CN104688749A - Ligustrum phenethyl alcohol glycoside composition for treating obesity and application thereof - Google Patents
Ligustrum phenethyl alcohol glycoside composition for treating obesity and application thereof Download PDFInfo
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Abstract
The invention discloses a ligustrum phenethyl alcohol glycoside composition for treating obesity and application thereof, and belongs to the field of obesity treatment. The ligustrum phenethyl alcohol glycoside composition for treating the obesity comprises osmanthuside B, ligupurpuroside A, cis-ligupurpuroside B and trans-ligupurpuroside B. The ligustrum phenethyl alcohol glycoside composition has the function of obviously losing weight, and the weight, fat weight, Lee's index and fat cell size of a fat mouse can be reduced obviously. A fluorescence real-time quantitative PCR detecting result indicates that action targets in the ligustrum phenethyl alcohol glycoside composition are DGAT and Lep genes in adipose tissue, the Lep genetic expression can be obviously improved, and therefore the expression of the DGAT genes is restrained, and synthesis of adipose tissue triglyceride is blocked. The ligustrum phenethyl alcohol glycoside composition can be applied to preparing medicine or healthcare products or food or drinks or animal feed for treating the obesity.
Description
Technical field
The present invention relates to the compositions for the treatment of of obesity, particularly relate to the phenethyl alcohol glycoside based composition of the treatment of obesity of extracting from Ligustrum plant, the invention still further relates to the purposes of described compositions, belong to the treatment field of obesity.
Background technology
Modern science and technology proves, Ligustrum Folium Ilicis has heat-clearing and toxic substances removing, bactericidal antiphlogistic, stomach invigorating removing food stagnancy, presses down the effects such as cancer anti-cancer, promoting the production of body fluid to quench thirst, diuresis heart tonifying, preventing phlegm from forming and stopping coughing, simultaneously can also radioprotective, defying age, adjusting blood lipid.
Along with the raising of living standards of the people, there is affluenza such as " hyperlipidemia ", " hypertension " and " obesity " in modern society.The effect of the blood fat reducing of Ligustrum Folium Ilicis, anti peroxidation of lipid and scavenging free radicals is more and more subject to people's attention.Therefore, the medicine developing a kind of novel treatment of obesity seems particularly important.
Summary of the invention
Technical problem to be solved by this invention is to provide a kind of Ligustrum phenethyl alcohol glycoside based composition for the treatment of of obesity, and said composition comprises Flos Osmanthi Fragrantis glycosides B, purplestem privet leaf glycosides A, cis-purplestem privet leaf glycosides B and trans-purplestem privet leaf glycosides B, has significant antiobesity action.
For solving the problems of the technologies described above, the technical solution used in the present invention is:
First the present invention discloses a kind of Ligustrum phenethyl alcohol glycoside based composition for the treatment of of obesity, comprises following component: Flos Osmanthi Fragrantis glycosides B, purplestem privet leaf glycosides A, cis-purplestem privet leaf glycosides B and trans-purplestem privet leaf glycosides B.
Wherein, the mass ratio of each component is: Flos Osmanthi Fragrantis glycosides B: purplestem privet leaf glycosides A: cis-purplestem privet leaf glycosides B: trans-purplestem privet leaf glycosides B=1-12:2-12:0.1-10:1-10.
Preferably, the mass ratio of each component is: Flos Osmanthi Fragrantis glycosides B: purplestem privet leaf glycosides A: cis-purplestem privet leaf glycosides B: trans-purplestem privet leaf glycosides B=1:11.22:0.35:2.
First the present invention sets up mice obese model, then the random compositions 4 kinds of different Ligustrum phenylethanoid glycoside monomeric compound formed according to mass ratio 1:1:1:1 is to the continuous gastric infusion of obese model mice, investigates different Ligustrum phenethyl alcohol glycoside based composition to the antiobesity action of obesity mice.Result shows, the compositions fat-reducing effect that Flos Osmanthi Fragrantis glycosides B, purplestem privet leaf glycosides A, cis-purplestem privet leaf glycosides B and trans-purplestem privet leaf glycosides B form significantly is better than other experimental grouies; Compare with model group, Mouse Weight decline 15% (P<0.01), fat weight alleviates 43% (P<0.01), Lee ' s index reduces by 5% (P<0.01), mouse adipocytes cross-sectional area decline 42% (P<0.01).
Above experimental result also shows, belongs to phenethyl alcohol glycoside compounds together, although the compound that core skeleton is identical, because substituent group is different with side chain, its effect is just different, and the curative effect on obesity shown has larger difference; Therefore, the different components be made up of different phenylethanoid glycoside monomeric compound, there were significant differences for the curative effect on obesity shown.
The present invention, determining that Flos Osmanthi Fragrantis glycosides B, purplestem privet leaf glycosides A, cis-purplestem privet leaf glycosides B and trans-purplestem privet leaf glycosides B form on the basis of Ligustrum phenethyl alcohol glycoside based composition, is optimized experiment to the consumption proportion of monomeric compound each in compositions further.Result shows, according to mass ratio meter, Flos Osmanthi Fragrantis glycosides B: purplestem privet leaf glycosides A: cis-purplestem privet leaf glycosides B: the fat-reducing effect of the compositions that trans-purplestem privet leaf glycosides B=1:11.22:0.35:2 forms significantly is better than other experimental grouies, compare with model group, Mouse Weight decline 17% (P<0.001), fat weight alleviates 47% (P<0.001), Lee ' s index reduces by 6% (P<0.001), mouse adipocytes cross-sectional area decline 49% (P<0.001), show obvious antiobesity action.
The present invention applies Real-time quantitative PCR further and detects the key enzyme of lipid metabolism related pathways and gene, the antiobesity action target spot of screening Ligustrum phenethyl alcohol glycoside based composition.Result shows, with the gene expression of model group for 1.000, the fatty tissue DGAT mRNA relative expression of Ligustrum phenethyl alcohol glycosides compositions-treated of the present invention obviously reduces (P<0.05), Lep mRNA relative expression obviously raises (P<0.05), all has no significant effect the relative expression of PPAR γ and C5L2mRNA.The above results shows; Ligustrum phenethyl alcohol glycoside based composition of the present invention obviously can raise leptin level of adipose tissue (Lep) gene expression; thus suppress the expression of downstream target enzyme diacylglycerol acyltransferase (DGAT) gene; make fatty tissue triglyceride biosynthesis block; and then alleviate fat weight, improve lipidosis.Therefore, tentatively determine that DGAT and Lep gene is the antiobesity action target spot of Ligustrum phenethyl alcohol glycoside based composition of the present invention, for the application of Ligustrum phenethyl alcohol glycoside fat-reducing provides reliable scientific basis.
In the present invention, Ligustrum phenethyl alcohol glycoside based composition can reduce the content of triglyceride in fatty tissue, and its action target spot is DGAT and the Lep gene in fatty tissue.And a clinical line/for reducing blood triglyceride or choice drug are fibrates at present, fibrate is mainly through activating peroxisome proliferator activated receptor alpha (PPAR α), the lipoprotein lipase (LPL) that induction is attached on capillary wall is expressed, increase LPL active, the effect of LPL makes triglyceride hydrolysis be glycerol and fatty acid, thus make blood triglyceride level decline (Zheng Gang, Wang Peixian. fibrate regulates the effect [J] of metabolism syndrome dyslipidemia. world clinical medicine .2005, (1), 30 ~ 33).
As can be seen here, because action target spot is different, the medicine that can reduce blood triglyceride not necessarily can reduce the content of triglyceride in fatty tissue, namely the medicine of blood fat reducing not necessarily can have antiobesity action.
Purplestem privet leaf glycosides A of the present invention, cis-purplestem privet leaf glycosides B can obtain in commercialization purchase; Or purplestem privet leaf glycosides A, cis-purplestem privet leaf glycosides B, Flos Osmanthi Fragrantis glycosides B and trans-purplestem privet leaf glycosides B all can be separated from Ligustrum plant purplestem privet leaf (L.purpurascens Y.C.Yang), purification obtains.
Flos Osmanthi Fragrantis glycosides B (Osmanthuside B) in the present invention, purplestem privet leaf glycosides A (LigupurpurosideA), the chemical structural formula of cis-purplestem privet leaf glycosides B (cis-Ligupurpuroside B) and trans-purplestem privet leaf glycosides B (trans-Ligupurpuroside B) is as follows:
Ligustrum phenethyl alcohol glycoside based composition of the present invention can be applied to medicine, health product, food or the beverage of preparing treatment of obesity.
Ligustrum phenethyl alcohol glycoside based composition of the present invention can also be applied to the animal feed of preparation treatment of obesity.Wherein, described animal is mammal.
Pharmaceutically acceptable various adjuvant required when preparing different dosage form can be added in the Ligustrum phenethyl alcohol glycoside based composition for the treatment of of obesity of the present invention, such as disintegrating agent, lubricant, adhesive etc., be prepared into any one with traditional drug formulations method and be suitable for common formulations, such as, can be pill, powder, granule, capsule, tablet, oral liquid, drop pill and injection etc.
Technical solution of the present invention compared with prior art, has following beneficial effect:
The Ligustrum phenethyl alcohol glycoside based composition for the treatment of of obesity of the present invention comprises Flos Osmanthi Fragrantis glycosides B, purplestem privet leaf glycosides A, cis-purplestem privet leaf glycosides B and trans-purplestem privet leaf glycosides B, significantly can reduce the body weight of obese model mice, fat weight, Lee ' s exponential sum adipose cell cross-sectional area; Its action target spot is DGAT and the Lep gene in fatty tissue, makes the biosynthesis block of fatty tissue triglyceride, and then alleviates fat weight, has significant antiobesity action.
the term definition arrived involved in the present invention
Unless otherwise defined, otherwise all technology used herein and scientific terminology all have with those skilled in the art usually understand identical implication.
Term " obesity " means body fat cell number to be increased or volume increases, athero too much cause body weight be above standard body weight more than 20% pathological state.
Term " hyperlipemia " means T-CHOL in blood (TC), triglyceride (TG), low density lipoprotein, LDL (LDL) are too high, a kind of whole body Anomalous lipid metablism disease that high density lipoprotein (HDL) is too low.
Accompanying drawing explanation
Fig. 1 is the impact that Ligustrum phenethyl alcohol glycoside based composition changes adipose tissues DGAT, PPAR γ, C5L2 and Lep mRNA relative expression
wherein, the gene expression of model group is 1.000, compares with model group: * * P<0.05; Wherein, Orlistat represents orlistat; LRTG represents Ligustrum phenethyl alcohol glycoside based composition.
Detailed description of the invention
Further describe the present invention below in conjunction with specific embodiment, advantage and disadvantage of the present invention will be more clear along with description.It should be understood that described embodiment is only exemplary, any restriction is not formed to scope of the present invention.It will be understood by those skilled in the art that and can modify to the details of technical solution of the present invention and form or replace down without departing from the spirit and scope of the present invention, but these amendments or replacement all fall into protection scope of the present invention.
1, experiment material
Ligustrum purplestem privet leaf (L.purpurascens Y.C.Yang) blade;
Purplestem privet leaf glycosides B (Ligupurpuroside B), purplestem privet leaf glycosides C (LigupurpurosideC), purplestem privet leaf glycosides D (Ligupurpuroside D) commercialization can buy or be separated preparation from Ligustrum purpurascens; Purplestem privet leaf glycosides B is purchased from Rui Fensi bio tech ltd, Chengdu; Purplestem privet leaf glycosides C, purplestem privet leaf glycosides D, Ligustrum robustum glycosides N (Ligurobustoside N) are purchased from Yuan Mu bio tech ltd, Shanghai.
Animal: male C 57 BL/6 J mouse, body weight 13-15g (3-4 age in week), purchased from Beijing HFK Bio-Technology Co., Ltd., production licence number: SCXK capital 2009-007.
Animal feeding condition: SPF level barrier environment, animal facility licence: SYXK (capital) 2008-0019.Room temperature 20-24 DEG C, humidity 50-70%, standard mice cage is raised, 10/cage.Quantitative picked-up Conventional solid feedstuff and high fat diet, freely drink water.
Feedstuff: mice high lipid food and conventional feed by Beijing HFK Bio-Technology Co., Ltd.'s processing and fabricating, production licence: SCXK (capital) 2009-0003.
Reagent: all chemical reagent are analytical pure, purchased from Beijing chemical reagents corporation.
Embodiment 1 Ligustrum phenethyl alcohol glycoside based composition
Take each component (g) according to following weight: Flos Osmanthi Fragrantis glycosides B 1, purplestem privet leaf glycosides A 2, cis-purplestem privet leaf glycosides B 0.1, trans-purplestem privet leaf glycosides B 1, mix homogeneously, to obtain final product.
Embodiment 2 Ligustrum phenethyl alcohol glycoside based composition
Take each component (g) according to following weight: Flos Osmanthi Fragrantis glycosides B 12, purplestem privet leaf glycosides A 12, cis-purplestem privet leaf glycosides B 10, trans-purplestem privet leaf glycosides B 10, mix homogeneously, to obtain final product.
Embodiment 3 Ligustrum phenethyl alcohol glycoside based composition
Take each component (g) according to following weight: Flos Osmanthi Fragrantis glycosides B 1, purplestem privet leaf glycosides A 11.22, cis-purplestem privet leaf glycosides B 0.35, trans-purplestem privet leaf glycosides B 2, mix homogeneously, to obtain final product.
The Isolation and Identification of experimental example 1 purplestem privet leaf glycosides A, Flos Osmanthi Fragrantis glycosides B, trans-purplestem privet leaf glycosides B and cis-purplestem privet leaf glycosides B
Gather the fresh leaf 20Kg of purplestem privet leaf, complete 10 seconds with 80 DEG C of hot water, drainage, dries fast, obtained 5Kg purplestem privet leaf cured leaf.With purplestem privet leaf cured leaf 5Kg for raw material, through twice 95% alcohol heating reflux, the time is respectively 2 hours and 1.5 hours, filters, merges twice filtrate that obtains, concentrating under reduced pressure, obtain ethanol extraction 4.2Kg.Ethanol extraction 4.2Kg adds water suspendible, after defat with petroleum ether, through the process of D macroporous adsorbent resin column chromatography, respectively with H
2o, 50%EtOH and 95%EtOH eluting, by 50%EtOH elution fraction concentrating under reduced pressure, obtains purplestem privet leaf total glycosides 650g.Purplestem privet leaf total glycosides 650g is separated with silica gel column chromatography, CHCl
3-MeOH-H
2o gradient elution.When silica gel column chromatography is separated, first with 4L CHCl
3-MeOH-H
2after O (60:10:1) eluting, use CHCl instead
3-MeOH-H
2o (50:10:1) eluting, collects and obtains eluent 6L, and concentrating under reduced pressure is dry, obtains part A 8.3g; With CHCl
3-MeOH-H
2o (45:10:1) eluting, collect eluent 3L, concentrate drying, obtains part B 20.5g; With CHCl
3-MeOH-H
2o (40:10:1) eluting, collect eluent 4L, concentrate drying, obtains C part 32.1g.
Get part A 8.3g, with silica gel H column chromatography purification, eluent is CHCl
3-MeOH-H
2o (50:10:1), every part have collected as 150ml, and merge fraction Fr.20-40, concentrate drying, obtains Flos Osmanthi Fragrantis glycosides B (5.45g); Get part B 20.5g, with silica gel H column chromatography and polydextran gel HP-20 column chromatography, under 4 DEG C of temperature conditions, exquisite purification, obtains trans-purplestem privet leaf glycosides B (9.16g) and cis-purplestem privet leaf glycosides B (2.23g) respectively; Get C part 32.1g, with silica gel H column chromatography purification, eluent is CHCl
3-MeOH-H
2o (40:10:1), every part have collected as 200ml, and merge fraction Fr.15-500, concentrate drying, obtains purplestem privet leaf glycosides A (27.45g).
The physics and chemistry of Flos Osmanthi Fragrantis glycosides B structure and spectroscopic data: white amorphous powder, bitter in the mouth; Ultraviolet spectra UV λ
max(log ε, EtOH): 201 (4.21), 215 (4.01), 226 (4.01), 318 (4.20) nm; IR ν
max(cm
-1, KBr): 3400,2940,1690,1590,1511,1438,1362,820; Fast atom bombardment MS FAB-MS (Neg.) m/z:591 [M (C
29h
36o
13)-H]
-, 445 [M-p-coumaroyl]
-;
1h-NMR (δ, CD
3oD): aglycone 7.051 (d, 8.6, H
2-2,6), 6.684 (d, 8.6, H
2-3,5), 2.831 (m, H
2-7), 3.751 (m, H-8a), 4.043 (m, H-8b), glucosyl 4.378 (d, 8.0, H-1), rhamnosyl 5.178 (d, 1.8, H-1), 1.075 (d, 6.2, H-1), p-coumaroyl 7.461 (d, 8.7, H
2-2), 6.811 (d, 8.7, H2-3,5), 7.658 (d, 16.0, H-7), 6.336 (d, 16.0, H-8);
13c-NMR (δ, CD
3oD): aglycone 131.31 (C-1), 130.89 (C-2), 116.22 (C-3), 156.72 (C-4), 116.22 (C-5), 130.89 (C-6), 36.31 (C-7), 72.20 (C-8), glucosyl 104.19 (C-1), 76.17 (C-2), 81.65 (C-3), 70.77 (C-4), 76.06 (C-5), 62.43 (C-6), rhamnosyl 102.95 (C-1), 72.20 (C-2), 72.34 (C-3), 74.85 (C-4), 70.37 (C-5), 18.16 (C-6); P-coumaroyl 127.20 (C-1), 131.30 (C-2), 116.21 (C-3), 161.35 (C-4), 116.21 (C-5), 131.30 (C-6), 147.64 (C-7), 114.88 (C-8), 168.38 (CO).
The physics and chemistry of purplestem privet leaf glycosides A structure and spectroscopic data: white amorphous powder, bitter in the mouth; Ultraviolet spectra UV λ
max(log ε, EtOH): 202 (4.45), 221 (4.29), 333 (4.38) nm; IR ν
max(cm
-1, KBr): 3400,2928,1690,1600,1515,1440,1265,1155,815; Fast atom bombardment MS FAB-MS (Neg.) m/z:769 [M (C
35h
46o
19)-H]
-, 607 [M-rhamnosyl]
-, 449 [M-2rhamnosyl-H]
-;
1h-NMR (δ, CD
3oD): aglycone6.716 (d, 1.9, H-2), 6.694 (d, 8.1, H-5), 6.575 (dd, 8.1,1.9, H-6), 2.801 (m, H
2-7), 3.749 (m, H-8a), 4.037 (m, H-8b), glucosyl 4.380 (d, 8.0, H-1), rhamnosyl 5.071 (d, 1.6, H-1), 1.076 (d, 6.3, H-6), rhamnosyl 5.215 (d, 1.3, H-1), 1.108 (d, 6.1, H-6), E-caffeoyl 7.072 (d, 2.0, H-2), 6.811 (d, 8.2, H-5), 7.854 (dd, 8.2,2.0, H-6), 7.596 (d, 15.8, H-7), 6.258 (d, 15.8, H-8);
13c-NMR (δ, CD
3oD): aglycone 131.63 (C-1), 116.39 (C-2), 144.64 (C-3), 146.11 (C-4), 117.17 (C-5), 121.30 (C-6), 36.53 (C-7), 72.18 (C-8), glucosyl 104.94 (C-1), 76.00 (C-2), 81.43 (C-3), 70.58 (C-4), 76.27 (C-5), 62.38 (C-6), rhamnosyl 103.31 (C-1), 72.37 (C-2), 70.58 (C-3), 81.33 (C-4), 68.61 (C-5), 19.11 (C-6); Rhamnosyl 102.53 (C-1), 72.87 (C-2), 72.46 (C-3), 73.89 (C-4), 70.28 (C-5), 17.68 (C-6); E-caffeoyl 127.62 (C-1), 115.44 (C-2), 146.77 (C-3), 149.85 (C-4), 116.39 (C-5), 123.34 (C-6), 147.90 (C-7), 114.80 (C-8), 168.14 (CO).
The physics and chemistry of trans-purplestem privet leaf glycosides B structure and spectroscopic data: white amorphous powder, bitter in the mouth; Ultraviolet spectra UV λ
max(log ε, EtOH): 201 (4.45), 224 (4.26), 319 (4.37) nm; IR ν
max(cm
-1, KBr): 3400,2930,1690,1600,1510,1440,1260,830; Fast atom bombardment MS FAB-MS (Neg.) m/z:737 [M (C
35h
46o
17)-H]
-, 591 [M-rhamnosyl-H or M-caffeoyl-H]
-, 445 [M-2rhamnosyl-H]
-, 163 [-O-rhamnosyl+H]
-;
1h-NMR (δ, CD
3oD): aglycone 7.071 (d, 9.6, H-2), 6.707 (d, 9.6, H-3), 6.707 (d, 9.6, H-5), 7.071 (d, 9.6, H-6), 2.818 (m, H
2-7), 3.889 (m, H-8a), 4.032 (m, H-8b), glucosyl 4.381 (d, 8.0, H-1), rhamnosyl 5.026 (d, 1.7, H-1), 1.022 (d, 6.2, H-6), rhamnosyl 5.179 (d, 1.6, H-1), 1.076 (d, 6.2, H-6), E-coumaroyl 7.481 (d, 8.7, H
2-2,6), 6.828 (d, 8.7, H-3,5), 7.659 (d, 15.8, H-7), 6.333 (d, 15.8, H-8);
13c-NMR (δ, CD
3oD): aglycone 130.78 (C-1), 130.89 (C-2), 116.18 (C-3), 156.66 (C-4), 116.18 (C-5), 130.89 (C-6), 36.27 (C-7), 72.27 (C-8), glucosyl 104.11 (C-1), 75.92 (C-2), 81.60 (C-3), 70.57 (C-4), 76.15 (C-5), 62.33 (C-6), rhamnosyl103.37 (C-1), 72.27 (C-2), 70.57 (C-3), 81.51 (C-4), 68.613 (C-5), 19.08 (C-6); Rhamnosyl 102.60 (C-1), 72.77 (C-2), 72.19 (C-3), 73.75 (C-4), 70.27 (C-5), 17.66 (C-6); E-coumaroyl 127.00 (C-1), 131.37 (C-2,6), 117.08 (C-3,5), 161.33 (C-4), 147.58 (C-7), 114.74 (C-8), 168.17 (CO).
The physics and chemistry of cis-purplestem privet leaf glycosides B structure and spectroscopic data: white amorphous powder, bitter in the mouth; Ultraviolet spectra UV λ
max(log ε, EtOH): 199 (4.00), 215 (3.98), 226 (4.17), 316 (4.30) nm; IR ν
max(cm
-1, KBr): 3400,2930,1700,1600,1510,1440,1360,830; Fast atom bombardment MS FAB-MS (Neg.) m/z:737 [M (C
35h
46o
17)-H]
-, 591 [M-rhamnosyl-H or M-caffeoyl-H]
-, 445 [M-2rhamnosyl-H]
-, 163 [-O-rhamnosyl+H]
-;
1h-NMR (δ, CD
3oD): aglycone 7.072 (d, 9.6, H-2), 6.706 (d, 9.6, H-3), 6.706 (d, 9.6, H-5), 7.072 (d, 9.6, H-6), 2.819 (m, H
2-7), 3.887 (m, H-8a), 4.031 (m, H-8b), glucosyl 4.380 (d, 8.0, H-1), rhamnosyl 5.026 (d, 1.7, H-1), 1.021 (d, 6.2, H-6), rhamnosyl 5.180 (d, 1.6, H-1), 1.078 (d, 6.2, H-6), E-coumaroyl 7.706 (d, 8.7, H
2-2,6), 6.755 (d, 8.7, H-3,5), 6.931 (d, 13.0, H-7), 5.760 (d, 13.0, H-8);
13c-NMR (δ, CD
3oD): aglycone 130.78 (C-1), 130.89 (C-2), 116.18 (C-3), 156.66 (C-4), 116.18 (C-5), 130.89 (C-6), 36.27 (C-7), 72.27 (C-8), glucosyl 104.11 (C-1), 75.92 (C-2), 81.84 (C-3), 70.61 (C-4), 76.15 (C-5), 62.33 (C-6), rhamnosyl103.37 (C-1), 72.27 (C-2), 70.57 (C-3), 81.51 (C-4), 68.613 (C-5), 19.07 (C-6); Rhamnosyl 102.60 (C-1), 72.77 (C-2), 72.19 (C-3), 73.75 (C-4), 70.27 (C-5), 17.69 (C-6); Z-coumaroyl 127.63 (C-1), 134.10 (C-2,6), 115.90 (C-3,5), 160.15 (C-4), 147.15 (C-7), 116.11 (C-8), 166.98 (CO).
The preparation of experimental example 2 purplestem privet leaf glycosides C, acteoside isomer, Flos Osmanthi Fragrantis glycosides B6, purplestem privet leaf glycosides B, purplestem privet leaf glycosides D
With Ligustrum Ligustrum purpurascens for raw material, alcohol reflux 3 times, each difference 2.0,1.5,1 hours, concentrate and obtain crude extract, add water standing, precipitation sedimentation and filtration is obtained water-soluble portion, through silica gel column chromatography, with chloroform: methanol: water elution, collect eluting drying nest, obtain phenethyl alcohol glycoside effective site.By several parts that dry for elution fraction post is divided into polarity ascending, respectively repeatedly cross polydextran gel, wherein main component is identified and mainly comprises: purplestem privet leaf glycosides C (Ligupurpuroside C), acteoside isomer (Isoaeteosi), Flos Osmanthi Fragrantis glycosides B6 (OsmanthusideB6), purplestem privet leaf glycosides A (Ligupurpuroside A), purplestem privet leaf glycosides B (LigupurpurosideB), purplestem privet leaf glycosides D (Ligupurpuroside D).
The antiobesity action of experimental example 3 Ligustrum phenethyl alcohol glycoside based composition
By different Ligustrum phenylethanoid glycoside monomeric compound random combine, carry out weight-reducing experiment; Wherein, purplestem privet leaf glycosides A, Flos Osmanthi Fragrantis glycosides B, trans-purplestem privet leaf glycosides B are separated according to experimental example 1 method with cis-purplestem privet leaf glycosides B.
1, experimental technique
1.1 Ligustrum phenethyl alcohol glycoside based compositions
4 kinds of different Ligustrum phenylethanoid glycoside monomeric compound combined at random, in each phenethyl alcohol glycoside based composition, the mass ratio of each monomeric compound is 1:1:1:1.
Concrete combination is as follows:
Compositions 1: Flos Osmanthi Fragrantis glycosides B, purplestem privet leaf glycosides A, cis-purplestem privet leaf glycosides B, purplestem privet leaf glycosides C;
Compositions 2: purplestem privet leaf glycosides D, purplestem privet leaf glycosides A, cis-purplestem privet leaf glycosides B, trans-purplestem privet leaf glycosides B;
Compositions 3: Flos Osmanthi Fragrantis glycosides B, purplestem privet leaf glycosides A, cis-purplestem privet leaf glycosides B, trans-purplestem privet leaf glycosides B;
Compositions 4: purplestem privet leaf glycosides A, purplestem privet leaf glycosides B, purplestem privet leaf glycosides C, purplestem privet leaf glycosides D;
Compositions 5: purplestem privet leaf glycosides A, purplestem privet leaf glycosides C, trans-purplestem privet leaf glycosides B, purplestem privet leaf glycosides D;
Compositions 6: Flos Osmanthi Fragrantis glycosides B6, purplestem privet leaf glycosides A, cis-purplestem privet leaf glycosides B, purplestem privet leaf glycosides C;
Compositions 7: purplestem privet leaf glycosides A, cis-purplestem privet leaf glycosides B, purplestem privet leaf glycosides D, Ligustrum robustum glycosides N;
Compositions 8: purplestem privet leaf glycosides A, cis-purplestem privet leaf glycosides B, acteoside isomer, Flos Osmanthi Fragrantis glycosides B6;
Compositions 9: purplestem privet leaf glycosides B, purplestem privet leaf glycosides C, purplestem privet leaf glycosides D, Ligustrum robustum glycosides N;
Compositions 10: purplestem privet leaf glycosides A, purplestem privet leaf glycosides C, purplestem privet leaf glycosides D, Ligustrum robustum glycosides N.
Take different Ligustrum phenethyl alcohol glycoside based composition, distilled water dissolves and is made into desired concn.
1.2 animal groupings and model are set up
After C57BL/6J mice adaptability is fed 3 days, be divided into 12 groups at random by body weight, be respectively Normal group (20/group), obese model group (20/group), experiment 1-10 group (10/group); Normal group is fed conventional feed, and all the other detoxification high lipid foods, set up fat animal model.
Modeling, after 4 weeks, gets Normal group and each half of obese model treated animal, and de-cervical vertebra is put to death, and takes fatty tissue, weighs weight in wet base, observes obese model situation.Then, experiment 1-10 group according to dosage gastric infusion, medicine is corresponding Ligustrum phenethyl alcohol glycoside based composition 1-10 respectively, and dosage is 0.6g/kg, once a day; Model and matched group give equal-volume distilled water gavage.Successive administration is after 4 weeks, and de-cervical vertebra puts to death whole mice, is separated and takes the whole fatty tissue of intraperitoneal, weighs weight in wet base, observes the change of fat weight.
1.3 body weight, fat weight and Lee ' s assessment of indices
Observe animal general status every day, record animal food-intake; Weigh weekly once; Experimental endpoints weighs Mouse Weight, measures body long (nose is to the distance of anus outer), calculating obesity index (Lee ' s index).Lee ' s index=[body weight (g) × 10
3/ body long (cm)]
1/3.Clean cut separation intraperitoneal (comprising around mesentery, bilateral epididymal, Bilateral Renal) fatty tissue, claims weight in wet base.
1.4 adipose cell norphometries
Dyeed by Hematoxylin-eosin (HE), observe fat tissue cell's morphology, and according to research method (the Juha Ketonen of JuhaKetonen etc., Jin Shi, Essi Martonen, et al.Periadventitial Adipose Tissue Promotes Endothelial Dysfunction viaOxidative Stress in Diet-Induced Obese C57Bl/6Mice [J] .Circ.J, 2010, 74:1479 – 87.) fat tissue cell's cross-sectional area is measured, after observing high lipid food induction, mouse adipose tissue cell cross-section area changes, and whether adipose cell area is had an impact after administration.
1.5 statistical procedures
Experimental data adopts SPSS 15.0 software to add up, with
represent, compare employing independent samples t test between two groups, significant level is P<0.05.
2, experimental result
2.1 model case
After high lipid food induces 4 weeks, model group Mouse Weight, fat weight and Lee ' s index and Normal group raise 17% (P<0.05), 72% (P<0.01) and 4% (P<0.05) more respectively, show to define obese model (table 1).
Table 1 modeling Mouse Weight, fat weight and Lee ' s index variation in 4 weeks
* P<0.05, * * P<0.01 compared with normal group.
2.2 different Ligustrum phenethyl alcohol glycoside based compositions are on the impact of obesity mice body weight, fat weight and Lee ' s index
After model is formed, with different components to the continuous gastric infusion of C57BL/6J obese model mice 4 weeks.At the end of experiment, model group Mouse Weight, fat weight, Lee ' s index and matched group raise 24% (P<0.01), 159% (P<0.01) and 7% (P<0.01) respectively.
Test 3 groups to compare (table 2) with model group, Mouse Weight decline 15% (P<0.01), fat weight alleviates 43% (P<0.01) respectively, Lee ' s index reduces by 5% (P<0.01) respectively, show obvious antiobesity action, be significantly better than other experimental grouies.
The different phenethyl alcohol glycoside based composition of table 2 is on the impact of obesity mice body weight, fat weight and Lee ' s index
* * P<0.01 compared with normal group; Compare with model group
▲p<0.05,
▲ ▲p<0.01.
2.3 Ligustrum phenethyl alcohol glycoside based compositions are on the impact of adipose cell volume
Administration is after 4 weeks, and model group adipose cell cross-sectional area is 2.2 times (P<0.01) of matched group.
Compare (table 3) with model group, test mouse adipocytes cross-sectional area decline 42% (P<0.01) of 3 groups, be obviously better than other experimental grouies.
The change of table 3 mouse adipocytes cross-sectional area (μm
2)
* * P<0.01 compared with normal group; Compare with model group
▲p<0.05,
▲ ▲p<0.01.
To sum up, on the basis that obese model is formed, test 3 groups and compare with model group, significantly can reduce obesity mice body weight, fat weight, Lee ' s index and adipose cell volume, effect is obviously better than other Ligustrum phenethyl alcohol glycoside based compositions.These results suggest that, although belong to phenethyl alcohol glycoside compounds together, in compositions, monomeric compound kind is different, and there were significant differences for the curative effect on obesity shown.Finishing screen of the present invention selects the Ligustrum phenethyl alcohol glycoside based composition that Flos Osmanthi Fragrantis glycosides B, purplestem privet leaf glycosides A, cis-purplestem privet leaf glycosides B and trans-purplestem privet leaf glycosides B form.
The consumption proportion optimization experiment of experimental example 4 Ligustrum phenethyl alcohol glycoside based composition
The present invention is optimized the consumption proportion of Flos Osmanthi Fragrantis glycosides B, purplestem privet leaf glycosides A, cis-purplestem privet leaf glycosides B, trans-purplestem privet leaf glycosides B in Ligustrum phenethyl alcohol glycoside based composition on experimental example 3 basis.
1, experimental technique
1.1 Experimental agents
In Ligustrum phenethyl alcohol glycoside based composition, the consumption proportion of Flos Osmanthi Fragrantis glycosides B, purplestem privet leaf glycosides A, cis-purplestem privet leaf glycosides B, trans-purplestem privet leaf glycosides B is in table 4.
The consumption proportion (g) of table 4 phenylethanoid glycoside monomeric compound
1.2 animal groupings and model are set up
After C57BL/6J mice adaptability is fed 3 days, be divided into 8 groups at random by body weight, be respectively Normal group (20/group), obese model group (20/group), experiment 1-6 group (10/group); Normal group is fed conventional feed, and all the other detoxification high lipid foods, set up fat animal model.
Modeling, after 4 weeks, gets Normal group and each half of obese model treated animal, and de-cervical vertebra is put to death, and takes fatty tissue, weighs weight in wet base, observes obese model situation.Then, experiment 1-6 group according to dosage gastric infusion, medicine is corresponding Ligustrum phenethyl alcohol glycoside based composition 1-6 respectively, and dosage is 0.6g/kg, once a day; Model and matched group give equal-volume distilled water gavage.Successive administration is after 4 weeks, and de-cervical vertebra puts to death whole mice, is separated and takes the whole fatty tissue of intraperitoneal, weighs weight in wet base, observes the change of fat weight.
1.3 body weight, fat weight, Lee ' s assessment of indices and adipose cell norphometry
Specific experiment method and statistical procedures are with reference to experimental example 3.
2, experimental result
2.1 Ligustrum phenethyl alcohol glycoside based compositions are on the impact of obesity mice body weight, fat weight and Lee ' s index
Successive administration is after 4 weeks, test 5 groups to compare (table 5) with model group, Mouse Weight decline 17% (P<0.001), fat weight alleviates 47% (P<0.001), Lee ' s index reduces by 6% (P<0.001), show obvious antiobesity action, be significantly better than other experimental grouies.
Table 5 phenethyl alcohol glycoside based composition is on the impact of obesity mice body weight, fat weight and Lee ' s index
* * P<0.01 compared with normal group; Compare with model group
▲p<0.05,
▲ ▲p<0.01,
▲ ▲ ▲p<0.001.
2.2 Ligustrum phenethyl alcohol glycoside based compositions are on the impact of adipose cell volume
Compare (table 6) with model group, test mouse adipocytes cross-sectional area decline 49% (P<0.001) of 5 groups, than other process reductions by more than 28%, be significantly better than other experimental grouies.
The change of table 6 mouse adipocytes cross-sectional area (μm
2)
* * P<0.01 compared with normal group; Compare with model group
▲p<0.05,
▲ ▲p<0.01,
▲ ▲ ▲p<0.001.
To sum up, Flos Osmanthi Fragrantis glycosides B, purplestem privet leaf glycosides A, cis-purplestem privet leaf glycosides B, trans-purplestem privet leaf glycosides B combine according to mass ratio 1:11.22:0.35:2, significantly can reduce obesity mice body weight, fat weight, Lee ' s index and adipose cell volume, fat-reducing effect is remarkable.
Experimental example 5 Ligustrum phenethyl alcohol glycoside based composition antiobesity action Mechanism Study
1, test material
Total RNA extraction reagent box (centrifugal column type, RNAsimple Total RNA Kit), Reverse Transcription box (TIANScript RT Kit), fluorescence real-time quantitative PCR test kit (RealMasterMixSYBRGreenI) are all purchased from TIANGEN biochemical technology (Beijing) company limited.
2, test method
Set up mice obese model with reference to experimental example 3, modeling is after 4 weeks, gastric infusion (Ligustrum phenethyl alcohol glycoside based composition prepared by the embodiment of the present invention 3), and dosage is 0.6g/kg, once a day; Model group gives equal-volume distilled water gavage.Successive administration, after 4 weeks, detects mouse adipose tissue diacylglycerol acyltransferase (DGAT), peroxisome proliferators activated receptor γ (PPAR γ), chemotactic protein receptor-like protein 2 (C5L2), the change of leptin (Lep) mrna expression by quantitative real-time PCR.Meanwhile, take Orlistat as contrast.
Extract mouse adipose tissue total serum IgE, RNA purity and Concentration Testing, reverse transcription, amplification complete detection, and primer sequence is in table 7.
Table 7 PCR primer sequence
3, statistical procedures
Experimental data adopts SPSS 15.0 software independent samples t test method to add up, with
represent, significant level is P<0.05.The data of gene expression use gene expression relative quantification software
2009 carry out data analysis, and significant level is P<0.05.
4, result of the test
The solubility curve of primer extension product is single main peak, illustrates without primer dimer and non-specific amplification.
Correct as internal reference using β-actin, and the amplification efficiency of each gene is revised, analyze fatty DGAT, PPAR γ, C5L2 and Lep gene relative expression change.With the gene expression of model group for 1.000, the fatty tissue DGAT mRNA relative expression of Ligustrum phenethyl alcohol glycosides compositions-treated obviously reduces (P<0.05), Lep mRNA relative expression obviously raises (P<0.05), all has no significant effect (Fig. 1) the relative expression of PPAR γ and C5L2mRNA.
The present invention's application Real-time quantitative PCR detects the key enzyme of lipid metabolism related pathways and gene; the antiobesity action target spot of screening Ligustrum phenethyl alcohol glycoside based composition; result shows; Ligustrum phenethyl alcohol glycoside based composition obviously can raise leptin level of adipose tissue (Lep) and express; thus suppress the expression in downstream target enzyme diacylglycerol acyltransferase (DGAT); make fatty tissue triglyceride biosynthesis block, and then alleviate fat weight, improve lipidosis.The present invention tentatively determines that DGAT and Lep is the antiobesity action target spot of Ligustrum phenethyl alcohol glycoside based composition, for the application of Ligustrum phenethyl alcohol glycoside compounds fat-reducing provides reliable scientific basis.
Claims (6)
1. a Ligustrum phenethyl alcohol glycoside based composition for treatment of obesity, is characterized in that, comprise following component: Flos Osmanthi Fragrantis glycosides B, purplestem privet leaf glycosides A, cis-purplestem privet leaf glycosides B and trans-purplestem privet leaf glycosides B.
2. according to Ligustrum phenethyl alcohol glycoside based composition according to claim 1, it is characterized in that, the mass ratio of each component is: Flos Osmanthi Fragrantis glycosides B: purplestem privet leaf glycosides A: cis-purplestem privet leaf glycosides B: trans-purplestem privet leaf glycosides B=1-12:2-12:0.1-10:1-10.
3. according to Ligustrum phenethyl alcohol glycoside based composition according to claim 2, it is characterized in that, the mass ratio of each component is: Flos Osmanthi Fragrantis glycosides B: purplestem privet leaf glycosides A: cis-purplestem privet leaf glycosides B: trans-purplestem privet leaf glycosides B=1:11.22:0.35:2.
4. the Ligustrum phenethyl alcohol glycoside based composition described in claim 1,2 or 3 is preparing the purposes in the medicine for the treatment of of obesity, health product, food or beverage.
5. the purposes of the Ligustrum phenethyl alcohol glycoside based composition described in claim 1,2 or 3 in the animal feed of preparation treatment of obesity.
6. according to purposes according to claim 5, it is characterized in that: described animal is mammal.
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| CN107485615A (en) * | 2017-08-11 | 2017-12-19 | 中国医学科学院药用植物研究所 | Purposes of the Ligustrum robust glycosides C and combinations thereof in treatment hyperlipidemia and slimming medicine is prepared |
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| CN116818918A (en) * | 2022-03-22 | 2023-09-29 | 广东一方制药有限公司 | Fingerprint construction method of ligustrum robustum and construction method of high-resolution mass spectrum component basic identification and application thereof |
| CN116818917A (en) * | 2022-03-22 | 2023-09-29 | 广东一方制药有限公司 | Method for measuring contents of four phenylpropanoid glycosides components in ligustrum robustum |
| CN116818917B (en) * | 2022-03-22 | 2024-06-04 | 广东一方制药有限公司 | Method for measuring contents of four phenylpropanoid glycosides components in ligustrum robustum |
| CN116818918B (en) * | 2022-03-22 | 2024-06-04 | 广东一方制药有限公司 | Fingerprint construction method of ligustrum robustum and construction method of high-resolution mass spectrum component basic identification and application thereof |
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