CN103304607B - The monoterpene glycoside compound obtained from Sibiraea angustata lowering blood-fat and reducing weight efficient part and application thereof - Google Patents
The monoterpene glycoside compound obtained from Sibiraea angustata lowering blood-fat and reducing weight efficient part and application thereof Download PDFInfo
- Publication number
- CN103304607B CN103304607B CN201310205003.4A CN201310205003A CN103304607B CN 103304607 B CN103304607 B CN 103304607B CN 201310205003 A CN201310205003 A CN 201310205003A CN 103304607 B CN103304607 B CN 103304607B
- Authority
- CN
- China
- Prior art keywords
- compound
- ethyl acetate
- extract
- monoterpene glycoside
- fat
- 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.)
- Active
Links
- 229930182470 glycoside Natural products 0.000 title claims abstract description 23
- 229930003658 monoterpene Natural products 0.000 title claims abstract description 18
- -1 monoterpene glycoside compound Chemical class 0.000 title claims abstract description 18
- 235000002577 monoterpenes Nutrition 0.000 title claims abstract description 18
- 241000040929 Sibiraea angustata Species 0.000 title claims abstract description 15
- 150000001875 compounds Chemical class 0.000 claims abstract description 45
- BUBVLQDEIIUIQG-UHFFFAOYSA-N 3,4,5-tris(phenylmethoxy)-6-(phenylmethoxymethyl)oxan-2-one Chemical compound C=1C=CC=CC=1COC1C(OCC=2C=CC=CC=2)C(OCC=2C=CC=CC=2)C(=O)OC1COCC1=CC=CC=C1 BUBVLQDEIIUIQG-UHFFFAOYSA-N 0.000 claims abstract description 28
- 239000003814 drug Substances 0.000 claims abstract description 19
- 208000008589 Obesity Diseases 0.000 claims abstract description 12
- 235000020824 obesity Nutrition 0.000 claims abstract description 12
- 201000010099 disease Diseases 0.000 claims abstract description 9
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 9
- 125000002252 acyl group Chemical group 0.000 claims abstract description 5
- 238000000746 purification Methods 0.000 claims abstract description 4
- 239000000284 extract Substances 0.000 claims description 31
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 21
- 239000003208 petroleum Substances 0.000 claims description 14
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 12
- 238000010828 elution Methods 0.000 claims description 12
- 239000000243 solution Substances 0.000 claims description 12
- 239000012043 crude product Substances 0.000 claims description 10
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 9
- SRCZQMGIVIYBBJ-UHFFFAOYSA-N ethoxyethane;ethyl acetate Chemical compound CCOCC.CCOC(C)=O SRCZQMGIVIYBBJ-UHFFFAOYSA-N 0.000 claims description 9
- 150000003839 salts Chemical class 0.000 claims description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 7
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 6
- 239000002024 ethyl acetate extract Substances 0.000 claims description 6
- 239000012530 fluid Substances 0.000 claims description 6
- 238000010898 silica gel chromatography Methods 0.000 claims description 6
- 230000002265 prevention Effects 0.000 claims description 5
- 239000007864 aqueous solution Substances 0.000 claims description 4
- 238000004440 column chromatography Methods 0.000 claims description 4
- 239000000499 gel Substances 0.000 claims description 4
- 239000007921 spray Substances 0.000 claims description 4
- 239000006185 dispersion Substances 0.000 claims description 3
- 238000000034 method Methods 0.000 claims description 3
- 230000002829 reductive effect Effects 0.000 claims description 3
- 238000002560 therapeutic procedure Methods 0.000 claims description 3
- 239000000654 additive Substances 0.000 claims description 2
- 230000000996 additive effect Effects 0.000 claims description 2
- 238000000605 extraction Methods 0.000 claims description 2
- 239000007788 liquid Substances 0.000 claims description 2
- 229910021645 metal ion Inorganic materials 0.000 claims description 2
- 239000012046 mixed solvent Substances 0.000 claims description 2
- 238000010992 reflux Methods 0.000 claims description 2
- 239000000377 silicon dioxide Substances 0.000 claims description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 claims 1
- 238000002360 preparation method Methods 0.000 claims 1
- OVARTBFNCCXQKS-UHFFFAOYSA-N propan-2-one;hydrate Chemical compound O.CC(C)=O OVARTBFNCCXQKS-UHFFFAOYSA-N 0.000 claims 1
- 238000010298 pulverizing process Methods 0.000 claims 1
- 230000004069 differentiation Effects 0.000 abstract description 8
- 208000031226 Hyperlipidaemia Diseases 0.000 abstract description 5
- 208000004930 Fatty Liver Diseases 0.000 abstract description 4
- 206010019708 Hepatic steatosis Diseases 0.000 abstract description 4
- 206010020772 Hypertension Diseases 0.000 abstract description 4
- 208000029078 coronary artery disease Diseases 0.000 abstract description 4
- 206010012601 diabetes mellitus Diseases 0.000 abstract description 4
- 230000000694 effects Effects 0.000 abstract description 4
- 208000010706 fatty liver disease Diseases 0.000 abstract description 4
- 201000002859 sleep apnea Diseases 0.000 abstract description 4
- 231100000240 steatosis hepatitis Toxicity 0.000 abstract description 4
- 230000035755 proliferation Effects 0.000 abstract description 2
- 238000000926 separation method Methods 0.000 abstract description 2
- 230000001629 suppression Effects 0.000 abstract 1
- 210000004027 cell Anatomy 0.000 description 11
- 230000004083 survival effect Effects 0.000 description 8
- 241000124033 Salix Species 0.000 description 7
- 244000269722 Thea sinensis Species 0.000 description 7
- 235000015097 nutrients Nutrition 0.000 description 7
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 6
- 230000009422 growth inhibiting effect Effects 0.000 description 6
- 239000000047 product Substances 0.000 description 6
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 5
- 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 5
- 229940079593 drug Drugs 0.000 description 5
- 239000008103 glucose Substances 0.000 description 5
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- 230000002401 inhibitory effect Effects 0.000 description 4
- 244000309466 calf Species 0.000 description 3
- 239000013078 crystal Substances 0.000 description 3
- 210000002966 serum Anatomy 0.000 description 3
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- 108010028554 LDL Cholesterol Proteins 0.000 description 2
- 241001529936 Murinae Species 0.000 description 2
- NPGIHFRTRXVWOY-UHFFFAOYSA-N Oil red O Chemical compound Cc1ccc(C)c(c1)N=Nc1cc(C)c(cc1C)N=Nc1c(O)ccc2ccccc12 NPGIHFRTRXVWOY-UHFFFAOYSA-N 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 239000000824 cytostatic agent Substances 0.000 description 2
- 230000001085 cytostatic effect Effects 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 238000011534 incubation Methods 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 230000003287 optical effect Effects 0.000 description 2
- 210000000229 preadipocyte Anatomy 0.000 description 2
- 230000000630 rising effect Effects 0.000 description 2
- 239000000741 silica gel Substances 0.000 description 2
- 229910002027 silica gel Inorganic materials 0.000 description 2
- 229960001866 silicon dioxide Drugs 0.000 description 2
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 2
- 102100040214 Apolipoprotein(a) Human genes 0.000 description 1
- 101710115418 Apolipoprotein(a) Proteins 0.000 description 1
- XUIIKFGFIJCVMT-GFCCVEGCSA-N D-thyroxine Chemical compound IC1=CC(C[C@@H](N)C(O)=O)=CC(I)=C1OC1=CC(I)=C(O)C(I)=C1 XUIIKFGFIJCVMT-GFCCVEGCSA-N 0.000 description 1
- 244000166102 Eucalyptus leucoxylon Species 0.000 description 1
- 235000004694 Eucalyptus leucoxylon Nutrition 0.000 description 1
- 208000035150 Hypercholesterolemia Diseases 0.000 description 1
- 102000004877 Insulin Human genes 0.000 description 1
- 108090001061 Insulin Proteins 0.000 description 1
- 235000004789 Rosa xanthina Nutrition 0.000 description 1
- 241000220222 Rosaceae Species 0.000 description 1
- 210000001789 adipocyte Anatomy 0.000 description 1
- 125000003368 amide group Chemical group 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 229940125904 compound 1 Drugs 0.000 description 1
- 229940125782 compound 2 Drugs 0.000 description 1
- UREBDLICKHMUKA-CXSFZGCWSA-N dexamethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O UREBDLICKHMUKA-CXSFZGCWSA-N 0.000 description 1
- 229960003957 dexamethasone Drugs 0.000 description 1
- 230000029087 digestion Effects 0.000 description 1
- 230000004927 fusion Effects 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 238000003919 heteronuclear multiple bond coherence Methods 0.000 description 1
- 238000005570 heteronuclear single quantum coherence Methods 0.000 description 1
- 238000004896 high resolution mass spectrometry Methods 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 238000001819 mass spectrum Methods 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 230000000452 restraining effect Effects 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 229940034208 thyroxine Drugs 0.000 description 1
- XUIIKFGFIJCVMT-UHFFFAOYSA-N thyroxine-binding globulin Natural products IC1=CC(CC([NH3+])C([O-])=O)=CC(I)=C1OC1=CC(I)=C(O)C(I)=C1 XUIIKFGFIJCVMT-UHFFFAOYSA-N 0.000 description 1
Landscapes
- Medicines Containing Plant Substances (AREA)
Abstract
The present invention relates to compound separation purification art, relate to the monoterpene glycoside compound and application thereof that obtain from Sibiraea angustata lowering blood-fat and reducing weight efficient part particularly.The monoterpene glycoside compound that the present invention obtains from Sibiraea angustata lowering blood-fat and reducing weight efficient part, such as 1-oxygen-β-D-(6 "-O-methyl asafoetide acyl group)-glucopyranosyl-Geraniol-10, 5-lactone (1) and 3, 7-dimethyl-3 (Z)-eight alkene-5-ketone 1-oxygen-β-D-Glucose glycosides (2), it has the effect of suppression PECTORAL LIMB SKELETON 3T3-L1 proliferation and differentiation, provide the hyperlipidemia that can be used for obesity and obesity and cause, hypertension, diabetes, fatty liver, coronary heart disease, the medicine of the diseases such as sleep apnea syndrome and the medicine relevant with above-mentioned disease and healthcare products purposes.
Description
Technical field
The present invention relates to compound separation purification art, relate to the monoterpene glycoside compound and application thereof that obtain from Sibiraea angustata lowering blood-fat and reducing weight efficient part particularly.
Background technology
Sibiraea angustata (Sibiraeaangustata (Rehd.) Hand.-Mazz) is Rosaceae Sibirae, and be Tibetan's common drug among the people, its leaf and spray are used as medicine, and have another name called willow tea, have clearing away the stomach-heat, aid digestion, regulate lipometabolic effect.Bibliographical information willow tea effective part extract can " obesity prevention and treatment hypercholesterolemia (reduce triglyceride level (TG), LDL-C (LDL-C) and the Lp(a) concentration in blood, improve blood viscosity) " (patent of invention " a kind of obesity prevention and the willow tea effective part extract reducing hyperlipidemia and its production and use " CN10173244A).Willow tea effective part extract (patent of invention " a kind of willow tea effective part extract and its production and use " CN102641352A) can be used for medicine or the healthcare products of fat reducing fat-reducing.The present inventor based on previous work, extracts and obtains the monoterpene glycoside compound that two kinds have functions of lowering blood-fat and reducing weight, and adopt nucleus magnetic resonance and high resolution mass spectrum technology to identify its chemical structure from Sibiraea angustata efficient part.
Summary of the invention
The object of this invention is to provide the monoterpene glycoside compound obtained from Sibiraea angustata (willow tea) lowering blood-fat and reducing weight efficient part.
Another object of the present invention is to provide monoterpene glycoside compound pharmacy acceptable salt.
Another object of the present invention is to provide above-mentioned monoterpene glycoside compound for prevention and therapy obesity and the medicine of the disease such as hyperlipidemia, hypertension, diabetes, fatty liver, coronary heart disease, sleep apnea syndrome caused by obesity and the medicine relevant with above-mentioned disease and healthcare products purposes.
According to the monoterpene glycoside compound obtained from Sibiraea angustata (willow tea) lowering blood-fat and reducing weight efficient part of the present invention, be separated by following steps and obtain:
(1) Sibiraea angustata (Rehd.) Hand.-Mazz. and the spray of drying and crushing is got, by hot water (can use methyl alcohol (10-90%) aqueous solution, ethanol (10-90%) solution, acetone (10-80%) solution) refluxing extraction, concentrating under reduced pressure removes desolventizing and obtains 1.1kg semi-fluid shape medicinal extract;
(2), after semi-fluid shape medicinal extract adds water (1L) dispersion, use sherwood oil (3 × 1L), methylene dichloride (3 × 1L), ethyl acetate (3 × 1L) to extract successively, concentrated extract, obtains sherwood oil medicinal extract, methylene dichloride medicinal extract, ethyl acetate extract;
(3) to ethyl acetate extract through silica gel column chromatography, adopt petroleum ether-ethyl acetate gradient elution, obtain A-D tetra-part medicinal extract, to D medicinal extract (petroleum ether-ethyl acetate (volume ratio 1:1) elution fraction) again through silica gel column chromatography, adopt petroleum ether-ethyl acetate-methanol mixed solvent gradient elution, obtain compound (1) crude product and compound (2) crude product respectively.Compound (1) and (2) crude product respectively through SephadexLH-20 gel column chromatography and silica column purification repeatedly, obtain sterling compound (1) and (2) again.The structure warp of compound (1) and (2)
1hNMR,
13cNMR and HMBC, HSQC, HR-MS carry out Structural Identification and attribution data.
According to monoterpene glycoside compound of the present invention; it is 1-O-β-D-(6 "-O-methyl asafoetide acyl group)-glucopyranosyl-Geraniol-10; 5-lactone (1) and 3; 7-dimethyl-3 (Z)-eight alkene-5-ketone 1-oxygen-β-D-Glucose glycosides (2, the structural formula of compound is such as formula (1) and formula (2):
The invention provides above-mentioned monoterpene glycoside compound pharmacy acceptable salt, can be the additive salt formed with following amido or metal ion: NH
4 +, Na
+, K
+, Mg
2+, Li
+, Ca
2+, Sr
2+, Ca
2+, Zn
2+deng.
Present invention also offers above-mentioned monoterpene glycoside compound; such as 1-oxygen-β-D-(6 "-O-methyl asafoetide acyl group)-glucopyranosyl-Geraniol-10; 5-lactone (1) and 3; 7-dimethyl-3 (Z)-eight alkene-5-ketone 1-oxygen-β-D-Glucose glycosides (2), and pharmaceutical salts is used for prevention and therapy obesity and the medicine of the disease such as hyperlipidemia, hypertension, diabetes, fatty liver, coronary heart disease, sleep apnea syndrome caused by obesity and the medicine relevant with above-mentioned disease and healthcare products purposes.
Feature of the present invention is, from the monoterpene glycoside compound that Sibiraea angustata is purified, such as compound (1) and compound (2), have and suppress the effect of PECTORAL LIMB SKELETON 3T3-L1 proliferation and differentiation, provide can be used for that obesity and obesity cause the medicine of the disease such as hyperlipidemia, hypertension, diabetes, fatty liver, coronary heart disease, sleep apnea syndrome and the medicine relevant with above-mentioned disease and healthcare products purposes.
Accompanying drawing explanation
Fig. 1 shows compound (1) has certain growth-inhibiting effect to 3T3-L1 PECTORAL LIMB SKELETON.
Fig. 2 shows compound (2) has certain growth-inhibiting effect to 3T3-L1 PECTORAL LIMB SKELETON.
Fig. 3 shows compound (1) and suppresses the differentiation of PECTORAL LIMB SKELETON 3T3-L1.
Fig. 4 shows compound (2) and suppresses the differentiation of PECTORAL LIMB SKELETON 3T3-L1.
Embodiment
By embodiment below, the present invention is described in further detail, but these embodiments not meaning that any restriction of the present invention.
Embodiment 1
Get Sibiraea angustata (Rehd.) Hand.-Mazz. and the spray 10kg of drying and crushing, extract with hot water return, concentrating under reduced pressure removes desolventizing and obtains 1.1kg semi-fluid shape medicinal extract.
Semi-fluid shape medicinal extract adds water after (1L) dispersion, uses sherwood oil (3 × 1L), methylene dichloride (3 × 1L), ethyl acetate (3 × 1L) to extract successively, concentrated extract, obtains sherwood oil medicinal extract, methylene dichloride medicinal extract, ethyl acetate extract (410g).
To ethyl acetate extract (200g) through silica gel column chromatography, adopt petroleum ether-ethyl acetate gradient elution, obtain A(petroleum ether-ethyl acetate (volume ratio is about 20-10:1) elution fraction, 85g), B(petroleum ether-ethyl acetate (volume ratio is about 5:1) elution fraction, 45g), C(petroleum ether-ethyl acetate (volume ratio is about 3:1) elution fraction, 35g), D(petroleum ether-ethyl acetate (volume ratio is about 1:1) elution fraction, 25g) four part medicinal extract.To D medicinal extract again through silica gel column chromatography, adopt petroleum ether-ethyl acetate-methyl alcohol (2:1:0-0:1:1, volume ratio) wash-out, obtain compound (1) crude product (35mg) and compound (2) crude product (25mg) respectively.Compound (1) crude product is through SephadexLH-20 gel column chromatography repeatedly (with methyl alcohol (10%-70%) aqueous solution gradient elution) and silicagel column (wash-out petroleum ether-ethyl acetate-methyl alcohol (2:1:0.1, volume ratio)) purifying, obtain sterling compound (1) (23mg).Compound (2) crude product, through SephadexLH-20 gel column chromatography repeatedly (with methyl alcohol (50%) aqueous solution wash-out) and silicagel column (wash-out petroleum ether-ethyl acetate-methyl alcohol (3:1:0.1, volume ratio)) purifying, obtains sterling compound (2) (15mg).
Compound (1), light yellow gum thing, is soluble in methyl alcohol, dissolves in acetone, water.
1h and
13cNMR data are see table 1.HR-FABMSm/z535.2174 [M+H]
+(Calcd [M+H]
+535.2139forC
27h
35o
11 +), can molecular formula C be used
27h
34o
11represent, and called after 1-oxygen-β-D-(6 "-O-methyl asafoetide acyl group)-glucopyranosyl-Geraniol-10,5-lactone.
Compound (2), colourless acicular crystal, is soluble in chloroform, methyl alcohol and ethanol, in water soluble.[α]
d 20-20.4 (c0.56, MeOH);
1h and
13cNMR data are see table 2; HR-FABMSm/z333.1917 [M+H]
+(Calcd333.1913forC
16h
29o
7 +).Molecular formula C can be used
16h
28o
7represent, called after 3,7-dimethyl-3 (Z)-eight alkene-5-ketone 1-oxygen-β-D-Glucose glycosides.
Table 1 compound (1)
1hNMR,
13cNMR data (CD
3oD, δ ppm, JHz)
Table 2 compound (2)
1hNMR,
13cNMR data (400MHz, CD
3oD, δ ppm, JHz)
Embodiment 2
Compound (1) is to the growth-inhibiting of PECTORAL LIMB SKELETON 3T3-L1
PECTORAL LIMB SKELETON 3T3-L1 is by 5 × 10
4the density of individual/mL is inoculated into 6 well culture plates, at DMEM in high glucose substratum 37 DEG C, 5%CO containing 10% calf serum
2cultivate in incubator.Discard nutrient solution after 24h, wherein 3 holes add the nutrient solution (150 ~ 1500 μ g/mL) that 100 μ L contain the compound (1) of different mass concentration, with the DMEM in high glucose not containing sample for blank, and incubation 72h.After removing nutrient solution, the DMEM10 substratum added containing 0.5mg/mLMTT incubates 4h, then adds 0.1g/mLSDS (containing the 0.1mol/LHCl) solutions overnight of 100 μ L, to dissolve MTT purple crystal product completely.Optical density value is measured 570nm place (taking 630nm as reference wavelength) by microplate reader.Experiment repetition 3 times.Carry out straight-line regression with the logarithm of drug level and cell survival rate and obtain IC
50(half-inhibition concentration, required drug level when namely cell survival rate is 50%).
As can be seen from Figure 1, compound (1) has certain growth-inhibiting effect to 3T3-L1 PECTORAL LIMB SKELETON.Along with the rising (150 ~ 800 μ g/mL) of compound (1) concentration, its cytostatic ability strengthens, and cell survival rate is down to 36% from about 100%.When extract quality concentration is between 900 ~ 1500 μ g/mL, cell survival rate is substantially constant.As calculated, compound (1) is (485.2 ± 18.2) μ g/mL to the growth inhibiting IC50 of 3T3-L1 PECTORAL LIMB SKELETON.Test-results shows that compound (1) has certain growth-inhibiting effect to Swiss murine preadipocyte cell 3T3-L1.
Embodiment 3
Compound (2) is to the growth-inhibiting of PECTORAL LIMB SKELETON 3T3-L1
PECTORAL LIMB SKELETON 3T3-L1 is by 5 × 10
4the density of individual/mL is inoculated into 6 well culture plates, at DMEM in high glucose substratum 37 DEG C, 5%CO containing 10% calf serum
2cultivate in incubator.Discard nutrient solution after 24h, wherein 3 holes add the nutrient solution (150 ~ 1500 μ g/mL) that 100 μ L contain the compound (2) of different mass concentration, with the DMEM in high glucose not containing sample for blank, and incubation 72h.After removing nutrient solution, the DMEM10 substratum added containing 0.5mg/mLMTT incubates 4h, then adds 0.1g/mLSDS (containing the 0.1mol/LHCl) solutions overnight of 100 μ L, to dissolve MTT purple crystal product completely.Optical density value is measured 570nm place (taking 630nm as reference wavelength) by microplate reader.Experiment repetition 3 times.Carry out straight-line regression with the logarithm of drug level and cell survival rate and obtain IC
50(half-inhibition concentration, required drug level when namely cell survival rate is 50%).
As can be seen from Figure 2, compound (2) has certain growth-inhibiting effect to 3T3-L1 PECTORAL LIMB SKELETON.Along with the rising (150 ~ 1000 μ g/mL) of compound (2) concentration, its cytostatic ability strengthens, and cell survival rate is down to 35% from about 100%.When extract quality concentration is between 1000 ~ 1500 μ g/mL, cell survival rate is substantially constant.As calculated, compound (2) is (349.5 ± 20.2) μ g/mL to the growth inhibiting IC50 of 3T3-L1 PECTORAL LIMB SKELETON.Test-results shows that compound (2) has certain growth-inhibiting effect to Swiss murine preadipocyte cell 3T3-L1.
Embodiment 4
Compound (1) and (2) suppress the differentiation of PECTORAL LIMB SKELETON 3T3-L1
3T3-L1 cell is inoculated into 24 well culture plates, if control group, medicine group 1(compound 1), medicine group (compound 2).DMEM nutrient solution not containing sample is blank, and the concentration of compound (1) and (2) is 30,40,50 μm of ol/L.At the DMEM in high glucose substratum containing lO% calf serum 37 DEG C, 5%CO
2cultivate in incubator, start to add division culture medium when cell reaches 70% fusion, wherein containing Regular Insulin O.25 μm ol/L, thyroxine 0.2nmol/L, dexamethasone O.25 μm ol/L, IBMXO.5nmol/L.Within every 48 hours, change liquid 1 time, to differentiation-inducing the 12nd day, by cell oil red O stain, extract oil red O dye liquor, survey and absorbancy (A) value at spectrophotometer 490nm wavelength place.
The display of red O stain test result (Fig. 3, Fig. 4), the 12nd day of differentiation, compare with control group, the triglyceride level (TG) produced in each group of adipocyte 3T3-L1 that medicine group (1) and group (2) process is all lower than control group.Illustrate that compound (1) and (2) all can suppress the differentiation of PECTORAL LIMB SKELETON to a certain extent, and its restraining effect presents certain dosage effect.
Claims (5)
1. monoterpene glycoside compound, is characterized in that, it is 1-O-β-D-(6 "-O-methyl asafoetide acyl group)-glucopyranosyl-Geraniol-10,5-lactone, compound (1); And 3,7-dimethyl-3 (Z)-eight alkene-5-ketone 1-oxygen-β-D-Glucose glycosides, compound (2), its structural formula is as follows:
2. the pharmacy acceptable salt of monoterpene glycoside compound described in claim 1.
3. pharmacy acceptable salt according to claim 2 is the additive salt formed with following ammonium ion or metal ion: NH
4 +, Na
+, K
+, Mg
2+, Li
+, Ca
2+, Sr
2+, or Zn
2+.
4. monoterpene glycoside compound described in claim 1 is for the preparation of the application in prevention and therapy obesity and the medicine of disease that caused by obesity.
5. the method for monoterpene glycoside compound described in the claim 1 obtained from Sibiraea angustata lowering blood-fat and reducing weight efficient part, is characterized in that, said method comprising the steps of:
(1) after getting dry Sibiraea angustata (Rehd.) Hand.-Mazz. and spray pulverizing, by hot water, 10-90% methanol aqueous solution, 10-90% aqueous ethanolic solution or 10-80% water acetone soln refluxing extraction, the mass volume ratio of feed liquid is 1:10-50, and concentrating under reduced pressure removes desolventizing and obtains semi-fluid shape medicinal extract;
(2) after semi-fluid shape medicinal extract adds water-dispersion, extract by sherwood oil, methylene dichloride, ethyl acetate successively, concentrated extract, obtain sherwood oil medicinal extract, methylene dichloride medicinal extract, ethyl acetate extract;
(3) to ethyl acetate extract through silica gel column chromatography, adopt petroleum ether-ethyl acetate gradient elution, obtain A-D tetra-part medicinal extract, to D medicinal extract, namely the petroleum ether-ethyl acetate elution fraction of volume ratio 1:1 is again through silica gel column chromatography, adopt petroleum ether-ethyl acetate-methanol mixed solvent gradient elution, obtain compound (1) crude product and compound (2) crude product respectively;
(4) compound (1) and (2) crude product are more respectively through SephadexLH-20 gel column chromatography and silica column purification repeatedly, obtain sterling compound (1) and (2).
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310205003.4A CN103304607B (en) | 2013-05-29 | 2013-05-29 | The monoterpene glycoside compound obtained from Sibiraea angustata lowering blood-fat and reducing weight efficient part and application thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310205003.4A CN103304607B (en) | 2013-05-29 | 2013-05-29 | The monoterpene glycoside compound obtained from Sibiraea angustata lowering blood-fat and reducing weight efficient part and application thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN103304607A CN103304607A (en) | 2013-09-18 |
| CN103304607B true CN103304607B (en) | 2016-01-13 |
Family
ID=49130363
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201310205003.4A Active CN103304607B (en) | 2013-05-29 | 2013-05-29 | The monoterpene glycoside compound obtained from Sibiraea angustata lowering blood-fat and reducing weight efficient part and application thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN103304607B (en) |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103463231A (en) * | 2013-10-09 | 2013-12-25 | 兰州大学 | Medicine for treating hypertension or health care products for lowering blood pressure |
| CN104585758B (en) * | 2015-01-12 | 2017-06-30 | 李元勋 | A kind of angustata alcohol disintoxication chewable tablet and preparation method thereof |
| CN108938768A (en) * | 2018-07-25 | 2018-12-07 | 甘肃奇正实业集团有限公司 | A kind of raising Xianbei an ancient nationality in China spends or the method for Sibiraea angustata effect of weight reducing and obtained product and application |
| CN115260253A (en) * | 2022-06-30 | 2022-11-01 | 北京工商大学 | Preparation method and application of dicarboxylic acid derivative Glansregionin A |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101732441A (en) * | 2010-01-22 | 2010-06-16 | 北京师范大学 | Extract of effective part of sibiraea augustata(rehd.) hand-mazz for preventing adiposity and lowering hyperlipoidemia, preparation method and application thereof |
| CN102641352A (en) * | 2012-04-24 | 2012-08-22 | 杭州柳茶医药科技有限公司 | Sibiraea effective-part extract, preparation method and use thereof |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2002241269A (en) * | 2001-02-16 | 2002-08-28 | Kaken Pharmaceut Co Ltd | Fat cell differentiation inhibitor containing terrain |
| JP2002241276A (en) * | 2001-02-16 | 2002-08-28 | Kaken Pharmaceut Co Ltd | Fat cell differentiation inhibitor containing mycophenolic acid |
-
2013
- 2013-05-29 CN CN201310205003.4A patent/CN103304607B/en active Active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101732441A (en) * | 2010-01-22 | 2010-06-16 | 北京师范大学 | Extract of effective part of sibiraea augustata(rehd.) hand-mazz for preventing adiposity and lowering hyperlipoidemia, preparation method and application thereof |
| CN102641352A (en) * | 2012-04-24 | 2012-08-22 | 杭州柳茶医药科技有限公司 | Sibiraea effective-part extract, preparation method and use thereof |
Non-Patent Citations (2)
| Title |
|---|
| Structure of New Monoterpene Glycoside from Sibiraea angustata RCHD. and Its Anti-obestic Effect;Yoshiaki ITO，等;《Chem. Pharm. Bull.》;20090108;第57卷(第3期);第294-297页 * |
| Two new monoterpenes from Sibiraea angustata;Bin Li，等;《J. Nat. Med.》;20090929;第64卷(第1期);第89-92页 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN103304607A (en) | 2013-09-18 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN103304607B (en) | The monoterpene glycoside compound obtained from Sibiraea angustata lowering blood-fat and reducing weight efficient part and application thereof | |
| CN104945408A (en) | Coumarin compounds, and preparation method and application thereof | |
| CN103054912B (en) | Taxus chinensis extractive with blood sugar reduction effect, as well as preparation method and application thereof | |
| CN105218489A (en) | A kind of assorted terpene compound newly and preparation method thereof and medicinal use | |
| CN101328114B (en) | Method for extracting walnuts ketone from walnut green husk | |
| CN101401829A (en) | Wild Jinchai liveness extract, preparation and uses thereof | |
| CN111377994A (en) | Seven withanolides compounds from cape gooseberry and preparation method and application thereof | |
| CN103040945B (en) | Preparation and detection method of gangsong general flavones | |
| CN105198943B (en) | A kind of entitled tea hill how glycosides A acylated flavonoids glucosides and its preparation method and application | |
| CN104382968A (en) | Method for extracting common andrographis paniculata total lactone, pharmaceutical composition of andrographis paniculata total lactone and use of pharmaceutical composition | |
| CN102603856A (en) | Anti-tumor saponin in anemone plants and preparation method thereof as well as application | |
| CN104370931A (en) | New flavone compound as well as preparation method and application thereof | |
| CN112851612A (en) | Active compound extracted from burdock leaves and having cholesterol reducing effect, and preparation method and application thereof | |
| CN104788525A (en) | Triterpene compounds with acetylcholinesterase inhibition activity, and preparation method thereof | |
| CN110585221A (en) | Albizzia julibrissin new lignan compound for improving steatosis and application thereof | |
| CN105418727A (en) | Novel ursanes diterpenoid compound and preparation method and medical application thereof | |
| CN104523819B (en) | A kind of false indigo extract and preparation method thereof | |
| CN109954015A (en) | A kind of preparation method and application of the distilled liquid of honeysuckle | |
| CN111484411B (en) | Extraction method and application of anti-inflammatory effective component of folium artemisiae argyi | |
| CN112920148B (en) | Novel compound NBY-16 extracted from burdock leaves and having anti-inflammatory activity, and preparation method and application thereof | |
| CN116535416A (en) | Matrine type alkaloid, preparation method thereof and application thereof in preparation of medicine with anti-neuroinflammation effect | |
| CN103214370B (en) | 1, 6-O-dicaffeoyl sorbitol ester as well as derivative thereof and application | |
| CN101514143A (en) | Method for preparing ginkgol | |
| CN110423232B (en) | Anti-tumor compound and preparation method and application thereof | |
| CN106431928B (en) | Caffeoylquinic acid derivative and application thereof as neuron repair and protection medicament |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| TR01 | Transfer of patent right |
Effective date of registration: 20231204 Address after: Room 205, Building 19, Huaqing Jiayuan, Wudaokou, Haidian District, Beijing, 100000 Patentee after: BEIJING LEADINGPHARM MEDICINE DEVELOPMENT CO.,LTD. Address before: 100875, 19, Xinjie street, Haidian District, Beijing Patentee before: He Lan |
|
| TR01 | Transfer of patent right |