CN113546074B - Composition containing 3-O-methyl quercetin and application thereof in alpha-glucosidase inhibition - Google Patents

Composition containing 3-O-methyl quercetin and application thereof in alpha-glucosidase inhibition Download PDF

Info

Publication number
CN113546074B
CN113546074B CN202110961983.5A CN202110961983A CN113546074B CN 113546074 B CN113546074 B CN 113546074B CN 202110961983 A CN202110961983 A CN 202110961983A CN 113546074 B CN113546074 B CN 113546074B
Authority
CN
China
Prior art keywords
methyl quercetin
quercetin
glucosidase
methyl
composition
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
Application number
CN202110961983.5A
Other languages
Chinese (zh)
Other versions
CN113546074A (en
Inventor
张强
焦中高
陈大磊
刘杰超
刘慧�
张春岭
杨文博
吕真真
潘俊坤
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Zhengzhou Fruit Research Institute CAAS
Original Assignee
Zhengzhou Fruit Research Institute CAAS
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Zhengzhou Fruit Research Institute CAAS filed Critical Zhengzhou Fruit Research Institute CAAS
Priority to CN202110961983.5A priority Critical patent/CN113546074B/en
Publication of CN113546074A publication Critical patent/CN113546074A/en
Application granted granted Critical
Publication of CN113546074B publication Critical patent/CN113546074B/en
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Images

Classifications

    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/335Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/35Heterocyclic 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
    • A61K31/352Heterocyclic 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 
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00Drugs for disorders of the metabolism
    • A61P3/08Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics

Landscapes

  • Health & Medical Sciences (AREA)
  • Diabetes (AREA)
  • Medicinal Chemistry (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Obesity (AREA)
  • Hematology (AREA)
  • Engineering & Computer Science (AREA)
  • Endocrinology (AREA)
  • Emergency Medicine (AREA)
  • Epidemiology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

The invention discloses a composition containing 3-O-methyl quercetin and application thereof in alpha-glucosidase inhibition, belonging to the technical field of natural active compounds. The composition comprises 3-O-methyl quercetin and one of dihydroquercetin and calycosin; wherein the mass ratio of the 3-O-methyl quercetin to the dihydroquercetin is 2-25-4; the mass ratio of the 3-O-methyl quercetin to the calycosin is 2. 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

Composition containing 3-O-methyl quercetin and application thereof in alpha-glucosidase inhibition
Technical Field
The invention belongs to the technical field of natural active compounds, and particularly relates to a composition containing 3-O-methyl quercetin and application thereof in alpha-glucosidase inhibition.
Background
In recent years, much research has been devoted to identify effective α -glucosidase inhibitors from natural sources and to develop antidiabetic drugs or lead compounds, including flavonoids, anthocyanins, phenols, and the like. Alpha-glucosidase inhibitors can delay the release of D-glucose from food carbohydrates and delay glucose absorption, resulting in a decrease in postprandial plasma glucose levels, thereby effectively controlling postprandial hyperglycemia.
The natural flavonoid exists in various fruits and vegetables such as grapes and blueberries, and researches report that the natural flavonoid has various biological activities such as blood sugar reduction, cancer resistance and oxidation resistance. Currently, the clinical drugs widely used for treating type II diabetes mellitus are oral hypoglycemic drugs such as acarbose, voglibose and miglitol. The medicine can effectively improve and prevent hyperglycemia and complications thereof by acting with alpha-glucosidase in small intestine, inhibiting enzyme activity, delaying glucose production, preventing postprandial blood sugar from reaching a certain peak value. However, these inhibitors cause a series of side effects, such as diarrhea, abdominal pain, liver injury, etc., some patients cannot fully accept the inhibitors, and new synthetic drugs have certain toxic and side effects and low efficiency, so that the search for alpha-glucosidase inhibitors derived from natural plants becomes one of the main directions for the current research and treatment of type II diabetes drugs (Guo Fenxia, zeng Yang, xueyong, etc.. The pharmacological research progress of alpha-glucosidase inhibitors [ J ]. University of Qinghai university: nature edition, 2011,27 (1): 63-66).
The strategy of drug combination is very important, on one hand, the drug sensitivity can be increased, and the drug resistance problem can be solved; on the other hand, the dosage can be reduced, and the toxic and side effects of the medicine can be reduced. Currently, most researches on alpha-glucosidase inhibitors focus on a single compound, and the continuous use of the compound can generate certain side effects and tolerance, but the reports of the synergistic interaction between active molecules are few. Therefore, the research on the combined application of the flavonoid compounds to inhibit alpha-glucosidase and improve the hypoglycemic activity has important significance for improving the human health.
Disclosure of Invention
The invention aims to provide a composition containing 3-O-methyl quercetin and application thereof in alpha-glucosidase inhibition, so as to solve the problems that in the prior art, a single active ingredient has limited effect of reducing blood sugar and is easy to generate drug resistance.
In order to achieve the purpose, the invention is realized by the following technical scheme:
a composition containing 3-O-methyl quercetin comprises 3-O-methyl quercetin and one of dihydroquercetin and calycosin;
wherein the mass ratio of the 3-O-methyl quercetin to the dihydroquercetin is 2-25-4; the mass ratio of the 3-O-methyl quercetin to the calycosin is 2.
In several embodiments, the mass ratio of 3-O-methyl quercetin to dihydroquercetin is 2; wherein when the mass ratio of the 3-O-methyl quercetin to the dihydroquercetin is 2 avg ) Is 0.50, is better than 4.
The application of the composition in preparing a preparation with the function of inhibiting alpha-glucosidase.
An alpha-glucosidase inhibitor contains 3-O-methyl quercetin and one of dihydroquercetin and calycosin as effective components; wherein the mass ratio of the 3-O-methyl quercetin to the dihydroquercetin is (2-25-4); the mass ratio of the 3-O-methyl quercetin to the calycosin is 2.
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 3-O-methyl quercetin and dihydroquercetin or 3-O-methyl quercetin and calycosin as effective components; wherein the mass ratio of the 3-O-methyl quercetin to the dihydroquercetin is 2-25-4; the mass ratio of the 3-O-methyl quercetin to the calycosin is 2.
Within the limited mass ratio range, 3-O-methyl quercetin and dihydroquercetin, 3-O-methyl quercetin and calycosin obtain 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
The composition of the 3-O-methyl quercetin, the dihydroquercetin, the 3-O-methyl quercetin and the calycosin 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 medicine and reduce the occurrence of drug resistance. When dihydroquercetin and calycosin are replaced by quercetin and formononetin with similar chemical structures, the synergistic effect disappears.
Through in vitro alpha-glucosidase inhibition tests, a Chou-Talalay method is applied to prove that the composition of 3-O-methyl quercetin and dihydroquercetin, 3-O-methyl quercetin and calycosin of the invention has obvious synergistic effect on alpha-glucosidase at the mass ratios of 2-4 50 )、75%(GI 75 ) And 90% (GI) 90 ) The CI values at the inhibition rates were all less than 1.0, and the intensity of synergy between drugs at high inhibition rates was generally higher than at low inhibition rates.
Drawings
FIG. 1 the inhibitory activity of the 3-O-methyl quercetin compositions of example 1 and example 4 on α -glucosidase;
FIG. 2 is a graph of the inhibition of α -glucosidase by the composition of-O-methyl quercetin + dihydroquercetin (2;
FIG. 3 Fa-CI trend plot for alpha-glucosidase inhibition by the O-methyl Quercetin + DihydroQuercetin (2);
FIG. 4 is a graph showing the inhibition of α -glucosidase by the composition of 3-O-methyl quercetin + calycosin (2);
FIG. 5 is a graph of Fa-CI trends for the 3-O-methylquercetin + calycosin (2) composition to inhibit alpha-glucosidase;
FIG. 6 the inhibitory activity of the 3-O-methyl quercetin compositions of example 2 and example 5 on α -glucosidase;
FIG. 7 is a graph of the inhibition of α -glucosidase by the composition of 3-O-methyl quercetin + dihydroquercetin (4);
FIG. 8 is a graph showing the inhibition of α -glucosidase by the composition of 3-O-methyl quercetin + calycosin (4);
FIG. 9 the inhibitory activity of the 3-O-methyl quercetin compositions of example 3 and example 6 on α -glucosidase;
FIG. 10 graph of the inhibition of alpha-glucosidase by the composition of 3-O-methyl quercetin + dihydroquercetin (2);
FIG. 11 is a graph showing the inhibition of α -glucosidase by the composition of 3-O-methyl quercetin + calycosin (2);
FIG. 12 the inhibitory activity of the 3-O-methyl quercetin compositions of comparative example 1 and comparative example 2 on α -glucosidase;
FIG. 13 is a graph of the inhibition of α -glucosidase by the-O-methyl quercetin + quercetin (2;
FIG. 14 is a graph of the inhibition of alpha-glucosidase by the 3-O-methyl quercetin + formononetin (2.
Detailed Description
The terms used in the present invention have generally the meanings that are commonly understood by those of ordinary skill in the art, unless otherwise specified.
3-O-Methyl Quercetin (3-O-Methyl Quercetin) is one of Quercetin derivatives, and has molecular formula of C 16 H 12 O 7 (ii) a Molecular weight: 316.26; CAS accession number: 1486-70-0, structural formula:
Figure BDA0003222657490000031
dihydroquercetin (Taxifolin) with molecular formula of C 15 H 12 O 7 (ii) a Molecular weight: 304.25; CAS accession No.: 480-18-2, the structural formula is as follows:
Figure BDA0003222657490000032
calycosin (Calycosin) with molecular formula of C 16 H 12 O 5 (ii) a Molecular weight: 284.26; CAS accession number: 20575-57-9, structural formula:
Figure BDA0003222657490000033
alpha-glucosidase (from saccharomyces cerevisiae, sigma);
4-nitrobenzene- α -D-glucopyranoside (pNPG, TOKYO chemical Industry co., LTD);
acarbose (Acarbose, TOKYO chemical Industry co., LTD);
3-O-methyl quercetin, dihydroquercetin, calycosin (beijing solibao);
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, but not to limit the scope of the invention in any way.
Example 1
A composition of 3-O-methyl quercetin and dihydroquercetin, wherein the mass ratio of 3-O-methyl quercetin to dihydroquercetin is 2; specifically, the concentrations of 3-O-methyl quercetin and dihydroquercetin in the composition are 2 μ g/mL and 25 μ g/mL, respectively.
Example 2
A composition of 3-O-methylquercetin and dihydroquercetin, wherein the mass ratio of 3-O-methylquercetin to dihydroquercetin is 4; specifically, the concentrations of 3-O-methyl quercetin and dihydroquercetin in the composition are 4 mug/mL and 25 mug/mL respectively.
Example 3
A composition of 3-O-methyl quercetin and dihydroquercetin, wherein the mass ratio of 3-O-methyl quercetin to dihydroquercetin is 2; specifically, the concentrations of 3-O-methyl quercetin and dihydroquercetin in the composition are 2 μ g/mL and 30 μ g/mL, respectively.
Example 4
A composition of 3-O-methyl quercetin and calycosin, wherein the mass ratio of the 3-O-methyl quercetin to the calycosin is 2; specifically, the concentrations of 3-O-methyl quercetin and piloectocin in the composition are 2 μ g/mL and 6 μ g/mL, respectively.
Example 5
A composition of 3-O-methyl quercetin and calycosin, wherein the mass ratio of the 3-O-methyl quercetin to the calycosin is 4; specifically, the concentrations of 3-O-methyl quercetin and piloectocin in the composition are 4 μ g/mL and 6 μ g/mL, respectively.
Example 6
A composition of 3-O-methyl quercetin and calycosin, wherein the mass ratio of the 3-O-methyl quercetin to the calycosin is 2; specifically, the concentrations of 3-O-methyl quercetin and verbascoisoflavone in the composition are 2 μ g/mL and 10 μ g/mL respectively.
Test of hypoglycemic Effect of 3-O-Methylquercetin 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.
Add 100. Mu.L of sample solution per well followed by 40. Mu.L of alpha-glucosidase (0.25U/mL), react at 37 ℃ for 15min, then add 60. Mu.L of the 5mmol/mL substrate p-nitrophenyl-alpha-D-glucopyranoside (pNPG); after the reaction was left at 37 ℃ for 15min, the reaction was measured by a microplate reader at a wavelength of 405 nm.
The sample solution to be tested is the 3-O-methyl quercetin composition described in the embodiment 1-6, firstly, dimethyl sulfoxide (DMSO) is adopted to prepare 3-O-methyl quercetin, dihydroquercetin and calycosin into mother liquor of 10mg/mL respectively; then PBS buffer solution is used for preparing 3-O-methyl quercetin, dihydroquercetin, calycosin and composition sample solution 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 antagonism among the drugs, and the combination of the drugs can reduce the respective curative effect.
1. The 3-O-methylquercetin compositions of example 1 and example 4 have alpha-glucosidase inhibitory activity
The α -glucosidase inhibitory activity of the 3-O-methylquercetin compositions of example 1 and example 4 is shown in FIG. 1: the inhibition rates of 2 mu g/mL 3-O-methyl quercetin, 25 mu g/mL dihydroquercetin, 6 mu g/mL calycosin and 350 mu g/mL acarbose on alpha-glucosidase under corresponding mass concentrations are 46.23 +/-1.2%, 40.12 +/-2.1%, 56.6 +/-4.3% and 46.25 +/-3.5% respectively; the inhibition rate of the 3-O-methyl quercetin and dihydroquercetin composition (2 +25 mug/mL) is 78.82 +/-3.4 percent, and the inhibition rate of the 3-O-methyl quercetin and calycosin (2 +6 mug/mL) is 73.21 +/-4.5 percent; 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 a 3-O-methyl quercetin and dihydroquercetin composition with a mass ratio of 2:2, 1, 12.5, 0.5, 6.25 and 0.25+3.125; the concentration gradient of 3-O-methyl quercetin was (μ g/mL): 2.1, 0.5, 0.25; the concentration gradient of dihydroquercetin is (mu g/mL): 25. 12.5, 6.25, 3.125; the results are shown in FIG. 2; the 3-O-methyl quercetin and dihydroquercetin composition with the mass ratio of 2. The Fa-CI trend of the 3-O-methyl quercetin and dihydroquercetin composition at a mass ratio of 2.
Detecting the alpha-glucosidase inhibitory activity of a 3-O-methyl quercetin and calycosin composition with a mass ratio of 2:2, 6,1, 0.5, 0.25, 0.75; concentration gradient of 3-O-methyl Quercetin (μ g/mL): 2.1, 0.5, 0.25; calycosin concentration gradient (μ g/mL): 6. 3, 1.5, 0.75; the results are shown in FIG. 4: the 3-O-methyl quercetin and calycosin composition with the mass ratio of 2. The Fa-CI trend of the 3-O-methylquercetin and calycosin composition at a mass ratio of 2:6 is shown in FIG. 5, and it can be seen from FIG. 5 that the CI values of 3-O-methylquercetin and calycosin are both below 1.0, showing a synergistic effect.
The combination Coefficient (CI) of the 3-O-methyl quercetin compositions of example 1 and example 4 is shown in Table 1:
TABLE 1 Combined administration Coefficients (CI) of the 3-O-methyl quercetin compositions of example 1 and example 4
Figure BDA0003222657490000061
Data are derived from the results of three independent experiments, expressed as mean ± sd
From the results in Table 1, it is seen that the combination coefficients CI of 3-O-methylquercetin and dihydroquercetin (2) 50 ,GI 75 And GI 90 Are all less than 0.60, show strong synergistic effect, and have combined medication index mean value (CI) avg ) Is 0.50; combination of 3-O-methyl quercetin and a piloecium isoflavone compositionThe administration factor is in GI 75 And GI 90 Are all less than 0.9, show synergistic effect, and have mean value of combined drug index (CI) avg ) Is 0.80.
2. The 3-O-methylquercetin compositions of example 2 and example 5 have alpha-glucosidase inhibitory activity
The α -glucosidase inhibitory activity of the 3-O-methylquercetin compositions of example 2 and example 5 is shown in FIG. 6: the inhibition rates of 4 mu g/mL 3-O-methyl quercetin, 25 mu g/mL dihydroquercetin, 6 mu g/mL calycosin and 350 mu g/mL acarbose on alpha-glucosidase under corresponding mass concentrations are 53.52 +/-3.2%, 40.12 +/-2.1%, 56.6 +/-4.3% and 46.25 +/-3.5% respectively; the inhibition rate of the 3-O-methyl quercetin and dihydroquercetin composition (4 +25 mug/mL) is 61.82 +/-4.4%, and the inhibition rate of the 3-O-methyl quercetin and calycosin (4 +6 mug/mL) is 55.54 +/-3.5%; the results show that the composition improves the inhibition activity to alpha-glucosidase when the 3-O-methyl quercetin and the dihydroquercetin are used together; the composition does not significantly improve the alpha-glucosidase inhibitory activity when the 3-O-methyl quercetin and calycosin are used in combination.
Detecting the alpha-glucosidase inhibitory activity of a 3-O-methyl quercetin and dihydroquercetin composition with a mass ratio of 4: 4, 25,2, 12.5, 1, 6.25, 0.5, 3.125; concentration gradient of 3-O-methyl Quercetin (μ g/mL): 4.2, 1, 0.5; the concentration gradient of dihydroquercetin is (mu g/mL): 25. 12.5, 6.25, 3.125; the results are shown in FIG. 7.
Detecting the alpha-glucosidase inhibitory activity of a 3-O-methyl quercetin and calycosin composition with a mass ratio of 4: 4, 6,2, 1, 5 and 0.5+0.75; the concentration gradient of 3-O-methyl quercetin was (μ g/mL): 4.2, 1, 0.5; calycosin concentration gradient (μ g/mL): 6. 3, 1.5, 0.75; the results are shown in FIG. 8.
The combination Coefficient (CI) of the 3-O-methyl quercetin compositions of example 2 and example 5 is shown in Table 2:
TABLE 2 Combined administration Coefficients (CI) of the 3-O-methyl quercetin compositions of example 2 and example 5
Figure BDA0003222657490000071
Data are derived from the results of three independent experiments, expressed as mean ± sd
As can be seen from the results in table 2, the co-administration coefficients CI of 3-O-methylquercetin and dihydroquercetin (4 avg ) Is 0.75; the 3-O-methyl quercetin and calycosin (4).
3. The 3-O-methyl quercetin compositions of example 3 and example 6 have alpha-glucosidase inhibitory activity
The α -glucosidase inhibitory activity of the 3-O-methyl quercetin compositions of example 3 and example 6 is shown in FIG. 9: the inhibition rates of 2 mu g/mL 3-O-methyl quercetin, 30 mu g/mL dihydroquercetin, 10 mu g/mL calycosin and 350 mu g/mL acarbose on alpha-glucosidase under corresponding mass concentrations are 46.23 +/-1.2%, 54.5 +/-4.1%, 62.12 +/-3.3% and 46.25 +/-3.5% respectively; the inhibition ratio of the 3-O-methyl quercetin and dihydroquercetin composition (2 +30 mug/mL) is 57.62 +/-5.7%, and the inhibition ratio of the 3-O-methyl quercetin and calycosin (2 +10 mug/mL) is 56.21 +/-4.5%; the results show that the composition does not obviously improve the inhibition activity on alpha-glucosidase when the composition is used in combination.
Detecting the alpha-glucosidase inhibitory activity of a 3-O-methyl quercetin and dihydro quercetin composition with the mass ratio of 2:2, 30,1, 7.5, 0.25, 3.75; the concentration gradient of 3-O-methyl quercetin was (μ g/mL): 2.1, 0.5, 0.25; the concentration gradient of dihydroquercetin is (mu g/mL): 30. 15, 7.5, 3.75; the results are shown in FIG. 10.
Detecting the alpha-glucosidase inhibitory activity of a 3-O-methyl quercetin and calycosin composition with a mass ratio of 2:2, 1, 2.5, 0.25+1.25; concentration gradient of 3-O-methyl Quercetin (μ g/mL): 2.1, 0.5, 0.25; calycosin concentration gradient (μ g/mL): 10. 5, 2.5, 1.25; the results are shown in FIG. 11.
The combination Coefficient (CI) of the 3-O-methylquercetin compositions of example 3 and example 6 is shown in Table 3:
TABLE 3 Combined administration Coefficients (CI) of the 3-O-methyl quercetin compositions of example 3 and example 6
Figure BDA0003222657490000081
Data are derived from the results of three independent experiments, expressed as mean ± standard deviation
From the results in table 3, it is understood that the combination coefficient CI of the combination of 3-O-methylquercetin and dihydroquercetin (2).
Comparative example 1
Quercetin (Quercitrin) has a structure similar to that of dihydroquercetin, and has a molecular formula of C 21 H 20 O 11 (ii) a Molecular weight: 448.38; CAS accession number: 522-12-3, the structural formula is:
Figure BDA0003222657490000082
the composition comprises 3-O-methyl quercetin and quercetin, wherein the mass ratio of the 3-O-methyl quercetin to the quercetin is 2.
Comparative example 2
Formononetin (Formononetin) with a molecular formula of C and a structure similar to calycosin 16 H 12 O 4 (ii) a Molecular weight: 268.26; CAS loginRecording number: 485-72-3, the structural formula is:
Figure BDA0003222657490000083
the composition of the 3-O-methyl quercetin and the formononetin is characterized in that the mass ratio of the 3-O-methyl quercetin to the formononetin is 2.
Hypoglycemic Effect of the compositions of comparative examples 1 and 2
The detection of the α -glucosidase inhibitory activity of the 3-O-methyl quercetin compositions of comparative example 1 and comparative example 2 is shown in FIG. 12: the inhibition rates of 2 mu g/mL of 3-O-methyl quercetin, 40 mu g/mL of quercetin, 20 mu g/mL of formononetin and 350 mu g/mL of acarbose on alpha-glucosidase under corresponding mass concentrations are 46.23 +/-1.2%, 53.52 +/-3.2%, 60.07 +/-5.3% and 46.25 +/-3.5% respectively; the inhibition ratio of the 3-O-methyl quercetin and quercetin composition (2 +40 mug/mL) is 60.8 +/-3.4%; the inhibition ratio of 3-O-methyl quercetin and formononetin composition (2 +20 μ g/mL) is 63.3 +/-5.1%; the results show that the two compositions do not obviously improve the inhibition activity on the alpha-glucosidase when the two compositions are used together.
Detecting the alpha-glucosidase inhibitory activity of a 3-O-methyl quercetin and quercetin composition with a mass ratio of 2:2, 40,1, 20, 0.5, 10, 0.25+5; the concentration gradient of 3-O-methyl quercetin was (μ g/mL): 2.1, 0.5, 0.25; the concentration gradient of quercetin was (μ g/mL): 40. 20, 10, 5; the results are shown in FIG. 13.
Detecting the alpha-glucosidase inhibitory activity of a 3-O-methyl quercetin and formononetin composition with the mass ratio of 2:2, 1, 5, 0.25+2.5; concentration gradient of 3-O-methyl Quercetin (μ g/mL): 2.1, 0.5, 0.25; the concentration gradient of formononetin is (mu g/mL): 20. 10, 5, 2.5; the results are shown in FIG. 14.
TABLE 4 Combined dosing factor (CI) for the 3-O-methyl quercetin compositions of comparative example 1 and comparative example 2
Figure BDA0003222657490000091
Data are derived from the results of three independent experiments, expressed as mean ± sd
As can be seen from the results in table 4, the combination coefficient CI of 3-O-methylquercetin and quercitrin (2) and 3-O-methylquercetin and formononetin (2) when used in combination was greater than 1, and an antagonistic effect 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 (6)

1. A composition containing 3-O-methyl quercetin is characterized by comprising 3-O-methyl quercetin and one of dihydroquercetin and calycosin;
wherein the mass ratio of the 3-O-methyl quercetin to the dihydroquercetin is (2-25-4); the mass ratio of the 3-O-methyl quercetin to the calycosin is 2.
2. Use of the composition of claim 1 for the preparation of a preparation having an alpha-glucosidase inhibitory effect.
3. An α -glucosidase inhibitor characterized in that the composition according to claim 1 is an active ingredient thereof.
4. Use of a composition according to claim 1 for the preparation of a medicament having a hypoglycemic effect.
5. The use according to claim 4, wherein the hypoglycemic effect is to control postprandial hyperglycemia by inhibiting the activity of α -glucosidase and blocking the digestion and absorption of carbohydrates.
6. A drug having a hypoglycemic effect, characterized in that the active ingredient thereof is the composition according to claim 1.
CN202110961983.5A 2021-08-20 2021-08-20 Composition containing 3-O-methyl quercetin and application thereof in alpha-glucosidase inhibition Active CN113546074B (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN202110961983.5A CN113546074B (en) 2021-08-20 2021-08-20 Composition containing 3-O-methyl quercetin and application thereof in alpha-glucosidase inhibition

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN202110961983.5A CN113546074B (en) 2021-08-20 2021-08-20 Composition containing 3-O-methyl quercetin and application thereof in alpha-glucosidase inhibition

Publications (2)

Publication Number Publication Date
CN113546074A CN113546074A (en) 2021-10-26
CN113546074B true CN113546074B (en) 2022-10-04

Family

ID=78105872

Family Applications (1)

Application Number Title Priority Date Filing Date
CN202110961983.5A Active CN113546074B (en) 2021-08-20 2021-08-20 Composition containing 3-O-methyl quercetin and application thereof in alpha-glucosidase inhibition

Country Status (1)

Country Link
CN (1) CN113546074B (en)

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN104984346A (en) * 2015-02-13 2015-10-21 大连理工大学 Pharmaceutical composition having alpha-glucosidase inhibition activity, and applications thereof

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN111388461B (en) * 2020-04-21 2020-12-08 中国农业科学院郑州果树研究所 Blood sugar reducing composition and application thereof

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN104984346A (en) * 2015-02-13 2015-10-21 大连理工大学 Pharmaceutical composition having alpha-glucosidase inhibition activity, and applications thereof

Also Published As

Publication number Publication date
CN113546074A (en) 2021-10-26

Similar Documents

Publication Publication Date Title
CN111388461B (en) Blood sugar reducing composition and application thereof
EP1585533A2 (en) Composition of berry extracts that prevents or inhibits angiogenesis and helicobacter pylori
WO2006074278A2 (en) Compositions for treating diabetes or obesity
CN104984346B (en) A kind of pharmaceutical composition and its application with alpha-glucoside inhibiting activity
CN100441590C (en) Compounds like quercetol and metal complex of their glycosides and uses
CN111388462B (en) Composition with blood sugar reducing effect and application
JP5524196B2 (en) Pharmaceutical composition for the treatment of diabetes
WO2023020344A1 (en) Hesperetin-containing composition and synergistic hypoglycemic application thereof
CN113440516B (en) Composition for inhibiting alpha-glucosidase and application thereof
CN113546074B (en) Composition containing 3-O-methyl quercetin and application thereof in alpha-glucosidase inhibition
US7494674B2 (en) Nutraceutical with tart cherries and method of treatment therewith
KR100577677B1 (en) Composition for lowering blood glucose
CN113440515B (en) Synergistic blood sugar reducing composition containing isoliquiritigenin and application thereof
US20040115285A1 (en) Method of normalizing glucose levels in blood of patients with diabetes mellitus by oral administration of proanthocyanidins containing plant extracts
CN113521057B (en) Blood sugar reducing composition containing genistein and application thereof
CN107397740B (en) Synergistic antitumor polyphenol composition and application thereof
CN113476438B (en) Hypoglycemic composition containing dihydro morin and application thereof
US9867860B2 (en) Formulations for preventing and treating decreasing platelet cell counts
WO2020111869A1 (en) Pharmaceutical composition for co-administration of acidosis-inducing drug
CN110872280A (en) Application of flavone C-glycoside monomeric compound
CN110623963B (en) Pharmaceutical composition for treating ovarian cancer and application thereof
KR20210101186A (en) A pharmaceutical composition for co-administration with acidosis inducing agent
CN116492350A (en) Galanthamine combination composition and application thereof
KR20090125918A (en) Antidiabetic composition and method of manufacturing the same
KR20240074517A (en) Composition for anti-diabetes containing Glochidion chodoense extract as an active ingredient

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