CN101322698A - Applications of betaine in preparing medicament for preventing and treating alimentary obesity - Google Patents
Applications of betaine in preparing medicament for preventing and treating alimentary obesity Download PDFInfo
- Publication number
- CN101322698A CN101322698A CNA2007100421941A CN200710042194A CN101322698A CN 101322698 A CN101322698 A CN 101322698A CN A2007100421941 A CNA2007100421941 A CN A2007100421941A CN 200710042194 A CN200710042194 A CN 200710042194A CN 101322698 A CN101322698 A CN 101322698A
- Authority
- CN
- China
- Prior art keywords
- betaine
- betanin
- rat
- differentiation
- application
- 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
Images
Abstract
The invention belongs to the technical field of the traditional Chinese medicines and relates to the new medicinal application of betaine, in particular to the application of betaine on the treatment and prevention of dietary obesity. The betaine described in the invention is one of the ingredients of radix rehmanniae extract. Proved by animal tests, the betaine can inhibit differentiation of fat cells and the expression of key transcription factors in the differentiation of fat cells; the proliferation of fat cells can be restrained when the differentiation of fat cells is inhibited; moreover, the betaine can prevent weight gain induced by high fat diet, raise high density lipoprotein level in plasma and reduce low density lipoprotein in plasma, thus the betaine can be used for preparing the drugs for preventing and treating dietary obesity.
Description
Technical field
The invention belongs to technical field of Chinese medicines, be specifically related to the new medicine use of betanin, more specifically, the present invention relates to the application of betanin in prevention and treatment alimentary obesity.
Background technology
Betanin is a kind of native compound, and is nontoxic, harmless, and stable in properties, is distributed widely in the animals and plants.The sixties, discover that betanin has significant regulating and controlling effect to rat body methyl metabolism, so with its certain drug as the congenital cystinuria of methyl donor treatment people.In recent years,, confirmed that betanin is an important methyl donor in the animal body on Animal nutrition, participated in aminoacid and lipid metabolism, had effects such as promoting to grow, improve the trunk composition along with deepening continuously that betanin is studied.
Studies show that the main effect of betanin has: 1. anti-fatty liver: rat is oral for a long time, the phospholipid level in can raise blood and the liver; Can resist the attenuating of phospholipid, total cholesterol level in the rats'liver that carbon tetrachloride causes, and increase; To tests such as BSP, SGPT, alkaline phosphatase, the acetylcholine esterase effect that all makes moderate progress.Known Fructus Lycii has effect to lipid metabolism or anti-fatty liver, and betanin plays the methyl supplying in vivo as one of composition that wherein contains; 2. blood pressure lowering: anesthetized animal there is slight hypotensive effect, but invalid to hypertension; 3. antitumor: with D-arabo-ascorbic acid combination drug, at the external mitosis that can suppress tumor cell, effect medication separately is strong; Other: its chloride aluminum salt has antiulcer action and treatment gastritis, promotes wound healing.So far, the report of relevant betanin prevention of Shang Weijian and treatment alimentary obesity.
Summary of the invention:
The new pharmaceutical usage that the purpose of this invention is to provide betanin.More specifically, provide the application of betanin in preparation prevention and treatment alimentary obesity medicine.
Betanin of the present invention (Betaine) is one of component in the Radix Rehmanniae extract, has the structure of formula A, and is structurally very similar to the L-carnitine (l-carnitine) of formula B, and L-carnitine is Duoed a methine and a hydroxyl than betanin.
The present invention is by each component of Atlantis HILIC Silica AG chromatogram column analysis Chinese medicine Radix Rehmanniae, the chemical compound of betanin, carried out betanin to the effect zoopery of the influence of adipose cell differentiation and betanin to alimentary obesity.Experimental result shows that betanin can suppress the expression of crucial transcription factor in adipose cell differentiation and the adipose cell atomization.Show that betanin has the effect that the rat obesity is induced in the prevention high fat diet, its mechanism of action comprises: thus 1. suppress the hypertrophy that the adipose cell differentiation suppresses fatty tissue: 2. promote the synthetic of l-carnitine, thereby promote l-carnitine to participate in fatty acid oxidation.
Betanin of the present invention can prepare the medicine that suppresses adipose cell differentiation and prevention alimentary obesity.
Technical scheme of the present invention realizes by following method and step:
1. utilize the component Hx in Atlantis HILIC Silica chromatographic column (AG) the analysis Chinese medicine Radix Rehmanniae extract;
2. adipose cell before the cultured cell 3T3-L1 is induced to differentiate into sophisticated adipose cell with containing the yellow fast cry of certain animals (Mix) of 0.5mM methyl-isobutyl, 1 μ M dexamethasone (Dex) and 1 μ g/ml insulin (Insulin).And handling cell with Betaine, Western Blotting detects the expression of C/EBP β, C/EBP α and 422/aP2;
3. utilize the adipose cell model, the experimentation betanin suppresses the adipose cell differentiation;
4. betanin is to the effect of alimentary obesity, set up high fat diet (HFD) rat model, handle through Betaine and l-carnitine (L-carnitine), measure the body weight of rat, after feeding for 15 weeks rat is put to death, measure the weight of fatty tissue, separation of serum detects serum triglycerides, T-CHOL, high density lipoprotein and ldl concn.
Description of drawings
Fig. 1 is the high performance liquid chromatography separating spectrum,
Wherein, adopt Waters Atlantis HILIC Silica chromatographic column, after Hx is separated, obtain six components altogether.
Fig. 2 is mass-spectrogram (mass range 100-900),
Wherein, retention time is the component of 8.90min, and its mass spectrogram is identical with the mass spectrum of betanin standard substance, shows the salt that this component contains betanin, betanin analog or formed by betanin.
Fig. 3 is that preceding adipose cell is cultivated, differentiation figure,
Wherein, the cellular control unit normal differentiation, the cell differentiation that adds the alkali solution of beet of 75mmol/L then has been subjected to inhibition, and adipose cell was divided into adipose cell before the alkali solution of beet of 150mmol/L then almost can suppress 3T3-L1 fully.
Fig. 4 is that the peculiar gene expression product of adipose cell is identified (Western Blotting),
Wherein, in two kinds of isomers of C/EBP β of the marker gene that the adipose cell differentiation is early stage, the band of 18kD does not change because of the adding of medicine, then expression reduces the band of 38kD gradually along with adding increasing of dose, and the alkali solution of beet of 150mmol/L almost completely can suppress C/EBP β 38kD protein expression level;
Adipose cell is eventually in two kinds of isomers of C/EBP α of end differentiation marker gene, the band of 30kD and 42kD all with add dose increase and expression reduce gradually, the expression of fatty acid binding protein 422/aP2 also reduces gradually along with adding increasing of dose.
The specific embodiment
By following embodiment technical scheme of the present invention is further described.
Embodiment 1:
1. utilize the component Hx in Atlantis HILIC Silica chromatographic column (AG) the analysis Chinese medicine Radix Rehmanniae extract.
Waters Alliance chromatographic system: comprise 2690 separative elements, 2487 UV-detector, Masslynx4.0 chromatograph management system, Waters ZQ 2000 mass spectrographs; Acetonitrile (Fisher), ultra-pure water (Millipore), formic acid (Shanghai chemical reagent factory).
The chromatographic condition of separation component Hx: chromatographic column Atlantis HILIC Silica Column (2.1mm i.d. * 150mm, 4 μ m), mobile phase A: 0.1% aqueous formic acid, Mobile phase B: 0.1% formic acid acetonitrile solution, gradient program: in the 0th to the 10th minute, rise to 50%A, in the 10th to the 25th minute by the 30%A linearity, return 30%A, flow velocity is 0.2ml/min.Sample room temperature and column temperature are respectively 10 ℃ and 20 ℃.2487 UV-detector wavelength set are 254nm and 280nm.Mass spectrum condition: ES+ pattern: capillary voltage is 4.5kV, taper hole voltage 110V, 100 ℃ of ion source temperatures, 200 ℃ of desolventizing temperature, gas flow rate 250L/hr, MS mass range 100-900.
2.Betaine and the l-carnitine standard substance are available from Sigma company, purity 99%.
3. the preceding adipose cell of cell culture: 3T3-L1 goes down to posterity with the DMEM culture medium that contains 10% calf serum and cultivates, when cell grows into contact inhibition (Day0) two days later, induce differentiation with the DMEM culture medium that contains 10% hyclone, contain the yellow fast cry of certain animals (Mix) of 0.5mM methyl-isobutyl in the induced liquid, 1 μ M dexamethasone (Dex) and 1 μ g/ml insulin (Insulin), after 48 hours, be changed to the DMEM culture medium that contains 1 μ g/ml insulin, 10% hyclone, later on every three days, be changed to the DMEM culture medium that contains 10% hyclone, up to being divided into sophisticated adipose cell.The alkali solution of beet effect 48hr that in the induced lipolysis cell differentiation, adds variable concentrations, final concentration is 75mmol/L and 150mmol/L, after this change at every turn do not add alkali solution of beet in the cell culture fluid process, after differentiation the 6th day by oil red dyeing observation of cell form.
4. oil red dyeing: oil red powder (Sigma) is dissolved in isopropyl alcohol with 0.5g/100mI, dissolves with 3: 2 with water again, gets oil red solution twice with 0.45 μ m membrane filtration.Before the dyeing earlier the PBS with ice bath wash cell 3 times, used 3.7% formaldehyde fixed then 1 hour, with oil red solution incubated cell 15min, ethanol with 70% and water clean cell respectively under the room temperature, with the inverted microscope observation and take painted cell.
5.Western Blotting:C/EBP β, C/EBP α and 422/aP2 first antibody are available from U.S. JohnsHopkins University Biochemical Research chamber, second antibody is available from Jackson Immun company.
Histone extracting: first day (Day1) after differentiation and the 6th day (Day6) be the extracting total protein of cell respectively: the PBS (pH7.4) with pre-cooling washes cell 3 times, add the cell pyrolysis liquid cell lysis that contains 1%SDS, 60mMTris-HCI (pH 6.8) in right amount then, place 30min on ice, scrape cell, the collecting cell lysate, with pyrolysis product at 100 ℃ of water-bath 10min, the centrifugal 10min of 5000rpm, the absorption supernatant is standby, and is frozen in-20 ℃;
Make protein quantification with the BCA test kit: (bovine serum albumin BSA), makes standard protein concentration be respectively 2000 μ g/ml, 1000 μ g/ml, 500 μ g/ml, 250 μ g/ml, 125 μ g/ml, 50 μ g/ml, 25 μ g/ml to dilution standard albumen; With BCA reaction reagent A and reagent B mixed, make working solution according to 50: 1; Add 5 μ l standard proteins or 5 μ l samples in the ELISA Plate, add 100 μ l BCA working solutions again, the concussion mixing is hatched 30min for 37 ℃, and microplate reader reads the 570nm absorbance.With the absorbance is vertical coordinate, and standard protein concentration is abscissa, the drawing standard curve.According to standard curve, the concentration of calculation sample;
SDS-PAGE: separation gel (12%), with protein sample and sample loading buffer mixing, 100 ℃ of water-bath 5min are in cooled on ice.Quality protein sample such as sample carries out electrophoresis on each swimming lane.C/EB β and C/EBP alpha protein are expressed in the analysis of cells, respectively need total protein of cell 20 μ g; 422/aP2 protein expression in the analysis of cells, albumen applied sample amount are 5 μ g;
Adopt wet commentaries on classics method to change film: pvdf membrane soaks 30min with methanol in advance, and the reuse transfering buffering liquid soaks 5min, and filter paper soaks 3min with transfering buffering liquid; Adopt constant voltage 100V to change film 2hr;
Sealing: after changeing the film end, film is placed on rinsing among the TTBS (0.05%Tween-20), spends the night with the 4 ℃ of sealings of TTBS (0.05%Tween-20) that contain 5% defatted milk powder;
One anti-hybridization: the pvdf membrane that transfer is finished is dipped in respectively and contains in corresponding one anti-TTBS (0.05%Tween-20) solution incubated at room 2hr;
Wash film: pvdf membrane is washed 3 times each 10-15min (decolorization swinging table shakes) with TTBS (0.05%Tween-20);
Two resist hybridization: pvdf membrane is dipped in contains in two TTBS (0.05%Tween-20) solution that resist incubated at room 1hr;
Wash film: the same;
Develop: with pvdf membrane and SuperSignal Western blotting chemical luminous substrate incubated at room 5min, exposure X-ray sheet, developing fixing then.
6. betanin is to the effect experiment of alimentary obesity
The preparation of high fat diet (HFD): add 1 in full-cream sweet milk powder 10g, Adeps Sus domestica 10g, egg, 15 at 100g normal feedstuff (common rat feed), 000 iu Vitamin A, 1,500 iu VitaminD and 250g bean sprout (the dehydration back adds), after the mixing, be pressed into and the identical type shape of normal diet, be stored in-20 ℃, from refrigerator, take out before using, 50 ℃ of bakings 12 hours;
Animal: 48 of heavily about 70g male SD rats (available from Chinese Academy of Sciences's Shanghai Experimental Animal Center), to put into independent metabolic cage respectively and raise, experimental temperature maintains 25 ℃, keeps Circadian rhythm at (turning on light 6 of every mornings, in evening turn off the light) at 8.Before the experiment beginning, rat ad lib normal diet is freely drunk water.When experiment formally begins, rat is enrolled 6 groups at random, 6 every group,
A organizes (normal diet matched group), gives normal diet,
B organizes (high fat diet matched group), gives high fat diet (HFD),
C organizes (betaine low dosage knob), gives high fat diet, the betaine aqueous solution (0.05g/ml) that dilutes simultaneously, and dosage is the 10ml/Kg body weight,
D organizes (betaine high dose group), gives high fat diet, the betaine aqueous solution (0.10g/ml) that dilutes simultaneously, and dosage is the 10ml/Kg body weight,
E organizes (l-carnitine low dose group), gives high fat diet, the l-carnitine aqueous solution (0.025g/ml) that dilutes simultaneously, and dosage is the 10ml/Kg body weight,
F organizes (l-carnitine high dose group), gives high fat diet, the l-carnitine aqueous solution (0.050g/ml) that dilutes simultaneously, and dosage is the 10ml/Kg body weight,
The rat sub-cage rearing is freely drunk water, and ambient temperature is controlled at 25 ℃, keeps its natural circadian rhythm.In experimentation, the food-intake of every rat of strict control, the food-intake of rat: first week and second all 13g/ days, the 3rd all 15g/ days, the 17g/ days all around, the 5th all 19g/ days, the 6th all 21g/ days, the 7th the thoughtful the 15 all 23g/ days.
Measurement index: measure the body weight of rat weekly, feed after 15 weeks rat is put to death, measure the weight of fatty tissue, separation of serum detects serum triglycerides, T-CHOL, high density lipoprotein and ldl concn.7. statistical analysis: experimental data is with average: (X ± S) expression relatively adopts t-test to standard error between group.
The result shows:
1. from Hx, obtain the material of similar betanin:
The method of separating the Hx employing from Radix Rehmanniae is by the C18 chromatographic column, and the part that does not keep is named as Hx.Hx belongs to that polarity is big, a water solublity class material preferably, can't separate with reversed phase chromatographic column.Adopt WatersAtlantis HILIC Silica chromatographic column.After Hx separated, obtain six components altogether, wherein retention time is the component of 8.90min, and its mass spectrogram is identical with the mass spectrum of betanin standard substance, determines the salt that contains betanin, betanin analog among the component Hx or formed by betanin.
2. betanin is to the inhibitory action of adipose cell differentiation
Adipose cell is divided into adipose cell before the 3T3-L1 after the yellow fast cry of certain animals (Mix) of 0.5mM methyl-isobutyl, 1 μ M dexamethasone (Dex) and 1 μ g/ml insulin (Insulin) are induced.
The preceding adipose cell of the 3T3-L1 of normal differentiation began to occur fat at the 3rd day that breaks up and drips, and along with the carrying out of differentiation, fat drips and increases, and by 6-8 days, differentiation degree was the most complete, and the quantity of later noble cells no longer increases, and drips and form more fusion fat.The alkali solution of beet effect 48hr that in the induced lipolysis cell differentiation, adds variable concentrations, after this change at every turn do not add alkali solution of beet in the cell culture fluid process, after differentiation the 6th day by oil red dyeing observation of cell form, the result shows, the cellular control unit normal differentiation, the cell differentiation that adds the alkali solution of beet of 75mmol/L then has been subjected to inhibition, and adipose cell was divided into adipose cell before the alkali solution of beet of 150mmol/L then almost can suppress 3T3-L1 fully.
For whether checking exists: alkali solution of beet directly suppresses the propagation of the preceding adipose cell of 3T3-L1, may produce this hypothesis that is similar to the false positive results that suppresses differentiation, the present invention adopts mtt assay to detect the influence of alkali solution of beet to preceding lipocyte proliferation ability, the result shows that alkali solution of beet does not suppress the propagation of cell, from the morphology as seen at valid density 75mmol/L and 150mmol/L, cell and cellular control unit that the garden beet aqueous slkali is handled are as broad as long, illustrate that alkali solution of beet does not produce the result who suppresses differentiation by the propagation of adipose cell before suppressing.
3. betanin is to the influence of the key gene expression of adipose cell differentiation
After adipose cell is induced differentiation the 1st day and the 6th day, extract normal respectively and handle the total protein of cell, detect the expression of C/EBP α and 422/aP2 in the total protein of cell of C/EBP β in the 1st day the total protein of cell in differentiation back and the 6th day with Western Blotting method through alkali solution of beet.
The result shows, in two kinds of isomers of C/EBP β as the early stage marker gene of adipose cell differentiation, the band of 18kD does not change because of the adding of medicine, then expression reduces the band of 38kD gradually along with adding increasing of dose, and the alkali solution of beet of 150mmol/L almost completely can suppress C/EBP β 38kD protein expression level; Break up in two kinds of isomers of C/EBP α of marker gene at the end eventually as adipose cell, all expression reduces the band of 30kD and 42kD gradually along with adding increasing of dose.The expression of fatty acid binding protein 422/aP2 also reduces gradually along with adding increasing of dose.
4. betanin is to the effect of the inductive obese rat of high fat diet
The present invention has set up the inductive obese rat model of high fat diet.In the inductive obese rat model of high fat diet, l-carnitine as positive control, is observed the effect of betanin in the prevention alimentary obesity.
When experiment finishes, the result of weighing rat body weight shows: the body weight of SD rat is fed in high fat diet, surpass normal diet and feed 25% (426.2 ± 16.9 vs 326.1 ± 28.3) of SD rat body weight, and the Body Mass Index of high fat diet group rat and fatty tissue weight is significantly higher than the normal diet rat feeding, illustrates that the present invention has successfully made up the inductive obese rat model of high fat diet.
The body weight (426.2 ± 16.9) of high fat diet matched group (B group) rat when testing for the 15th week, be significantly higher than body weight (360.8 ± 25.1) of betaine low dose group (C group) rat and the body weight (352.9 ± 3.7) of betaine high dose group (D group) rat, difference has statistical significance (p＜0.05), illustrates that betaine has the effect that the inductive rat body weight of prevention high fat diet increases; The body weight (426.2 ± 16.9) of high fat diet matched group (B group) rat, be significantly higher than body weight (350.7 ± 26.8) of l-carnitine low dose group (E group) rat and the body weight (339.6 ± 14.9) of l-carnitine high dose group (F group) rat, difference has statistical significance (p＜0.05), illustrates that l-carnitine has the effect that the inductive rat body weight of prevention high fat diet increases.
The measurement result of Body Mass Index: the Body Mass Index of high fat diet control rats is significantly higher than the rat of Betaine low dose group and high dose group, and difference has statistical significance (p＜0.05).The weighing result of fatty tissue (comprising omentum majus fatty tissue, epididymal adipose and stomach wall fatty tissue) is, the fatty tissue weight of high fat diet control rats is higher than Betaine low dose group rat, be significantly higher than Betaine high dose group rat, difference has statistical significance (p＜0.05).TG of Betaine low dosage and high dose group rat and TO are lower than high fat diet group rat.The HDL of Betaine low dose group rat is higher than high fat diet group rat, and the high density lipoprotein (HDL) of Betaine high dose group rat is significantly higher than high fat diet group rat, and difference has statistical significance (p＜0.05).The LDL of Betaine low dose group rat is lower than high fat diet group rat, and the low density lipoprotein, LDL (LDL) of Betaine high dose group rat significantly is lower than high fat diet group rat, and difference has statistical significance (p＜0.05).
To sum up, the effect of Betaine prevention alimentary obesity shows as this Betaine and has effect and the raising blood plasma HDL level that the inductive rat body weight of prevention high fat diet increases, and reduces the effect of LDL level.
As the l-carnitine treatment group of positive control, the measurement result of Body Mass Index is: the Body Mass Index of high fat diet control rats is significantly higher than the rat of l-carnitine low dose group and high dose group, and difference has statistical significance (p＜0.05).The weighing result of fatty tissue (comprising omentum majus fatty tissue, attached inferior fatty tissue and stomach wall fatty tissue) is: the fatty tissue weight of high fat diet control rats is higher than l-carnitine low dose group rat, be significantly higher than l-carnitine high dose group rat, difference has statistical significance (p＜0.05).The TG of l-carnitine low dosage and high dose group rat significantly is lower than high fat diet group rat.The TC of l-carnitine low dose group rat significantly is lower than high fat diet group rat, and the TC of high dose group rat also is the rat that is lower than the high fat diet group.The HDL of l-carnitine low dose group and high dose group rat is lower than high fat diet group rat.The LDL of l-carnitine low dose group rat is lower than high fat diet group rat, and the LDL of l-carnitine high dose group rat equals high fat diet group rat.Illustrate that in the adjusting to blood fat, the effect of Betaine and l-carnitine is also not quite identical.
Claims (7)
1, the application of betanin in preparation prevention and treatment alimentary obesity medicine.
2, the application of betanin in the preparation medicine for inhibiting adipocyte differentiation.
3, the application of betanin in preparation reduction adipose cell key gene expression medicine.
4, according to the application of claim 3, wherein said key gene is C/EBP β.
5, according to the application of claim 1, wherein said alimentary obesity is the inductive weight increase of high fat diet.
6, the application of betanin in preparation raising plasma hdl level medicine.
7, the application of betanin in preparation reduction low-density lipoprotein white level medicine.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA2007100421941A CN101322698A (en) | 2007-06-15 | 2007-06-15 | Applications of betaine in preparing medicament for preventing and treating alimentary obesity |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA2007100421941A CN101322698A (en) | 2007-06-15 | 2007-06-15 | Applications of betaine in preparing medicament for preventing and treating alimentary obesity |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN101322698A true CN101322698A (en) | 2008-12-17 |
Family
ID=40186502
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNA2007100421941A Pending CN101322698A (en) | 2007-06-15 | 2007-06-15 | Applications of betaine in preparing medicament for preventing and treating alimentary obesity |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN101322698A (en) |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20140050810A1 (en) * | 2012-08-14 | 2014-02-20 | Bionutrigen Co., Ltd. | Anti-obesity composition comprising lycium chinensis leaf extract and betaine as active ingredient |
| EP3400935A1 (en) * | 2017-05-12 | 2018-11-14 | Hospital Sant Joan de Deu | Betaine for the prevention of obesity |
| CN110934294A (en) * | 2019-12-22 | 2020-03-31 | 重庆申高生化制药股份有限公司 | Composition with weight-losing and beauty-maintaining effects and preparation method thereof |
| CN115634221A (en) * | 2022-10-21 | 2023-01-24 | 拜澳泰克(沈阳)生物医学集团有限公司 | Application of betaine in regulating mesenchymal stem cell adipogenic and osteogenic differentiation |
-
2007
- 2007-06-15 CN CNA2007100421941A patent/CN101322698A/en active Pending
Cited By (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20140050810A1 (en) * | 2012-08-14 | 2014-02-20 | Bionutrigen Co., Ltd. | Anti-obesity composition comprising lycium chinensis leaf extract and betaine as active ingredient |
| CN105530928A (en) * | 2012-08-14 | 2016-04-27 | 韩国百益珍株式会社 | Anti-obesity composition containing lycium chinense miller leaf extract powder and betaine as active ingredients |
| CN105530928B (en) * | 2012-08-14 | 2018-12-04 | 韩国百益珍株式会社 | Prevent and treat the pharmaceutical composition of the fat and fat metabolic syndrome induced |
| EP3400935A1 (en) * | 2017-05-12 | 2018-11-14 | Hospital Sant Joan de Deu | Betaine for the prevention of obesity |
| WO2018206763A1 (en) * | 2017-05-12 | 2018-11-15 | Hospital Sant Joan De Deu | Betaine for the prevention of obesity |
| CN110831587A (en) * | 2017-05-12 | 2020-02-21 | 圣胡安德申医院 | Betaine for preventing obesity |
| US11464754B2 (en) * | 2017-05-12 | 2022-10-11 | Hospital Sant Joan De Deu | Betaine for the prevention of obesity |
| CN110934294A (en) * | 2019-12-22 | 2020-03-31 | 重庆申高生化制药股份有限公司 | Composition with weight-losing and beauty-maintaining effects and preparation method thereof |
| CN115634221A (en) * | 2022-10-21 | 2023-01-24 | 拜澳泰克(沈阳)生物医学集团有限公司 | Application of betaine in regulating mesenchymal stem cell adipogenic and osteogenic differentiation |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Park et al. | Antiobesity effect of ethanolic extract of Ramulus mori in differentiated 3T3-L1 adipocytes and high-fat diet-induced obese mice | |
| Panigrahi et al. | Extract of Sesbania grandiflora ameliorates hyperglycemia in high fat diet-streptozotocin induced experimental diabetes mellitus | |
| Liu et al. | Cerasus humilis cherry polyphenol reduces high-fat diet-induced obesity in C57BL/6 mice by mitigating fat deposition, inflammation, and oxidation | |
| Choi et al. | Coix seed extract attenuates the high-fat induced mouse obesity via PPAR γ and C/EBP α a downregulation | |
| Liu et al. | Polyphenols from blue honeysuckle (Lonicera caerulea var. edulis) berry inhibit lipid accumulation in adipocytes by suppressing lipogenesis | |
| Yu et al. | Onion (Allium cepa L.) peel extract effects on 3T3-L1 adipocytes and high-fat diet-induced obese mice | |
| CN101322698A (en) | Applications of betaine in preparing medicament for preventing and treating alimentary obesity | |
| CN112645808A (en) | 5-hydroxy-1, 7-diphenyl-3-heptanone separated from galangal and application thereof | |
| Kim et al. | Corni fructus containing formulation attenuates weight gain in mice with diet-induced obesity and regulates adipogenesis through AMPK | |
| Liu et al. | Atractylenolide III from Atractylodes macrocephala Koidz promotes the activation of brown and white adipose tissue through SIRT1/PGC-1α signaling pathway | |
| Baek et al. | Antihyperglycemic and antilipidemic effects of the ethanol extract mixture of Ligularia fischeri and Momordica charantia in type II diabetes-mimicking mice | |
| Park et al. | Veratri nigri rhizoma et radix (Veratrum nigrum L.) and its constituent jervine prevent adipogenesis via activation of the LKB1-AMPKα-ACC axis in vivo and in vitro | |
| CN102058567B (en) | Application of 3',4-dyhydroxyl-3,5'-dimethoxybibenzyl in preparing medicaments for treating cataract | |
| CN112552155A (en) | 1, 7-diphenyl-4-heptylene-3-ketone separated from galangal and application thereof | |
| Li et al. | Preparative purification of bioactive compounds from Flos Chrysanthemi indici and evaluation of its antiosteoporosis effect | |
| CN111317830A (en) | Research method of pharmacological effect of mangiferin on diabetes of mice | |
| Li et al. | Radix Astragali decoction improves liver regeneration by upregulating hepatic expression of aquaporin-9 | |
| CN104447783B (en) | Ganoderma cochlear phenols A and B, pharmaceutical compositions of ganoderma cochlear phenols A and B and applications of ganoderma cochlear phenols A and B and pharmaceutical compositions in preparation of medicines and food | |
| Chu et al. | The protective effects of mangiferin on metabolic and organs functions in the adolescent rat model of alcohol abuse | |
| CN101099814B (en) | Medicinal composition for delaying male senility | |
| CN105395808B (en) | It is a kind of for treating the synergism medicine composition of diabetes | |
| Shaker et al. | Effect of resistance training and garlic extract on insulin sensitivity/resistance and biochemical parameters in diabetic rats | |
| CN110693876B (en) | Application of andrographolide in preparing medicine for preventing or/and treating muscle injury | |
| KR102043056B1 (en) | Food Composition for Preventing or Improving Obesity Including Extracts from Ramulus mori | |
| CN110898119B (en) | Application of xanthoceras sorbifolia bunge and/or extract of xanthoceras sorbifolia bunge in preparation of medicine for treating and preventing benign prostatic hyperplasia |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C12 | Rejection of a patent application after its publication | ||
| RJ01 | Rejection of invention patent application after publication |
Open date: 20081217 |