CN111588708B - Application of mugwort ketone A in preparing hypoglycemic and hypolipidemic drugs - Google Patents
Application of mugwort ketone A in preparing hypoglycemic and hypolipidemic drugs Download PDFInfo
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- CN111588708B CN111588708B CN202010598487.3A CN202010598487A CN111588708B CN 111588708 B CN111588708 B CN 111588708B CN 202010598487 A CN202010598487 A CN 202010598487A CN 111588708 B CN111588708 B CN 111588708B
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- mugwort
- ketone
- deacetyl
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- 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
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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
- A61P3/06—Antihyperlipidemics
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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
Abstract
The invention discloses application of mugwort ketone A in preparation of a blood sugar and lipid reducing medicine. The blood sugar and the blood fat are two important indexes reflecting the health level of the human body, and have important reference significance in the aspects of disease treatment and health care. Therefore, maintaining the stability of blood sugar and blood lipid indexes becomes an important research direction for treating related diseases. The invention discovers that the mugwort ketone A has excellent alpha-glucosidase inhibitory activity and pancreatic lipase inhibitory activity, and therefore has the prospect of being developed into a blood sugar-reducing and blood fat-reducing medicine.
Description
Technical Field
The invention belongs to the field of medicines, relates to a new application of a known compound mugwort keton A, and particularly relates to an application of the mugwort keton A in preparation of a blood glucose and lipid reducing medicine.
Background
The blood sugar and the blood fat are two important indexes reflecting the health level of the human body, and have important reference significance in the aspects of disease treatment and health care. Therefore, maintaining the stability of blood sugar and blood lipid indexes becomes an important research direction for treating related diseases.
Mugwort ketonic A is a compound separated from mugwort, and has the following chemical structural formula:
at present, no report on the activity of mugwort ketone A in reducing blood sugar and blood fat is found.
Disclosure of Invention
The invention aims to provide application of mugwort ketone A in preparing a medicament for reducing blood sugar and fat.
The above purpose of the invention is realized by the following technical scheme:
application of mugwort ketone A in preparing hypoglycemic agent is provided.
Application of mugwort ketone A in preparing medicine for reducing blood lipid is provided.
A medicinal preparation with effects of lowering blood sugar and blood lipid comprises mugwort ketone A as active ingredient.
Furthermore, the pharmaceutical preparation also contains pharmaceutically acceptable auxiliary materials.
Further, the dosage form is a solid, liquid or semi-solid dosage form.
Has the advantages that:
the invention discovers that the mugwort ketone A has excellent alpha-glucosidase inhibitory activity and pancreatic lipase inhibitory activity, and therefore has the prospect of being developed into a blood sugar-reducing and blood fat-reducing medicine.
Drawings
FIG. 1 is IC of the inhibitory effect of compounds on pancreatic lipase50Values, half Inhibitory Concentration (IC) of mugwort ketone A, dehydro-deacetyloxy-matrixin, deacetyl-matrixin on pancreatic lipase50) Respectively is 0.78 plus or minus 0.01 mg/mL-1、1.04±0.02mg·mL-1And 0.84. + -. 0.02 mg. mL-1Positive drug orlistat IC50Is 0.57 +/-0.01 mg/mL-1The results suggest that mugwort ketone A, dehydro-deacetyl oxymatricin, and deacetyl matrimonen all exhibit better pancreatic lipase inhibitory activity;
FIG. 2 shows the IC50 values of the inhibitory effect of compounds on alpha-glucosidase, the half Inhibitory Concentrations (IC) of mugwort ketone A, dehydro-deacetyl-oxymatrine, deacetyl-matrixin on alpha-glucosidase50) Respectively is 1.14 +/-0.02 mg.mL-1、1.51±0.03mg·mL-1And 1.26. + -. 0.02 mg. mL-1Positive drug acarbose IC50Is 1.08 +/-0.02 mg.mL-1The results suggest that mugwort ketone A, dehydro-deacetyl oxymatricin, and deacetyl matricarin all exhibit better alpha-glucosidase inhibitory activity.
Detailed Description
The following detailed description of the present invention is provided in connection with the accompanying drawings and examples, but not intended to limit the scope of the invention.
First, experimental material
1. Reagent
Orlistat (CAS: 96829-58-2), 4-methylumbelliferone oleate (CAS: 18323-58-5), pancrelipase (CAS: 9001-62-1), acarbose (CAS: 56180-94-0), alpha-glucosidase (CAS: 9001-42-7), p-nitrobenzene-alpha-D-glucopyranoside (CAS: 3767-28-0) were purchased from Sigma-Aldrich; ultrapure water was prepared by Milli-Q system; other chemicals were analytically pure. The purity of the compounds of mugwort ketone A, dehydro-deacetyl-oxymatricin and deacetyl-matrixins is not less than 98%.
2. Instrument for measuring the position of a moving object
Victorivo plate reader (perkin elmer instruments ltd); XS205 DU model electronic analytical balance (Mettler-Torledo instruments, Inc.); high speed centrifuges (edn gmbh, germany); dry nitrogen blowing instruments (shanghai darlo scientific instruments ltd); KS-5200B ultrasonic cleaning machine (Kunshan Jielimei ultrasonic Instrument Co., Ltd.).
Second, Experimental methods
1. Pancreatic lipase inhibitory Activity
1.1 preparation of the solution
Pancreatic lipase solution: pancreatic lipase was dissolved in Tris-HCl buffer (13mM Tris-HCl, 150mM NaCl, 1.3mM CaCl)2(ii) a pH 8.0) to give a concentration of 1.0 mg. mL-1The pancrelipase solution (the enzyme solution is ready for use).
Substrate solution: precisely weighing appropriate amount of 4-methylumbelliferone oleate (4-MUO), dissolving in small amount of dimethyl sulfoxide (DMSO), and diluting with Tris-HCl buffer solution to obtain 0.1 mmol.L-1A substrate solution of 4-methylumbelliferone oleate (the amount of DMSO in the reaction system is not more than 1%).
Test solution: respectively and precisely weighing appropriate amount of mugwort ketone A, dehydro-deacetyl-oxymatricin and deacetyl-matrixin samples, dissolving in a small amount of dimethyl sulfoxide (DMSO), and diluting with Tris-HCl buffer solution to obtain test solution with series concentration (the amount of DMSO in the reaction system is not more than 1%).
1.2 measurement of pancreatic Lipase inhibitory Activity
Precisely sucking 25 μ L of test solution with different concentrations and 25 μ L of pancrelipase solution, and mixing in 96-well plate. Incubating at 37 deg.C for 10min, adding 50 μ L4-methylumbelliferone oleate to start reaction, and adding 100 μ L sodium citrate (0.1 moL. L) after 20min-1) The reaction was terminated. The amount of 4-methylumbelliferone was measured by fluorescence under the conditions of excitation wavelength of 355nm and emission wavelength of 460 nm. A sample determination group, a sample control group, an enzyme solution control group, a blank control group and a positive control group (orlistat) are respectively arranged, and each group of experiments are repeated for 3 times.
Calculating the inhibition rate of different samples on pancreatic lipase by the following method, setting 5 different concentrations of the mugwort ketone A, dehydro-deacetyl-oxy-matricin and deacetyl-matrixin samples respectively, and calculating the half Inhibition Concentration (IC) of the mugwort ketone A, dehydro-deacetyl-oxy-matrixin and deacetyl matrixin on the pancreatic lipase inhibition effect50)：
In the formula: a. thexiFor the sample assay set (25. mu.L enzyme solution + 25. mu.L sample);
Axas a sample control (25. mu.L buffer + 25. mu.L sample);
Aienzyme solution control (25. mu.L buffer + 25. mu.L enzyme solution);
A0blank control (50. mu.L buffer).
2. Alpha-glucosidase inhibitory activity
2.1 preparation of the solution
α -glucosidase solution: dissolving appropriate amount of alpha-glucosidase in phosphate buffer (pH 6.8) to obtain a solution with a concentration of 4 U.mL-1The alpha-glucosidase solution of (1).
Substrate solution: precisely weighing appropriate amount of P-nitrophenol-alpha-D-glucopyranoside (P)NPG) prepared with mixed phosphate solution to a concentration of 2.0 mmoL.L-1The p-nitrophenol-alpha-D-glucopyranoside substrate solution.
Test solution: respectively and precisely weighing appropriate amount of mugwort ketone A, dehydro-deacetyl-oxymatricin and deacetyl-matrixin samples, and diluting with phosphate buffer solution to obtain test solution with series concentration (the amount of DMSO in the reaction system is not more than 1%).
2.2 measurement of alpha-glucosidase inhibitory Activity
Precisely sucking 16 mu L of sample solution with different concentrations, 60 mu L of phosphate buffer solution and 24 mu L of p-nitrophenyl-alpha-D-glucopyranoside substrate solution, and uniformly mixing in a 96-well plate. Incubate at 37 deg.C for 10min, then add 52. mu.L of alpha-glucosidase solution (1U. mL)-1) The reaction was started. After 20min, 40. mu. LNa was added2CO3(0.2mol·L-1) To stop the reaction. The amount of p-nitrophenol was measured at a wavelength of 405 nm. A sample determination group, a sample control group, an enzyme solution control group, a blank control group and a positive control group (acarbose) are respectively arranged, and each group of experiments are repeated for 3 times.
The inhibition rate of the different samples on alpha-glucosidase was calculated as follows. Respectively setting 5 different concentrations of mugwort ketone A, dehydro-deacetoxymatricin, and deacetylmatricin, and calculating half Inhibitory Concentration (IC) of mugwort ketone A, dehydro-deacetoxymatricin, and deacetylmatricin on alpha-glucosidase inhibition50)：
In the formula: a. thexiFor the sample assay set (60. mu.L phosphate buffer + 16. mu.L sample + 52. mu.L enzyme solution);
Axas a sample control (112. mu.L phosphate buffer + 16. mu.L sample);
Aienzyme solution control (76. mu.L buffer + 52. mu.L enzyme solution);
A0blank control (128. mu.L buffer).
3. Statistical treatment
Samples of different concentrations of the mugwort leaf extract were assayed in parallel 3 times. The inhibition rates of various concentrations of mugwort extract were introduced into IBM SPSS25 software and the median inhibitory concentration (IC50) was calculated.
Third, experimental results
1. Pancreatic lipase inhibitory Activity
The inhibition of pancreatic lipase by mugwort ketone A, dehydro-deacetyl-oxy-matrixin, deacetyl-matrixin was determined by the established method, and as can be seen from Table 1 and FIG. 1, the half Inhibitory Concentrations (IC) of mugwort ketone A, dehydro-deacetyl-oxy-matrixin, deacetyl-matrixin to pancreatic lipase50) Respectively is 0.78 plus or minus 0.01 mg/mL-1、1.04±0.02mg·mL-1And 0.84. + -. 0.02 mg. mL-1Positive drug orlistat IC50Is 0.57 +/-0.01 mg/mL-1The results suggest that mugwort ketone A, dehydro-deacetyl oxymatricin, and deacetyl matrimonen all showed better pancreatic lipase inhibitory activity.
Inhibition of pancreatic lipase by the compounds of Table 1
2. Alpha-glucosidase inhibitory activity
The inhibition of alpha-glucosidase by mugwort ketone A, dehydro-deacetyl-oxymatrine, deacetyl-matrixin was determined by the established method, and as can be seen from Table 2 and FIG. 2, the half Inhibitory Concentration (IC) of mugwort ketone A, dehydro-deacetyl-oxymatrine, deacetyl-matrixin to alpha-glucosidase was determined50) Respectively is 1.14 +/-0.02 mg.mL-1、1.51±0.03mg·mL-1And 1.26. + -. 0.02 mg. mL-1Positive drug acarbose IC50Is 1.08 +/-0.02 mg.mL-1The results suggest that mugwort ketone A, dehydro-deacetyl oxymatricin, and deacetyl matricarin all exhibit better alpha-glucosidase inhibitory activity.
TABLE 2 inhibition of alpha-glucosidase by compounds
The experimental results show that the mugwort ketone A, the dehydro-deacetyl oxymatrine and the deacetyl matricarine have excellent alpha-glucosidase inhibitory activity and pancreatic lipase inhibitory activity, and therefore, the mugwort ketone A, the dehydro-deacetyl oxymatrine and the deacetyl matricarine have the prospect of being developed into the blood sugar and blood fat reducing medicines.
The above-described embodiments are intended to be illustrative of the nature of the invention, but those skilled in the art will recognize that the scope of the invention is not limited to the specific embodiments.
Claims (1)
1. The application of mugwort ketone A in preparing a medicament for reducing blood sugar or blood fat is disclosed, wherein the chemical structure of the mugwort ketone A is as follows:
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Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2000229869A (en) * | 1999-02-09 | 2000-08-22 | Nippon Synthetic Chem Ind Co Ltd:The | Alpha-glucosidase inhibitor |
| CN101933965A (en) * | 2010-09-19 | 2011-01-05 | 韩淑英 | Mugwort extract and preparation process thereof, and application in controlling postmeal gucose |
| CN107929350A (en) * | 2018-01-20 | 2018-04-20 | 张志青 | A kind of Chinese patent drug for treating type II diabetes and preparation method thereof |
| KR20190090362A (en) * | 2018-01-24 | 2019-08-01 | 경상대학교산학협력단 | A composition for imobesity containing dicaffeoylquinic acid |
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Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2000229869A (en) * | 1999-02-09 | 2000-08-22 | Nippon Synthetic Chem Ind Co Ltd:The | Alpha-glucosidase inhibitor |
| CN101933965A (en) * | 2010-09-19 | 2011-01-05 | 韩淑英 | Mugwort extract and preparation process thereof, and application in controlling postmeal gucose |
| CN107929350A (en) * | 2018-01-20 | 2018-04-20 | 张志青 | A kind of Chinese patent drug for treating type II diabetes and preparation method thereof |
| KR20190090362A (en) * | 2018-01-24 | 2019-08-01 | 경상대학교산학협력단 | A composition for imobesity containing dicaffeoylquinic acid |
Non-Patent Citations (1)
| Title |
|---|
| 野艾蒿中1个新的倍半萜;丁林芬等;《中草药》;20180531;第49卷(第9期);第1995-1999页 * |
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