CN113181200A - Application of panax japonicus saponin IV in preparation of medicine for preventing and/or treating obesity - Google Patents
Application of panax japonicus saponin IV in preparation of medicine for preventing and/or treating obesity Download PDFInfo
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- CN113181200A CN113181200A CN202110607797.1A CN202110607797A CN113181200A CN 113181200 A CN113181200 A CN 113181200A CN 202110607797 A CN202110607797 A CN 202110607797A CN 113181200 A CN113181200 A CN 113181200A
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- A61K31/7028—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages
- A61K31/7034—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin
- A61K31/704—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin attached to a condensed carbocyclic ring system, e.g. sennosides, thiocolchicosides, escin, daunorubicin
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- A61K36/25—Araliaceae (Ginseng family), e.g. ivy, aralia, schefflera or tetrapanax
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/04—Anorexiants; Antiobesity agents
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Abstract
The invention discloses application of panax japonicus saponin IV in preparation of a medicament for preventing and/or treating obesity. Compared with the prior art, the invention discloses a new medical application of panax japonicus saponin IV, and finds that the panax japonicus saponin IV has an excellent effect of preventing and/or treating obesity. The invention shows that the chikusetsusaponin IV can obviously inhibit the weight gain of high fat induced obesity through research. And the chikusetsusaponin IV mainly reduces fat weight and has little influence on lean body mass. In addition, it can also significantly improve the basal metabolic rate and fat utilization rate of mice. The research of molecular level shows that the panax japonicus saponin IV can obviously improve the expression of a browning molecular marker of white adipose tissues and promote the browning of the white adipose tissues.
Description
Technical Field
The invention belongs to the technical field of new medical application of panax japonicus saponin IV, and particularly relates to application of panax japonicus saponin IV in preparation of a medicine for preventing and/or treating obesity.
Background
With the continuous improvement of the living standard of people, obesity becomes an important factor seriously threatening public health in the 12 th century. Obesity can cause various metabolic diseases, such as dyslipidemia, type 2 diabetes (T2DM), cardiovascular and cerebrovascular diseases and the like, and can even increase the incidence of certain cancers. In 2014, over one third (39%) of the adults worldwide were overweight, with over 5 billion adults classified as obese. Such high morbidity and a variety of serious complications make obesity an urgent problem for contemporary society. The brown change of white adipose tissues, discovered in 2010, means that the white adipose tissues are changed into light brown under certain factors and thereby consume more energy, and the effects of the brown change of white adipose tissues are weight loss, insulin sensitivity optimization, glycolipid metabolism improvement and the like.
The panax japonicus is one of the most widely distributed species in the genus panax, and has the effects of nourishing and strengthening the ginseng and promoting blood circulation and removing blood stasis of the panax notoginseng. A large number of modern pharmacological studies show that panax japonicus has pharmacological activities of different degrees in the fields of anti-inflammation, analgesia, fatigue resistance, aging resistance, oxidation resistance, tumor resistance and the like. The main active component of the panax japonicus is triterpenoid saponin, wherein panax japonicus saponin monomers IV, IVa and V are 3 representative oleanane type saponins with the highest content in panax japonicus saponin. The panax japonicus saponin IV is one of monomer compounds extracted and separated from panax japonicus total saponins. The research shows that the panax japonicus IV has the effects of inhibiting gastric cancer SGC-7901 cell proliferation, migration and invasion. There is no report that chikusetsusaponin IV can prevent or treat obesity by promoting browning of white fat.
Disclosure of Invention
The purpose of the invention is as follows: aiming at the defects in the prior art, the invention provides the application of panax japonicus saponin IV in preparing the medicament for preventing and/or treating obesity, wherein the panax japonicus saponin IV can be used as a white adipose tissue brown sample change stimulant and can effectively prevent and/or treat obesity.
The technical scheme is as follows: in order to achieve the purpose, the invention adopts the following technical scheme:
the panax japonicus saponin IV and CAS of the invention are 7518-22-1, and the molecular formula is as follows: c47H74O18Average molecular weight: 927.09.
the invention discloses application of panax japonicus saponin IV in preparation of a medicament for preventing and/or treating obesity.
Application of a white adipose tissue brown sample change stimulant in preparation of a medicament, wherein the white adipose tissue brown sample change stimulant is panax japonicus saponin IV.
Further, the medicament is used for preventing and/or treating obesity.
A composition for preventing and/or treating obesity, which comprises chikusetsusaponin IV or a pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable auxiliary material, such as a carrier, a diluent, an excipient or an adjuvant.
Preferably, the dosage form of the composition is selected from one of tablets, powders, granules, capsules, oral liquid, sustained release agents, injections, infusion and sterile powder for injection.
Application of a composition containing chikusetsusaponin IV in preparing a medicament for preventing and/or treating obesity.
Use of a white adipose tissue brown-like stimulant in the manufacture of a medicament, the white adipose tissue brown-like stimulant being a composition comprising chikusetsusaponin IV.
Further, the medicament is used for preventing and/or treating obesity.
When the panax japonicus saponin IV or the composition containing the panax japonicus saponin IV is applied, the panax japonicus saponin IV or the composition containing the panax japonicus saponin IV is preferably:
the medicine exists in a form of administration within a dosage range of 20mg/kg of chikusetsusaponin IV per time.
The drug is administered intraperitoneally.
The drug is in the form of a once daily administration.
The invention adopts a C57BL/6 mouse fed with 60% high fat diet as a research object, and discloses the medicinal application of 20mg/kg panax japonicus saponin IV capable of remarkably resisting and treating obesity for the first time. The experimental mice are divided into panax japonicus saponin IV (20mg/kg) and control solvent (DMSO) injection groups, and the weight and the food intake are measured every day. After the panax japonicus saponin IV is injected for 14 days, body fat and lean body mass are detected through MRI, and brown sample change marker molecules in adipose tissues are detected through qPCR. The experimental results show that: the 20mg/kg panax japonicus saponin IV can obviously stimulate the browning of white adipose tissues, improve energy consumption, promote lipolysis, inhibit fat synthesis, can obviously prevent and treat obesity, has low toxicity and no metabolic inhibition effect, and provides a new direction for preventing and treating obesity.
Has the advantages that: compared with the prior art, the invention discloses a new medical application of panax japonicus saponin IV, and finds that the panax japonicus saponin IV has an excellent effect of preventing and/or treating obesity. The invention shows that the chikusetsusaponin IV can obviously inhibit the weight gain of high fat induced obesity through research. And the chikusetsusaponin IV mainly reduces fat weight and has little influence on lean body mass. In addition, it can also significantly improve the basal metabolic rate and fat utilization rate of mice. The research of molecular level shows that the panax japonicus saponin IV can obviously improve the expression of a browning molecular marker of white adipose tissues and promote the browning of the white adipose tissues.
Drawings
FIG. 1: the left figure is a body weight diagram of a mouse in a diet induced obesity mouse model drug activity test experiment; the right graph is the food intake of the mice in the experiment of the mouse model drug activity test of diet induced obesity.
FIG. 2: diet-induced obesity mouse model drug activity test in the experiment, the weight plots of inguinal white fat (iWAT), epididymal white fat (eWAT), and perirenal white fat (pWAT) of the mouse after the end of the administration.
FIG. 3: a is a body fat weight diagram of the body composition analysis result of the mice in the diet induced obesity mouse model drug activity test experiment; b is a body fat rate graph of the analysis result of body components of the mice in a diet induced obesity mouse model drug activity test experiment; c is a weight graph of the lean body mass of the mouse body composition analysis result in the diet induced obesity mouse model drug activity test experiment; and D is a lean body mass ratio graph of the mouse body composition analysis result in the diet induced obesity mouse model drug activity test experiment.
FIG. 4: a is a graph of the oxygen consumption of the mice in the respiratory energy metabolism cage result in the diet induced obesity mouse model drug activity test experiment; b is a mouse respiration entropy diagram in a respiration energy metabolism cage result in a diet induced obesity mouse model drug activity test experiment; c is a mouse carbon dioxide generation amount graph in a respiratory energy metabolism cage result in a diet induced obese mouse model drug activity test experiment; and D is a mouse energy consumption graph in a respiratory energy metabolism cage result in a diet induced obesity mouse model drug activity test experiment.
FIG. 5: a is a mouse activity condition diagram in a respiratory energy metabolism cage result in a diet induced obese mouse drug activity test experiment; and B is a graph of the small amount of perilla food in the results of the respiratory energy metabolism cage in the test experiment of the drug activity of the diet-induced obese mouse.
FIG. 6: qPCR result graph of mouse white fat browning related gene in diet induced obesity mouse drug activity test experiment.
Detailed Description
The present invention is described in further detail below with reference to specific embodiments, which are given for the purpose of illustration only and are not intended to limit the scope of the invention. The experimental methods in the examples described below are all conventional methods unless otherwise specified; the materials, reagents, instruments, etc. used are commercially available unless otherwise specified.
Examples
C57BL/6J mice, male, 8 weeks, 20-22 g, purchased from department of medicine, Ministry of medicine, Beijing university.
Maintaining the feed: the department of medicine, republic of Beijing.
High-fat feed: purchase and boaopek.
All animal experiments were strictly in accordance with the guidelines for the management and use of laboratory animals and were approved by the North Committee for the management of laboratory animals. During the sacrifice of the animals, the animals were anesthetized and the pain was minimized.
Panax japonicus saponins IV are provided by Shanghai pottery element Biotechnology limited. Chikusetsusaponin IV has a molecular formula: c47H74O18Average molecular weight 927.09, poor water solubility.
The first experiment method comprises the following steps:
1.6-8 week-old male C57BL/6 mice, feeding conditions: the ambient temperature is 22 ℃ plus or minus 0.5 ℃, and the light and shade are alternated for 12 hours/12 hours. All experimental data are expressed as mean ± standard error. Mice were fed a high fat diet (research diet, D12492) containing 60% fat, 20% protein and 20% carbohydrate. During the feeding period, mice were injected intraperitoneally (i.p.) once a day for 14 consecutive days with vehicle (DMSO), vehicle containing compound chikusetsusaponin IV (20mg/kg), and the body weight and food intake of the mice were measured.
14 days after the 2.20 mg/kg IV injection of panax japonicus saponin, white fat of inguinal, epididymis, perirenal and brown fat of scapula were taken, and the fat weight was recorded by weighing.
3. C57BL/6 mice were given a 60% high fat diet and were injected once daily with 20mg/kg chikusetsusaponin IV for 14 consecutive days. The weight of body fat and lean body mass of mice in the administration group and the control group was measured by MRI, and the data was counted.
4. After a C57BL/6 mouse is given 60% high fat diet and is injected with 20mg/kg chikusetsusaponin IV, the mouse is placed in a respiratory metabolism cage, and the oxygen consumption, the carbon dioxide production and the energy consumption and the physical movement of the mouse are continuously monitored for 24 h.
5. 60% high fat diet is given to a C57BL/6 mouse, 20mg/kg of panax japonicus saponin IV is injected for 14 consecutive days, inguinal fat of the mouse is taken, and qPCR technology is utilized to detect the influence of the panax japonicus saponin IV on the mRNA level of the fat browning marker molecules in white adipose tissues of the inguinal.
II, experimental results:
1. panax japonicus saponin IV remarkably reduces the weight gain of diet-induced obese mice
As shown in fig. 1, the body weight of the control vehicle group mice increased significantly under high fat diet. However, the weight of the mice in the panax japonicus saponin IV group is slowly increased, namely, the weight increase of diet-induced obese mice (9.8%) is remarkably reduced by the panax japonicus saponin IV, and the food intake of the mice is not inhibited by the panax japonicus saponin IV.
2. Panax japonicus saponin IV for reducing fat content of diet-induced obese mice
As shown in fig. 2, in the mice given chikusetsusaponin IV, white inguinal fat (iWAT), white epididymal fat (eWAT), and perirenal white fat (pWAT) were significantly reduced and brown fat was not significantly changed, compared to the control vehicle group, which was high-fat-fed.
3. Panax japonicus saponin IV does not reduce the lean body mass of diet-induced obese mice
As shown in fig. 3, the MRI analysis results show that the fat content of the mice fed with high-fat control vehicle is significantly reduced and the body fat rate is significantly reduced compared to the mice fed with high-fat control vehicle. However, the lean body mass of the panax japonicus saponin IV mice is not obviously changed.
4. The chikusetsusaponin IV remarkably improves the energy consumption of mice and promotes the utilization rate of fat
As shown in FIG. 4, it is known from the results of respiratory metabolism cage that chikusetsusaponin IV significantly increases oxygen consumption (VO) of mice2) Carbon dioxide production, and increased Energy Expenditure (EE) and decreased RER (respiratory exchange Rate, VCO) in mice2/VO2). As shown in fig. 5, the physical activities and food intake of the panax japonicus saponin IV mice were not significantly different from those of the control mice. The results show that the panax japonicus saponin IV improves the basal metabolic rate and the fat utilization rate of the mice.
5. Rhizoma Panacis Japonici Saponin IV can promote browning of white fat
As shown in fig. 6, after 14 days of panax japonicus saponin IV administration, inguinal fat of mice in the drug and control vehicle group was taken, and qPCR technology was used to detect the gene expression of white adipose tissue and browning related white adipose tissue, and as a result, it was found that panax japonicus saponin IV can significantly improve the expression of white adipose tissue UCP-1, Prdm16, Cidea, CD137, Tmem26, PGC1 α, Ppar γ, Nrf1, HSP70, Cpt1, Dio2, Adrb3 genes.
The above-mentioned embodiments only express several embodiments of the present invention, and the description thereof is more specific and detailed, but not construed as limiting the scope of the invention. It should be noted that, for a person skilled in the art, several variations and modifications can be made without departing from the inventive concept, which falls within the scope of the present invention. Therefore, the protection scope of the present invention should be subject to the appended claims.
Claims (8)
1. Application of chikusetsusaponin IV in preparing medicine for preventing and/or treating obesity is provided.
2. The application of the white adipose tissue brown sample change stimulant in preparing a medicament is characterized in that the white adipose tissue brown sample change stimulant is panax japonicus saponin IV.
3. Use according to claim 2, wherein the medicament is for the prevention and/or treatment of obesity.
4. A composition for preventing and/or treating obesity, which comprises chikusetsusaponin IV or a pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable auxiliary material.
5. The composition according to claim 4, wherein the composition is in a dosage form selected from one of tablets, powders, granules, capsules, oral liquids, sustained release preparations, injections, infusions, and sterile powders for injections.
6. Application of a composition containing chikusetsusaponin IV in preparing a medicament for preventing and/or treating obesity.
7. The application of the white adipose tissue brown-like change stimulant in the preparation of medicines is characterized in that the white adipose tissue brown-like change stimulant is a composition containing panax japonicus saponin IV.
8. Use according to claim 7, wherein the medicament is for the prevention and/or treatment of obesity.
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103211828A (en) * | 2013-05-07 | 2013-07-24 | 中国药科大学 | Application of panax japonicus saponin IV to preparation of antilipemic agent |
| US20150231139A1 (en) * | 2012-10-31 | 2015-08-20 | Blair G. LAMB | Therapy for constipation |
| CN106983753A (en) * | 2017-03-27 | 2017-07-28 | 北京大学 | White adipose tissue brown sample becomes stimulant and prepares the application for resisting antiobesity agents |
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- 2021-06-01 CN CN202110607797.1A patent/CN113181200A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20150231139A1 (en) * | 2012-10-31 | 2015-08-20 | Blair G. LAMB | Therapy for constipation |
| CN103211828A (en) * | 2013-05-07 | 2013-07-24 | 中国药科大学 | Application of panax japonicus saponin IV to preparation of antilipemic agent |
| CN106983753A (en) * | 2017-03-27 | 2017-07-28 | 北京大学 | White adipose tissue brown sample becomes stimulant and prepares the application for resisting antiobesity agents |
Non-Patent Citations (1)
| Title |
|---|
| LI-KUN HAN等: "Anti-obesity effects of chikusetsusaponins isolated from Panax japonicas rhizomes", 《BMC COMPLEMENTARY AND ALTERNATIVE MEDICINE》 * |
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