CN113440515B - Synergistic blood sugar reducing composition containing isoliquiritigenin and application thereof - Google Patents
Synergistic blood sugar reducing composition containing isoliquiritigenin and application thereof Download PDFInfo
- Publication number
- CN113440515B CN113440515B CN202110961501.6A CN202110961501A CN113440515B CN 113440515 B CN113440515 B CN 113440515B CN 202110961501 A CN202110961501 A CN 202110961501A CN 113440515 B CN113440515 B CN 113440515B
- Authority
- CN
- China
- Prior art keywords
- isoliquiritigenin
- diosmetin
- quercetin
- composition
- glucosidase
- 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
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/12—Ketones
- A61K31/122—Ketones having the oxygen directly attached to a ring, e.g. quinones, vitamin K1, anthralin
-
- 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
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
- A61K31/352—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Diabetes (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Obesity (AREA)
- Hematology (AREA)
- Engineering & Computer Science (AREA)
- Endocrinology (AREA)
- Emergency Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention discloses a synergistic blood sugar reducing composition containing isoliquiritigenin and application thereof, and belongs to the technical field of natural active compounds. The composition of the present invention comprises isoliquiritigenin and compound X; the compound X is diosmetin or quercetin; wherein the mass ratio of isoliquiritigenin to diosmetin is 4:150-6: 100; the mass ratio of the isoliquiritigenin to the quercetin is 4: 2.5. The composition has obvious synergistic effect of inhibiting alpha-glucosidase, has better effect than that of singly using the flavone compound, can reduce the dosage of the medicament, and reduces the occurrence of medicament resistance.
Description
Technical Field
The invention belongs to the technical field of natural active compounds, and particularly relates to a synergistic blood sugar reducing composition containing isoliquiritigenin and application thereof.
Background
Isoliquiritigenin (Isoliquitirigenin) is an isoflavonoid compound, is a yellow needle crystal, is insoluble in water, is soluble in a solvent with small polarity, and widely exists in leguminous plants. Epidemiological and animal studies have shown that isoliquiritigenin has a wide range of pharmacological activities, such as anticancer, antioxidant, anti-inflammatory, hypoglycemic, cardiovascular system regulating and free radical scavenging. Korea Fenxia et al found that isoliquiritigenin inhibited alpha-glucosidase in a competitive and non-competitive mixed manner, and the inhibition effect was significantly better than acarbose. Fluorescence quenching analysis results show that isoliquiritigenin can be combined with alpha-glucosidase to generate a compound under the drive of hydrophobic acting force, and the number of the combined sites is 1. The molecular docking results verify the conclusion of the relevant experiments: isoliquiritigenin is located in a hydrophobic pocket of the enzyme, binds to residues Asp202 and Arg400 by hydrogen bonds, and has hydrophobic interaction with numerous hydrophobic residues around, and maintains the complex structure (Korean Fenxia, fangxin, Gunn Juanjuan, Lianggui million, Liu native. isoliquiritigenin inhibits the molecular mechanism of alpha-glucosidase [ J ] food science, 2019,40(15): 37-42.).
Diabetes is a global chronic disease characterized by persistent hyperglycemia, including type I diabetes, type II diabetes, gestational diabetes, and other special types of diabetes, and type II diabetes, also called non-insulin-dependent diabetes, accounts for more than 95% of the number of diabetes. Alpha-glucosidase (alpha-D-glucoside hydrolase) is a carbohydrate hydrolase. When the activity of alpha-glucosidase is too high in a human body, hyperglycemia in the body is caused, and diabetes is caused. Alpha-glucosidase inhibitors can delay carbohydrate absorption and lower postprandial and fasting blood glucose levels by competitively inhibiting alpha-glucosidase activity. Alpha-glucosidase inhibitors are recommended by the Chinese diabetes Association and the International diabetes Union as first-line drugs for the treatment of diabetes because of their high efficacy, safety and low toxicity. However, most studies are currently focused on the action of a single active ingredient as an α -glucosidase inhibitor for lowering blood glucose; the single active component has limited hypoglycemic effect and is easy to generate drug resistance after long-term use, and the research on the inhibition effect of the combined use of two or more active components on the alpha-glucosidase has important significance for developing the alpha-glucosidase inhibitor with high efficiency, low dosage and drug resistance delay.
Disclosure of Invention
The invention aims to provide a synergistic hypoglycemic composition containing isoliquiritigenin, which aims to solve the problems that in the prior art, a single active ingredient has limited hypoglycemic effect and is easy to generate drug resistance.
In order to achieve the purpose, the invention is realized by the following technical scheme:
a synergistic hypoglycemic composition containing isoliquiritigenin comprises isoliquiritigenin and compound X; the compound X is diosmetin or quercetin;
wherein the mass ratio of the isoliquiritigenin to the diosmetin is 4:150-6: 100; the mass ratio of the isoliquiritigenin to the quercetin is 4: 2.5.
In several specific embodiments, the mass ratio of isoliquiritigenin to diosmetin is 4:150, 4:100, 6:100, 8: 150; wherein when the mass ratio of isoliquiritigenin to diosmetin is 4:150 and 4:100, the combined medication index mean value (CI) is avg ) Less than 0.6, and has strong synergistic effect.
The application of the composition in preparing preparations with alpha-glucosidase inhibiting effect.
An alpha-glucosidase inhibitor comprises isoliquiritigenin and diosmetin or isoliquiritigenin and quercetin as effective components; wherein the mass ratio of the isoliquiritigenin to the diosmetin is 4:150-6: 100; the mass ratio of the isoliquiritigenin to the quercetin is 4: 2.5.
The application of the composition in preparing a medicament with the hypoglycemic effect is to achieve the purpose of controlling postprandial hyperglycemia by inhibiting the activity of alpha-glucosidase and blocking the digestion and absorption of carbohydrate.
A medicine with blood sugar lowering effect contains isoliquiritigenin and diosmetin or isoliquiritigenin and quercetin as effective components; wherein the mass ratio of the isoliquiritigenin to the diosmetin is 4:150-6: 100; the mass ratio of the isoliquiritigenin to the quercetin is 4: 2.5.
Within the limited mass ratio range, isoliquiritigenin and diosmetin, isoliquiritigenin and quercetin achieve synergistic technical effect.
The medicine comprises pharmaceutically acceptable carriers, solvents, diluents, excipients and other media which are mixed, and can be prepared into powder, granules, capsules, injections, oral liquid or tablets according to different requirements.
The technical scheme of the invention has the advantages
Through an in vitro alpha-glucosidase inhibition test, a Chou-Talalay method is used to prove that the isoliquiritigenin, diosmetin, isoliquiritigenin and quercetin composition respectively have obvious synergistic effect on alpha-glucosidase at the mass ratio of 4:150-6:100 and 4:2.5, and the synergistic effect is 50% (GI) 50 )、75％(GI 75 ) And 90% (GI) 90 ) The CI values of the inhibition rates are all less than 1.0; wherein the isoliquiritigenin and diosmetin, isoliquiritigenin and quercetin composition have combined administration index mean value (CI) at mass ratio of 4:100 and 4:2.5 respectively avg ) Less than 0.6; has strong synergistic effect.
The isoliquiritigenin and the carvacrol, the isoliquiritigenin and the quercetin composition within the specific dosage ratio range defined by the invention have obvious synergistic effect of inhibiting alpha-glucosidase, the inhibiting effect is better than the effect of singly using one of the components, and the combined use of the two components improves the inhibiting activity of the alpha-glucosidase, so that the dosage of the medicament can be reduced, and the occurrence of medicament resistance can be reduced.
Drawings
FIG. 1 the isoliquiritigenin compositions of example 1 and example 5 have alpha-glucosidase inhibitory activity;
FIG. 2 is a graph of the inhibition of alpha-glucosidase by isoliquiritigenin + diosmetin (4:100) compositions;
FIG. 3 Fa-CI trend plot for isoliquiritigenin + diosmetin (4:100) composition inhibiting alpha-glucosidase;
FIG. 4 is a graph of the inhibition of alpha-glucosidase by isoliquiritigenin + quercetin (4:2.5) composition;
FIG. 5 Fa-CI trend plot for isoliquiritigenin + quercetin (4:2.5) composition to inhibit alpha-glucosidase;
FIG. 6 the isoliquiritigenin compositions of example 2 and example 6 have alpha-glucosidase inhibitory activity;
FIG. 7 is a graph of the inhibition of alpha-glucosidase by isoliquiritigenin + diosmetin (4:150) compositions;
FIG. 8 is a graph of the inhibition of alpha-glucosidase by isoliquiritigenin + quercetin (4:4) compositions;
FIG. 9 the isoliquiritigenin compositions of example 3 and example 7 have alpha-glucosidase inhibitory activity;
FIG. 10 is a graph of the inhibition of alpha-glucosidase by isoliquiritigenin + diosmetin (6:100) compositions;
FIG. 11 is a graph of the inhibition of alpha-glucosidase by isoliquiritigenin + quercetin (6:2.5) composition;
FIG. 12 the isoliquiritigenin compositions of example 4 and example 8 have alpha-glucosidase inhibitory activity;
FIG. 13 is a graph of the inhibition of alpha-glucosidase by isoliquiritigenin + diosmetin (8:150) compositions;
FIG. 14 is a graph of the inhibition of alpha-glucosidase by isoliquiritigenin + quercetin (8:4) composition.
Detailed Description
Terms used in the present invention have generally meanings as commonly understood by one of ordinary skill in the art, unless otherwise specified.
Isoliquiritigenin (Isooliquitiritigenin) with molecular formula of C 15 H 12 O 4 (ii) a Molecular weight: 256.25 parts of; CAS accession number: 961-29-5, the structural formula is:
diosmetin (Diosmetin), formula C 16 H 12 O 6 (ii) a Molecular weight: 300.26; CAS accession number: 520-34-3, the structural formula is:
quercetin (Quercetin) with molecular formula of C 15 H 10 O 7 (ii) a Molecular weight: 302.24, respectively; CAS accession number: 117-39-5, structural formula:
alpha-glucosidase (from saccharomyces cerevisiae, Sigma);
4-nitrobenzene- α -D-glucopyranoside (pNPG, TOKYO chemical Industry co., LTD);
acarbose (TOKYO chemical Industry co., LTD);
isoliquiritigenin, diosmetin, quercetin (Beijing Solebao);
millipore silicon water purification system (Millipore, france);
sodium phosphate salt buffer (pH 6.8,0.1mol L) -1 )；
The microplate reader TECAN infinite M200 PRO (Teacan Group ltd., Swizerland).
The present invention will be described in further detail with reference to the following data in conjunction with specific examples. The following examples are intended to illustrate the invention and are not intended to limit the scope of the invention in any way.
Example 1
The composition comprises isoliquiritigenin and diosmetin, wherein the mass ratio of isoliquiritigenin to diosmetin is 4:100, and the concentrations of isoliquiritigenin and diosmetin in the composition are 4 mug/mL and 100 mug/mL respectively.
Example 2
The composition of isoliquiritigenin and diosmetin is characterized in that the mass ratio of isoliquiritigenin to diosmetin is 4:150, and the concentrations of isoliquiritigenin and diosmetin in the composition are 4 mug/mL and 150 mug/mL respectively.
Example 3
The composition of isoliquiritigenin and diosmetin is characterized in that the mass ratio of isoliquiritigenin to diosmetin is 6:100, and the concentrations of isoliquiritigenin and diosmetin in the composition are 6 mug/mL and 100 mug/mL respectively.
Example 4
The composition of isoliquiritigenin and diosmetin is characterized in that the mass ratio of isoliquiritigenin to diosmetin is 8:100, and the concentrations of isoliquiritigenin and diosmetin in the composition are 8 mug/mL and 100 mug/mL respectively.
Example 5
The composition comprises isoliquiritigenin and quercetin, wherein the mass ratio of isoliquiritigenin to quercetin is 4:2.5, and the concentrations of isoliquiritigenin and quercetin in the composition are 4 mug/mL and 2.5 mug/mL respectively.
Example 6
The composition comprises isoliquiritigenin and quercetin, wherein the mass ratio of isoliquiritigenin to quercetin is 4:4, and the concentrations of isoliquiritigenin and quercetin in the composition are 4 mug/mL and 4 mug/mL respectively.
Example 7
The composition comprises isoliquiritigenin and quercetin, wherein the mass ratio of the isoliquiritigenin to the quercetin is 6:2.5, and the concentrations of the isoliquiritigenin and the quercetin in the composition are respectively 6 mug/mL and 2.5 mug/mL.
Example 8
The composition comprises isoliquiritigenin and quercetin, wherein the mass ratio of the isoliquiritigenin to the quercetin is 8:2.5, and the concentrations of the isoliquiritigenin and the quercetin in the composition are 8 mug/mL and 2.5 mug/mL respectively.
Blood sugar lowering effect test of isoliquiritigenin composition
The experimental method comprises the following steps:
with 0.1mol L -1 PBS buffer solution with pH 6.8 is used for preparing alpha-glucosidase solution with concentration of 0.25U/mL and substrate p-nitrobenzene-alpha-D-glucopyranoside (pNPG) solution with concentration of 5 mmol/mL.
Accurately transferring 40 mu L of alpha-glucosidase solution, respectively adding 100 mu L of sample solution to be detected, reacting at 37 ℃ for 10min, then adding 60 mu L of substrate p-nitrobenzene-alpha-D-glucopyranoside (pNPG) solution, reacting at 37 ℃ for 15min, and then measuring at 405nm wavelength by an enzyme-labeling instrument.
The sample solution to be tested is the isoliquiritigenin composition described in the embodiment 1-8, firstly, dimethyl sulfoxide (DMSO) is adopted to prepare isoliquiritigenin, diosmetin and quercetin into mother liquor of 10mg/mL respectively; and then PBS buffer solution is used for preparing sample solution of isoliquiritigenin, diosmetin, quercetin and the composition with specific concentration.
The positive control was acarbose (350. mu.g/mL), the blank was without sample and enzyme, and the sample blank was without enzyme.
Calculating the formula: inhibition rate [1- (OD) Sample (I) –OD Sample blank )/(OD Negative control -OD Blank space )]×100％
The CI values were calculated according to the software CompuSyn to evaluate the synergy between drugs.
Combination Index (CI) was used to describe the magnitude of drug synergy: CI <1 represents that the medicines have synergistic effect, the combined medicine can enhance the curative effect of each monomer medicine, and the smaller the CI value is, the stronger the synergistic effect is; CI-1 represents that the drugs have additive effect, and the combined drug result is only the linear superposition of the curative effect of each monomer drug; CI >1 represents that the medicines have antagonism, and the combined medication can reduce the respective curative effect.
1. The isoliquiritigenin compositions of examples 1 and 5 have alpha-glucosidase inhibitory activity
The α -glucosidase inhibitory activity of the isoliquiritigenin compositions of examples 1 and 5 is shown in fig. 1: the inhibition rates of 4 mu g/mL isoliquiritigenin, 100 mu g/mL diosmetin, 2.5 mu g/mL quercetin and 350 mu g/mL acarbose on alpha-glucosidase under corresponding mass concentrations are 35.2 +/-2.5%, 43.0 +/-2.1%, 42.9 +/-1.2% and 46.25 +/-3.5% respectively; the inhibition rate of isoliquiritigenin and diosmetin composition (4+100 mug/mL) is 79.45 +/-3.35%, and the inhibition rate of isoliquiritigenin and quercetin (4+2.5 mug/mL) is 67.2 +/-1.4%; the results show that the composition remarkably improves the inhibitory activity to alpha-glucosidase when the composition is used in combination.
Detecting the alpha-glucosidase inhibitory activity of the isoliquiritigenin and the diosmetin composition with the mass ratio of 4:100 under different concentration gradients, wherein the concentration gradient of the isoliquiritigenin and the diosmetin composition is (mu g/mL): 4+100, 2+50, 1+25, 0.5+ 12.5; the concentration gradient of the isoliquiritigenin is (mu g/mL): 4, 2, 1, 0.5; the concentration gradient of diosmetin was (μ g/mL): 100, 50, 25, 12.5; the results are shown in FIG. 2: the isoliquiritigenin and the diosmetin composition with the mass ratio of 4:100 improve the inhibitory activity to alpha-glucosidase under different concentration gradients. The Fa-CI trend of isoliquiritigenin and diosmetin composition with the mass ratio of 4:100 is shown in FIG. 3, and it is known from FIG. 3 that the CI values of isoliquiritigenin and diosmetin are basically below 0.5, and strong synergistic effect is shown.
Detecting the alpha-glucosidase inhibitory activity of the isoliquiritigenin and quercetin composition with the mass ratio of 4:2.5 under different concentration gradients, wherein the concentration gradient of the isoliquiritigenin and quercetin composition is (mu g/mL): 4+2.5, 2+1.25, 1+0.625, 0.5+ 0.3125; the concentration gradient of the isoliquiritigenin is (mu g/mL): 4, 2, 1, 0.5; the concentration gradient of quercetin was (μ g/mL): 2.5, 1.25, 0.625, 0.3125; the results are shown in FIG. 4: the isoliquiritigenin and quercetin composition with the mass ratio of 4:2.5 also correspondingly improves the inhibition activity on alpha-glucosidase under different concentration gradients. The Fa-CI trend chart of the isoliquiritigenin and quercetin composition with the mass ratio of 4:2.5 is shown in figure 5, and the CI values of isoliquiritigenin and quercetin are both below 1.0 and show synergistic effect as shown in figure 5.
The co-administration Coefficients (CI) of the isoliquiritigenin compositions of example 1 and example 5 are shown in table 1:
TABLE 1 Combined dosing Coefficient (CI) for isoliquiritigenin compositions of example 1 and example 5
Data are derived from the results of three independent experiments, expressed as mean ± standard deviation
As can be seen from the results in Table 1, the combination coefficient CI of isoliquiritigenin and diosmetin (4+ 100. mu.g/mL) and isoliquiritigenin and quercetin (4+ 2.5. mu.g/mL) were less than 1, and showed a synergistic effect, whereinThe combined administration coefficient of isoliquiritigenin and diosmetin (4:100) is in GI 50 ，GI 75 And GI 90 Are all less than 0.40, show strong synergistic effect, and have combined administration index mean value (CI) avg ) Is 0.20; the combined administration coefficient of isoliquiritigenin and quercetin (4:2.5) is in GI 50 ，GI 75 And GI 90 Are all less than 0.5, show strong synergistic effect, and have combined medication index mean value (CI) avg ) Is 0.46.
2. Isoliquiritigenin compositions of examples 2 and 6 have alpha-glucosidase inhibitory activity
The α -glucosidase inhibitory activity of the isoliquiritigenin compositions of example 2 and example 6 is shown in fig. 6: the inhibition rates of 4 mu g/mL isoliquiritigenin, 150 mu g/mL diosmetin, 4 mu g/mL quercetin and 350 mu g/mL acarbose on alpha-glucosidase under corresponding mass concentrations are respectively 35.2 +/-2.5%, 52.52 +/-2.4%, 51.52 +/-1.2% and 46.25 +/-3.5%; the inhibition rate of isoliquiritigenin and diosmetin composition (4+150 mug/mL) is 70.12 +/-4.5%, and the inhibition rate of isoliquiritigenin and quercetin (4+4 mug/mL) is 52.12 +/-3.4%; the results show that the isoliquiritigenin and the isoquercitrin composition remarkably improve the inhibitory activity to alpha-glucosidase when the isoliquiritigenin and the quercitrin composition are used in combination, but the isoliquiritigenin and the quercitrin composition are not obviously changed.
Detecting the alpha-glucosidase inhibitory activity of the isoliquiritigenin and the diosmetin composition with the mass ratio of 4:150 under different concentration gradients, wherein the concentration gradient of the isoliquiritigenin and the diosmetin composition is (mu g/mL): 4+150, 2+75, 1+37.5, 0.5+ 18.75; the concentration gradient of the isoliquiritigenin is (mu g/mL): 4, 2, 1, 0.5; the concentration gradient of diosmetin was (μ g/mL): 150, 75, 37.5, 18.75; the results are shown in FIG. 7: the isoliquiritigenin and the diosmetin composition with the mass ratio of 4:150 improve the inhibitory activity to alpha-glucosidase under different concentration gradients.
Detecting the alpha-glucosidase inhibitory activity of the isoliquiritigenin and quercetin composition with the mass ratio of 4:4 under different concentration gradients, wherein the concentration gradient of the isoliquiritigenin and quercetin composition is (mu g/mL): 4+4, 2+2, 1+1, 0.5+ 0.5; the concentration gradient of the isoliquiritigenin is (mu g/mL): 4, 2, 1, 0.5; the concentration gradient of quercetin was (μ g/mL): 4, 2, 1, 0.5; the results are shown in FIG. 8.
The co-administration Coefficients (CI) of the isoliquiritigenin compositions of example 2 and example 6 are shown in table 2:
table 2 co-administration Coefficient (CI) of isoliquiritigenin compositions of example 2 and example 6
Data are derived from the results of three independent experiments, expressed as mean ± standard deviation
The results in table 2 show that the combination of isoliquiritigenin and diosmetin (4:150) significantly improves the inhibitory activity to alpha-glucosidase, while the combination of isoliquiritigenin and quercetin (4:4) does not significantly improve the inhibitory activity to alpha-glucosidase; wherein the combined administration coefficient of isoliquiritigenin and diosmetin (4:150) is in GI 50 ，GI 75 And GI 90 Are all less than 0.70, show synergistic effect, and have mean value of combined drug index (CI) avg ) Is 0.56, the synergistic effect is strong; when isoliquiritigenin and quercetin (4:4) are used together, the combined medication coefficient CI is larger than 1, and antagonism is shown.
3. Isoliquiritigenin compositions of examples 3 and 7 have alpha-glucosidase inhibitory activity
The α -glucosidase inhibitory activity of the isoliquiritigenin compositions of examples 3 and 7 is shown in fig. 9: the inhibition rates of 6 mu g/mL isoliquiritigenin, 100 mu g/mL diosmetin, 2.5 mu g/mL quercetin and 350 mu g/mL acarbose on alpha-glucosidase under corresponding mass concentrations are respectively 56.4 +/-2.7%, 43.0 +/-2.1%, 42.9 +/-1.2% and 46.25 +/-3.5%; the inhibition rate of isoliquiritigenin and diosgenin composition (6+100 μ g/mL) is 67.8 + -3.7%, and the inhibition rate of isoliquiritigenin and quercetin (6+2.5 μ g/mL) is 65.3 + -3.4%; the results show that the composition improves the inhibitory activity on alpha-glucosidase when the composition is used in combination.
Detecting the alpha-glucosidase inhibitory activity of the isoliquiritigenin and the diosmetin composition with the mass ratio of 6:100 under different concentration gradients, wherein the concentration gradient of the isoliquiritigenin and the diosmetin composition is (mu g/mL): 6+100, 3+50, 1.5+25, 0.75+ 12.5; the concentration gradient of the isoliquiritigenin is (mu g/mL): 6, 3, 1.5, 0.75; the concentration gradient of diosmetin was (μ g/mL): 100, 50, 25, 12.5; the results are shown in FIG. 10: the isoliquiritigenin and the diosmetin composition with the mass ratio of 6:100 improve the inhibitory activity to alpha-glucosidase under different concentration gradients.
Detecting the alpha-glucosidase inhibitory activity of the isoliquiritigenin and quercetin composition with the mass ratio of 6:2.5 under different concentration gradients, wherein the concentration gradient of the isoliquiritigenin and quercetin composition is (mu g/mL): 6+2.5, 3+1.25, 1.5+0.625, 0.75+ 0.3125; the concentration gradient of the isoliquiritigenin is (mu g/mL): 6, 3, 1.5, 0.75; the concentration gradient of quercetin was (μ g/mL): 2.5, 1.25, 0.625, 0.3125; the results are shown in FIG. 11.
The co-administration Coefficients (CI) of the isoliquiritigenin compositions of example 3 and example 7 are shown in table 3:
table 3 co-administration Coefficient (CI) of isoliquiritigenin compositions of example 3 and example 7
Data are derived from the results of three independent experiments, expressed as mean ± sd
From the results in Table 3, it can be seen that the combination coefficient CI of isoliquiritigenin and diosmetin (6:100) is close to 1, and the mean value of the Combination Index (CI) avg ) 0.99, showing weak synergy; when the isoliquiritigenin and the quercetin (6:2.5) are used together, the joint medication coefficient CI is larger than 1.0, and antagonism is shown.
4. The isoliquiritigenin compositions of examples 4 and 8 have alpha-glucosidase inhibitory activity
The α -glucosidase inhibitory activity of the isoliquiritigenin compositions of example 4 and example 8 is shown in fig. 12: the inhibition rates of isoliquiritigenin of 8 mu g/mL, diosmetin of 150 mu g/mL, quercetin of 4 mu g/mL and acarbose of 350 mu g/mL on alpha-glucosidase under corresponding mass concentrations are 70.12 +/-2.5%, 52.52 +/-2.4%, 51.52 +/-1.2% and 46.25 +/-3.5% respectively; the inhibition rate of isoliquiritigenin and isogelonin composition (8+150 mug/mL) is 72.3 +/-1.7%, and the inhibition rate of isoliquiritigenin and quercetin (8+4 mug/mL) is 61.2 +/-2.5%; the results show that the combination does not obviously improve the inhibition activity to alpha-glucosidase when used together.
Detecting the alpha-glucosidase inhibitory activity of the isoliquiritigenin and the diosmetin composition with the mass ratio of 8:150 under different concentration gradients, wherein the concentration gradient of the isoliquiritigenin and the diosmetin composition is (mu g/mL): 8+150, 4+75, 2+37.5, 1+ 18.75; the concentration gradient of the isoliquiritigenin is (mu g/mL): 8, 4, 2, 1; the concentration gradient of diosmetin was (μ g/mL): 150, 75, 37.5, 18.75; the results are shown in FIG. 13: the isoliquiritigenin and the diosmetin composition with the mass ratio of 8:150 improve the inhibitory activity to alpha-glucosidase under different concentration gradients.
Detecting the alpha-glucosidase inhibitory activity of the isoliquiritigenin and quercetin composition with the mass ratio of 8:4 under different concentration gradients, wherein the concentration gradient of the isoliquiritigenin and quercetin composition is (mu g/mL): 8+4, 4+2, 2+1, 1+ 0.5; the concentration gradient of the isoliquiritigenin is (mu g/mL): 8, 4, 2, 1; the concentration gradient of quercetin was (μ g/mL): 4, 2, 1, 0.5; the results are shown in FIG. 14.
The combined administration Coefficient (CI) of the daidzein compositions of example 4 and example 8 are shown in table 4:
TABLE 4 Combined dosing factor (CI) for daidzein compositions of example 4 and example 8
Data are derived from the results of three independent experiments, expressed as mean ± standard deviation
As is clear from the results in Table 4, the combination coefficient CI of isoliquiritigenin and diosmetin (8:150) and isoliquiritigenin and quercetin (8:4) was more than 1, and antagonism was exhibited.
The foregoing is directed to preferred embodiments of the present invention, other and further embodiments of the invention may be devised without departing from the basic scope thereof, and the scope thereof is determined by the claims that follow. However, any simple modification, equivalent change and modification of the above embodiments according to the technical essence of the present invention are within the protection scope of the technical solution of the present invention.
Claims (5)
1. A synergistic hypoglycemic composition containing isoliquiritigenin is characterized by comprising isoliquiritigenin and compound X; the compound X is diosmetin or quercetin;
wherein the mass ratio of the isoliquiritigenin to the diosmetin is 4:150-6: 100; the mass ratio of the isoliquiritigenin to the quercetin is 4: 2.5.
2. Use of a composition according to claim 1 for the preparation of a formulation with a synergistic effect on the inhibition of α -glucosidase.
3. An alpha-glucosidase synergistic inhibitor is characterized in that the effective components comprise isoliquiritigenin and diosmetin or isoliquiritigenin and quercetin; wherein the mass ratio of the isoliquiritigenin to the diosmetin is 4:150-6: 100; the mass ratio of the isoliquiritigenin to the quercetin is 4: 2.5.
4. Use of the composition of claim 1 for the preparation of a medicament having a synergistic hypoglycemic effect; the synergistic hypoglycemic effect is to achieve the purpose of controlling postprandial hyperglycemia by synergistically inhibiting the activity of alpha-glucosidase and blocking the digestion and absorption of carbohydrates.
5. A medicine with synergistic hypoglycemic effect is characterized in that the effective components comprise isoliquiritigenin and diosmetin or isoliquiritigenin and quercetin; wherein the mass ratio of the isoliquiritigenin to the diosmetin is 4:150-6: 100; the mass ratio of the isoliquiritigenin to the quercetin is 4: 2.5.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202110961501.6A CN113440515B (en) | 2021-08-20 | 2021-08-20 | Synergistic blood sugar reducing composition containing isoliquiritigenin and application thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202110961501.6A CN113440515B (en) | 2021-08-20 | 2021-08-20 | Synergistic blood sugar reducing composition containing isoliquiritigenin and application thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN113440515A CN113440515A (en) | 2021-09-28 |
| CN113440515B true CN113440515B (en) | 2022-08-12 |
Family
ID=77818802
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202110961501.6A Active CN113440515B (en) | 2021-08-20 | 2021-08-20 | Synergistic blood sugar reducing composition containing isoliquiritigenin and application thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN113440515B (en) |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111388461A (en) * | 2020-04-21 | 2020-07-10 | 中国农业科学院郑州果树研究所 | Blood sugar reducing composition and application thereof |
| CN111388462A (en) * | 2020-04-21 | 2020-07-10 | 中国农业科学院郑州果树研究所 | Composition with blood sugar reducing effect and application |
| WO2021071334A1 (en) * | 2019-10-11 | 2021-04-15 | 가톨릭대학교산학협력단 | Pharmaceutical composition for preventing and treating type 2 diabetes, containing quercetin-3-o-xyloside |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2003252784A (en) * | 2002-02-27 | 2003-09-10 | Kanegafuchi Chem Ind Co Ltd | alpha-GLUCOSIDASE INHIBITOR |
-
2021
- 2021-08-20 CN CN202110961501.6A patent/CN113440515B/en active Active
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2021071334A1 (en) * | 2019-10-11 | 2021-04-15 | 가톨릭대학교산학협력단 | Pharmaceutical composition for preventing and treating type 2 diabetes, containing quercetin-3-o-xyloside |
| CN111388461A (en) * | 2020-04-21 | 2020-07-10 | 中国农业科学院郑州果树研究所 | Blood sugar reducing composition and application thereof |
| CN111388462A (en) * | 2020-04-21 | 2020-07-10 | 中国农业科学院郑州果树研究所 | Composition with blood sugar reducing effect and application |
Non-Patent Citations (3)
| Title |
|---|
| Interaction Mechanism of Flavonoids and α-Glucosidase：Experimental and Molecular Modelling Studies;Chengyun He等;《Foods》;20190821;第8卷(第335期);第4页表1 * |
| Quercetin-induced apoptosis prevents EBV infection;Minjung Lee等;《Oncotarget》;20150329;第6卷(第14期);第12603-12624页 * |
| 天然产物对2型糖尿病的降血糖作用机制分析;张蒙等;《生命科学》;20210531;第33卷(第5期);第672页左栏第2段、右栏第1-3行 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN113440515A (en) | 2021-09-28 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Babu et al. | Recent advances in understanding the anti-diabetic actions of dietary flavonoids | |
| Apostolidis et al. | Potential of cranberry-based herbal synergies for diabetes and hypertension management. | |
| CN111388461B (en) | Blood sugar reducing composition and application thereof | |
| Ji et al. | In vitro and in vivo inhibitory effect of anthocyanin-rich bilberry extract on α-glucosidase and α-amylase | |
| Ertracht et al. | The mitochondria as a target for cardioprotection in acute myocardial ischemia | |
| US6908630B2 (en) | Combinations of sesquiterpene lactones and ditepene triepoxide lactones for synergistic inhibition of cyclooxygenase-2 | |
| SA517380987B1 (en) | Composition containing a mixture of plant extracts or a mixture of molecules contained in said plants | |
| KR102012554B1 (en) | Cytoprotective composition for protection of cell containing Cyclo His-Pro as Active Ingredient | |
| CN102228517B (en) | Plantain seed extract and application thereof | |
| JP5524196B2 (en) | Pharmaceutical composition for the treatment of diabetes | |
| CN111388462B (en) | Composition with blood sugar reducing effect and application | |
| CN113440516B (en) | Composition for inhibiting alpha-glucosidase and application thereof | |
| WO2023020344A1 (en) | Hesperetin-containing composition and synergistic hypoglycemic application thereof | |
| CN113440515B (en) | Synergistic blood sugar reducing composition containing isoliquiritigenin and application thereof | |
| Wang et al. | | Therapeutic and preventive effects of apigenin in cerebral ischemia: a review | |
| CN113546074B (en) | Composition containing 3-O-methyl quercetin and application thereof in alpha-glucosidase inhibition | |
| CN101732578A (en) | Medicinal composition for treating essential hypertension, preparation method and use thereof | |
| CN113521057B (en) | Blood sugar reducing composition containing genistein and application thereof | |
| CN113476438B (en) | Hypoglycemic composition containing dihydro morin and application thereof | |
| CN100396289C (en) | Scutellarin injection preparation and its preparing method | |
| JP2024525957A (en) | Hesperetin-containing composition and its synergistic application in lowering blood sugar | |
| CN105535951A (en) | Ulinastatin injection and preparation method for same | |
| US20140275138A1 (en) | Method and products for treating diabetes | |
| JP2024525958A (en) | α-Glucosidase inhibitor composition and its application | |
| LU500100B1 (en) | Antihypertensive pharmaceutical composition, and preparation method and use thereof |
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 |