CN113797190A - Application of diethyl n-butylmalonate in preparation of obesity prevention and treatment medicines - Google Patents
Application of diethyl n-butylmalonate in preparation of obesity prevention and treatment medicines Download PDFInfo
- Publication number
- CN113797190A CN113797190A CN202111119817.7A CN202111119817A CN113797190A CN 113797190 A CN113797190 A CN 113797190A CN 202111119817 A CN202111119817 A CN 202111119817A CN 113797190 A CN113797190 A CN 113797190A
- Authority
- CN
- China
- Prior art keywords
- diethyl
- butylmalonate
- preventing
- obesity
- treating
- 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.)
- Pending
Links
- RPNFNBGRHCUORR-UHFFFAOYSA-N diethyl 2-butylpropanedioate Chemical compound CCCCC(C(=O)OCC)C(=O)OCC RPNFNBGRHCUORR-UHFFFAOYSA-N 0.000 title claims abstract description 72
- 239000003814 drug Substances 0.000 title claims abstract description 70
- 208000008589 Obesity Diseases 0.000 title claims abstract description 66
- 235000020824 obesity Nutrition 0.000 title claims abstract description 66
- 238000002360 preparation method Methods 0.000 title claims abstract description 13
- 229940079593 drug Drugs 0.000 title claims description 19
- 230000002265 prevention Effects 0.000 title claims description 7
- 238000011282 treatment Methods 0.000 title claims description 6
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 claims abstract description 19
- 239000008103 glucose Substances 0.000 claims abstract description 19
- 230000003647 oxidation Effects 0.000 claims abstract description 14
- 238000007254 oxidation reaction Methods 0.000 claims abstract description 14
- 206010022489 Insulin Resistance Diseases 0.000 claims abstract description 13
- 208000001072 type 2 diabetes mellitus Diseases 0.000 claims abstract description 13
- 235000014113 dietary fatty acids Nutrition 0.000 claims abstract description 12
- 229930195729 fatty acid Natural products 0.000 claims abstract description 12
- 239000000194 fatty acid Substances 0.000 claims abstract description 12
- 150000004665 fatty acids Chemical class 0.000 claims abstract description 12
- 210000005228 liver tissue Anatomy 0.000 claims abstract description 11
- 238000005265 energy consumption Methods 0.000 claims abstract description 8
- 239000004480 active ingredient Substances 0.000 claims description 7
- 239000000969 carrier Substances 0.000 claims description 7
- 230000001965 increasing effect Effects 0.000 claims description 7
- 239000000463 material Substances 0.000 claims description 7
- 230000006372 lipid accumulation Effects 0.000 claims description 5
- 230000002708 enhancing effect Effects 0.000 claims description 3
- 230000000694 effects Effects 0.000 abstract description 18
- 210000004185 liver Anatomy 0.000 abstract description 10
- 208000030159 metabolic disease Diseases 0.000 abstract description 8
- 238000013116 obese mouse model Methods 0.000 abstract description 8
- 150000002632 lipids Chemical class 0.000 abstract description 7
- 238000009825 accumulation Methods 0.000 abstract description 4
- 241000699670 Mus sp. Species 0.000 description 34
- 241000699666 Mus <mouse, genus> Species 0.000 description 21
- 238000000034 method Methods 0.000 description 13
- 210000004369 blood Anatomy 0.000 description 12
- 239000008280 blood Substances 0.000 description 12
- 239000007924 injection Substances 0.000 description 12
- 238000002347 injection Methods 0.000 description 12
- 230000037396 body weight Effects 0.000 description 11
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 10
- 238000002474 experimental method Methods 0.000 description 8
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 6
- 102000004877 Insulin Human genes 0.000 description 5
- 108090001061 Insulin Proteins 0.000 description 5
- 241001465754 Metazoa Species 0.000 description 5
- 230000003579 anti-obesity Effects 0.000 description 5
- 235000019577 caloric intake Nutrition 0.000 description 5
- 229940125396 insulin Drugs 0.000 description 5
- 239000007928 intraperitoneal injection Substances 0.000 description 5
- 238000004519 manufacturing process Methods 0.000 description 5
- 210000000683 abdominal cavity Anatomy 0.000 description 4
- 229910002092 carbon dioxide Inorganic materials 0.000 description 4
- 230000008021 deposition Effects 0.000 description 4
- 235000009200 high fat diet Nutrition 0.000 description 4
- 230000002829 reductive effect Effects 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- 102000004190 Enzymes Human genes 0.000 description 3
- 108090000790 Enzymes Proteins 0.000 description 3
- NPGIHFRTRXVWOY-UHFFFAOYSA-N Oil red O Chemical compound Cc1ccc(C)c(c1)N=Nc1cc(C)c(cc1C)N=Nc1c(O)ccc2ccccc12 NPGIHFRTRXVWOY-UHFFFAOYSA-N 0.000 description 3
- 102000019259 Succinate Dehydrogenase Human genes 0.000 description 3
- 108010012901 Succinate Dehydrogenase Proteins 0.000 description 3
- 230000002159 abnormal effect Effects 0.000 description 3
- 230000035508 accumulation Effects 0.000 description 3
- 239000001569 carbon dioxide Substances 0.000 description 3
- 210000002966 serum Anatomy 0.000 description 3
- 230000009885 systemic effect Effects 0.000 description 3
- 208000002705 Glucose Intolerance Diseases 0.000 description 2
- 206010018429 Glucose tolerance impaired Diseases 0.000 description 2
- 229930040373 Paraformaldehyde Natural products 0.000 description 2
- 210000003486 adipose tissue brown Anatomy 0.000 description 2
- 230000007547 defect Effects 0.000 description 2
- 230000007850 degeneration Effects 0.000 description 2
- 230000037149 energy metabolism Effects 0.000 description 2
- 230000036541 health Effects 0.000 description 2
- 230000006872 improvement Effects 0.000 description 2
- 239000003112 inhibitor Substances 0.000 description 2
- 230000002147 killing effect Effects 0.000 description 2
- 210000002540 macrophage Anatomy 0.000 description 2
- 229920002866 paraformaldehyde Polymers 0.000 description 2
- 230000001737 promoting effect Effects 0.000 description 2
- 238000010186 staining Methods 0.000 description 2
- 238000005303 weighing Methods 0.000 description 2
- 241000237519 Bivalvia Species 0.000 description 1
- 238000011746 C57BL/6J (JAX™ mouse strain) Methods 0.000 description 1
- 208000024172 Cardiovascular disease Diseases 0.000 description 1
- 238000002965 ELISA Methods 0.000 description 1
- 208000004930 Fatty Liver Diseases 0.000 description 1
- 206010019708 Hepatic steatosis Diseases 0.000 description 1
- 208000031226 Hyperlipidaemia Diseases 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 208000001145 Metabolic Syndrome Diseases 0.000 description 1
- 208000018737 Parkinson disease Diseases 0.000 description 1
- 201000000690 abdominal obesity-metabolic syndrome Diseases 0.000 description 1
- 230000003044 adaptive effect Effects 0.000 description 1
- 238000000540 analysis of variance Methods 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 238000010241 blood sampling Methods 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 235000020639 clam Nutrition 0.000 description 1
- 208000010877 cognitive disease Diseases 0.000 description 1
- 230000002860 competitive effect Effects 0.000 description 1
- 230000001186 cumulative effect Effects 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- WYACBZDAHNBPPB-UHFFFAOYSA-N diethyl oxalate Chemical compound CCOC(=O)C(=O)OCC WYACBZDAHNBPPB-UHFFFAOYSA-N 0.000 description 1
- 208000016097 disease of metabolism Diseases 0.000 description 1
- 238000002224 dissection Methods 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 239000003596 drug target Substances 0.000 description 1
- 239000002158 endotoxin Substances 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 208000010706 fatty liver disease Diseases 0.000 description 1
- 238000007446 glucose tolerance test Methods 0.000 description 1
- 230000005802 health problem Effects 0.000 description 1
- 238000007489 histopathology method Methods 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 230000028709 inflammatory response Effects 0.000 description 1
- 238000007689 inspection Methods 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 229920006008 lipopolysaccharide Polymers 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 230000002438 mitochondrial effect Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 230000004770 neurodegeneration Effects 0.000 description 1
- 208000015122 neurodegenerative disease Diseases 0.000 description 1
- 238000001543 one-way ANOVA Methods 0.000 description 1
- 238000007410 oral glucose tolerance test Methods 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 230000036284 oxygen consumption Effects 0.000 description 1
- 238000010827 pathological analysis Methods 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 230000003285 pharmacodynamic effect Effects 0.000 description 1
- 238000004321 preservation Methods 0.000 description 1
- 230000003449 preventive effect Effects 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000000241 respiratory effect Effects 0.000 description 1
- 238000007619 statistical method Methods 0.000 description 1
- 231100000240 steatosis hepatitis Toxicity 0.000 description 1
- 210000004003 subcutaneous fat Anatomy 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 230000035924 thermogenesis Effects 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 238000011269 treatment regimen Methods 0.000 description 1
- 230000004102 tricarboxylic acid cycle Effects 0.000 description 1
- 230000003827 upregulation Effects 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 230000004584 weight gain Effects 0.000 description 1
- 235000019786 weight gain Nutrition 0.000 description 1
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
- A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
- A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
- A61K31/22—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin
- A61K31/225—Polycarboxylic acids
-
- 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
- A61P3/04—Anorexiants; Antiobesity agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/48—Drugs for disorders of the endocrine system of the pancreatic hormones
- A61P5/50—Drugs for disorders of the endocrine system of the pancreatic hormones for increasing or potentiating the activity of insulin
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)
- Organic Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Engineering & Computer Science (AREA)
- Obesity (AREA)
- Hematology (AREA)
- Emergency Medicine (AREA)
- Endocrinology (AREA)
- Child & Adolescent Psychology (AREA)
- Epidemiology (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention provides application of diethyl n-butylmalonate in preparation of a medicament for preventing and treating obesity, and belongs to the technical field of biomedicine. The diethyl n-butylmalonate can reduce the weight and the liver weight of the obese mouse, prevent the accumulation of liver tissue lipid, enhance the oxidation of fatty acid in the organism of the obese mouse and increase the energy consumption, thereby exerting the weight-losing effect; and can improve glucose tolerance and insulin resistance, and has effect in correcting obesity-related metabolic disorder.
Description
Technical Field
The invention belongs to the technical field of biomedicine, and particularly relates to application of diethyl n-butylmalonate in preparation of a medicament for preventing and treating obesity.
Background
Obesity is an epidemic, systemic metabolic disease that seriously harms human health. Obesity is a metabolic syndrome in which energy metabolism is abnormal, fat accumulation in a body is excessive, and distribution is abnormal due to various factors such as heredity, lifestyle, and immune state. It is closely related to insulin resistance, diabetes, hyperlipidemia, hypertension, fatty liver, cardiovascular diseases and cognitive disorder. Most of the prior weight-reducing methods have the defects of large side effect, high recurrence rate and the like, and particularly, a large number of weight-reducing medicines are released from the market due to the safety problem. In view of the worldwide increasing incidence of obesity and metabolic diseases caused by obesity, a safe and effective novel prevention and treatment strategy is sought, and the method has important significance for reducing the incidence of obesity, intervening in obesity-related health problems and guaranteeing the life health of people.
Succinate dehydrogenase is a metabolic enzyme in the cellular mitochondrial tricarboxylic acid cycle. The research finds that the expression up-regulation or activity increase of the enzyme can promote the progress of the Parkinson disease, so the enzyme is regarded as a potential drug target for intervening neurodegenerative diseases. Recent studies have also shown that succinate dehydrogenase is also involved in the regulation of macrophage-induced inflammatory responses.
Diethyl n-butylmalonate is a known competitive inhibitor of succinate dehydrogenase. Recent evidence at in vitro levels suggests that the inhibitors may down-regulate lipopolysaccharide-induced macrophage inflammation and thus have anti-inflammatory effects. However, whether the traditional Chinese medicine can prevent and treat obesity has not been reported.
Disclosure of Invention
In order to overcome the defects of the prior art, the invention aims to provide the application of diethyl n-butylmalonate in preparing the medicament for preventing and treating obesity, which can prevent and treat obesity.
The invention is realized by the following technical scheme: application of diethyl n-butylmalonate in preparing medicine for preventing and treating obesity is provided.
The preferable scheme of the application of the diethyl n-butylmalonate in preparing the medicament for preventing and treating the obesity comprises the following steps: the obesity preventing and treating medicine comprises a weight-losing medicine.
The preferable scheme of the application of the diethyl n-butylmalonate in preparing the medicament for preventing and treating the obesity comprises the following steps: the medicine for preventing and treating obesity comprises a medicine for preventing and treating liver tissue lipid accumulation.
The preferable scheme of the application of the diethyl n-butylmalonate in preparing the medicament for preventing and treating the obesity comprises the following steps: the obesity preventing and treating medicine comprises a medicine for improving glucose tolerance.
The preferable scheme of the application of the diethyl n-butylmalonate in preparing the medicament for preventing and treating the obesity comprises the following steps: the obesity preventing and treating medicine comprises a medicine for improving insulin resistance.
The preferable scheme of the application of the diethyl n-butylmalonate in preparing the medicament for preventing and treating the obesity comprises the following steps: the medicine for preventing and treating obesity comprises medicines for enhancing body fatty acid oxidation and increasing energy consumption.
The preferable scheme of the application of the diethyl n-butylmalonate in preparing the medicament for preventing and treating the obesity comprises the following steps: the medicament for preventing and treating obesity takes diethyl n-butylmalonate as an active ingredient and is supplemented with pharmaceutically acceptable auxiliary materials or carriers.
The invention has the beneficial technical effects that: the invention provides application of diethyl n-butylmalonate in preparation of a medicament for preventing and treating obesity. In addition, diethyl n-butylmalonate can improve glucose tolerance and insulin resistance, and has the effect of correcting obesity-related metabolic disorders.
The results of the embodiments of the present invention show that: diethyl n-butylmalonate can prevent lipid accumulation in liver tissue, increase fatty acid oxidation and energy consumption of organism, prevent and treat obesity, improve glucose tolerance and insulin resistance, and improve obesity-related metabolic disorder.
Drawings
FIG. 1 shows the effect of diethylbutylmalonate on the body weight and cumulative body weight (curve) of mice;
FIG. 2 is a graph showing the effect of diethylbutylmalonate on body weight of mice at the time of killing;
FIG. 3 is a graph showing the effect of diethylbutylmalonate on mouse liver weight;
FIG. 4 is a photograph of pathological sections (x400) showing the effect of diethylbutylmalonate on mouse liver histomorphology;
FIG. 5 is a graph of the effect of diethylbutylmalonate on mouse oral glucose tolerance;
FIG. 6 shows the effect of diethylbutylmalonate on fasting insulin levels and HOMA-IR index in mice;
FIG. 7 is a graph of the effect of diethyl n-butylmalonate on mouse energy expenditure;
FIG. 8 is a graph of the effect of diethyl n-butylmalonate on mouse fatty acid oxidation;
FIG. 9 is a graph of the effect of diethyl n-butylmalonate on energy intake in mice.
Detailed Description
The invention is further illustrated by the following examples and figures.
The invention provides application of diethyl n-butylmalonate in preparing a medicament for preventing and treating obesity.
In the invention, the diethyl n-butylmalonate can reduce the weight of the mouse and the weight of the liver, reduce the accumulation of liver tissues, promote the oxidation of fatty acid and the energy consumption of the mouse, and further can prevent and treat obesity. In the invention, the diethyl n-butylmalonate can prevent the accumulation of liver tissue lipid, can improve glucose tolerance and insulin resistance, and has the effect of correcting obesity-related metabolic disorders.
The diethyl n-butylmalonate is prepared into the anti-obesity drug, wherein the diethyl n-butylmalonate in the anti-obesity drug is administrated according to 25 mg/kg of body weight, the administration method is preferably intraperitoneal injection, and the number of injections per week is preferably 2; the time of injection is not particularly limited.
In the invention, the medicament for preventing and treating obesity takes diethyl n-butylmalonate as an active ingredient, and can be supplemented with pharmaceutically acceptable auxiliary materials or carriers.
In the present invention, the obesity prevention and treatment drug further includes a drug for preventing lipid accumulation in liver tissue. In the invention, the diethylbutylmalonate in the anti-obesity drug is administered at 25 mg/kg body weight; the administration method of the medicine for preventing and treating obesity is preferably intraperitoneal injection, and the frequency of injection in each week is preferably 2 times; the time of injection is not particularly limited. In the invention, the medicament for preventing and treating obesity takes diethyl butylmalonate as an active ingredient, and can be supplemented with pharmaceutically acceptable auxiliary materials or carriers.
In the present invention, the obesity preventive drug further includes a drug for improving glucose tolerance. In the invention, the diethylbutylmalonate in the anti-obesity drug is administered at 25 mg/kg body weight; the administration method of the medicine for preventing and treating obesity is preferably intraperitoneal injection, and the number of injections per week is preferably 2. The present invention is not particularly limited with respect to the time of injection. In the invention, the medicament for preventing and treating obesity takes diethyl butylmalonate as an active ingredient, and can be supplemented with pharmaceutically acceptable auxiliary materials or carriers.
In the present invention, the obesity prevention and treatment drugs further include drugs that improve insulin resistance. In the invention, the diethylbutylmalonate in the anti-obesity drug is administered at 25 mg/kg body weight; the administration method of the medicine for preventing and treating obesity is preferably intraperitoneal injection, and the number of injections per week is preferably 2. The present invention is not particularly limited with respect to the time of injection. In the invention, the medicament for preventing and treating obesity takes diethyl butylmalonate as an active ingredient, and can be supplemented with pharmaceutically acceptable auxiliary materials or carriers.
In the present invention, the obesity prevention and treatment drugs further include drugs that enhance fatty acid oxidation and energy expenditure. In the present invention, the drug is administered with 25 mg/kg body weight of diethyl n-butylmalonate; the administration method of the medicine for preventing and treating obesity is preferably intraperitoneal injection, and the number of injections per week is preferably 2. The present invention is not particularly limited with respect to the time of injection. In the invention, the medicament for preventing and treating obesity takes diethyl butylmalonate as an active ingredient, and can be supplemented with pharmaceutically acceptable auxiliary materials or carriers.
The application of diethyl n-butylmalonate in the preparation of the medicament for preventing and treating obesity provided by the invention is described in detail by the following examples, but the application of diethyl n-butylmalonate in the preparation of the medicament for preventing and treating obesity is not to be construed as limiting the scope of the invention. Any modification, equivalent replacement, or improvement made within the spirit and principle of the present invention should be included in the protection scope of the present invention.
Pharmacodynamic study on improvement of obesity and related metabolic diseases by diethyl n-butylmalonate
First, experiment method
1. Design of animal experiments
The 7-week-old C57BL/6J mice were purchased from Beijing Wittingle laboratory animal technology, Inc., and were housed in the laboratory animal center of Xuzhou medical university under 12 h light-dark alternation at a temperature of 23 + -3 deg.C and a relative humidity of 50%. After 1 week of adaptive feeding, mice were randomized into 4 groups (n-10) designed to be:
LC group: conventional feed feeding, i.e. 100. mu.l of sterile PBS solution per mouse is injected into abdominal cavity 2 times per week;
LC + DM group: feeding with conventional feed, injecting 100 μ l PBS solution containing diethyl n-butylmalonate (DM, Cat. STBB9585V, Sigma-Aldrich) into abdominal cavity of each mouse, and administering 25 mg/kg per mouse 2 times per week;
HF group: feeding with high fat feed, injecting 100 μ l sterile PBS solution into abdominal cavity of mouse, and 2 times per week;
HF + DM group: each mouse was injected intraperitoneally with 100. mu.l of sterile PBS containing DM 2 times per week, 25 mg/kg per mouse.
Weigh once every 7 days, mice were free to eat and drink water during the experiment; the method comprises the following steps of fasting a mouse for 12 hours before the experiment is finished, weighing the weight, conducting cervical dislocation and sacrifice on the mouse after blood is taken from an orbit, rapidly picking out liver, brown fat, subcutaneous fat and brown fat, taking a small part of fat and liver tissues to perform fixed preservation in 4% paraformaldehyde, placing the rest tissues in a refrigerator at minus 80 ℃, centrifuging a blood sample at 8000 rpm for 5 min, and taking serum to preserve.
2. Small animal energy metabolism monitoring
At week 13 of the experiment, the respiratory quotient, heat production, oxygen consumption, carbon dioxide (CO) were monitored over 24 h using a small animal energy metabolizer (Oxymax CLAMS system)2) Amount of produced, oxygen (O)2) The amount produced. The following indices are calculated according to the formula:
carbohydrate oxidation level = [ (4.585 CO =)2Production amount) - (3.226 x O2Production amount)]*4；
Fat oxidation level = [ (1.695 x O)2Production amount) - (1.701 × CO2Production amount)]*9。
3. Oral Glucose Tolerance Test (OGTT)
At week 11 of the experiment, a glucose tolerance test was performed. Before detection, mice are fasted for 16 h, and glucose is injected into the abdominal cavity, wherein the injection amount is 2g/kg body weight. Whole blood was obtained by a rat tail blood sampling method, and blood glucose concentrations (mmol/L) were measured with a blood glucose meter at 0, 15 min, 30 min, 45 min, 1 h and 2 h after injection, respectively.
4. HOMA-IR assay
At week 12 of the experiment, steady-state model insulin resistance index (HOMA-IR) measurements were performed. After fasting for 6 hours, whole blood was collected by a rat tail blood collection method, and fasting blood glucose (mmol/L) and fasting insulin (mU/L) were measured by an ELISA method. HOMA-IR = blood glucose concentration (mmol/L) x insulin concentration (mU/L)/22.5 was calculated.
5. Pathological analysis
Oil red O staining analysis: liver tissues of each group of animals were taken, fixed with 4% paraformaldehyde, paraffin-embedded, sectioned, dehydrated, fixed, stained with oil red O, and histopathological analysis was performed under a microscope.
6. Statistical analysis
Experimental data were analyzed for variance and significance using SPSS 22.0 statistical software. Normally distributed metrology data is expressed as mean ± standard deviation. Through the test of normality and homogeneity of variance, the difference comparison among a plurality of groups of metering data with normality and homogeneity of variance adopts one-way analysis of variance (ANOVA), and the two-by-two comparison among each group is tested by a Turkey's method. Inspection level α = 0.05.
Second, experimental results
1. Diethyl n-butylmalonate can reduce the weight of a mouse and increase the accumulated weight
As can be seen from fig. 1, the experimental mice did not develop abnormal clinical symptoms during the course of the 16-week experiment, and after the induction of high fat diet for 15 weeks, the high fat group (HF) mice developed significant obesity compared to the normal control group (LC); the weight and the accumulated weight gain of obese mice (HF + DM) affected by diethyl n-butylmalonate were significantly lower than those of the HF group, and diethyl n-butylmalonate had no significant effect on the weight and the accumulated weight proliferation of normal mice (FIG. 1). Experimental results show that the diethyl n-butylmalonate can effectively slow down the weight increase of mice caused by high-fat diet.
2. The diethyl n-butylmalonate can reduce the weight of mice and the weight of livers
Mice were killed by dissection at week 16. Weighing before killing revealed that diethyl n-butylmalonate significantly reduced the body weight of obese mice (fig. 2). When the livers were taken and weighed, the weight of the livers was significantly increased in the HF group mice compared to the LC group, while the weight of the livers was significantly decreased after the intervention of diethylbutylmalonate (fig. 3).
3. Diethyl n-butylmalonate can reduce lipid deposition in liver tissue of mice
As shown in fig. 4, oil red O staining revealed significant vacuolar degeneration of liver and increased lipid deposition in HF group mice relative to LC mice; diethyl oxalate intervenes in the reduction of vacuolar degeneration and lipid deposition in obese mice.
4. Diethyl n-butylmalonate can improve oral glucose tolerance of mice
As shown in fig. 5, fasting blood glucose levels were significantly higher in the HF group mice than in the LC and HF + DM groups. After the mice are perfused with the glucose solution (2 g/kg), the blood glucose level of each group of mice reaches the highest after 30 min and then tends to decline, and the blood glucose level of the HF group is still obviously higher than that of the LC and HF + DM group by 120 min. Experimental data show that the HF mice have obvious glucose intolerance compared with the LC mice, and the diethyl n-butylmalonate can improve the glucose intolerance of the fat mice induced by high fat diet.
5. Diethyl n-butylmalonate can improve insulin resistance of mice
As shown in fig. 6, the insulin levels in the fasting serum of HF mice were significantly higher than in the LC group; fasting serum insulin levels were significantly reduced in HF + DM mice compared to HF. Calculating a steady-state model insulin resistance index (HOMA-IR), and finding that the HOMA-IR index of the HF mouse is obviously higher than that of the LC group; compared with the HF group, the HOMA-IR index of the mice in the HF + DM group is obviously reduced. The results show that diethyl n-butylmalonate can improve high-fat diet-induced insulin resistance.
6. Diethyl n-butylmalonate can promote mouse systemic fatty acid oxidation capacity
Figure 7 shows that HF mice have significantly reduced systemic fatty acid oxidation compared to the LC group; compared with the HF group, the oxidation capability of the fatty acid of the HF + DM group mice is obviously improved. This result suggests that diethyl n-butylmalonate can reduce lipid deposition in obese mice by enhancing fatty acid oxidation, promoting lipid breakdown or consumption.
7. Diethyl n-butylmalonate can increase energy consumption of mouse body
Figure 8 shows that HF mice consumed significantly less energy than the LC group; whereas the HF + DM group mice had a significant increase in energy expenditure compared to the HF group. The results show that the diethyl n-butylmalonate can reduce the body weight of the obese mouse by promoting thermogenesis, increasing energy consumption and consuming redundant energy of the body.
8. Diethyl n-butylmalonate did not affect energy intake in mice
Figure 9 shows that the average energy intake per HF mouse per day is significantly increased compared to the LC group; but energy intake was not significantly changed in the HF + DM group mice relative to the HF group. The results show that diethyl n-butylmalonate does not affect energy intake in obese mice.
In conclusion, the above embodiments show that diethyl n-butylmalonate can prevent lipid accumulation in liver tissues, increase fatty acid oxidation and energy consumption of mouse bodies, and further prevent and treat obesity; and can improve glucose tolerance and insulin resistance, and has effect in correcting obesity-related metabolic disorder.
The above disclosure is only for the specific embodiment of the present invention, but the embodiment of the present invention is not limited thereto, and any variations that can be made by those skilled in the art should fall within the scope of the present invention.
Claims (7)
1. Application of diethyl n-butylmalonate in preparing medicine for preventing and treating obesity is provided.
2. The use of diethyl n-butylmalonate in the preparation of a medicament for preventing and treating obesity according to claim 1, wherein: the obesity preventing and treating medicine comprises a weight-losing medicine.
3. The use of diethyl n-butylmalonate in the preparation of a medicament for preventing and treating obesity according to claim 1, wherein: the medicine for preventing and treating obesity comprises a medicine for preventing and treating liver tissue lipid accumulation.
4. The use of diethyl n-butylmalonate in the preparation of a medicament for preventing and treating obesity according to claim 1, wherein: the obesity preventing and treating medicine comprises a medicine for improving glucose tolerance.
5. The use of diethyl n-butylmalonate in the preparation of a medicament for preventing and treating obesity according to claim 1, wherein: the obesity preventing and treating medicine comprises a medicine for improving insulin resistance.
6. The use of diethyl n-butylmalonate in the preparation of a medicament for preventing and treating obesity according to claim 1, wherein: the medicine for preventing and treating obesity comprises medicines for enhancing body fatty acid oxidation and increasing energy consumption.
7. Use of diethyl n-butylmalonate according to claims 1-6 in the preparation of a medicament for the prevention and treatment of obesity, characterized in that: the medicament for preventing and treating obesity takes diethyl n-butylmalonate as an active ingredient and is supplemented with pharmaceutically acceptable auxiliary materials or carriers.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202111119817.7A CN113797190A (en) | 2021-09-24 | 2021-09-24 | Application of diethyl n-butylmalonate in preparation of obesity prevention and treatment medicines |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202111119817.7A CN113797190A (en) | 2021-09-24 | 2021-09-24 | Application of diethyl n-butylmalonate in preparation of obesity prevention and treatment medicines |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN113797190A true CN113797190A (en) | 2021-12-17 |
Family
ID=78940048
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202111119817.7A Pending CN113797190A (en) | 2021-09-24 | 2021-09-24 | Application of diethyl n-butylmalonate in preparation of obesity prevention and treatment medicines |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN113797190A (en) |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6528525B1 (en) * | 1997-10-02 | 2003-03-04 | Sankyo Company, Limited | Amidocarboxylic acid derivatives |
| US20070155704A1 (en) * | 2003-12-24 | 2007-07-05 | Esperion Therapeutics, Inc. | Ketone compounds and compositions for cholesterol management and related uses |
| US20200375929A1 (en) * | 2017-08-14 | 2020-12-03 | Washington University | Methods and compositions for the treatment of diseases associated with cancer, inflammation, or immune response |
-
2021
- 2021-09-24 CN CN202111119817.7A patent/CN113797190A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6528525B1 (en) * | 1997-10-02 | 2003-03-04 | Sankyo Company, Limited | Amidocarboxylic acid derivatives |
| US20070155704A1 (en) * | 2003-12-24 | 2007-07-05 | Esperion Therapeutics, Inc. | Ketone compounds and compositions for cholesterol management and related uses |
| US20200375929A1 (en) * | 2017-08-14 | 2020-12-03 | Washington University | Methods and compositions for the treatment of diseases associated with cancer, inflammation, or immune response |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| EP2409696A1 (en) | Agent for promoting energy consumption | |
| Shi et al. | The effects of supplementation with blueberry, cyanidin-3-O-β-glucoside, yoghurt and its peptides on obesity and related comorbidities in a diet-induced obese mouse model | |
| CN111568945A (en) | Compound cyclocarya paliurus preparation | |
| US20240082213A1 (en) | Composition for Preventing or Treating Obesity or Lipid-Related Metabolic Disorders | |
| US20170320825A1 (en) | Novel pentadienoyl piperidine derivative and use thereof | |
| EP3260121A1 (en) | Composition for preventing, alleviating or treating metabolic diseases, containing amodiaquine as active ingredient | |
| CN113797190A (en) | Application of diethyl n-butylmalonate in preparation of obesity prevention and treatment medicines | |
| WO2015184990A1 (en) | Use of rutin in treatment of obesity and related diseases or delaying senescence | |
| EP3718552A1 (en) | Combination drug suitable for treatment and prevention of non-alcoholic fatty liver disease (naflad) and/or non-alcoholic steatohepatitis (nash), and/or hepatic steatosis | |
| CN114053254A (en) | Combined medicine for treating diabetes and/or hyperlipidemia | |
| CN108771682A (en) | Betulinic acid promotes the application of fatty acid oxidation | |
| CN115998726B (en) | Application of coltsfoot ketone in preparing medicament for preventing and treating liver steatosis or fatty liver | |
| CN115944640B (en) | Application of stemonine in preparing medicine for treating non-alcoholic fatty liver | |
| EP3574912A1 (en) | Composition for treating diabetic disease | |
| EP4082553A1 (en) | Composition for inducing browning, containing milk exosomes | |
| US20240115530A1 (en) | Administration of baiba to increase benefit of losing weight of intermittent fasting | |
| KR102246627B1 (en) | A composition comprising hmba for preventing and treating obesity | |
| KR20140082081A (en) | Pharmaceutial composition comprising silkworm extract for regulation of blood glucose, herbal medicine and health food | |
| CN107929304A (en) | Application of the gentiamarin in non-alcohol fatty liver treatment | |
| CN115998726A (en) | Application of coltsfoot ketone in preparing medicament for preventing and treating liver steatosis or fatty liver | |
| US11058718B2 (en) | Method for treating non-alcoholic steatohepatitis (NASH) with the combination of polaprezinc and sodium selenite | |
| US20220079975A1 (en) | Method for mitigation of non-alcoholic fatty liver disease by use of a composition comprising small-molecule fucoidan and fucoxanthin | |
| TWI698244B (en) | Use of a combination of small-molecule fucoidan and fucoxanthin for preparing a composition for improving non-alcoholic fatty liver | |
| CN116077506A (en) | Application of echinocystic acid in preparation of medicine and food for preventing and treating type II diabetes or nonalcoholic fatty liver disease | |
| ÇAKIR | The Effect of Royal Jelly on Irisin in Experimentally Diabetic Rats |
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 | ||
| RJ01 | Rejection of invention patent application after publication | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20211217 |