108685931A CN108685931A CN201810707191.3A CN201810707191A CN108685931A CN 108685931 A CN108685931 A CN 108685931A CN 201810707191 A CN201810707191 A CN 201810707191A CN 108685931 A CN108685931 A CN 108685931A
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- ginsenoside
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- panaxsaponin composition
- hypoglycemic
- panaxsaponin
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- NODILNFGTFIURN-USYOXQFSSA-N ginsenoside Rb3 Chemical compound C([C@H]1O[C@H]([C@@H]([C@@H](O)[C@@H]1O)O)O[C@@](C)(CCC=C(C)C)[C@@H]1[C@@H]2[C@@]([C@@]3(CC[C@H]4C(C)(C)[C@@H](O[C@H]5[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O5)O[C@H]5[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O5)O)CC[C@]4(C)[C@H]3C[C@H]2O)C)(C)CC1)O[C@@H]1OC[C@@H](O)[C@H](O)[C@H]1O NODILNFGTFIURN-USYOXQFSSA-N 0.000 description 1
- PFSIGTQOILYIIU-UHFFFAOYSA-N ginsenoside Rb3 Natural products CC(=CCCC(C)(O)C1CCC2(C)C3CCC4C(C)(C)C(CCC4(C)C3CC(OC5OC(COC6OCC(O)C(O)C6O)C(O)C(O)C5O)C12C)OC7OC(CO)C(O)C(O)C7OC8OC(CO)C(O)C(O)C8O)C PFSIGTQOILYIIU-UHFFFAOYSA-N 0.000 description 1
- UVBLDLGZDSGCSN-UHFFFAOYSA-N ginsenoside-Rb3 Natural products C1=CC2C3(C)CCC(O)C(C)(C)C3CCC2(C)C2(C)CCC34CCC(C)C(C)C4C21OC3=O UVBLDLGZDSGCSN-UHFFFAOYSA-N 0.000 description 1
- 230000004153 glucose metabolism Effects 0.000 description 1
- 229940112611 glucovance Drugs 0.000 description 1
- 235000011187 glycerol Nutrition 0.000 description 1
- 229930182470 glycoside Natural products 0.000 description 1
- 150000002338 glycosides Chemical class 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- 230000002440 hepatic effect Effects 0.000 description 1
- 235000008216 herbs Nutrition 0.000 description 1
- 235000009200 high fat diet Nutrition 0.000 description 1
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
- 230000036039 immunity Effects 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 230000002779 inactivation Effects 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 238000011081 inoculation Methods 0.000 description 1
- 210000004153 islets of langerhan Anatomy 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- 231100001231 less toxic Toxicity 0.000 description 1
- 230000003908 liver function Effects 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 239000002075 main ingredient Substances 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 238000000034 method Methods 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
- 238000012544 monitoring process Methods 0.000 description 1
- WQEPLUUGTLDZJY-UHFFFAOYSA-N n-Pentadecanoic acid Natural products CCCCCCCCCCCCCCC(O)=O WQEPLUUGTLDZJY-UHFFFAOYSA-N 0.000 description 1
- 235000020824 obesity Nutrition 0.000 description 1
- 238000011017 operating method Methods 0.000 description 1
- 238000003305 oral gavage Methods 0.000 description 1
- 229940126701 oral medication Drugs 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 210000000229 preadipocyte Anatomy 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 229940076376 protein agonist Drugs 0.000 description 1
- 238000011552 rat model Methods 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 230000008439 repair process Effects 0.000 description 1
- 239000000837 restrainer Substances 0.000 description 1
- 239000000344 soap Substances 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- 239000011122 softwood Substances 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 230000006641 stabilisation Effects 0.000 description 1
- 238000011105 stabilization Methods 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- YROXIXLRRCOBKF-UHFFFAOYSA-N sulfonylurea Chemical class OC(=N)N=S(=O)=O YROXIXLRRCOBKF-UHFFFAOYSA-N 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- 150000001467 thiazolidinediones Chemical class 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 238000012549 training Methods 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 239000012588 trypsin Substances 0.000 description 1
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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
- A61K31/7028—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages
- A61K31/7034—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin
- A61K31/704—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin attached to a condensed carbocyclic ring system, e.g. sennosides, thiocolchicosides, escin, daunorubicin
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- 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
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- 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
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- 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
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Abstract
The present invention relates to hypoglycemic activity Panaxsaponin composition and its application, the Panaxsaponin composition include glycol group ginsenoside and triol group ginsenoside;Glycol group ginsenoside is selected from one or both of ginsenoside Rk1, Rg3, Rg5 or three kinds;Triol group ginsenoside is selected from one or both of 3beta,6alpha,12beta-Trihydroxydammar-20(21),24-diene-6-O-beta-D-glucopyranoside, Rh4.The present invention is by the way that by the combination between different type ginsenoside monomer, the ratio of reasonably optimizing monomer has given full play to the complementary characteristic of each monomer hypoglycemic mechanism, significantly improved hypoglycemic effect;While ensureing hypoglycemic effect, the usage amount of ginsenoside does not obviously increase, and reduces the cost of production, while also providing guarantee for the biological safety of product;Compared to the hypoglycemic effect of single ginsenoside monomer, Panaxsaponin composition can more reach the requirement of new drug development in drug effect, the characteristics of having druggability strong, be easy to large-scale production, be more amenable for use with patent medicine exploitation.
Description
Technical field
The invention belongs to biological chemical fields, and in particular to a kind of Panaxsaponin composition with hypoglycemic activity and its answer
With.
Background technology
Diabetes are that a kind of generation to insulin and effect are abnormal related, disorderly as the metabolism of main feature using hyperglycemia
Random syndrome is a kind of chronic disease seriously endangering health, is one of the major health concern that current mankind is faced.Glycosuria
Disease can be divided into insulin-dependent diabetes mellitus (type-1 diabetes mellitus) and Non-Insulin Dependent Diabetes Mellitus (type-2 diabetes mellitus), wherein
90% or more is type-2 diabetes mellitus.With the development of social economy and the change of people life style, the quantity of diabetic is fast
Speed increases.According to recent statistics statistics indicate that the whole world there are about 2.46 hundred million people suffer from type-2 diabetes mellitus, it is contemplated that in 20 years II types sugar
Urine patient's number will increase to 3.8 hundred million.The current diabetic's number in China has been up to ten thousand people more than 8000, accounts for whole world diabetes
The one third of patient populations becomes the first big country of global diabetes.Diabetes morbidity is in the world and rises at present
Trend, especially more obvious in the trend that developing country rises, the death rate is only second to cardiovascular and cerebrovascular disease, cancer, is recognized
To be the third-largest killer of the mankind.Therefore, active prevention and treatment diabetes are extremely urgent.
The drug for the treatment of type-2 diabetes mellitus is mainly traditional antidiabetic medicine, including sulfonylurea, Ge Lienai at this stage
Class, biguanides, thiazolidinediones, alpha-glucosidase restrainer and insulin etc., these drugs exist different degrees of
Adverse reaction, such as cause hypoglycemia, gastrointestinal discomfort, obesity.With going deep into Diabetes Foundation theoretical research, exploitation is made
For novel targets, the side effect that avoids traditional hypoglycemic medicine, have to beta Cell of islet the treating diabetes new drug of protective effect at
For the hot spot studied both at home and abroad.
Ginseng is the rhizome of Araliaceae Panax, is herbaceos perennial, is the rare medicinal herbs having won fame both at home and abroad.It is existing
Show ginseng in Immunity regulation for medical research, anti-diabetic, improves cardiovascular and cerebrovascular obstacle, anti-artery at enhancing liver function
Hardening, blood pressure control etc. have apparent effect, therefore principle active component of the ginsenoside as ginseng, in anti-sugar
The application in the sick field of urine is just becoming the hot spot of Glucovance exploitation.
Chinese patent application 201510612222.3, it discloses 20 (S)-ginseng sapoglycoside Rg 3s can concentration dependent swash
SIRT1 albumen living participates in energetic supersession as SIRT1 protein agonists, plays blood sugar reducing function, and disclose it and controlled in diabetes drug
Treat the application in drug.
Chinese patent application 201510012423.X, it discloses 20 (R)-ginseng sapoglycoside Rg 3s to alleviate and treat preparing
New opplication in diabetes medicament.
Chinese patent 201110005851.1, it discloses prepared by the composition of active constituent of ginsenoside Rb3
Treat the application of diabetes medicament.
It is the medicinal application of the single saponin constituent of ginsenoside above, rarely has in the prior art to ginsenoside difference soap
The composition that glycosides is mixed to form can improve the report of blood sugar reducing function.
Invention content
The object of the present invention is to provide a kind of Panaxsaponin compositions with hypoglycemic activity, as new ginsenoside group
Object is closed, the hypoglycemic activity of each component is given full play to, improves hypoglycemic effect;In addition, the present invention also provides ginsenoside combinations
Object is preparing the application in preventing and treating diabetic Products.
The technical solution adopted in the present invention is:
Panaxsaponin composition with hypoglycemic activity, it is characterised in that:
The Panaxsaponin composition includes glycol group ginsenoside and triol group ginsenoside;
Glycol group ginsenoside is selected from one or both of ginsenoside Rk1, Rg3, Rg5 or three kinds;
Triol group ginsenoside is selected from one or both of 3beta,6alpha,12beta-Trihydroxydammar-20(21),24-diene-6-O-beta-D-glucopyranoside, Rh4.
Glycol group ginsenoside and the mass ratio of triol group ginsenoside are(20:1)~(1:5).
Glycol group ginsenoside and the mass ratio of triol group ginsenoside are(3:1)~(1:1).
Glycol group ginsenoside includes ginsenoside Rg 5.
Triol group ginsenoside includes Ginsenoside Rh4.
Two kinds in ginsenoside Rk1, Rg3, Rg5 of glycol group ginsenoside, mixing quality ratio are(1:1)~(1:
3).
Three kinds in ginsenoside Rk1, Rg3, Rg5 of glycol group ginsenoside, mixing quality ratio are(1:1:2)~(1:
2:4).
Two kinds in 3beta,6alpha,12beta-Trihydroxydammar-20(21),24-diene-6-O-beta-D-glucopyranoside, Rh4 of triol group ginsenoside, mixing quality ratio are(1:1)~(1:3).
The application of Panaxsaponin composition with hypoglycemic activity as mentioned, it is characterised in that:
The Panaxsaponin composition is as hypoglycemic medicine, blood-sugar lowering type health-care food, the function of polysaccharide for preventing or treating diabetes
The active ingredient of food.
The present invention has the following advantages:
1)By the combination between different type ginsenoside monomer, the ratio of reasonably optimizing monomer has given full play to each monomer
The complementary characteristic of hypoglycemic mechanism, significantly improves hypoglycemic effect;
2)While ensureing hypoglycemic effect, the usage amount of ginsenoside does not obviously increase, and reduces the cost of production, simultaneously
Also guarantee is provided for the biological safety of product;
3)Compared to the hypoglycemic effect of single ginsenoside monomer, Panaxsaponin composition can more reach new drug development in drug effect
Requirement, have druggability it is strong, be easy to large-scale production the characteristics of, be more amenable for use with patent medicine exploitation.
Description of the drawings
Fig. 1:The type-2 diabetes mellitus in ginsenoside monomer and composition are to the therapeutic process of type-2 diabetes mellitus mouse model
The changes of weight of mouse.
Fig. 2:The type-2 diabetes mellitus in ginsenoside monomer and composition are to the therapeutic process of type-2 diabetes mellitus mouse model
The liver HE stained slices of mouse.
Specific implementation mode
The present invention will be described in detail With reference to embodiment.
The application has found the different monomers of ginsenoside caused by fighting different diabetes models by research and practice
Hypoglycemic effect is shown when hyperglycemia has notable difference, on this basis further study show that different saponin(es were mixed to form
Composition blood sugar reducing function compared with single saponin constituent significantly improves.Simultaneously by a large amount of experiment, summary and induction obtains one
Kind composition, is made of glycol group ginsenoside and triol group ginsenoside, can give full play to the effect of each component, simultaneously
The use concentration of single saponin(e is reduced, there is the features such as efficient, low cost, less toxic side effect, druggability is very strong.
The present invention relates to a kind of Panaxsaponin compositions with hypoglycemic activity, include glycol group ginsenoside and triol
Group ginsenoside, wherein glycol group ginsenoside is selected from one or both of ginsenoside Rk1, Rg3, Rg5 or three kinds, and three
Alcohol group ginsenoside is selected from one or both of 3beta,6alpha,12beta-Trihydroxydammar-20(21),24-diene-6-O-beta-D-glucopyranoside, Rh4.
Glycol group ginsenoside and the mass ratio of triol group ginsenoside are(20:1)~(1:5), preferably(3:1)~(1:1),
More preferable 2:1.
Glycol group ginsenoside preferably includes ginsenoside Rg 5.Triol group ginsenoside preferably includes ginsenoside
Rh4。
When two kinds in ginsenoside Rk1, Rg3, Rg5 of glycol group ginsenoside, mixing quality ratio is(1:1)~(1:
3), when three kinds in ginsenoside Rk1, Rg3, Rg5 of glycol group ginsenoside, mixing quality ratio is(1:1:2)~(1:2:
4).
When two kinds in 3beta,6alpha,12beta-Trihydroxydammar-20(21),24-diene-6-O-beta-D-glucopyranoside, Rh4 of triol group ginsenoside, mixing quality ratio is(1:1)~(1:3).
The above-mentioned Panaxsaponin composition with hypoglycemic activity, can as prevention and treatment diabetes hypoglycemic medicine,
The active ingredient of blood-sugar lowering type health-care food, food with function of reducing blood sugar.
When above-mentioned Panaxsaponin composition is used to prepare the hypoglycemic medicine of prevention and treatment diabetes, also wrapped in medicine preparation
Pharmaceutically acceptable adjuvant is included, pharmaceutically acceptable adjuvant includes pharmaceutically acceptable carrier, excipient, diluent
Deng, and it is compatible with active constituent Panaxsaponin composition.By active constituent Panaxsaponin composition and pharmaceutically acceptable auxiliary
Agent is combined, and various medicine preparations, preferably oral drug preparation or injection are configured to, as granule, tablet, pill and
Capsule, most preferably tablet or capsule.
The content further illustrated the present invention by the following examples.If do not specialized, used in embodiment is this
Conventional means known to field technology personnel and commercially available common instrument.
The external hypoglycemic experiment of 1 ginsenoside monomer of embodiment
Experimental drug:Glycol group ginsenoside:Ginsenoside Rk1, Rg3, Rg5;
Triol group ginsenoside:3beta,6alpha,12beta-Trihydroxydammar-20(21),24-diene-6-O-beta-D-glucopyranoside, Rh4;
The equal > of above drug purity 98%.
Experimental cell:INS-1 rat Langerhans islets oncocyte, HepG2 human liver cancer cells and 3T3-L1 murine preadipocyte cells are equal
Purchased from Shanghai bio tech ltd conversant with things of the past, algebraically is within 10 generations.
Test method and result:
1. the influence for the INS-1 damage model cell viabilities that ginsenoside monomer induces alloxan is tested
It is transferred in 100ml culture bottles with the RPMI 1640 culture mediums containing 10% inactivation calf serum after INS-1 cell recoveries, 37
℃,5%CO2Under the conditions of cultivate.After cell is adherent to be covered with, incline culture medium, with 0.25% trypsin digestion, presses 1 within every 3 days:3
Ratio passes on 1 time, and the cell of exponential phase is for testing.
The cell of logarithmic growth phase is adjusted to suitable cell concentration with the RPMI1640 culture mediums containing 10% FBS and is connect
For kind in 96 well culture plates, experiment is divided into Normal group and alloxan group (30,25,20,15,10,5 mM).Wait for that cell is given birth to
When length to 90% fusion, according to experiment packet dosing, in 37 DEG C, 5% CO2After cultivating 48h in incubator, MTT colorimetric methods are in 570
Each group absorbance value is measured under nM wavelength, and calculates cell survival rate and IC50(half inhibiting rate).Alloxan is thin to INS-1
The IC of born of the same parents50Therefore in evaluating drug effect, 16 mM is selected to induce the dense of INS-1 cellular damages as alloxan for 16 mM
Degree.
By after the cell dissociation of exponential phase, cell is diluted to 1 × 105Cell/mL is inoculated in 96 orifice plates
In, 100 μ L are inoculated with per hole.96 orifice plates after inoculating cell are placed in 5%CO2, cultivate in 37 DEG C of constant incubators, wait for cell
When growing to 90% fusion, cell is randomly divided into:Blank control group:The DMEM culture mediums of 2%FBS;Model control group:Four oxygen
Pyrimidine a concentration of 16 be mM's and the DMEM culture mediums containing 2%FBS;Administration group:Alloxan a concentration of 16 mM's and contains
The liquid of different samples is given while the DMEM medium cultures of 2%FBS;Melbine group:A concentration of 16 mM of alloxan
And DMEM medium cultures containing 2%FBS whiles give 1 mM melbine.After cultivating 48h, MTT colorimetric methods are in 570
Each group absorbance value is measured under nM wavelength.Ginsenoside monomer is calculated to INS-1 damage model cell viabilities according to following formula
Increment rate the results are shown in Table 1.
The increment rate of INS-1 cell viabilities=(Administration group cell viability-model group cell viability)/ model group cell viability *
100%
Experimental result:16 mM alloxans processing INS-1 cells 48h can establish stable cellular damage model, tested medicine
Addition can effectively improve the cell viability of damage model, compared with glycol group ginsenoside, triol group ginsenoside
Damage model ability is repaired with better, the cell viability of wherein Ginsenoside Rh4's effect is improved up to 93.96%, repairs effect
Fruit is ideal.
2. the shadow for the HepG2 insulin resistance grape cell sugar consumptions effect that ginsenoside monomer induces high glucose and high fat
It rings
10000/the holes human liver cancer cell HepG2 are inoculated in 96 orifice plates, per 100 μ L culture solutions of hole.After for 24 hours, culture solution is changed
At ginsenoside monomer containing various concentration, 0.5 mM palmitic acids, 0.5% BSA, 1nM insulin, the DMEM in high glucose training without serum
Base is supported, experiment separately sets acellular blank group(Acellular serum-free low sugar DMEM cultures containing 0.5%BSA, 1 nM insulin
Base), control group(Serum-free low sugar DMEM culture mediums containing 0.5% BSA, 1 nM insulin), model group(0.5 mM palmitic acids,
0.5% BSA, 1 nM insulin, the DMEM in high glucose culture medium without serum)With positive drug group(1 mM melbine, 0.5 mM palm fibres
Palmitic acid acid, 0.5% BSA, 1 nM insulin, the DMEM in high glucose culture medium without serum).After being incubated for 24 hours, 10 μ L supernatants are taken per hole
Liquid uses Glucose estimation kit(Glucose oxidase-peroxidase method)Measure the glucose utilization per hole.Remove 96
Culture solution in orifice plate, MTT colorimetric methods measure each hole absorbance value under 570 nM wavelength.
The glucose content in the instrument connection of inoculating cell is subtracted with the glucose content of acellular blank group to get each hole
Glucose utilization.Meanwhile divided by each hole cell MTT values carry out cell quantity correction.
Experimental result:The results are shown in Table 2, and 0.5 mM palmitic acids can establish stable HepG2 pancreases under high saccharide ring border
Insulin resistance model, the addition of tested medicine can improve the glucose consumption of model cell, have and alleviate the work that pancreas islet is resisted
With.Glycol group ginsenoside(Ginsenoside Rk1, Rg3, Rg5), resisted on modelling effect releasing the pancreas islet that high glucose and high fat is established
It is substantially better than triol group ginsenoside(3beta,6alpha,12beta-Trihydroxydammar-20(21),24-diene-6-O-beta-D-glucopyranoside, Rh4), wherein glycol group ginseng sapoglycoside Rg 3 promotes insulin resistance
The effect of the glucose consumption of HepG2 cells is the most notable, is secondly ginsenoside Rg5.
3. the influence that ginsenoside monomer acts on 3T3-L1 insulin resistance grape cell sugar consumptions
30000/hole of 3T3-L1 PECTORAL LIMB SKELETONs is inoculated in 48 orifice plates, per 0.5 mL culture solutions of hole.After waiting for cell confluency, after
Continuous culture two days, culture solution is changed into containing 1 μM of dexamethasone, 0.5 mM 3-isobutyl-1-methylxanthines(IBMX),10 μ
The DMEM in high glucose culture solution culture 2 days of g/mL insulin, 10% FBS;Then by culture solution change into containing 10 μ g/mL insulin,
The DMEM in high glucose culture solution culture of 10% FBS 2 days;Finally change culture solution into DMEM in high glucose culture solution containing 10% FBS, every 2
It changes a culture solution.After induction differentiation 10-12 days, about 80% 3T3-L1 cell differentiations are mature fat cell.With 1 μM of ground
Sai meter Song handles cell for 24 hours, and cell is made to generate insulin resistance.Then change culture solution into containing various concentration ginsenoside monomer
DMEM in high glucose culture medium, while acellular blank group, control group, model group and positive drug group are set(1 mM melbine),
Continue to cultivate 48h.
The glucose utilization per hole is measured with Glucose estimation kit.Then the culture solution in 96 orifice plates is exhausted,
MTT colorimetric methods measure each hole absorbance value under 570 nM wavelength, and it is thin to subtract inoculation with the glucose content of acellular blank group
Glucose content in the instrument connection of born of the same parents to get each hole glucose utilization.Meanwhile divided by each hole cell MTT values carry out
The correction of cell quantity.
Experimental result:As shown in table 3, ginsenoside Rk1, Rk3, Rg3, Rg5, Rh4 is to insulin resistance 3T3-L1 cells
Glucose consumption have a degree of facilitation, wherein ginseng sapoglycoside Rg 3 promotes the 3T3-L1 cells of insulin resistance
Glucose consumption effect it is the most notable, secondly be ginsenoside Rg5.It is resisted on modelling effect releasing 3T3-L1 pancreas islet,
Glycol group ginsenoside is substantially better than triol group ginsenoside, this is consistent with the result of HepG2 cell insulin resistant models.
Above-mentioned ginsenoside external model the results show that ginsenoside monomer have to the diabetes external model of foundation it is slow
Solution effect, but the alleviation that glycol saponins are showed from the external model that triol saponins are established under different modeling mechanisms
There are apparent differences for effect.
The therapeutic effect of 2 ginsenoside monomer of embodiment and pharmaceutical composition to type II diabetes mouse model
Modeling:The C57BL/6 mouse of healthy male, 5~6 week old of cleaning grade(18 ± 2 g of weight)110, purchase is handed in Xi'an
Logical University Medical College animal center.Mouse adaptability is raised 7 days, is randomly divided into two groups, one group 10, is given basal feed;One
Group 100, gives high-sugar-fat-diet.After 6 weeks, after high-carbonhydrate diet group high in fat is deprived of food but not water 12h, STZ (lemons are injected intraperitoneally
Acid buffer is prepared) 30 mg/kg, once a day, diabetes model is established in continuous injection 5 days.By mouse fasting (can't help water)
12h, every mouse eyeground vein clump take 0.2 mL of blood, detach serum.10 μ L serum are taken to illustrate according to kit in sample cell
Operating method measure mouse fasting blood sugar.It is small that the mouse of the mmol/L of fasting blood sugar >=11.1 is considered as diabetes model
Mouse can be used for subsequent experimental.
Animal packet:Hyperglycemia mouse is randomly divided into 8 groups, every group of 10 animals, respectively model group, glycol group Rg3(60
mg/kg)Group, triol group Rh4(60 mg/kg)Group, glycol group Rg5(60 mg/kg)Group, glycol group Rg3(40 mg/kg)+ triol
Group Rh4(20 mg/kg)Group, glycol group Rg3(40 mg/kg)+ glycol group Rg5(20 mg/kg)Group, triol group Rh4(20 mg/
kg)+ glycol group Rg5(40mg/kg)Group, positive drug melbine group (100 mg/kg).Drug is dissolved in 0.5% carboxymethyl cellulose
The drug of plain sodium solution, all daily gavage corresponding dosages of mouse is primary, and it is molten that control group and model group mouse give equal volume
0.5% carboxymethylcellulose sodium solution of agent.Successive administration three weeks.
Indexs measure:The fasting blood-glucose of a mouse is measured before administration and after administration weekly, concrete operations are as follows:Animal is prohibited
(can't help water) 12h is eaten, tail vein blood test glucose level is fasting blood-glucose.Since modeling, terminate to administration, weekly
It is primary to weigh mouse weight.Administration terminates, and puts to death mouse, takes mouse liver, carries out HE dyeing, makes pathological section.
Experimental result:
1)Blood sugar test
Ginsenoside monomer and pharmaceutical composition can significantly reduce the fasting blood glucose level of diabetic mice, improve blood glucose generation
It thanks, ginsenoside pharmaceutical composition Rg3+Rh4, Rg3+Rg5, Rh4+Rg5 hypoglycemic effect is mono- better than ginseng sapoglycoside Rg 3, Rh4 and Rg5
Body.Compared with existing antidiabetic drug melbine, it is double that its improvement glucose metabolism ability of ginsenoside pharmaceutical composition is not weaker than diformazan
Guanidine, concrete outcome are shown in Table 4.
2)Safety evaluatio
Avoirdupois monitoring:Original body mass no significant difference before the administration of each group mouse, after 3 weeks, normal mouse weight stabilization of organizing increases gavage
Add, model group mouse weight more normally organizes significant decrease.Ginsenoside group and melbine group mouse weight and model group are basic
Quite, drug itself will not cause mouse weight to be decreased obviously, the result is shown in Figure 1.
HE is dyed:Lobuli hepatis structure is normal under control group light microscopic, and cell boundaries are clear, and nucleus is rounded and is located at cell
Center, liver cell are arranged centered on central vein at strand;Model group liver rope is disorderly, liver cell soft edge, nucleus wrinkle
There is apparent lesion in contracting or cracking, vacuolar degeneration of hepatic cell, hepatic tissue;Melbine group lobuli hepatis structure is complete, liver cell wheel
Exterior feature is clear compared with model group, and vacuolar degeneration of hepatic cell is reduced;It is substantially complete that Ginsenoside Rh4 organizes lobuli hepatis structure, it is seen that slight
Steatosis and vacuolar degeneration;Ginseng sapoglycoside Rg 3, Rg5, Rg3+Rh4, Rg3+Rg5, Rh4+Rg5 group lobuli hepatis structure are complete, liver
Cell rope is slightly disorderly, and caryoplasm is more visible, and steatosis is alleviated with vacuolar degeneration height.Pathological section is shown in Fig. 2.
Experimental result shows that Panaxsaponin composition improves blood in Panaxsaponin composition treatment type II diabetes Mice Body
The with obvious effects of glycometabolism is higher than each ginsenoside monomer, suitable with a clinical line medicine melbine.3 weeks animal subjects are administered not
See with the relevant toxic reaction of drug toxicity, show the composition good security.
The preparation of 3 ginsenoside tablet of embodiment
Take Panaxsaponin composition(30 g of 5 60 g of ginsenoside Rg and Ginsenoside Rh4)90 g, sodium carboxymethylcellulose 70
G, 200 g of microcrystalline cellulose, 70 g of carboxyrnethyl starch sodium, 2 g of magnesium stearate are raw material.
Above-mentioned main ingredient and auxiliary material are crossed to 80 mesh sieve respectively, mixes well, uses 80% ethyl alcohol for adhesive, with 16 mesh screens
Granulation, 55 ~ 60 DEG C of dryings, 14 mesh screen whole grains, tabletting, every 0.4 g.
The preparation of 4 ginsenoside capsule of embodiment
Take Panaxsaponin composition(40 g of 5 80 g of ginsenoside Rg and Ginsenoside Rh4)120 g, 350 g of the fruit of Chinese wolfberry, know
350 g of mother, 300 g of Chinese yam are raw material.
The fruit of Chinese wolfberry, rhizoma anemarrhenae, Chinese yam are taken, is added water to cook 2 times, every time plus 12 times are measured water, respectively decoct 2h, and decocting liquid filtering merges
Filtrate, reduced pressure dry, pulverize, and after crossing 80 mesh sieve, be mixed with Panaxsaponin composition, using 80% ethyl alcohol softwood, 16
Mesh sieve granulation, 55 ~ 60 DEG C of dryings are sub-packed in No. 0 capsule, every 0.4 g.
Therapeutic effect of the 5 Panaxsaponin composition product of embodiment to type II diabetes rat model
Take Wistar rats(200±20 g)60, Adaptable growth is divided into blank group after 7 days(10)And model group(50),
Model group gives high glucose and high fat feed, and blank group gives chow diet.After feeding one month, take the total courage of its empty stomach of hematometry solid
Chain is injected intraperitoneally in the content of alcohol, triglyceride, insulin and blood glucose, the dosage that the rat of insulin resistance is pressed to 30 mg/kg again
Urea helps rhzomorph(STZ), fasting blood-glucose is measured after 7 days, blood glucose value is more than the rat totally 40 of 11.1 mmol/L, is randomly divided into 4 groups
(Model group, Panaxsaponin composition tablet suspension group, Panaxsaponin composition capsule suspension group, melbine group, institute
Panaxsaponin composition tablet and Panaxsaponin composition capsule is stated to prepare by embodiment 3), every group 10.To sugar after grouping
The sick rat of urine is fed again with high glucose and high fat diet, and in daily gastric infusion.Blank group and model group give 0.5% CMC-Na
Solution;Ginsenoside tablet suspension group is that ginsenoside tablet is suspended in 0.5% CMC-Na solution, ginsenoside capsule
Agent suspension group is that ginsenoside capsule is suspended in 0.5% CMC-Na solution, is given by 50 mg/kg ginsenoside dosage
Rat oral gavage;Melbine group gavage gives 50 mg/kg melbine.After successive administration 4 weeks, it is deprived of food but not water 12h posterior orbits
Blood is taken, rat is put to death, collects serum.
Treat diabetes index determining:Measure changes of weight after rat is administered, serum glucose, total cholesterol, glycerine three
Fat.The above index uses kit measurement, kit to build up Bioengineering Research Institute purchased from Nanjing.
Experimental result:As shown in table 5, to increase type II diabetes with Panaxsaponin composition product as main component big
The weight of mouse significantly reduces its blood glucose, reduces total cholesterol, and triglyceride content improves the symptom of glucose -lipid metabolism disorder, changes
The effect of kind glucose -lipid metabolism disorder is suitable with positive drug melbine.
Present disclosure is not limited to cited by embodiment, and those of ordinary skill in the art are by reading description of the invention
And to any equivalent transformation that technical solution of the present invention is taken, it is that claim of the invention is covered.
Claims (9)
1. the Panaxsaponin composition with hypoglycemic activity, it is characterised in that:
The Panaxsaponin composition includes glycol group ginsenoside and triol group ginsenoside;
Glycol group ginsenoside is selected from one or both of ginsenoside Rk1, Rg3, Rg5 or three kinds;
Triol group ginsenoside is selected from one or both of 3beta,6alpha,12beta-Trihydroxydammar-20(21),24-diene-6-O-beta-D-glucopyranoside, Rh4.
2. the Panaxsaponin composition according to claim 1 with hypoglycemic activity, it is characterised in that:
Glycol group ginsenoside and the mass ratio of triol group ginsenoside are(20:1)~(1:5).
3. the Panaxsaponin composition according to claim 1 with hypoglycemic activity, it is characterised in that:
Glycol group ginsenoside and the mass ratio of triol group ginsenoside are(3:1)~(1:1).
4. the Panaxsaponin composition according to claim 1 with hypoglycemic activity, it is characterised in that:
Glycol group ginsenoside includes ginsenoside Rg 5.
5. the Panaxsaponin composition according to claim 1 with hypoglycemic activity, it is characterised in that:
Triol group ginsenoside includes Ginsenoside Rh4.
6. the Panaxsaponin composition according to claim 1 with hypoglycemic activity, it is characterised in that:
Two kinds in ginsenoside Rk1, Rg3, Rg5 of glycol group ginsenoside, mixing quality ratio are(1:1)~(1:3).
7. the Panaxsaponin composition according to claim 1 with hypoglycemic activity, it is characterised in that:
Three kinds in ginsenoside Rk1, Rg3, Rg5 of glycol group ginsenoside, mixing quality ratio are(1:1:2)~(1:2:
4).
8. the Panaxsaponin composition according to claim 1 with hypoglycemic activity, it is characterised in that:
Two kinds in 3beta,6alpha,12beta-Trihydroxydammar-20(21),24-diene-6-O-beta-D-glucopyranoside, Rh4 of triol group ginsenoside, mixing quality ratio are(1:1)~(1:3).
9. the application of the Panaxsaponin composition with hypoglycemic activity as described in claim 1, it is characterised in that:
The Panaxsaponin composition is as hypoglycemic medicine, blood-sugar lowering type health-care food, the function of polysaccharide for preventing or treating diabetes
The active ingredient of food.
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN111388490A (en) * | 2020-04-17 | 2020-07-10 | 陕西巨子生物技术有限公司 | Ginsenoside composition with function of preventing and treating alcoholic fatty liver |
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