CN107126437A - A kind of medicinal usage of Sophoricoside - Google Patents
A kind of medicinal usage of Sophoricoside Download PDFInfo
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- CN107126437A CN107126437A CN201610111882.8A CN201610111882A CN107126437A CN 107126437 A CN107126437 A CN 107126437A CN 201610111882 A CN201610111882 A CN 201610111882A CN 107126437 A CN107126437 A CN 107126437A
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- sophoricoside
- lxr
- lxrβ
- mouse
- liver
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- ISQRJFLLIDGZEP-CMWLGVBASA-N Sophoricoside Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1OC1=CC=C(C=2C(C3=C(O)C=C(O)C=C3OC=2)=O)C=C1 ISQRJFLLIDGZEP-CMWLGVBASA-N 0.000 title description 64
- ISQRJFLLIDGZEP-KJRRRBQDSA-N Sophoricoside Natural products O([C@@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@H](CO)O1)c1ccc(C=2C(=O)c3c(O)cc(O)cc3OC=2)cc1 ISQRJFLLIDGZEP-KJRRRBQDSA-N 0.000 title description 64
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
- A61K31/7048—Compounds having saccharide radicals and heterocyclic rings having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin, digitoxin or digoxin
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- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Molecular Biology (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
本发明公开了一种槐角苷的药物用途，所述的药物用途是指以槐角苷作为活性成分用于制备肝X受体-β拮抗剂。本发明的实验结果表明：槐角苷能够选择性的抑制LXRβ的转录活性，具有明显的抑制脂肪细胞分化的体外效果，以及阻断高脂餐诱导的C57BL/6小鼠体重增加、抑制体脂肪细胞的体积增加、改善小鼠空腹血糖、胰岛素抵抗和小鼠的血脂异常等体内效果，可通过选择性的抑制LXRβ的转录活性达到预防、缓解和/或治疗由LXRβ介导的代谢性疾病，可望开发为一种低毒高效的LXRβ拮抗剂及用于制备预防、缓解和/或治疗由LXRβ介导的代谢性疾病的药物，尤其可望开发为一种制备治疗脂肪肝的药物。The invention discloses a medicinal use of sophoridoside, and the medicinal use refers to using sophoridoside as an active ingredient to prepare a liver X receptor-β antagonist. The experimental results of the present invention show that: sophoridoside can selectively inhibit the transcriptional activity of LXRβ, has an obvious in vitro effect of inhibiting adipocyte differentiation, and blocks the weight gain of C57BL/6 mice induced by a high-fat meal, and inhibits body fat The in vivo effect of increasing the volume of cells, improving fasting blood glucose, insulin resistance and dyslipidemia in mice can prevent, alleviate and/or treat metabolic diseases mediated by LXRβ by selectively inhibiting the transcriptional activity of LXRβ. It is expected to be developed as a low-toxic and high-efficiency LXRβ antagonist and a drug for preventing, alleviating and/or treating metabolic diseases mediated by LXRβ, especially a drug for treating fatty liver.
Description
Technical field
The present invention is to be related to a kind of new pharmaceutical uses of Sophoricoside, belongs to pharmaceutical technology field.
Background technology
Non-alcohol fatty liver (nonalcoholic fatty liver disease, NAFLD) is the lipopexia mistake in liver cell
Common liver diseases caused by many, when lipid content exceedes the 10%~15% of liver weight in wet base in hepatic tissue, or histologically exceed
There is fatty infiltration in 50% liver cell, you can be diagnosed as fatty liver.Recent studies have shown that：Morbidity in fatty liver crowd
Rate is about up to 8.9~23.1% to suffer from NAFLD in 1.85~5.2%/year, adult.NAFLD is a chronic lasting hair
Exhibition process, can from simple fatty liver to fat hepatitis, the pathologic process development such as fatty liver fibrosis and hepatic sclerosis, and
And it is close with the generation of the angiocardiopathy such as insulin resistance, high fat of blood, atherosclerosis, endothelial dysfunction and coronary heart disease
Cut is closed and influenced each other.Currently used for treatment fatty liver medicine include insulin sensitizer, it is lipid-lowering medicine, slimming drugs, anti-
Oxidative drug and urso etc..Vitamin E is also used for the preventing and treating of fatty liver as antioxidant, is what U.S. FDA was recommended
Unique fatty liver medicament.But include the medicines such as vitamin E, melbine so far and be not clinically proven improvement fatty liver
The effect of hepatic function and lipoid degeneration.Therefore, NAFLD medicine is safely and effectively treated in urgent clinical needs.
Liver X receptor (1iver X receptors, LXR) includes two kinds of homologous subtypes of LXR α and LXR β, is ligand activation
Nuclear receptor transcription factor superfamily member.Research shows：LXR β wide expressions are in each histoorgan；LXRs matches somebody with somebody as one kind
Body activating transcription factor, adjusts the expression of downstream target gene, influence body cholesterol, triglycerides, glucose, aliphatic acid
Many physiological functions such as metabolism；LXR ligand binding domain can be combined with multiple compounds, and regulate and control its activated transcription activity,
Therefore LXR is preferable drug target；LXR functional transcriptions are adjusted using ligands specific, after some time it is possible to reach regulation is intracellular
Glycolipid metabolism balances and treats the metabolic diseases such as hyperlipidemia, atherosclerosis, diabetes.
Study the dual agonists that more LXR parts are generally LXR α and LXR β at present, such as T0901317 and GW3965,
Zoopery is proved：These parts tool is significantly reduced serum cholesterol effect, but also promotes liver fat acid to synthesize simultaneously,
So as to increase serum and liver tg content, increase liver volume, Severe fatty liver can be caused；Therefore, LXR is developed
Antagonist or organizing specific activator become the target of current medical research.
Sophoricoside, is the compound extracted from the Fructus Sophorae, is white tip-like crystallization, is insoluble in water, ethanol, is slightly dissolved in hot second
Alcohol, is dissolved in pyridine, diluted alkaline, and insoluble in ethyl acetate, acetone, its chemical structural formula is as follows：
At present, the pharmacological activity report on Sophoricoside is main
Anti-inflammatory, antitumor and antioxidation, the correlation of so far there are no Sophoricoside has liver X receptor-β (LXR β) antagonistic activity
Report.
The content of the invention
It is an object of the invention to provide a kind of new pharmaceutical uses of Sophoricoside, to expand the application value of Sophoricoside.
The medicinal usage of Sophoricoside of the present invention, refers to be used to prepare liver X receptor-β using Sophoricoside as active component
(LXR β) antagonist.
Furtherly, the medicinal usage of Sophoricoside of the present invention, refers to pre- for preparing using Sophoricoside as active component
Prevent, alleviate and/or treat the medicine by metabolic disease beta mediated LXR.
Furtherly, described metabolic disease includes but is not limited to：Metabolic syndrome, diabetes (are more preferably II type sugar
Urine disease), insulin resistance, hyperlipidemia, obesity, atherosclerosis, fatty liver and/or their complication.
Preferably, the medicine for preparing treatment fatty liver is used for using Sophoricoside as active component.
It will be understood by those skilled in the art that heretofore described Sophoricoside can pass through a variety of methods well known in the art, utilization
Known raw material is obtained, such as chemical synthesis or extraction separation etc. from plant.
The formulation of medicine of the present invention can be diversified, as long as it is internal that active component can be made effectively to reach
Formulation is all possible, and is included but is not limited to：Tablet, capsule, powder, granule, syrup, solution, suspension,
The common dosage forms such as injection, tincture, oral liquid, aerosol, mouth containing agent, electuary, pill, powder or nanometer formulation etc. delay
Release dosage form.
Compared with prior art, the present invention has following conspicuousness beneficial effect：
The present invention test result indicates that：Sophoricoside is capable of the suppression LXR β of selectivity transcriptional activity, with obvious suppression
The in vitro effects of Adipocyte Differentiation processed, and block the C57BL/6 mouse weights increase of high-fat meal induction, suppress body fat
The volume of cell increases, improves the vivo efficacies such as mouse fasting blood-glucose, insulin resistance and the dyslipidemia of mouse, can pass through
The suppression LXR β of selectivity transcriptional activity reaches prevention, alleviates and/or treat by metabolic disease beta mediated LXR, can
Hope exploitation for a kind of efficient LXR beta antagonists of low toxicity and prevent, alleviate and/or treat by generation beta mediated LXR for preparing
The medicine of thanking property disease, it is a kind of medicine for preparing treatment fatty liver to be especially expected exploitation.
Brief description of the drawings
Figure 1A embodies influence of the Sophoricoside to nuclear receptor LXR alpha transcriptionals activity；1B embodies Sophoricoside to nuclear receptor LXR β
The influence of transcriptional activity.
Fig. 2A and Fig. 2 B embody lxr agonist GW3965 and LXR α and β combination respectively, and Fig. 2 C embody
The combination of Sophoricoside and LXR α and β.
Fig. 3 embodies reduction of the Sophoricoside to obesity mice fat cell volume and acted on.
Fig. 4 A and Fig. 4 B embody C57BL/6 mouse glucose tolerances ability and the pancreas that Sophoricoside is induced high lipid food respectively
The influence of island element tolerance.
Fig. 5 A to Fig. 5 C embody C57BL/6 mice serums insulin, the adiponectin that Sophoricoside is induced high lipid food respectively
With the effect of leptin.
Fig. 6 embodies the therapeutic action for the C57BL/6 lipid of mice exception that Sophoricoside is induced high lipid food.
Fig. 7 A and Fig. 7 B embody the triglycerides and courage for the C57BL/6 mouse livers that Sophoricoside is induced high lipid food respectively
The influence of sterol content.
Fig. 8 embodies the morphologic influence of C57BL/6 mouse livers that Sophoricoside is induced high lipid food.
In figure：* represent to be compared with control group, P<0.05.
Embodiment
The present invention is made further in detail, intactly illustrate with reference to embodiment, but and be not so limited the present invention；Ability
Some nonessential improvement or replacement that the technical staff in domain is made according to the description below belong to protection scope of the present invention.
The experimental method of unreceipted actual conditions in the following example, generally according to normal condition or according to proposed by manufacturer
Condition.In addition, percentage described in text is mass percent.
I. material and method
1. medicine and animal
8 week old C57BL/6 mouse, about 22~25 grams of body weight/only.Rearing conditions are SPF grades, and raising temperature is 22~23
℃.Day alternates with night within 12 hours.Animal feed is purchased from Research Diet companies of the U.S. (high fat D12492, low fat D12450B).
Sophoricoside is monomeric compound, purity>98%, from purchased in market.
2. experiment reagent and instrument
DMEM nutrient solutions (Hyclone, Logan, UT)；
Trypsase (Gibco, USA)；
Calf serum (Gibco, USA)；
Oil Red O (Sigma, St.Louis, MO)；
Dexamethasone (Sigma, St.Louis, MO)；
Insulin (Sigma, St.Louis, MO)；
DMSO (Sigma, St.Louis, MO)；
HD Transfection Reagent (Roche, Mannheim, Germany)；
Rosiglitazone (Sigma, St.Louis, MO)；
GW3965 (Sigma, St.Louis, MO)；
Dual-Luciferase Reporter Assay System (Promega, USA)；
Plasmid Midi Kit (25) (Qiagen, Germany)；
CO2gas incubator (Thermo Scientific, RS-485, USA)；
Clean bench (AIRTECH, SW-CJ, USA)；
Microcytoscope (Olympus, CKX41, Japan)；
Electron-microscope scanning instrument (Philip, XL-30, USA)；
High speed freezing centrifuge (Eppendorf Centrifuge 5810R, Germany)；
Small desk high speed freezing centrifuge (Eppendorf Centrifuge 5424R, Germany)；
Common bench refrigerated centrifuge (Eppendorf Centrifuge 5415R, Germany)；
Multi-function microplate reader (Bio-Tek, Synergy HT, USA)；
Ice machine (Xue Ke Electrical Appliances Co., Ltd, IMS-40, China)；
Gel imager (Shanghai Tian Neng Science and Technology Ltd.s, Tanon-2500, China)；
Pipettor (Eppendorf Research, Germany)；
Constant incubator (the permanent Science and Technology Ltd. in Shanghai one, DHP-9082, China)；
48 orifice plates (Corning, USA)；
0.22 μm, 0.45 μm of miillpore filter (Millipore, Germany)；
Isopropanol, formalin, pretty young woman's acid (analyzing pure, Chinese medicines group Solution on Chemical Reagents in Shanghai company)；
3.LXR α/β reporter gene assays
(1) 293T cell culture
293T cell lines (human embryonic kidney cell line) with containing 10% calf serum and 1% dual anti-DMEM high glucose mediums in
37 DEG C, 5%CO2Cultivated in incubator.Take the logarithm the 293T plating cells in growth period, cell density is 1 × 105~2 × 105
Individual/mL is plated in 48 orifice plates.
(2) transfected plasmids are supplied
PCMX-Gal-mLXR α, β LBD plasmids, Gal4reporter vector MH100 × 4-TK-Luc recombinant plasmids and
Renilla luciferase internal reference plasmids.
(3) transfect
Overnight, when the density of cell length to 50~80%, transfected.Prepared and turned with DMEM (serum-free is without dual anti-)
Dye system：Total plasmid containing 10 μ g in every milliliter of DMEM, and 15 μ L transfection reagent-FuGENE
Rotaring redyeing system, is then vortexed and mixes by HD (Roche, Mannheim, Germany), and room temperature places 15min, then will turn
Dye system cotransfection after 4~6h of culture, uses complete medium (DMEM, 10%FBS, 1% couple instead in 293T cells
It is anti-) continue to cultivate to 24h.
(4) dosing intervention
After 24h, the Sophoricoside of various concentrations gradient that addition is diluted with complete medium (10,25,50 μM) is intervened,
250 μ L final concentration drug solutions are added per hole, while adding lxr agonist GW3965 (10 μM).
(5) cell is handled
1. after 24h, remove remaining cell culture fluid with PBS cell twice；
2. 65 μ L lysate is added per hole, shaking table vibration 15min treats that cell cracking is complete, cell pyrolysis liquid is shifted
Into 1.5mL centrifuge tubes；
3. cell pyrolysis liquid is centrifuged into 5min in 1000rpm, takes the μ L of supernatant 10 in new centrifuge tube, it is to be measured.
(6) determine and the plain enzyme intensity of analysis of fluorescence
1. plus the μ L of II liquid of LAR 20, mix, survey fluorescence, postpone within 2 seconds, read 10 seconds；Transfection efficiency utilizes internal reference Renilla
Uciferase activity is corrected, all transfection experiments at least it is independent in triplicate, each experimental group at least two secondary orifices.
2. Bio-Tek is utilized, Synergy HT multi-function microplate readers carry out firefly and the detection of ocean coelenteron fluorescence intensity, firefly
Noctiluca luciferase expression intensity represents with the ratio of firefly fluorescent and ocean coelenteron fluorescence intensity, the relative intensity of fluorescence=light of firefly
Worm fluorescence intensity/ocean coelenteron fluorescence intensity, i.e., it is main whether to be passed through using the additional medicine of luciferase relative expression's active reaction
With LXR α, beta receptor generating function combines to influence LXR α, β transcriptional activities.
4. animal and packet
The C57BL/6 mouse that high lipid food is fed may occur in which the classical symptom of fat, hyperlipidemia and type ii diabetes.Pass through
Animal is administered orally, observation the weight of animals, body fat content, blood fat, plasma glucose levels, plasma insulin, Portugal
Grape sugar resistance test, Glucose Tolerance Test etc..
8 week old mouse use the high lipid food of the fat containing 60% (w/w) to feed three months, and mouse forms obesity, hyperlipidemia, pancreas
Insulin resistance etc., feed is mixed into by Sophoricoside in 0.01% ratio, allow mouse ad lib, drinking-water, altogether treat 4 weeks, every
Day entry mouse weight and food ration.
5. lipid determination
Mouse fasting 12 hours, Culling heart blood stands 2 hours, 3000rpm centrifugation 15min, collects mice serum, entirely
Automatic biochemical analyzer surveys triglycerides, cholesterol, HDL and low-density lipoprotein white level.
6. liver fat is determined
Mouse fasting 12 hours, takes liver after execution, clip liver organization about 50mg or so weighs, is placed in tissue and splits
Solve liquid in, liver is crushed with Ultrasonic cell smash, isometric chloroform recovery liver fat composition, by 12000rpm from
The heart 10 minutes, takes chloroform layer, and the dissolving of 50 μ L isopropanols is added after chloroform layer is spontaneously dried, triglycerides and cholesterol is surveyed
Lipid content in level, liver is represented with the result of lipid content (mg)/liver weight (g).
7. liver section is dyed
Tissue fixative solution of the liver organization through 10% formalin is fixed, and is cut into slices, is dyed, made film using HE dyeing and oil red.
8. fatty section statining
Each group mouse takes animal white adipose tissue to be fixed with the tissue fixative solution containing 10% formalin after anesthesia is put to death
Section, dyeing, film making.
9. blood sugar detection
Treatment end surveys mouse glucose tolerance test：Mouse peritoneal injection 1g/kg body weight glucose, 0,15,30,60,
90th, mouse tail vein blood glucose value is surveyed during 120min.
Survey the sugared resistance test of mouse islets element：Mouse has three days off, insulin injection 10U/kg body weight, respectively at 0,15,
30th, 60 mouse tail vein blood glucose value, is surveyed during 90min.
10. statistics
Two groups of data are examined using T, and multi-group data uses ANOVA statistical dispositions, and data are represented with mean ± standard error,
P<0.05 represents significant difference.
II. embodiment
Embodiment 1：Influence of the Sophoricoside to nuclear receptor LXR α, β transcriptional activities
Use LXR α, the luciferase reporting of GAL4-DBD-LBD expression plasmids and the GAL4 response of two kinds of nuclear receptors of β
Genic system analyzes influence of the Sophoricoside to 2 seed nucleus receptor transcriptional activities.
By GAL4-DBD-LBD expression plasmids and GAL4- luciferase reporter plasmids cotransfection in after 293T cells
Handled 24 hours through lxr agonist GW3965 (10 μM) and Sophoricoside (5,10,20 μ g/mL), detect its firefly
Uciferase activity, using Renilla activity as internal reference to judge reporter gene activity, data are three experimental results, are used
Means ± SE represents, * P<0.05.
As a result show：In the presence of lxr agonist GW3965, Sophoricoside is competed in the way of a kind of concentration dependant
The activity for inhibiting LXR β of property, medicine is 12.5, it is aobvious to show under the medicining condition of 25,50 μM of three kinds of various concentrations
The inhibition of work (see shown in Figure 1B)；But under identical medication disposition, Sophoricoside is not shown to LXR α
Activity have significant regulating effect (see shown in Figure 1A), illustrate Sophoricoside can as active component be used for prepare liver X receptor
- β (LXR beta receptors) antagonist.
Embodiment 2：Application time resolved fluorescent resonance energy transfer (TR-FRET) experiment detection Sophoricoside and nuclear receptor
LXR binding ability
Detect that Sophoricoside displaces the energy of tagged ligand from acceptor site by application time resolved fluorescent resonance energy transfer experiments
Power carrys out the binding ability of indirect reaction Sophoricoside and nuclear receptor LXR α and β.
Using Invitrogen companies test LXR transcriptional coactivators detection kit (TR-FRET), first add
2X testing compounds, the 2X positive reference compounds of 10 μ L various concentrations gradients add 5 μ L 4 into 384 orifice plates, then
X LXR α and β-LBD/Tb-anti-GST antibody, 5 μ L 4X fluorescent dyes, lucifuge gently shakes 30s after 1000rpm
Centrifugation, then 1~2h is being incubated at room temperature, 495nm and 520nm fluorescence signal is tested with Envision.
Experimental result refers to Fig. 2A~Fig. 2 C, wherein：Fig. 2A and Fig. 2 B are respectively shown in lxr agonist GW3965 and LXR α
With β combination, Fig. 2 C show the combination of Sophoricoside and LXR α and β；It is visible with reference to Fig. 2A~Fig. 2 C：The Fructus Sophorae
Glycosides competes LXR β binding sites with lxr agonist GW3965, but does not compete LXR α binding sites, illustrates that Sophoricoside has
LXR beta selective antagonistic activities.
Embodiment 3：The antiobesity action checking of Sophoricoside
Because LXR β transcriptional activity is synthesized and the metabolism of triglyceride is closely related with aliphatic acid, suppress LXR β transcription
Activity can play the effect for suppressing triglyceride synthesis and fat-reducing.So inventor herein is using obesity mice, (mouse passes through
Chow diet, high lipid food and the high lipid food feeding 8 weeks for being mixed with 0.01% Sophoricoside, measure weekly mouse weight；Data
For mean ± SE, each group n=7) come verify Sophoricoside whether have suppress fat cell effect.
As a result show：Sophoricoside feeding can not block the increased weight of high-fat meal induction C57BL/6 mouse for 2 weeks, but use is cut
HE dyeing detects the white fatty size of mouse after piece, finds the effect with suppression obesity mice adipocyte hypertrophy (see Fig. 3
It is shown), illustrate that Sophoricoside has certain antiobesity action.
Embodiment 4：The hypoglycemic effect checking of Sophoricoside
1. fasting blood-glucose experiment and the glucose tolerance test of Sophoricoside administration mouse
Because obesity is closely related with insulin resistance, hyperglycaemia.Because we make through chow diet, high fat in example 2
Feed and mouse fasting of the high lipid food feeding of 0.01% Sophoricoside after 4 weeks 12 hours is mixed with, the side of blood is then taken with tail point
Formula is collected and measures the fasting blood-glucose (0min) of each group mouse, then notes glucose sugared (1g glucose/kg body weight) with abdominal cavity
The mode penetrated gives each group mouse, and 15min, 30min, 60min, 90min and 120min after are tested respectively respectively
The blood glucose value of group mouse, data are mean ± SE, each group n=7.
As a result show：The mouse fasting blood-glucose that high lipid food is raised is significantly higher than low fat control mice, after being administered through Sophoricoside
The higher fat control group mice of blood glucose value of the mouse in 120min has significant reduction (see shown in Fig. 4 A), illustrates Sophoricoside
It can significantly improve the fasting blood-glucose of high-fat meal inducing mouse and the tolerance of glucose.
2. the Glucose Tolerance Test of mouse is administered in Sophoricoside
After clear and definite Sophoricoside can improve mouse glucose tolerance, we make through chow diet, high lipid food and are mixed with 0.01%
Mouse test mouse tail vein random blood sugar (0min) of the high lipid food feeding of Sophoricoside after 4 weeks, and by insulin (1U/kg
Body weight) each group mouse is injected in, mouse tail vein blood glucose value is surveyed when 30,60,90min, data are mean ± SE,
Each group n=7.
As a result show：The higher fat control group mice of blood glucose value of the mouse in 120min after being administered through Sophoricoside has significantly
Reduction illustrates that Sophoricoside can improve the insulin resistance of high-fat meal inducing mouse (see shown in Fig. 4 B).
3. the insulin of Sophoricoside administration mouse, adiponectin and leptin experiment
Because obesity can make obesity mice serum insulin and leptin bright with the insulin and leptin resistance of obesity-induced mice
Aobvious rise, and adiponectin declines；And the serum of the obesity mice after being treated 4 weeks through Sophoricoside is detected, find therein
Insulin and leptin are substantially reduced, and adiponectin significantly raises (see shown in Fig. 5 A to Fig. 5 C), illustrate Sophoricoside energy
Improve obesity mice insulin resistance, be conducive to the treatment of diabetes and fatty liver diseases.
Embodiment 5：The therapeutic action checking for the C57BL/6 lipid of mice exception that Sophoricoside is induced high-fat meal
The high lipid food feeding of 0.01% Sophoricoside is mixed with to being given through the trimestral obesity mice of high lipid food nursing 4 weeks, so
After make mouse fasting 12 hours, collect the blood sample of mouse after fasting using the mode of Culling heart blood, determine in each group mice serum
T-CHOL (TC), triglyceride (TG), HDL-C (HDL-c), LDL-C
(LDL-c) level, data are mean ± SE, each group n=7.Experiment is found：Triglyceride levels in mice serum are notable
Less than high fat control group, but to cholesterol, low-density lipoprotein and HDL without obvious effect (as shown in Figure 6),
Illustrate that Sophoricoside can treat hypertriglyceridemia.
Embodiment 6：Sophoricoside is verified to the improvement result of obesity mice fatty liver
Obesity mice after to being treated 4 weeks through Sophoricoside carries out analysis and found, the triglycerides and cholesterol level of mouse liver
Substantially less than high fat control group (see shown in Fig. 7 A and Fig. 7 B)；Further cut into slices using mouse liver, through oil red dyeing and
HE is dyed, and is as a result displayed that：The mouse liver fat treated through Sophoricoside is substantially less than control group, and liver morphology is substantially excellent
In control group mice (as shown in Figure 8), illustrate that Sophoricoside has significant therapeutic effect to fatty liver.
To sum up test visible：Sophoricoside is capable of the suppression LXR β of selectivity transcriptional activity, and fat is suppressed carefully with obvious
The in vitro effects of born of the same parents' differentiation, and block the C57BL/6 mouse weights increase of high-fat meal induction, suppress the body of body fat cell
Product increases, improves the vivo efficacies such as mouse fasting blood-glucose, insulin resistance and the dyslipidemia of mouse, can pass through selectivity
The transcriptional activity for suppressing LXR β reaches prevention, alleviates and/or treats the effect by metabolic disease beta mediated LXR, it is expected to
Develop for a kind of efficient LXR beta receptors antagonist of low toxicity and for preparing prevention, alleviation and/or treating beta mediated by LXR
The medicine of metabolic disease, it is a kind of medicine for preparing treatment fatty liver to be especially expected exploitation.
Finally need described herein be：All documents referred in the present invention are all incorporated as reference in this application, as
It is individually recited with each document as with reference to such.In addition, it is to be understood that read the present invention above-mentioned instruction content it
Afterwards, those skilled in the art can be made various changes or modifications to the present invention, and these equivalent form of values are equally fallen within appended by the application
Claims limited range.
Claims (4)
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|---|---|---|---|---|
| WO2003053336A2 (en) * | 2001-12-19 | 2003-07-03 | The Quigley Corporation | Methods for the treatment of peripheral neural and vascular ailments |
| WO2008010663A1 (en) * | 2006-07-18 | 2008-01-24 | Eurapharm, Inc. | Sophoricoside-containing composition for reducing body-weight or body-fat |
| CN103597071A (en) * | 2011-01-07 | 2014-02-19 | 埃尔舍利克斯治疗公司 | Chemosensory receptor ligand-based therapies |
| CN105998045A (en) * | 2016-06-27 | 2016-10-12 | 王双喜 | Pharmaceutical composition for treating atherosclerosis and application thereof |
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2016
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| WO2003053336A2 (en) * | 2001-12-19 | 2003-07-03 | The Quigley Corporation | Methods for the treatment of peripheral neural and vascular ailments |
| WO2008010663A1 (en) * | 2006-07-18 | 2008-01-24 | Eurapharm, Inc. | Sophoricoside-containing composition for reducing body-weight or body-fat |
| CN103597071A (en) * | 2011-01-07 | 2014-02-19 | 埃尔舍利克斯治疗公司 | Chemosensory receptor ligand-based therapies |
| CN105998045A (en) * | 2016-06-27 | 2016-10-12 | 王双喜 | Pharmaceutical composition for treating atherosclerosis and application thereof |
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