CN116983305A - Application of granisetron in preparation of medicine for preventing and treating metabolic syndrome - Google Patents
Application of granisetron in preparation of medicine for preventing and treating metabolic syndrome Download PDFInfo
- Publication number
- CN116983305A CN116983305A CN202311234538.4A CN202311234538A CN116983305A CN 116983305 A CN116983305 A CN 116983305A CN 202311234538 A CN202311234538 A CN 202311234538A CN 116983305 A CN116983305 A CN 116983305A
- Authority
- CN
- China
- Prior art keywords
- metabolic syndrome
- granisetron
- mice
- vitamin
- preventing
- 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
- MFWNKCLOYSRHCJ-BTTYYORXSA-N granisetron Chemical compound C1=CC=C2C(C(=O)N[C@H]3C[C@H]4CCC[C@@H](C3)N4C)=NN(C)C2=C1 MFWNKCLOYSRHCJ-BTTYYORXSA-N 0.000 title claims abstract description 58
- 208000001145 Metabolic Syndrome Diseases 0.000 title claims abstract description 56
- 201000000690 abdominal obesity-metabolic syndrome Diseases 0.000 title claims abstract description 56
- 229960003727 granisetron Drugs 0.000 title claims abstract description 56
- 239000003814 drug Substances 0.000 title claims abstract description 32
- 238000002360 preparation method Methods 0.000 title abstract description 8
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 claims abstract description 49
- 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 claims abstract description 34
- ZZZCUOFIHGPKAK-UHFFFAOYSA-N D-erythro-ascorbic acid Natural products OCC1OC(=O)C(O)=C1O ZZZCUOFIHGPKAK-UHFFFAOYSA-N 0.000 claims abstract description 24
- 229930003268 Vitamin C Natural products 0.000 claims abstract description 24
- 235000019154 vitamin C Nutrition 0.000 claims abstract description 24
- 239000011718 vitamin C Substances 0.000 claims abstract description 24
- 208000001072 type 2 diabetes mellitus Diseases 0.000 claims abstract description 21
- 206010022489 Insulin Resistance Diseases 0.000 claims abstract description 19
- 102000004877 Insulin Human genes 0.000 claims abstract description 17
- 108090001061 Insulin Proteins 0.000 claims abstract description 17
- 229940125396 insulin Drugs 0.000 claims abstract description 17
- 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 description 23
- 239000008103 glucose Substances 0.000 claims description 21
- 239000003963 antioxidant agent Substances 0.000 claims description 10
- 230000003078 antioxidant effect Effects 0.000 claims description 10
- 230000003247 decreasing effect Effects 0.000 claims description 10
- 235000006708 antioxidants Nutrition 0.000 claims description 9
- 230000037396 body weight Effects 0.000 claims description 5
- 208000024891 symptom Diseases 0.000 claims description 3
- 208000020060 Increased inflammatory response Diseases 0.000 claims description 2
- 206010012601 diabetes mellitus Diseases 0.000 claims description 2
- 241000699670 Mus sp. Species 0.000 abstract description 40
- 229940079593 drug Drugs 0.000 abstract description 11
- 230000000694 effects Effects 0.000 abstract description 11
- 230000028709 inflammatory response Effects 0.000 abstract description 5
- 241000699666 Mus <mouse, genus> Species 0.000 abstract description 4
- 230000002265 prevention Effects 0.000 abstract description 4
- 230000036542 oxidative stress Effects 0.000 abstract description 3
- 210000004369 blood Anatomy 0.000 description 14
- 239000008280 blood Substances 0.000 description 14
- 239000000203 mixture Chemical group 0.000 description 13
- 210000002966 serum Anatomy 0.000 description 12
- 238000012360 testing method Methods 0.000 description 10
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 7
- 239000003651 drinking water Substances 0.000 description 6
- 235000020188 drinking water Nutrition 0.000 description 6
- 241000124008 Mammalia Species 0.000 description 5
- 239000012153 distilled water Substances 0.000 description 5
- 239000000243 solution Substances 0.000 description 5
- 102000016938 Catalase Human genes 0.000 description 4
- 108010053835 Catalase Proteins 0.000 description 4
- WSMYVTOQOOLQHP-UHFFFAOYSA-N Malondialdehyde Chemical compound O=CCC=O WSMYVTOQOOLQHP-UHFFFAOYSA-N 0.000 description 4
- 102000019197 Superoxide Dismutase Human genes 0.000 description 4
- 108010012715 Superoxide dismutase Proteins 0.000 description 4
- 229940118019 malondialdehyde Drugs 0.000 description 4
- 210000002784 stomach Anatomy 0.000 description 4
- 102000003814 Interleukin-10 Human genes 0.000 description 3
- 108090000174 Interleukin-10 Proteins 0.000 description 3
- 102000004889 Interleukin-6 Human genes 0.000 description 3
- 108090001005 Interleukin-6 Proteins 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 3
- 230000003110 anti-inflammatory effect Effects 0.000 description 3
- 238000007446 glucose tolerance test Methods 0.000 description 3
- 230000002757 inflammatory effect Effects 0.000 description 3
- 229940076144 interleukin-10 Drugs 0.000 description 3
- 229940100601 interleukin-6 Drugs 0.000 description 3
- 239000007928 intraperitoneal injection Substances 0.000 description 3
- 230000000770 proinflammatory effect Effects 0.000 description 3
- 206010061218 Inflammation Diseases 0.000 description 2
- 102000008070 Interferon-gamma Human genes 0.000 description 2
- 108010074328 Interferon-gamma Proteins 0.000 description 2
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 2
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 2
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 2
- 230000006378 damage Effects 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 230000035622 drinking Effects 0.000 description 2
- 229940093181 glucose injection Drugs 0.000 description 2
- 230000004054 inflammatory process Effects 0.000 description 2
- 229960003130 interferon gamma Drugs 0.000 description 2
- 238000010172 mouse model Methods 0.000 description 2
- 238000012545 processing Methods 0.000 description 2
- 210000003462 vein Anatomy 0.000 description 2
- XDIYNQZUNSSENW-UUBOPVPUSA-N (2R,3S,4R,5R)-2,3,4,5,6-pentahydroxyhexanal Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C=O.OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C=O XDIYNQZUNSSENW-UUBOPVPUSA-N 0.000 description 1
- 229940113081 5 Hydroxytryptamine 3 receptor antagonist Drugs 0.000 description 1
- 206010002091 Anaesthesia Diseases 0.000 description 1
- 208000019901 Anxiety disease Diseases 0.000 description 1
- 206010003210 Arteriosclerosis Diseases 0.000 description 1
- 201000001320 Atherosclerosis Diseases 0.000 description 1
- 208000024172 Cardiovascular disease Diseases 0.000 description 1
- 206010013954 Dysphoria Diseases 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 102000006587 Glutathione peroxidase Human genes 0.000 description 1
- 108700016172 Glutathione peroxidases Proteins 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- 208000008589 Obesity Diseases 0.000 description 1
- 210000000683 abdominal cavity Anatomy 0.000 description 1
- 230000001133 acceleration Effects 0.000 description 1
- 230000037005 anaesthesia Effects 0.000 description 1
- 230000036506 anxiety Effects 0.000 description 1
- 230000000949 anxiolytic effect Effects 0.000 description 1
- 208000011775 arteriosclerosis disease Diseases 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 208000037976 chronic inflammation Diseases 0.000 description 1
- 230000006020 chronic inflammation Effects 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000000378 dietary effect Effects 0.000 description 1
- 208000016097 disease of metabolism Diseases 0.000 description 1
- 229960001031 glucose Drugs 0.000 description 1
- 208000018914 glucose metabolism disease Diseases 0.000 description 1
- 208000019622 heart disease Diseases 0.000 description 1
- 230000000147 hypnotic effect Effects 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 229940090044 injection Drugs 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 230000002262 irrigation Effects 0.000 description 1
- 238000003973 irrigation Methods 0.000 description 1
- 208000030159 metabolic disease Diseases 0.000 description 1
- 238000000034 method Methods 0.000 description 1
- 235000020824 obesity Nutrition 0.000 description 1
- 230000036407 pain Effects 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000011506 response to oxidative stress Effects 0.000 description 1
- 239000000932 sedative agent Substances 0.000 description 1
- 230000001624 sedative effect Effects 0.000 description 1
- 239000003369 serotonin 5-HT3 receptor antagonist Substances 0.000 description 1
- 210000003556 vascular endothelial cell Anatomy 0.000 description 1
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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/439—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom the ring forming part of a bridged ring system, e.g. quinuclidine
-
- 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
- A61K31/365—Lactones
- A61K31/375—Ascorbic acid, i.e. vitamin C; Salts thereof
-
- 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
-
- 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)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Organic Chemistry (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Endocrinology (AREA)
- Epidemiology (AREA)
- Emergency Medicine (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
The invention relates to the technical field of medicines, in particular to application of granisetron in preparation of medicines for preventing and treating metabolic syndrome. According to the invention, the granisetron has a good prevention and treatment effect on the metabolic syndrome through a mouse experiment, so that the insulin level of a metabolic syndrome mouse can be reduced; significantly improving insulin sensitivity in metabolic syndrome mice; significantly reducing the inflammatory response in mice with metabolic syndrome; significantly relieves the oxidative stress of mice with metabolic syndrome, can be used for preparing medicines for relieving metabolic syndrome and type II diabetes, and has wide application prospect. In addition, the invention also discovers that the combined use of granisetron and vitamin C has better prevention and treatment effect on metabolic syndrome, is better than Shan Yongge granisetron, and can be used for preparing medicines for relieving metabolic syndrome and type II diabetes.
Description
Technical Field
The invention relates to the technical field of medicines, in particular to application of granisetron in preparation of medicines for preventing and treating metabolic syndrome.
Background
With the acceleration of the urban process, the continuous change of life habits and dietary structures causes obesity and metabolic syndrome (Metabolic syndrome) to occur, which are manifested by chronic inflammation, glucose metabolic disorder, insulin resistance and the like, and worsens the life quality of people. Among these, insulin resistance is the core of the metabolic syndrome, with which oxidative stress and inflammatory reactions are accompanied by the pathogenesis of the metabolic syndrome. At the same time, insulin resistance is also a typical condition of the metabolic disease type two diabetes. If not effectively managed and controlled, type II diabetes can cause serious harm to human health, patients can easily develop cardiovascular diseases such as hypertension, arteriosclerosis and the like, damage vascular endothelial cells and promote the formation of atherosclerosis, thereby increasing the risk of heart disease and stroke.
Granisetron is a highly selective 5-HT3 receptor antagonist, can produce sedative, hypnotic and anxiolytic effects by modulating central nervous system activity, can be used for helping to control dysphoria, reduce anxiety and pain in patients, and has not been reported in research on granisetron in other indications.
Disclosure of Invention
In order to solve the problems, the invention provides application of granisetron in preparing medicines for preventing and treating metabolic syndrome. The invention discovers that granisetron has good prevention and treatment effects on metabolic syndrome.
In order to achieve the above object, the present invention provides the following technical solutions:
the invention provides application of granisetron in preparing a medicament for preventing and treating metabolic syndrome and/or type II diabetes.
The invention provides application of granisetron and vitamin C in preparation of medicines for preventing and treating metabolic syndrome and/or type II diabetes.
Preferably, the symptoms of the metabolic syndrome include one or more of increased insulin levels, decreased glucose tolerance, decreased insulin sensitivity, increased inflammatory response, and decreased antioxidant capacity.
The invention provides a medicine for preventing and treating metabolic syndrome and/or type II diabetes, which comprises granisetron and vitamin C.
Preferably, the mass ratio of granisetron to vitamin C in the medicine is (0.2-0.3): (42-73.5).
The beneficial effects are that:
the invention provides application of granisetron in preparation of a medicament for preventing and treating metabolic syndrome. The invention discovers that granisetron has good control effect on metabolic syndrome, and the experimental result of mice shows that granisetron can reduce the insulin level of mice with metabolic syndrome; significantly improving insulin sensitivity in metabolic syndrome mice; significantly reducing the inflammatory response in mice with metabolic syndrome; significantly relieves the oxidative stress of mice with metabolic syndrome, can be used for preparing medicines for relieving metabolic syndrome and type II diabetes, and has wide application prospect.
In addition, the invention also discovers that the combined use of granisetron and vitamin C has better prevention and treatment effect on metabolic syndrome, is better than Shan Yongge granisetron, and can be used for preparing medicines for relieving metabolic syndrome and type II diabetes.
Detailed Description
The invention provides application of granisetron in preparing a medicament for preventing and treating metabolic syndrome and/or type II diabetes. In the invention, the effective amount of granisetron in the medicine is preferably 8-12 mg/kg, more preferably 10mg/kg per kg of the weight.
The invention provides application of granisetron and vitamin C in preparation of medicines for preventing and treating metabolic syndrome and/or type II diabetes. When granisetron and vitamin C are combined, the effective dose of granisetron is preferably 8-12 mg/kg, more preferably 10mg/kg per kg of body weight; the effective concentration of vitamin C is preferably 1 to 1.5g/L, more preferably 1.5g/L.
In the present invention, the symptoms of the metabolic syndrome preferably include one or more of an increase in insulin level, a decrease in glucose tolerance, a decrease in insulin sensitivity, an increase in inflammatory response, and a decrease in antioxidant capacity.
The blood insulin level of the mammal with metabolic syndrome can be reduced by using granisetron or a medicine prepared by granisetron and vitamin C in combination; improving glucose tolerance in a mammal with metabolic syndrome; improving insulin sensitivity in a mammal having metabolic syndrome; reducing inflammatory response in a mammal suffering from metabolic syndrome and improving antioxidant capacity in a mammal suffering from metabolic syndrome.
The invention provides a medicine for preventing and treating metabolic syndrome and/or type II diabetes, which comprises granisetron and vitamin C. In the invention, the mass ratio of granisetron to vitamin C in the medicine is preferably (0.2-0.3): (42 to 73.5), more preferably 0.25: (42 to 73.5), more preferably 0.25:73.5. the mass ratio of granisetron to vitamin C is preferably calculated according to the dosage of granisetron to vitamin C in the embodiment, wherein the weight of mice is 25 g/mouse, and the water intake is calculated according to the dosage of 4-7 ml/d of each mouse.
In the embodiment of the invention, granisetron is preferably subjected to stomach-filling and medicine taking, and vitamin C is added into drinking water; when the medicine is taken by stomach irrigation, the dosage of granisetron per week is preferably 8-12 mg/kg, more preferably 10mg/kg, based on the weight of the mice, and the medicine is administered once per week; the concentration of vitamin C in the drinking water is preferably 1-1.5 g/L, more preferably 1.5g/L.
For further explanation of the present invention, the application of granisetron provided by the present invention in the preparation of a medicament for preventing and treating metabolic syndrome is described in detail below with reference to examples, but they should not be construed as limiting the scope of the present invention.
Example 1
1. Test animals
40C 57BL/6 mice (purchased from Beijing Bei Fu Biotechnology Co., ltd.) of 4-week-old male, SPF grade were randomly divided into 4 groups of 10 animals each, a control group, a high-fat model group, a granisetron group and a composition group, and the feeding and drinking of the mice during the test were not limited by any factor.
2. Test design
(1) Animal modeling, grouping and processing
Control group: feeding control feed (fat calorie ratio 10%, product number is H10010, purchased from Fukang biotechnology Co., beijing), and daily drinking water is distilled water, and the daily drinking water is 0.2 mL distilled water filled 1 time per week;
high-fat model group: feeding high-fat feed (fat calorie ratio 60%, product number is H10060, purchased from Fukang biotechnology Co., ltd., beijing), and adding distilled water 1 times per week into daily drinking water, wherein the distilled water is 0.2 mL;
granisetron group: feeding high-fat feed, wherein the daily drinking water is distilled water, and the granisetron solution is infused 1 time per week according to the weight of 10mg/kg. Granisetron available from seleck biotechnology limited under the product number S1345;
composition group: feeding high-fat feed, and drinking 1.5g/L vitamin C water solution, and filling the stomach 1 time of granisetron solution according to 10mg/kg body weight per week. Granisetron is available from Selleck Biotechnology Inc., and vitamin C is available from Shi Jiu (Shijia) of Shi Zhou Jiu, under the number 50-81-7.
(2) Index detection
The total duration of the test was 8 weeks. On test week 6, mice were fasted for 6 hours in the morning and were subjected to glucose tolerance test by intraperitoneal injection of glucose solution of 2 g/kg body weight, blood was collected from the tail vein, and blood glucose levels of the mice on an empty stomach and 15, 30, 60, 90 and 120 minutes after glucose injection were measured with a glucometer. At the 7 th week of the test, mice were fasted for 6 hours in the morning and were subjected to insulin resistance test by intraperitoneal injection of insulin of 0.75U/kg body weight, blood was collected from the tail vein, and blood glucose was measured by a blood glucose meter for the mice on an empty stomach and for 15, 30, 60, 90 and 120 minutes after insulin injection. The Area under the blood glucose curve (AUC) was calculated from the blood glucose values at each time point of the glucose tolerance test and the insulin tolerance test, and the glucose tolerance and insulin sensitivity of the mice were judged from the AUC, and the lower the AUC was, the stronger the glucose tolerance and insulin sensitivity of the mice was.
Mice were fasted 12 h after the end of the week 8 trial, and serum samples were collected after anesthesia and sacrificed and stored at-20 ℃ for the detection of blood glucose, insulin, serum inflammatory factors and serum antioxidant indicators. Serum inflammatory factors include the pro-inflammatory factors tumor necrosis factor alpha (TNF-alpha), interferon gamma (IFN-gamma), interleukin 6 (IL-6), and the anti-inflammatory factor interleukin 10 (IL-10). Serum antioxidant indicators include total antioxidant capacity (T-AOC), superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) activities and Malondialdehyde (MDA) content, as measured using a kit purchased from the institute of biotechnology (china) of south kyo, operating according to the kit instructions. The Insulin resistance index HOMA-IR was calculated from blood Glucose (Glucose) and Insulin level (Insulin). The calculation formula is as follows: HOMA-ir=glucose (mmol/L) ×ins (μiu/mL)/22.5.
(3) Data processing
Raw data were collated using Excel 2013, experimental data were analyzed and compared using SAS (SAS 9.2), and differences between groups were tested using independent samples. P <0.05 is significant, P <0.01 is extremely significant, P is more than or equal to 0.05 and less than or equal to 0.10, and the variation trend is presented.
3. Test results
TABLE 1 influence of different treatment groups on glucose tolerance in mice with Metabolic syndrome (mmol/L)
Note that: Δp <0.05, ΔΔp <0.01 compared to the control group; compared with a high-fat model group, p is less than 0.05, p is less than 0.01, 15-120 min is blood sugar after 15-120 min of intraperitoneal glucose injection, and the following table is similar.
From the glucose tolerance test (table 1), after the glucose is injected into the abdominal cavity, the AUC of the mice in the high-fat model group is obviously increased (P < 0.05), the AUC of the mice in the high-fat model group can be obviously reduced (P < 0.05) by the composition, and the granisetron has no influence on the AUC of the mice in the high-fat model group, so that the glucose tolerance of the mice in the metabolic syndrome is obviously improved by the composition.
TABLE 2 influence of different treatment groups on insulin sensitivity (mmol/L) in mice with metabolic syndrome
Note that: Δp <0.05, ΔΔp <0.01 compared to the control group; p <0.05, < p <0.01 compared to the hyperlipidemic model group.
TABLE 3 effects of different treatment groups on fasting blood glucose, insulin and insulin resistance index in mice with metabolic syndrome
Note that: Δp <0.05, ΔΔp <0.01 compared to the control group; p <0.05, < p <0.01 compared to the hyperlipidemic model group.
From the insulin resistance test (table 2), the AUC of the mice in the high-fat model group was significantly increased (P < 0.01) compared with the control group after the intraperitoneal injection of insulin, the granisetron tended to decrease (p=0.07) in the AUC of the mice in the high-fat model group, and the composition significantly decreased (P < 0.01). In combination with Table 3, it can be seen that the fasting blood glucose level, serum insulin level and insulin resistance index HOMA-IR of the mice in the high-fat model group were significantly increased, the serum insulin level and HOMA-IR of the mice in the high-fat model group were significantly decreased by granisetron, and the fasting blood glucose level, serum insulin level and HOMA-IR of the mice in the composition group were significantly decreased as compared with the control group. From the above, the composition significantly improves insulin sensitivity in mice with metabolic syndrome and has better effect than granisetron alone.
TABLE 4 influence of different treatment groups on serum inflammatory factor levels in mice with Metabolic syndrome (pg/mL)
Note that: Δp <0.05, ΔΔp <0.01 compared to the control group; p <0.05, < p <0.01 compared to the hyperlipidemic model group.
As can be seen from Table 4, the serum levels of the pro-inflammatory factors TNF-. Alpha., IFN-. Gamma.and IL-6 were significantly increased (P < 0.01) and the anti-inflammatory factor IL-10 was decreased (P < 0.01) in the mice of the high-fat model group, compared to the control group. Both granisetron and the composition significantly reduced the pro-inflammatory factor levels in the high-fat model mice and increased the anti-inflammatory factor levels (P < 0.01), indicating that both granisetron and the composition reduced the inflammatory response in the metabolic syndrome mice.
TABLE 5 influence of different treatment groups on the antioxidant capacity of mice with metabolic syndrome
Note that: Δp <0.05, ΔΔp <0.01 compared to the control group; p <0.05, < p <0.01 compared to the hyperlipidemic model group.
As can be seen from table 5, the serum antioxidant enzymes T-AOC, SOD and CAT were significantly reduced (P < 0.01) and the MDA content was significantly increased (P < 0.01) in the mice of the high-fat model group compared to the control group. Both granisetron and the composition significantly raise the activity of T-AOC, SOD, CAT and GSH-Px of the high-fat model mice, and significantly reduce the level of serum MDA, indicating that both granisetron and the composition thereof improve the antioxidant capacity of the metabolic syndrome mice.
In conclusion, granisetron and a composition thereof (granisetron and vitamin C) can improve glucose tolerance and insulin sensitivity of metabolic syndrome mice, reduce inflammatory reaction and oxidative stress of the metabolic syndrome mice, and the effect of the composition is superior to that of granisetron which is singly used.
Although the foregoing embodiments have been described in some, but not all, embodiments of the invention, it should be understood that other embodiments may be devised in accordance with the present embodiments without departing from the spirit and scope of the invention.
Claims (7)
1. The application of granisetron in preparing medicine for preventing and treating metabolic syndrome and/or type II diabetes.
2. The use according to claim 1, wherein the effective amount of granisetron in the medicament is 8-12 mg/kg per kg of weight.
3. The application of granisetron and vitamin C in preparing medicine for preventing and treating metabolic syndrome and/or type II diabetes.
4. The use according to claim 3, wherein the effective amount of granisetron and vitamin C is 8-12 mg/kg per kg of body weight when granisetron and vitamin C are co-administered; the effective concentration of the vitamin C is 1-1.5 g/L.
5. The use according to any one of claims 1 to 4, wherein the symptoms of metabolic syndrome comprise one or more of increased insulin levels, decreased glucose tolerance, decreased insulin sensitivity, increased inflammatory response and decreased antioxidant capacity.
6. A medicament for preventing and treating metabolic syndrome and/or type two diabetes mellitus, which is characterized by comprising granisetron and vitamin C.
7. The medicine according to claim 6, wherein the mass ratio of granisetron to vitamin C in the medicine is (0.2-0.3): (42-73.5).
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202311234538.4A CN116983305A (en) | 2023-09-25 | 2023-09-25 | Application of granisetron in preparation of medicine for preventing and treating metabolic syndrome |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202311234538.4A CN116983305A (en) | 2023-09-25 | 2023-09-25 | Application of granisetron in preparation of medicine for preventing and treating metabolic syndrome |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN116983305A true CN116983305A (en) | 2023-11-03 |
Family
ID=88532349
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202311234538.4A Pending CN116983305A (en) | 2023-09-25 | 2023-09-25 | Application of granisetron in preparation of medicine for preventing and treating metabolic syndrome |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN116983305A (en) |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1460476A (en) * | 2003-06-08 | 2003-12-10 | 胡秀爱 | Apomorphine sublingual dripping pill preparation with adjustable medicine-releasing rate |
| KR101111534B1 (en) * | 2010-12-24 | 2012-02-15 | (주)비씨월드제약 | Composition for Orally disintegrating tablet and process for obtaining thereof |
-
2023
- 2023-09-25 CN CN202311234538.4A patent/CN116983305A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1460476A (en) * | 2003-06-08 | 2003-12-10 | 胡秀爱 | Apomorphine sublingual dripping pill preparation with adjustable medicine-releasing rate |
| KR101111534B1 (en) * | 2010-12-24 | 2012-02-15 | (주)비씨월드제약 | Composition for Orally disintegrating tablet and process for obtaining thereof |
Non-Patent Citations (2)
| Title |
|---|
| PENGGUANG ZHANG等: ""Maternal consumption of l-malic acid enriched diets improves antioxidant capacity and glucose metabolism in offspring by regulating the gut microbiota"", 《REDOX BIOLOGY》, vol. 67, pages 1 - 18 * |
| 韩睿等编: "《内分泌代谢性疾病的运动处方及饮食治疗》", vol. 1, 云南科技出版社, pages: 24 * |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Butler et al. | Relationship between hyperglycemia and infection in critically ill patients | |
| EP3165227A1 (en) | Composition for treating or preventing metabolic disease, containing, as active ingredient, extracellular vesicles derived from akkermansia muciniphila bacteria | |
| CN111568945A (en) | Compound cyclocarya paliurus preparation | |
| CN102526479A (en) | Health-care medicine formula with functions of enhancing immunity and lowering blood sugar | |
| CN112603923A (en) | Application of phillyrin in preparation of medicine for preventing or/and treating type II diabetes | |
| CN116983305A (en) | Application of granisetron in preparation of medicine for preventing and treating metabolic syndrome | |
| WO2019170153A1 (en) | GLP-1 Composition for Treating Obesity and Weight Management | |
| CN109999019B (en) | Application of myristoleic acid methyl ester in preparation of product for preventing or treating metabolic syndrome or improving body energy metabolism | |
| US20190336523A1 (en) | Combination drug suitable for treatment and prevention of non-alcoholic fatty liver disease (NAFLD) and/or non-alcoholic steatohepatitis (NASH), and/or hepatic fatty degeneration | |
| CN112587528B (en) | Pharmaceutical composition and application thereof in preparing medicines for improving insulin resistance and reducing blood sugar | |
| EP3403664A1 (en) | Use ofcistanche tubulosa | |
| CN1939310A (en) | Composition for losing weight | |
| CN113384600A (en) | Application of inactivated lactobacillus compound in preparation of product for treating and/or preventing diabetes | |
| CN107007821A (en) | Interleukin Ⅲ 8 is preparing the application in preventing and treating obesity and metabolic syndrome product | |
| EP3804705B1 (en) | Pharmaceutical composition for preventing diabetes and use thereof | |
| JP2013063941A (en) | Prophylactic or improving agent of irritable bowel syndrome | |
| CN114099493B (en) | Active compound for inhibiting insulin resistance and application thereof | |
| CN104605349A (en) | Health-care product containing D-pinitol and having blood glucose lowering function and function assessment method | |
| US11058718B2 (en) | Method for treating non-alcoholic steatohepatitis (NASH) with the combination of polaprezinc and sodium selenite | |
| TWI692361B (en) | Use of antrodia salmonea mycelium in alleviation of cancer cachexia | |
| CN110876717A (en) | Preparation method of product capable of stabilizing blood sugar | |
| CN115400126B (en) | Composition and medical application thereof | |
| CN108404016A (en) | A kind of mongolian veterinary drug and its application in anti-animal cold stress | |
| CN117017961A (en) | Application of sulforaphane and composition thereof in preparation of anti-fatigue products | |
| WO2022061962A1 (en) | Method for effectively intervening diabetes by using l-type amino acid transporter inhibitor or antagonist |
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 |