CN104341478A - Novel triterpenoid saponins compound celosin K in seed of Celosia atgentea L. and medical application thereof - Google Patents
Novel triterpenoid saponins compound celosin K in seed of Celosia atgentea L. and medical application thereof Download PDFInfo
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Abstract
The invention relates to a triterpenoid saponins compound celosin K with a novel structure, which is separated from traditional Chinese medicine seed of Celosia atgentea L. and a medical application thereof. A novel compound with a liver protection effect can be obtained by extracting dried mature seeds of Celosia atgentea L. of Amaranthaceae plants, refining, carrying out structure identification and separating; the structure is identified by adopting infrared spectroscopy, high resolution mass spectrum, one-dimensional/two-dimensional nuclear magnetic resonance spectrum and physical and chemical analysis.
Description
Technical field
The present invention relates to triterpene saponin componds new in Semen Celosiae and uses thereof, belong to natural drug medical art.
Background technology
Semen Celosiae is traditional Chinese medical science conventional Chinese medicine, has another name called Semen Cassiae, pheasant hat beggar, dog tail, cow's tail beggar.For the mature seed of Amaranthaceae (Amaranthacea) annual herb plant feather cockscomb (Celosia argentea L.), all there is wild or cultivation in most of China area.Its bitter, cold nature, return Liver Channel, has clearing liver, improving eyesight, moves back effect of screen.Be usually used in the treatment of conjunctival congestion with pain and swelling of the eye, keratitis, nebula, iridocyclitis, dizzy, skin wind-heat itch, mange.Contained by Semen Celosiae, chemical composition is more, and that now reports mainly contains sterols, cyclic peptide, saponins, organic acid etc.The research such as Lin Wenqun finds containing abundant amino acid and fatty oil (palmitinic acid, stearic acid, oleic acid, linolic acid and linolenic acid etc.) in Semen Celosiae, and containing nicotinic acid and abundant saltpetre
[1,2].Xue Qian etc. separate β-sitosterol, palmitinic acid, Stigmasterol, daucosterol, Oleanolic Acid from Semen Celosiae
[3].Morita etc. isolate a series of cyclic peptide material (moroidin, celogentin A-K)
[4-6].Guo Meili etc. isolate triterpenoid saponins (comprising Celosin A, B, C, D, C1, D1, E, F, G, Flos Celosiae Cristatae glycosides), and research finds that these saponin components have pharmacologically actives such as protecting the liver, antitumor
[7-11].Also having clinically with Semen Celosiae is the Chinese patent medicine of main flavour of a drug, and as feather cockscomb ball derives from Golden Mirror of Medicine volume 78, be traditional Chinese medicine preparation, it consists of South Dodder Seed Chinese Dodder Seed 1 liang, Motherwort Fruit 1 liang, Radix Rehmanniae 2 liang, Semen Celosiae 2 liang, windproof 1 liang, shizandra berry 3 money, black ginseng 1 liang, radix bupleuri 1 liang, rhizoma alismatis 1 liang, the root of Chinese wild ginger 3 money, Semen Plantaginis 1 liang, 1 liang, Poria cocos, be mainly used in the empty accumulated heat of liver, eyes is congestion and swelling pain photophobia originally, puckery tear difficulty is opened, and then gradually gives birth to screen film for a long time, poor vision; Green wind also eyeball ball derives from " gold mirror " volume 77, and it consists of 1 liang, Radix Glycyrrhizae, the bighead atractylodes rhizome 1 liang, ginseng 1 liang, 1 liang, Poria cocos, notopterygium root 1 liang, windproof 1 liang, chrysanthemum 1 liang, Radix Rehmanniae 1 liang, puncture vine 1 liang, Herba Cistanches 1 liang, Chinese yam 1 liang, the root of bidentate achyranthes 1 liang, Semen Celosiae 1 liang, Pale Butterflybush Flower 1 liang, South Dodder Seed Chinese Dodder Seed 1 liang, scouring rush 1 liang, Ligusticum wallichii 1 liang.Cure mainly cataract or glaucoma, Cheng Lvfeng not sequitur.
Non-alcoholic fatty liver disease (nonalcoholic fatty liver disease, NAFLD) be a kind of without excessive drinking history, fat accumulation in the liver cell caused by a variety of causes, with the clinical pathology syndrome that hepatic cell fattydegeneration and accumulation of lipid are principal character, it is also a kind of common clinical disease.Along with the development of society, the change of people life style and dietary structure, the sickness rate of NAFLD is on the rise, the health of the positive serious threat mankind.
Summary of the invention
The object of this invention is to provide two kinds from Amaranthaceae (Amaranthacea) plant feather cockscomb (Celosia argentea L.), be separated the compound with hepatoprotective effect obtained, and adopt spectroscopic techniques, comprise infrared, high resolution mass spectrum, nucleus magnetic resonance and acid hydrolysis-derivatize-high performance liquid chromatography identifies its structure.Called after: feather cockscomb glycosides K (celosin K), feather cockscomb glycosides L (celosin L).Its chemical structure is as follows:
The preferred method of feather cockscomb glycosides K extracting and developing
The preparation method of triterpene saponin componds feather cockscomb glycosides K new in Semen Celosiae is as follows:
1, extract: after dry Semen Celosiae pulverizing medicinal materials, 40 ~ 70% ethanolic soln cold soakings adding medicinal material weight 5 ~ 10 times of volumes spend the night, 40 ~ 80 DEG C of heating and refluxing extraction 2 ~ 4 times, merge ethanol extract, concentratedly to obtain general extractive.
2, rough segmentation: by said extracted gained general extractive, after adding the water dissolution of general extractive weight 5 ~ 15 times amount, by Semen Celosiae medicinal material with resin quality than 1: (1 ~ 10), through macroporous adsorbent resin, respectively with water, 10 ~ 20% ethanolic solns, 40 ~ 80% ethanolic solns, 85 ~ 95% ethanolic soln gradient elutions, each gradient elution 2 ~ 6 retention volume, collect 40 ~ 80% ethanolic soln wash-out positions, obtain crude extract in 60 DEG C of concentrating under reduced pressure.
3, refining: above-mentioned crude extract mixes sample with thick silica gel (100 ~ 200 order), through silica gel column chromatography, with methylene chloride-methanol gradient elution (100: 1 ~ 1: 1).By methylene chloride-methanol (1: 4) ~ (4: 1) elution fraction through anti-phase ODS chromatographic separation (separation condition: chromatographic column internal diameter 2cm, filler height 40cm in post; With methanol-water (10% ~ 100%) gradient elution), the methanol-eluted fractions position of 50%-55%, through lyophilize, obtains target compound feather cockscomb glycosides K.
The preferred method of feather cockscomb glycosides L extracting and developing
The preparation method of triterpene saponin componds feather cockscomb glycosides L new in Semen Celosiae is as follows:
1, extract: after dry Semen Celosiae pulverizing medicinal materials, 40 ~ 70% ethanolic soln cold soakings adding medicinal material weight 8 ~ 12 times of volumes spend the night, 40 ~ 80 DEG C of heating and refluxing extraction 2 ~ 4 times, merge ethanol extract, concentratedly to obtain general extractive.
2, rough segmentation: by said extracted gained general extractive, after adding the water dissolution of general extractive weight 8 ~ 12 times amount, by Semen Celosiae medicinal material with resin quality than 1: (1 ~ 10), through macroporous adsorbent resin, respectively with water, 10 ~ 20% ethanolic solns, 40 ~ 80% ethanolic solns, 85 ~ 95% ethanolic soln gradient elutions, each gradient elution 2 ~ 6 retention volume, collect 40 ~ 80% ethanolic soln wash-out positions, obtain crude extract in 60 DEG C of concentrating under reduced pressure.
3, refining: above-mentioned crude extract mixes sample with thick silica gel (100 ~ 200 order), through silica gel column chromatography, with methylene chloride-methanol gradient elution (100: 1 ~ 1: 1).By methylene chloride-methanol (1: 4) ~ (4: 1) elution fraction through anti-phase ODS chromatographic separation (separation condition: chromatographic column internal diameter 2cm, filler height 40cm in post; With methanol-water (10% ~ 100%) gradient elution), collect the methanol-eluted fractions position of 60% ~ 70%, then be separated (separation condition: column diameter 3cm, long 0.8m through Sephadex LH-20; Wet method loading; Loading volume accounts for 1% of post cumulative volume; With methanol-water (10% ~ 100%) gradient elution; Eluent flow rate 1ml/min), collect 50% methanol-eluted fractions cut, be dissolved in methanol solution after recycling design ,-4 DEG C of recrystallizations obtain feather cockscomb glycosides L compound monomer composition.
The method of Structural Identification
Utilize spectroscopic techniques, comprise infrared, high resolution mass spectrum, nucleus magnetic resonance and acid hydrolysis-derivatize-high performance liquid chromatography identifies its structure.
Two kinds of new triterpene saponin componds in Semen Celosiae
This new triterpene saponin componds spectral data is as follows:
(1) compound is white powder, [α]
d 20+ 38.2 ° (c 0.130, MeOH).IR v
max3899,3444,2950,2310,1638,1400,1153,1072,545 and 518cm
-1.ESI-QTOF-MS m/z:941.4739 [M-H]
-(calculated value is 941.4752), can know its molecular formula by inference is C
47h
74o
19.
1hNMR (C
5d
5n, 500MHz) compose high field region and occur 7 angular methyl(group) signal: δ
h1.01 (s, H
3-23), 1.02 (s, H
3-24), 1.07 (s, H
3-25), 0.75 (s, H
3-26), 0.96 (s, H
3-27), 0.74 (s, H
3-29), 0.71 (s, H
3-30); There is an alkene hydrogen signal δ low place
h5.16 (br s, H-12); And the proton signal δ on two company's oxygen carbon
h4.36 (d, J=3.5Hz, H-2), 3.09 (d, J=3.5Hz, H-3);
13c NMR (C
5d
5n, 125MHz) show 7 methyl carbon signal: δ
c28.8 (C-23), 17.6 (C-24), 15.7 (C-25), 16.6 (C-26), 25.3 (C-27), 32.3 (C-29), 22.8 (C-30); Two olefinic carbon signal δ
c122.4 (C-12), 143.2 (C-13); The secondary carbon signal δ of company's oxygen
c89.3 (C-3); And a carboxyl signal δ
c177.4 (C-28).Determine that the aglycon of this compound is 2 beta-hydroxies-Oleanolic Acid.
D-Glucose aldehydic acid, D-wood sugar and D-Glucose is detected through acid hydrolysis.
1h NMR (C
5d
5n, 500MHz) show corresponding end group hydrogen signal: δ
h4.66 (d, J=7.5Hz), δ
h4.99 (d, J=7.5Hz), δ
h5.73 (d, J=8.5Hz); Corresponding end group carbon signal: δ
c104.5 (C-1 " '), δ
c103.8 (C-1 "), δ
c94.4 (C-1 " ').Can determine that in this compound sugar chain, glucuronic acid, xylose and glucose are beta comfiguration according to the size of each sugared anomeric proton signal coupling constant.In HMBC spectrum, δ
h4.99 with C-2 ' (δ
c84.1) have relevant, can infer that this compound has two sugar 1 → 2 to connect, δ
h4.66 with δ
c89.3 (C-3), δ
h5.73 with δ
c177.4 (C-28) have relevant, can infer that sugar chain is connected in (table 1) on C-3 and C-28 respectively.
The NMR data of table 1 compound and crucial HMBC dependency
Comprehensive above information, determines that this compound structure is 2 beta-hydroxy 3-O-[β-D-xylopyranosyl-(1 → 2)-beta d glucopyranosiduronic acid]-28-O-β-D-glucopyranosyl-Oleanolic Acid (Fig. 1).Through being retrieved as a new compound, called after feather cockscomb glycosides K (celosin K).
(2) compound is white powder, [α]
d 20+ 84 ° (c 0.016, MeOH).IR v
max3423,2946,2319,1751,1631,1400,1259,1146,1074,1000,904,625,518,458,443 and 419cm
-1.ESI-QTOF-MS m/z:793.4074 [M-H]
-(calculated value is 793.4016), can know its molecular formula by inference is C
41h
62o
20.
In conjunction with
1h,
13c NMR information, this compound has 6 methyl singlets signal: δ
h1.25 (s, H
3-24), 1.05 (s, H
3-25), 0.66 (s, H
3-26), 0.88 (s, H
3-27), 0.66 (s, H
3-29), 0.79 (s, H
3-30); An alkene hydrogen signal δ
h5.15 (br s, H-12) and two hydroxyls replace the proton signal δ on carbon
h4.37 (m, H-2), 3.73 (d, J=4.0Hz, H-3);
13c NMR (C
5d
5n, 125MHz) show six methyl signals: δ
c10.4 (C-24), 15.8 (C-25), 16.6 (C-26), 25.4 (C-27), 32.5 (C-29), 22.9 (C-30); Two olefinic carbon signal δ
c121.1 (C-12), 144.6 (C-13); Two company oxygen carbon signal δ
c68.5 (C-2), 82.3 (C-3); And two carbonyl signals δ
c176.7 (C-28), 209.7 (C-23).The aglycon of this compound is 2 beta-hydroxy-23-aldehyde radical-Oleanolic Acids in summary.
D-Glucose aldehydic acid and D-wood sugar is detected through acid hydrolysis.Can know corresponding terminal hydrogen signal by inference in conjunction with 1D, 2D-NMR is δ
h4.49 (d, J=8Hz, H-1 '), 4.84 (d, J=8Hz), corresponding carbon signal is δ
c102.9 (C-1 '), 103.4 (C-1 ").Glucuronic acid is gone out and wood sugar is beta comfiguration by the size deducibility of coupling constant.In HMBC spectrum, δ
h4.84 with δ
c83.4 (C-2 ") is correlated with, and can infer that two sugar 1 → 2 this compound connect; δ
h4.49 with δ
c82.3 (C-3) are correlated with, and can infer that sugar chain is connected in (table 2) on C-3.
The NMR data of table 2 compound are relevant with crucial HMBC
Comprehensive above information, identifies that this compound structure is 2 beta-hydroxy-23-aldehyde radical-3-O-[β-D-xylopyranosyl-(1 → 2)-beta d glucopyranosiduronic acid]-Oleanolic Acids ((Fig. 2).Through being retrieved as a new compound, called after feather cockscomb glycosides L (celosin L).
The above-mentioned Compound nomenclature prepared is: feather cockscomb glycosides K (celosin K), feather cockscomb glycosides L (celosin L), and its spectral data is as follows:
(1) compound is white powder, [α]
d 20+ 38.2 ° (c 0.130, MeOH).IR v
max3899,3444,2950,2310,1638,1400,1153,1072,545 and 518cm
-1.ESI-QTOF-MS m/z:941.4739 [M-H]
-(calculated value is 941.4752), can know its molecular formula by inference is C
47h
74o
19.
1hNMR (C
5d
5n, 500MHz) compose high field region and occur 7 angular methyl(group) signal: δ
h1.01 (s, H
3-23), 1.02 (s, H
3-24), 1.07 (s, H
3-25), 0.75 (s, H
3-26), 0.96 (s, H
3-27), 0.74 (s, H
3-29), 0.71 (s, H
3-30); There is an alkene hydrogen signal δ low place
h5.16 (br s, H-12); And the proton signal δ on two company's oxygen carbon
h4.36 (d, J=3.5Hz, H-2), 3.09 (d, J=3.5Hz, H-3);
13c NMR (C
5d
5n, 125MHz) show 7 methyl carbon signal: δ
c28.8 (C-23), 17.6 (C-24), 15.7 (C-25), 16.6 (C-26), 25.3 (C-27), 32.3 (C-29), 22.8 (C-30); Two olefinic carbon signal δ
c122.4 (C-12), 143.2 (C-13); The secondary carbon signal δ of company's oxygen
c89.3 (C-3); And a carboxyl signal δ
c177.4 (C-28).Determine that the aglycon of this compound is 2 beta-hydroxies-Oleanolic Acid.
D-Glucose aldehydic acid, D-wood sugar and D-Glucose is detected through acid hydrolysis.
1h NMR (C
5d
5n, 500MHz) show corresponding end group hydrogen signal: δ
h4.66 (d, J=7.5Hz), δ
h4.99 (d, J=7.5Hz), δ
h5.73 (d, J=8.5Hz); Corresponding end group carbon signal: δ
c104.5 (C-1 " '), δ
c103.8 (C-1 "), δ
c94.4 (C-1 " ').Can determine that in this compound sugar chain, glucuronic acid, xylose and glucose are beta comfiguration according to the size of each sugared anomeric proton signal coupling constant.In HMBC spectrum, δ
h4.99 with C-2 ' (δ
c84.1) have relevant, can infer that this compound has two sugar 1 → 2 to connect, δ
h4.66 with δ
c89.3 (C-3), δ
h5.73 with δ
c177.4 (C-28) have relevant, can infer that sugar chain is connected on C-3 and C-28 respectively.
Comprehensive above information, determines that this compound structure is 2 beta-hydroxy-3-O-[β-D-xylopyranosyl-(1 → 2)-beta d glucopyranosiduronic acid]-28-O-β-D-glucopyranosyl-Oleanolic Acid.Through being retrieved as a new compound, called after feather cockscomb glycosides K (celosin K).
(2) compound is white powder, [α] D20+84 ° (c 0.016, MeOH).IR v
max3423,2946,2319,1751,1631,1400,1259,1146,1074,1000,904,625,518,458,443 and 419cm
-1.ESI-QTOF-MS m/z:793.4074 [M-H]
-(calculated value is 793.4016), can know its molecular formula by inference is C
41h
62o
20.
In conjunction with
1h,
13c NMR information, this compound has 6 methyl singlets signal: δ
h1.25 (s, H
3-24), 1.05 (s, H
3-25), 0.66 (s, H
3-26), 0.88 (s, H
3-27), 0.66 (s, H
3-29), 0.79 (s, H
3-30); An alkene hydrogen signal δ
h5.15 (br s, H-12) and two hydroxyls replace the proton signal δ on carbon
h4.37 (m, H-2), 3.73 (d, J=4.0Hz, H-3);
13c NMR (C
5d
5n, 125MHz) show six methyl signals: δ
c10.4 (C-24), 15.8 (C-25), 16.6 (C-26), 25.4 (C-27), 32.5 (C-29), 22.9 (C-30); Two olefinic carbon signal δ
c121.1 (C-12), 144.6 (C-13); Two company oxygen carbon signal δ
c68.5 (C-2), 82.3 (C-3); And two carbonyl signals δ
c176.7 (C-28), 209.7 (C-23).The aglycon of this compound is 2 beta-hydroxy-23-aldehyde radical-Oleanolic Acids in summary.
Detect D-Glucose aldehydic acid and D-wood sugar through acid hydrolysis, can know corresponding terminal hydrogen signal by inference in conjunction with 1D, 2D-NMR is δ
h4.49 (d, J=8Hz, H-1 '), 4.84 (d, J=8Hz), corresponding carbon signal is δ
c102.9 (C-1 '), 103.4 (C-1 ").Glucuronic acid is gone out and wood sugar is beta comfiguration by the size deducibility of coupling constant.In HMBC spectrum, δ
h4.84 with δ
c83.4 (C-2 ") is correlated with, and can infer that two sugar 1 → 2 this compound connect; δ
h4.49 with δ
c82.3 (C-3) are correlated with, and can infer that sugar chain is connected on C-3.
Comprehensive above information, identifies that this compound structure is 2 beta-hydroxy-23-aldehyde radical-3-O-[β-D-xylopyranosyl-(1 → 2)-beta d glucopyranosiduronic acid]-Oleanolic Acids.Through being retrieved as a new compound, called after feather cockscomb glycosides L (celosin L).
Triterpene saponin componds new in Semen Celosiae of the present invention is treated in preparation or is prevented the application on the composition of fatty liver sex change.
The application of triterpene saponin componds new in Semen Celosiae of the present invention on the composition that preparation is treated or prevention of liver damages.
Effect experiment
To the therapeutic action of non-alcoholic fatty liver disease
1, laboratory animal and method:
C57BL mouse, SPF level, male, body weight (20+2) g, is divided into two groups at random, first group 12, for normal group, give and chow diet, all the other mouse (44) are divided into second group, are freely ingested with high lipid food (50% chow diet, 15% lard, 10% yolk powder, 15% milk powder, 5% sucrose, 3% cholesterol, 2% Sodium cholic acid), drink water.Continuous nursing, after 5 weeks, from dead 4 mouse of Normal group and Models of Fatty Liver component other places, compares serum and the liver biochemical indexes of two groups of mouse, and liver organization pathological section, judges whether nonalcoholic fatty liver model mouse is successfully established.Modeling success mouse 40 is divided into 5 groups at random, often organize 8, be respectively model control group, positive drug Kezhi capsule group (100mg/kg, 1 time/d), feather cockscomb glycosides K (2mg/kg, 1 time/d), feather cockscomb glycosides L treatment group (2mg/kg, 1 time/d), continuous gastric infusion 6 weeks, Normal group (8) and model control group give normal saline.During administration, except Normal group standard mouse material is raised, all the other each group is continued to give high fat diet, until experiment terminates.
2, observation index:
The generalized case of a animal
B liver function index of correlation: Serum ALT, AST, SOD, liver index, body fat index
C blood lipids: TC, TG, HDL, LDL
D pathological examination: paraffin section, HE dye, observes pathological change
3, experimental result:
Result shows: feather cockscomb glycosides K and feather cockscomb glycosides L all obviously can reduce total cholesterol (TC) in blood plasma and triglyceride level (TG), high density lipoprotein increasing (HDL), reduce low-density lipoprotein (LDL), the non-alcoholic fatty liver disease sex change that effective alleviation high lipid food causes, improves the hepatic disorder caused because of steatosis.The results are shown in Table 1 and table 2.
The change of lipid of mice index respectively organized by table 1
Compare with control group:
▲p < 0.05
▲ ▲p < 0.01
▲ ▲ ▲p < 0.001; Compare with model group:
*p < 0.05
*p < 0.01,
* *p < 0.001 time with
The change of Mouse Liver function index of correlation respectively organized by table 2
Accompanying drawing explanation
Fig. 1 feather cockscomb glycosides K's
1h-NMR composes (500MHz, C
5d
5n)
Fig. 2 feather cockscomb glycosides K's
13c-NMR composes (125MHz, C
5d
5n)
The DEPT of Fig. 3 feather cockscomb glycosides K composes (125MHz, C
5d
5n)
Hsqc spectrum (500MHz, the C of Fig. 4 feather cockscomb glycosides K
5d
5n)
The HMBC of Fig. 5 feather cockscomb glycosides K composes (5 () () MHz, C
5d
5n)
Fig. 6 feather cockscomb glycosides K's
1h-
1h COSY composes (500MHz, C
5d
5n)
The NOESYNMR of Fig. 7 feather cockscomb glycosides K composes (500MHz, C
5d
5n)
The HR-ESI-MS spectrum of Fig. 8 feather cockscomb glycosides K
Fig. 9 AST
Figure 10 ALT
Figure 11 TC
Figure 12 TG
Figure 13 HDL
Figure 14 LDL
Figure 15 body fat index
Figure 16 pathological examination
Embodiment:
Embodiment 1: the preparation method 1 of feather cockscomb glycosides K
1, extract: after dry for 1500g Semen Celosiae pulverizing medicinal materials, the 50% ethanolic soln cold soaking adding medicinal material weight 10 times of volumes spends the night, 65 DEG C of heating and refluxing extraction 3 times, merge ethanol extract, concentratedly to obtain general extractive 165g;
2, rough segmentation: by said extracted gained general extractive, after adding the water dissolution of general extractive weight 10 times amount, by Semen Celosiae medicinal material with resin quality than 1: 1, through D-101 type macroporous adsorbent resin, respectively with water, 20% ethanolic soln, 70% ethanolic soln, 95% ethanolic soln gradient elution, each gradient elution 4 retention volume, collect 70% ethanolic soln wash-out position, obtain crude extract 32g in 60 DEG C of concentrating under reduced pressure;
3, refining: above-mentioned crude extract mixes sample with thick silica gel (100 ~ 200 order), through silica gel column chromatography, with methylene chloride-methanol gradient elution (100: 1 ~ 1: 1).By methylene chloride-methanol (6: 4) elution fraction through anti-phase ODS chromatographic separation (separation condition: chromatographic column internal diameter 2cm, filler height 40cm in post; With methanol-water (10% ~ 100%) gradient elution), (methanol-water) wash-out position of 53%, through lyophilize, obtains feather cockscomb glycosides K compound 0.13g;
4, Structural Identification: utilize spectroscopic techniques, comprises infrared, high resolution mass spectrum, nucleus magnetic resonance and acid hydrolysis-derivatize-high performance liquid chromatography identifies its structure.
Embodiment 2: the preparation method 2 of feather cockscomb glycosides K
1, extract: after dry for 5600g Semen Celosiae pulverizing medicinal materials, the 50% ethanolic soln cold soaking adding medicinal material weight 10 times of volumes spends the night, 70 DEG C of heating and refluxing extraction 3 times, merge ethanol extract, concentratedly to obtain general extractive 484g;
2, rough segmentation: by said extracted gained general extractive, after adding the water dissolution of general extractive weight 10 times amount, by Semen Celosiae medicinal material with resin quality than 1: 1, through D-101 type macroporous adsorbent resin, respectively with water, 20% ethanolic soln, 70% ethanolic soln, 95% ethanolic soln gradient elution, each gradient elution 4 retention volume, collect 70% ethanolic soln wash-out position, obtain crude extract 114g in 60 DEG C of concentrating under reduced pressure;
3, refining: above-mentioned crude extract mixes sample with thick silica gel (100 ~ 200 order), through silica gel column chromatography, with methylene chloride-methanol gradient elution (100: 1 ~ 1: 1).By methylene chloride-methanol (6: 4) elution fraction through anti-phase ODS chromatographic separation (separation condition: chromatographic column internal diameter 2cm, filler height 40cm in post; With methanol-water (10% ~ 100%) gradient elution), (methanol-water) wash-out position of 53%, through lyophilize, obtains feather cockscomb glycosides K compound 0.62g;
4, Structural Identification: utilize spectroscopic techniques, comprises infrared, high resolution mass spectrum, nucleus magnetic resonance and acid hydrolysis-derivatize-high performance liquid chromatography identifies its structure;
5, active testing: feather cockscomb glycosides K obviously can reduce total cholesterol (TC) in blood plasma and triglyceride level (TG), high density lipoprotein increasing (HDL), reduce low-density lipoprotein (LDL), the non-alcoholic fatty liver disease sex change that effective alleviation high lipid food causes, improves the hepatic disorder caused because of steatosis.
Embodiment 3: the preparation method 1 of feather cockscomb glycosides L
1, extract: after dry for 2000g Semen Celosiae pulverizing medicinal materials, the 50% ethanolic soln cold soaking adding medicinal material weight 12 times of volumes spends the night, 65 DEG C of heating and refluxing extraction 3 times, merge ethanol extract, concentratedly to obtain general extractive 156g;
2, rough segmentation: by said extracted gained general extractive, after adding the water dissolution of general extractive weight 10 times amount, by Semen Celosiae medicinal material with resin quality than 1: 1, through D-101 type macroporous adsorbent resin, respectively with water, 20% ethanolic soln, 70% ethanolic soln, 95% ethanolic soln gradient elution, each gradient elution 4 retention volume, collect 70% ethanolic soln wash-out position, obtain crude extract 34g in 60 DEG C of concentrating under reduced pressure;
3, refining: above-mentioned crude extract mixes sample with thick silica gel (100 ~ 200 order), through silica gel column chromatography, with methylene chloride-methanol gradient elution (100: 1 ~ 1: 1).By methylene chloride-methanol (6: 4) elution fraction through anti-phase ODS chromatographic separation (separation condition: chromatographic column internal diameter 2cm, filler height 40cm in post; With methanol-water (10% ~ 100%) gradient elution), collect the methanol-eluted fractions position of 65%, then be separated (separation condition: column diameter 3cm, long 0.8m through Sephadex LH-20; Wet method loading; Loading volume accounts for 1% of post cumulative volume; With methanol-water (10% ~ 100%) gradient elution; Eluent flow rate 1ml/min), collect 50% methanol-eluted fractions cut, be dissolved in methanol solution after recycling design ,-4 DEG C of recrystallizations obtain compound feather cockscomb glycosides L monomer component 0.18g;
4, Structural Identification: utilize spectroscopic techniques, comprises infrared, high resolution mass spectrum, nucleus magnetic resonance and acid hydrolysis-derivatize-high performance liquid chromatography identifies its structure.
Embodiment 4: the preparation method 2 of feather cockscomb glycosides L
1, extract: after dry for 6000g Semen Celosiae pulverizing medicinal materials, the 50% ethanolic soln cold soaking adding medicinal material weight 12 times of volumes spends the night, 70 DEG C of heating and refluxing extraction 3 times, merge ethanol extract, concentratedly to obtain general extractive 438g;
2, rough segmentation: by said extracted gained general extractive, after adding the water dissolution of general extractive weight 12 times amount, by Semen Celosiae medicinal material with resin quality than 1: 1, through D-101 type macroporous adsorbent resin, respectively with water, 20% ethanolic soln, 70% ethanolic soln, 95% ethanolic soln gradient elution, each gradient elution 4 retention volume, collect 65% ethanolic soln wash-out position, obtain crude extract 127g in 60 DEG C of concentrating under reduced pressure;
3, refining: above-mentioned crude extract mixes sample with thick silica gel (100 ~ 200 order), through silica gel column chromatography, with methylene chloride-methanol gradient elution (100: 1 ~ 1: 1).By methylene chloride-methanol (6: 4) elution fraction through anti-phase ODS chromatographic separation (separation condition: chromatographic column internal diameter 2cm, filler height 40cm in post; With methanol-water (10% ~ 100%) gradient elution), collect the methanol-eluted fractions position of 70%, then be separated (separation condition: column diameter 3cm, long 0.8m through Sephadex LH-20; Wet method loading; Loading volume accounts for 1% of post cumulative volume; With methanol-water (10% ~ 100%) gradient elution; Eluent flow rate 1ml/min), collect 50% methanol-eluted fractions cut, be dissolved in methanol solution after recycling design ,-4 DEG C of recrystallizations obtain compound feather cockscomb glycosides L monomer component 0.61g;
4, Structural Identification: utilize spectroscopic techniques, comprises infrared, high resolution mass spectrum, nucleus magnetic resonance and acid hydrolysis-derivatize-high performance liquid chromatography identifies its structure;
Reference:
[1] Lin Wenqun, Chen Zhong, Liu Jianqiu. the chemical composition [J] of Semen Celosiae and wild perilla seed is produced in Fujian. Chinese medicine biotechnology applications magazine, 2002,4 (3): 57.
[2] Lin Wenqun, Chen Zhong, Liu Jianqiu. Semen Celosiae chemical composition preliminary study [J]. subtropical plant science, 2003,32 (1): 20.
[3] Xue Qian, Guo Meili, Zhang Ge. Semen Celosiae chemical constitution study [J]. pharmaceutical services and research, 2006,6 (5): 345-347.
[4]Morita H，Suzuki H，Kobayashi J.Celogenamide A，a new cyclic peptide from the seeds of Celosia argentea[J].J Nat Prod，2004，67(9)：1628-1630
[5]Suzuki H，Morita H，Kobayashi J，et al.New antimitotic bicyclic peptides，celogentins D-H，and J，from the seeds of Celosia argentea[J].Tetrahedron，2003，59(28)：5307-5315.
[6]Suzuki H，Morita H，Iwasaki S，et al.Celogentin K，a new cyclic peptide from the seeds of Celosia argentea and X-ray structure of moroidin[J].Tetrahedron，2004，60(11)：2489-2495.
[7]Sun ZL，Wang Y，Li YX，et al.Two new hepaprotective saponins from Semen Celosiae[J].Fitoterapia，2010，81(5)：375-380.
[8]Wang Y，Lou ZY，Guo ML，et al.A novel hepatoprotective saponin from Celosia cristata L.[J].Fitoterapia，2010，81(8)：1246-1252.
[9]Wu QB，Wang Y，Guo ML，Triterpenoid saponins from the seeds of Celosia argentea and theiranti-inflammatory and antitumor activities[J].Chem Pharm Bull，2011，59(5)：666-671.
[10]Xue Q，Guo ML，Sun ZL，et al.Two new compounds from semen celosiae and their protective effects against CCl4-induced hepatotoxicity[J].J Nat Prod Res，2011，25(8)：772-780.
[11
]Wu QB，Wang Y，Guo ML，et al.Isolation and purification of tWo saponins from Semen Celosiae by high-speed counter-current chromatography coupled with ELSD[J].J NatProdRes，2012，24(5)：481-485.
Claims (5)
1. a triterpene saponin componds new in Semen Celosiae, is characterized by:
Feather cockscomb glycosides K, its chemical structure is as follows:
2. according to triterpene saponin componds new in the Semen Celosiae in claim 1, it is characterized by: preparation method is as follows:
extract: after dry Semen Celosiae pulverizing medicinal materials, 40 ~ 70% ethanolic soln cold soakings adding medicinal material weight 5 ~ 10 times of volumes spend the night, 40 ~ 80 DEG C of circumfluence distillation 2 ~ 4 times, merge ethanol extract, concentratedly to obtain general extractive.
rough segmentation: by said extracted gained general extractive, after adding the water dissolution of general extractive weight 5 ~ 15 times amount, by Semen Celosiae medicinal material with resin quality than 1: (1 ~ 10), through D-101 type macroporous adsorbent resin, respectively with water, 10 ~ 20% ethanolic solns, 40 ~ 80% ethanolic solns, 85 ~ 95% ethanolic soln gradient elutions, each gradient elution 2 ~ 6 retention volume, collect 40 ~ 80% ethanolic soln wash-out positions, obtain crude extract in 60 DEG C of concentrating under reduced pressure.
refining: above-mentioned crude extract mixes sample with thick silica gel (100 ~ 200 order), through silica gel column chromatography, with methylene chloride-methanol gradient elution (100: 1 ~ 1: 1).By methylene chloride-methanol (1: 4) ~ (4: 1) elution fraction through anti-phase ODS chromatographic separation (separation condition: chromatographic column internal diameter 2cm, filler height 40cm in post; With methanol-water (10% ~ 100%) gradient elution), the methanol-water wash-out position of 50% ~ 55%, through lyophilize, obtains feather cockscomb glycosides K compound.
3. according to triterpene saponin componds new in the Semen Celosiae of claim 2-3, it is characterized by: preparation method is as follows:
Structural Identification: utilize spectrum spectral technology, comprises infrared, high resolution mass spectrum, nucleus magnetic resonance, acid hydrolysis-derivatize-high performance liquid chromatography identifies its structure.
4. triterpene saponin componds new in Semen Celosiae according to claim 1 is treated in preparation or is prevented the application on the composition of fatty liver sex change.
5. the application of triterpene saponin componds new in Semen Celosiae according to claim 1 on the composition that preparation is treated or prevention of liver damages.
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| CN104945355A (en) * | 2015-06-19 | 2015-09-30 | 武汉光谷人福生物医药有限公司 | Method and system for extracting and separating dihydro-phaseic acid from desmodium styracifolium |
| CN109021060A (en) * | 2018-09-26 | 2018-12-18 | 上海诗丹德标准技术服务有限公司 | The preparation method of momordin Ic |
| CN114478700A (en) * | 2022-02-22 | 2022-05-13 | 南京医科大学 | Preparation method of urticaceae cyclic peptide in cockscomb seeds and application of urticaceae cyclic peptide in antitumor drugs |
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104945355A (en) * | 2015-06-19 | 2015-09-30 | 武汉光谷人福生物医药有限公司 | Method and system for extracting and separating dihydro-phaseic acid from desmodium styracifolium |
| CN109021060A (en) * | 2018-09-26 | 2018-12-18 | 上海诗丹德标准技术服务有限公司 | The preparation method of momordin Ic |
| CN109021060B (en) * | 2018-09-26 | 2021-05-18 | 上海诗丹德标准技术服务有限公司 | Preparation method of broom cypress fruit saponin Ic |
| CN114478700A (en) * | 2022-02-22 | 2022-05-13 | 南京医科大学 | Preparation method of urticaceae cyclic peptide in cockscomb seeds and application of urticaceae cyclic peptide in antitumor drugs |
| CN114478700B (en) * | 2022-02-22 | 2023-09-08 | 南京医科大学 | Preparation method of nettle type cyclic peptide in cockscomb seed and application of nettle type cyclic peptide in anti-tumor drugs |
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