CN1615829A - Use of sinapine in preparing medicine for preventing and curing senile dementia - Google Patents
Use of sinapine in preparing medicine for preventing and curing senile dementia Download PDFInfo
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Abstract
Sinapine originated from cruciferae plant seed is used in preparing active acetylcholinesterase medicine and/or medicine for inhibiting inward flow of outer calcium, and may be used in treating senile dementia, especially senile dementia accompanied by hypertension. It has strong extracorpooreal AchE inhibiting capacity, strong cerebral tissue AchE inhibiting effect, weak serum AchE inhibiting capacity, IC50SERUM/IC50BRAIN =6.042, and Glu caused PC12 intracellular calcium raise inhibiting effect stronger than KCl caused intracellular calcium raise inhibiting effect; and exhibits acceptor dependent calcium channel blocking effect stronger than voltage dependent calcium channel blocking effect.
Description
Technical field
The invention belongs to a kind of sinapic acid choline ester. in pharmaceutically new application, be specially the purposes aspect preparation treatment alzheimer disease disease medicament.
Background technology
The alzheimer disease disease (Alzheimer ' s disease, be called for short AD, claim presenile dementia again, down together) be a kind of senile neurodegenerative diseases, its clinical carrying out property hypomnesis, language and behavior disorder of mainly showing as is the main pathogenic factor of senile dementia.AD biochemistry shows as the interior neurotransmitter of brain such as levels such as acetylcholine (ACh), 5-hydroxy tryptamine (5-HT), norepinephrine (NE), dopamine (DA), glutamic acid (Glu) and P material obviously descend, and is wherein obvious with the reduction of ACh level.Acetylcholine is a kind of important neurotransmitter in the human brain, and is relevant with study, memory function.Modern pharmacology studies have shown that, presenile dementia is an a kind of cholinergic nerve of centrum system degenerative disease, and the acetyl choline content of patient's cerebral cortex and hippocampus obviously reduces.Acetylcholinesterase is to be the enzyme of choline with the acetylcholine catalytic decomposition, mainly is distributed in nervous tissue, as alba and grey matter, spinal cord, intraganglionic neurocyte and neuromuscular junction, also is distributed in the non-nervous tissues such as erythrocyte and serum.Acetylcholinesteraseinhibitors inhibitors is that a class can combine with acetylcholinesterase (AChE), and suppresses the active medicine of AChE (also claiming anticholinesterase drug), thereby acetylcholinesterase is the enzyme that rapid hydrolysis acetylcholine makes the Ach inactivation in the body.The AChE inhibitor suppresses the decomposition that the AChE activity can suppress acetylcholine, the Ach that the cholinergic nerve tip is discharged stores the time of piling up in synaptic space longer, thereby prolonged the excitation of ACh to cholinoceptor in the brain, performance M sample and the effect of N sample strengthen, improve patient's AD cholinergic nerve function, so such medicine claims cholinomimetic again.Can be divided into: 1. easily contrary property or transience cholinesterase inhibitor, as neostigmine, physostigmine etc.; This class medicine has therapeutical effect clinically.2. difficult contrary property (or irreversibility) cholinesterase inhibitor as organic phosphoric acid ester, comprises agricultural fungicides and war gas.
Acetylcholinesterase (AChE) inhibitor is topmost, also is a unique up to now class is used for the treatment of AD by drugs approved by FDA medicine.There are 4 kinds of AChE inhibitor to obtain drugs approved by FDA at present and are used for the treatment of AD, be the tacrine (Tacrine of Warner-Lambert AG Safnern's development, trade name Cognex), the donepezil (Donepezil of Japanese Wei Cai company and Pfizer Inc. development, trade name Aricept) and the profit of Novartis Co.,Ltd development cut down department for bright (Rivastigmine, trade name Exelon Exelon), the galantamine of Shire company (Reminyl R, galanth amine) was got permission to go on the market in the U.S. respectively at 1993,1997,2000 and 2002.In addition, still there is multiple AChE inhibitor to be in conceptual phase or entered clinical trial.But existing cholinesterase inhibitor exists the half-life short, and main is that shortcomings such as more serious periphery cholinergic system side effect and liver toxicity are arranged, and their potential applicability in clinical practice is restricted.Therefore, searching long action time, the little cholinesterase inhibitor of new generation of side effect are still the focus that international each big pharmaceutical factory is paid close attention to.
Summary of the invention
Because senile dementia treatment needs long-term prescription, thus the technical problem to be solved in the present invention be seek derive from plant, reversibility, efficient, high selectivity, long action time and the little natural A ChE inhibitor of side effect.
For addressing the above problem, the invention provides following technical proposals.
Sinapic acid choline ester. is the application in the stream medicine in the calcium at preparation acetylcholine esterase inhibition activity medicine and/or outside suppressing, and described acetylcholinesteraseinhibitors inhibitors is to prevent and treat the alzheimer disease medicine.The present invention comprises that also sinapic acid choline ester. is preparing treatment with the application in hypertensive alzheimer disease patient's medicine.A kind of alzheimer disease compositions of preventing and treating is characterized in that containing sinapic acid choline ester..
So the present invention's sinapic acid choline ester. is the natural A ChE inhibitor that comes from plant, when being used for preparation control acetylcholine esterase active medicine and/or the interior stream of the outer calcium of inhibition medicine, as when preventing and treating the alzheimer disease medicine and especially preventing and treating with hypertensive alzheimer disease patient's medicine, have reversibility, efficient, high selectivity, the little advantage of side effect, can satisfy senile dementia treatment needs the long-term prescription demand.
When sinapic acid choline ester. of the present invention flows medicine at the preparation acetylcholine esterase inhibitor medication and/or outside suppressing in the calcium, as when preventing and treating alzheimer disease medicine or control with hypertensive alzheimer disease medicine, can add various mineral in addition, especially preferably can replenish the mineral of easy insufficient indispensable element, micro-indispensable element effect in the organism.In addition, can also add other natural drug, aminoacid and/or vitamin in addition.Included natural drug does not have special restriction, and is first-selected to the effective Ganoderma of stable spirit, Radix Rehmanniae, Fructus Jujubae, Fructus Schisandrae Chinensis, Semen Ziziphi Spinosae, Radix Ginseng, Radix Et Caulis Acanthopanacis Senticosi, Semen Ginkgo, Shi Shan, Rhizoma Dioscoreae, Semen Coicis, Radix Polygoni Multiflori, Radix Angelicae Sinensis, BAIYAO, Rhizoma Polygonati, Fructus Corni, Fructus Lycii, Fructus Hippophae, semen juglandis, Fructus Mori, Hippocampus, Herba Epimedii, Rhizoma Coptidis, Rhizoma Acori Graminei, Rhizoma Arisaematis, Radix Curcumae, Rhizoma Chuanxiong, Radix Salviae Miltiorrhizae, Radix Puerariae, Fructus Crataegi, Rhizoma Gastrodiae, Cornu Cervi Pantotrichum, Poria, Radix Notoginseng, Cordyceps, Semen Ginkgo, Semen Strychni, Moschus, Herba Cistanches, the Radix Astragali, Radix Codonopsis, Fructus Alpiniae Oxyphyllae, Radix Paeoniae Rubra etc.In addition, also can select the lavandula angustifolia, Semen Platycladi, Radix Polygalae, Cortex Albiziae, Caulis Polygoni Multiflori, Rhizoma Cyperi, Radix Bupleuri, Fructus Aurantii, Bulbus Lilii, the Rhizoma Anemarrhenae, Arisaema Cum Bile etc. of calm and relaxation effect for use.The form of these plant amedica can be the extractum that extracts, quintessence oil, medicated tea etc., there is no special restriction.Aminoacid does not have special restriction yet, for example can be glu famine, tryptophan, lysine, leucine, glutamic acid, isoleucine, methionine etc.Vitamin does not have special restriction yet, for example can be vitamin B6, vitamin B1, vitamin B2, folic acid, vitamin C, vitamin E etc.When sinapic acid choline ester. of the present invention flows medicine at the preparation acetylcholine esterase inhibitor medication and/or outside suppressing in the calcium, other composition be can add in addition, Aloe, Lac regis apis, spirulina, Folium Ginkgo, bacillus bifidus etc. for example added.
The specific embodiment
One. the separation and purification of sinapic acid choline ester.:
(1. Li Shu etc., the research of chemical constituents of Sinapis seeds, Shaanxi new medicine, 12 (9), 1983:57-58,2; Wang Weilan etc., the research of Semen Raphani antihypertensive activity composition, Chinese herbal medicine, 18 (3), 1987:5-7.)
The present invention's experiment shows that the extracting method of three kind of plant is basic identical.
Extracting method: after getting each 20kg coarse crushing such as Cruciferae medicinal plants Semen Sinapis Albae, Semen Raphani, Semen Lepidii (Semen Descurainiae), add 10 times of amount 95% soak with ethanol 72hr respectively, the percolator of packing into is collected 10 times of amount percolates, is evaporated to every milliliter and is equivalent to crude drug 5g, put in the refrigerator 2-3 days, separate out coarse crystallization, the leaching precipitation replaces recrystallization with 95% second alcohol and water and gets faint yellow fine needle crystalline substance three times, (content is greater than 98%, HPLC) for pure product sinapic acid choline ester. rhodanate.
Structural formula:
Molecular formula: C
16H
24NO
5.SCN; Molecular weight: 368; Fusing point: 177-178 ℃.
Two. with the acetylcholinesterase is target spot, observation in vitro the influence of sinapic acid choline ester. to the acetylcholinesterase vigor.
(1) sinapic acid choline ester. is to the influence of acetylcholinesterase (AchE) vigor in brain, the serum
Cholinesterase inhibitor increases the content of acetylcholine in the brain by suppressing the activity of acetylcholine esterase, recovers the cholinergic nerve conduction, and senile dementia patient light, moderate has been obtained excellent curative.This experiment is target spot with the acetylcholinesterase, observation in vitro the influence of sinapic acid choline ester. to the acetylcholinesterase vigor.
1 experiment material
1.1 animal: SD male rat, body weight 210 ± 20g.Provide by China Medicine University's animal center.
1.2 medicine and reagent acetylcholinesterase are measured test kit: bio-engineering research institute is built up in Nanjing, lot number: 20040507 biuret total proteins are measured test kit: bio-engineering research institute is built up in Nanjing, lot number: 20040425 test-compounds: sinapic acid choline ester. is dissolved in dilute hydrochloric acid, is diluted to desired concn with PBS.
Other reagent are commercially available AR level.
1.3 instrument and equipment
UV-722 ultraviolet spectrophotometer: Shanghai the 3rd analytical tool factory
Electric-heated thermostatic water bath: Dongtai City, Jiangsu Province electrical apparatus factory, model HH-S
Centrifugal precipitation mechanism: Shanghai Surgical Operation Equipment Factory, model is 80-1
Electronic balance: go up Nereid section balance, model is JA1003
2 methods
2.1 the preparation of AchE
Male rat, body weight 210 ± 20g, 3.Eyeball breaks end after getting blood 3ml, and the ice platform is got brain fast, puts into glass dish (glass dish adds a small amount of ice-cold PBS) rinsing, inhales the moisture and the blood of decerebrate tissue surface with clean filter paper.Precision is weighed, and rat brain is 2.351g heavily, puts into small beaker.(g/L:NaCl 8, and KCl 0.2, Na to add a small amount of ice-cold PBS
2HPO
412H
2O 3.5, KH
2PO
40.2, pH7.4) in beaker, shred piece of tissue as early as possible with eye scissors.The tissue that shreds is poured in the glass homogenizer, and a little ice-cold PBS flushing of reuse remains in the broken piece of tissue in the beaker, pours into together and carries out ice bath homogenate in the homogenizer.And then add refrigerated PBS, and in brain weight and 1: 10 ratio of homogenate cumulative volume, the dilution mixing.With 10% brain homogenate for preparing with 3000r/min centrifugal 15 minutes, it was to be measured to get supernatant.The blood that takes out centrifugal 8 minutes with 1000r/min is got upper serum.During survey serum is diluted by 1: 9 with PBS.
2.2 the mensuration of total protein content
Recording big rat brain tissue homogenate's total protein content with biuret method is 3.97mg prot/ml.
2.3 rat blood serum, brain homogenate AchE enzyme activity determination
With the vigor of improvement Ellman colorimetric method for determining AchE, measure the method for test kit by acetylcholine esterase and measure.Measuring principle: acetylcholine esterase hydrolysis acetylcholine generates choline and acetic acid, choline can generate the trinitrobenzene yellow compound with the reaction of sulfydryl developer, carry out colorimetric assay according to shade, the quantity of hydrolyzate choline can reflect the vigor of acetylcholine esterase.If the pipe group is measured in standard pipe group, not dosing, test-compound is measured the pipe group, all to establish the blank pipe and measure pipe for every group, big rat brain tissue homogenate's liquid and serum sampling amount are every pipe 30 μ l.The reaction system mixing, 37 ℃ of accurate responses 6 minutes, cessation reaction then, mixing was placed 15 minutes, measured at the 412nm wavelength and respectively managed absorbance (returning to zero with PBS).Be subjected to that reagent is mixed with 0.0005,0.001,0.005,0.01,0.05,0.1,0.5 respectively, the 1mg/ml aqueous solution, n=3.Record the suppression ratio of sinapic acid choline ester. by following formula to AchE.
AchE vigor (U/mgprot) in the brain homogenate=(measuring pipe OD value-control tube OD value)/(standard pipe OD value-blank pipe OD value) * standard pipe concentration (1 μ mol/ml)/protein content (mgprot/ml)
Every milligram of histone sample is at 37 ℃ of insulation 6min, and 1 μ mol substrate is 1 unit of activity (U) in the hydrolysis reaction system.
Extension rate before AchE vigor (U/ml) in the serum=(measuring pipe OD value-control tube OD value)/(standard pipe OD value-blank pipe OD value) * standard pipe concentration (1 μ mol/ml) * sample test
Every milliliter of serum sample is at 37 ℃ of insulation 6min, and 1 μ mol substrate is 1 unit of activity (U) in the hydrolysis reaction system.
Medicine is to suppression ratio (%)=(not dosing group enzyme activity-medicine group enzyme activity)/not dosing group enzyme activity * 100% of AchE
Table 1, sinapic acid choline ester. to the vitro inhibition effect of rat brain homogenate Ach E (x ± s, n=3).
Medication medication concentration enzyme activity suppression ratio IC
50
(mg/ml) (μM) (U/mgprot) (％) (μM)
Not dosing 0 0.971 ± 0.283/
0.0005 1.359 0.705±0.119 27.41
0.001 2.717 0.579±0.178
* 40.33
0.005 13.59 0.205±0.046
** 78.92 3.661
0.01 27.17 0.159±0.031
** 83.65
0.05 135.9 0.074±0.018
** 92.37
0.1 271.7 0.031±0.010
** 96.81
0.5 1359 0.003±0.001
** 99.69
1 2717 0.000±0.001
** 100
Compare with not dosing group,
*P＜0.05,
*P＜0.01.The data linear regression, y (suppression ratio)=a+bx (lgC): y=35.93+24.96x r=0.9301
According to the literature, galantamine is 0.005,0.01,0.05,0.1,0.5 and 1 o'clock in concentration (mg/ml), the extracorporeal inhibiting rate of rat cerebral even slurry AchE is respectively: 39.10%, 45.68%, 65.61%, 77.32%, 91.69% and 93.46%.The present invention studies show that sinapic acid choline ester. is being better than galantamine with the vitro inhibition effect to rat cerebral even slurry AchE under the concentration.
Table 2, sinapic acid choline ester. to the vitro inhibition effect of rat blood serum AchE (x ± s, n=3).
Medication medication concentration enzyme activity suppression ratio IC
50
(mg/ml) (μM) (U/ml) (％) (μM)
Not dosing 0 8.692 ± 2.433/
0.0005 1.359 7.118±1.708 18.11
0.001 2.717 6.129±1.783 29.48
0.005 13.59 5.098±0.969
* 41.35 22.12
0.01 27.17 3.127±0.844
** 64.02
0.05 135.9 1.918±0.431
** 77.93
0.1 271.7 1.219±0.365
** 85.98
0.5 1359 0.284±0.049
** 96.73
1 2717 0.012±0.004
** 99.86
Compare with not dosing group,
*P＜0.05,
*P＜0.01.The data linear regression, y (suppression ratio)=a+bx (lgC): y=8.522+30.84x r=0.9741
Above-mentioned experimental data shows: sinapic acid choline ester. has the effect of very strong vitro inhibition AchE, and strong to the inhibitory action of cerebral tissue AchE, and to a little less than the active inhibition of plasma A chE, IC
50Serum/IC
50Brain=6.042 (doubly).This shows that sinapic acid choline ester. may not only optionally suppress the maincenter acetylcholinesterase, and might significantly weaken side effect of periphery cholinergic system and liver toxicity as maincenter acetylcholinesteraseinhibitors inhibitors application of treatment senile dementia disease.
(2) influence of calcium in the sinapic acid choline ester. pair cell:
Mass data shows that oxidative stress causes neurocyte to be degenerated and deadly plays an important role in the AD pathogenic process, to cause calcium overload be the neurocyte dead final path of degenerating and the intracellular Ca2+ that a variety of causes causes raises.Generally speaking, suppress the interior stream of outer calcium and not only have the periphery hypotensive effect, and the neuroprotective cell, AD has synergism to control.The influence of stream does not appear in the newspapers in the outer calcium of relevant sinapic acid choline ester. pair cell.This experiment is a material with PC12 cell and VSMC, adopt fluorescence indicator Fluo-3/AM load cell, measure sinapic acid choline ester. to high potassium depolarization, stream and endocellular liberation calcium concentration ([Ca in the outer calcium of PC12 cell that glutamic acid (Glu) and norepinephrine (NE) cause and VSMC
2+]
i) influence, further explore the mechanism of action of sinapic acid choline ester. from cellular level.
1, experiment material
1.1 cell strain
PC12 cell and aortic smooth muscle cell are all available from Shanghai cell institute.
1.2 medicine and reagent
DMEM culture medium: sigma product.Be made into the DMEM culture fluid with ultra-pure water, contain NaHCO in every liter of solution
33.7g, Hepes3.6g, penicillin, each 100mg of streptomycin, PH7.4.0.22 after the degerming of μ m filtering with microporous membrane, packing, 4 ℃ of refrigerators are preserved standby.
The import of Fluo-3/AM:Sigma company, the 1mM mother solution is made in the DMSO dissolving, and-20 ℃ of packing are preserved.
Calf serum: be Hangzhou Ilex purpurea Hassk.[I.chinensis Sims engineering material institute product.56 ℃ of deactivations in 30 minutes ,-20 ℃ of preservations after the packing.
L-sodium glutamate (L-Glu): Shanghai chemical reagents corporation of Chinese Medicine group product.
Noradrenaline bitartrate (NE): produce in Chinese Tian Feng pharmaceutical factory.
Trypsin: Huamei Bio-Engrg Co.,'s product.
PBS(g/L)：NaCl?8，KCl?0.2，NaHCO
312H
2O?3.49，KH
2PO
4?0.2。Fully dissolve with ultra-pure water, be settled to 1000ml.Autoclaving, 4 ℃ of preservations are standby.
D-Hanks solution (g/L): NaCl 8, and KCl 0.4, Na
2HPO
412H
2O 0.134, KH
2PO
40.06, NaHCO
30.35, phenol red 0.02.Fully dissolve with ultra-pure water, be settled to 1000ml.Autoclaving, 4 ℃ of preservations are standby.
Krebs liquid (g/L): NaCl 8, and KCl 0.4, MgSO
4.7H
2O 3, NaH
2PO
4.2H
2O 1.872, NaHCO
32.1, Glucose2, CaCl
20.2.
The test-compound sinapic acid choline ester.: molecular weight 368 with the 37%HCL dissolving, adds PBS and is diluted to desired concn.
Trypsin: be made into 0.25% enzymatic solution with D-Hanks solution
1.3 key instrument: XIDP super-clean bench, Wuzhong, Suzhou laboratory animal equipment factory product; Victor II 1420 multi-functional labelled immune analysers, PerkinElmer Life science Co.
2, method
2.1 cell culture
Cell inoculation uses the DMEM culture fluid that contains 15% calf serum in 37 ℃, 5%CO in culture bottle
2Cultivate in the incubator.Behind the cell attachment, observe upgrowth situation, treat that cell is paved with bottle at the bottom of, the culture fluid that inclines, with 0.25% trypsinization 2-3min, digestion back fully adds the DMEM culture medium that contains calf serum and stops digesting, suction pipe is blown and beaten to single cell suspension.Seed cells in 96 well culture plates and cultivate.After treating that cell covers with monolayer, can experimentize.
2.2 intracellular Ca2+ is measured
Principle: Fluo-3/AM be 1989 synthetic the 3rd generation fluorescent probe, but cell is advanced in its esterified form permeate through cell membranes load.The Fluo-3/AM that enters in the born of the same parents is hydrolyzed into Fluo-3 under the effect of enzyme, with the Free Ca in the born of the same parents
2+In conjunction with forming complex, be to inspire fluorescence about 500nm at wavelength.The high more measured fluorescence intensity of free calcium ion concentration is strong more in the born of the same parents.Therefore can reflect the variation of intracellular free calcium level by fluorescence intensity level.
Method: cell inoculation is divided into KCl (final concentration 75mM) model group, L-Glu (final concentration 10mM) model group, NE (final concentration 1 μ M) model group, is subjected to reagent thing group (final concentration is respectively 10,1,0.1 μ M) in 96 well culture plates.After covering with monolayer, inhale and remove culture fluid, wash 3 times with D-Hanks, every hole adds the Krebs liquid (Ca that contains Fluo-3/AM (final concentration 5 μ M)
2+2mM) 45 μ l were hatched 45 minutes in 37 ℃ of lucifuge loads, and sucking-off load liquid swings gently with Krebs washes 3 times, added Krebs liquid 45 μ l/ holes then.Model group adds the L-Glu of KCl, 10mM that final concentration is 75mM, the NE of 1 μ M respectively.Added earlier by the reagent group and be subjected to reagent thing effect 15 minutes, and then add each model stimulant.(Fluorescent intensity FI) is respectively 488nm and the detection of 535nm place with Victor II 1420 multi-functional labelled immune analysers in excitation wavelength and emission wavelength to fluorescence intensity in the cell.[Ca
2+]
iVariation represent with Δ FI.
Suppression ratio=(Δ FI that calcium raises in the medicine pair cell
Model group-Δ FI
The medicine group)/Δ FI
Model group* 100%
Δ FI represents to compare the value added of respectively organizing fluorescent value with tranquillization calcium fluorescent value
Δ FI
Model group=FI
Model group-FI
TranquillizationΔ FI
The medicine group=FI
The medicine group-FI
Tranquillization
Statistical method: adopt t check between two sample means group relatively, the result represents with x ± S.
The influence that table 3, sinapic acid choline ester. raise to the caused PC12 intracellular Ca2+ of KCl 75mmol/L (x ± S, n=10)
Medicine tranquillization FI KCI FI
Peak valueΔ FI suppression ratio (%)
(μmol/L)
Model group (not dosing) 1188 ± 163 4270 ± 982
b3082 ± 854/
0.1 1167±148 3032±711
bc 1865±491 39.5
1.0 1149±236 2586±804
bd 1437±445 53.7
10 1141±217 2009±614
ad 868±283 71.8
Compare with corresponding tranquillization FI value,
aP＜0.01,
bP＜0.001; Compare with high potassium model group FI,
cP＜0.05,
dP＜0.01.
The influence that table 4, sinapic acid choline ester. raise to the inductive PC12 intracellular Ca2+ of Glu 10mmol/L (x ± S, n=10)
Medicine tranquillization FI Glu FI
Peak valueΔ FI suppression ratio (%)
(μmol/L)
Model group (does not add 1256 ± 175 3096 ± 402
b1840 ± 313/
Medicine)
0.1 1222±237 2038±417
bd 816±220 55.7
1.0 1184±239 1764±545
ad 580±191 68.5
10 1210±318 1592±473
ad 382±116 79.2
Compare with corresponding tranquillization FI value,
aP＜0.01,
bP＜0.001; FI compares with the Glu model group,
cP＜0.05,
dP＜0.01.
The influence that table 5, sinapic acid choline ester. raise to calcium in the caused aortic smooth muscle cell of KCl 75mmol/L (x ± S, n=10)
Medicine tranquillization FI KCl FI
Peak valueΔ FI suppression ratio (%)
(μmol/L)
Model group (does not add 1201 ± 143 4991 ± 848
b3790 ± 603/
Medicine)
0.1 1259±291 3476±869
bc 2217±447 41.5
1.0 1197±227 2702±574
bd 1505±406 60.3
10 1225±381 2165±642
ad 940±298 75.2
Compare with corresponding tranquillization FI value,
aP＜0.01,
bP＜0.001; Compare with high potassium model group FI,
cP＜0.05,
dP＜0.01.
The influence that table 6, sinapic acid choline ester. raise to calcium in the inductive aortic smooth muscle cell of NE 1 μ mol/L (x ± S, n=10)
Medicine tranquillization FI NE FI
Peak valueΔ FI suppression ratio (%)
(μmol/L)
Model group (not dosing) 1248 ± 262 5298 ± 1197
b4050 ± 1093/
0.1 1216±294 2941±823
bd 1725±362 57.4
1.0 1177±348 2420±759
bd 1243±395 69.3
10 1193±391 1958±642
ad 765±214 81.1
Compare aP＜0.01, bP＜0.001 with corresponding tranquillization FI value; FI compares with the NE model group, cP＜0.05, dP＜0.01.
The present invention experiment shows: sinapic acid choline ester. can blocking voltage dependent form calcium channel and the outer calcium that causes of receptor dependent form calcium channel opening in stream, obviously suppress Ca
2+Intravasation smooth muscle cell and PC12 cell make Cytoplasmic Ca
2+Reduce.Ca is bioactive substances such as second message,second messenger in the cell, many regulation of blood vessels agent in the body, hormone, cytokine, finally changes Ca concentration in the cell by all means and brings into play the effect of regulating growth, propagation.Intracellular calcium concentration increases can impel vascular smooth muscle propagation and plumpness, makes vessel wall thickening, and Peripheral resistance increases, and impels hypertension.Therefore, it is to stop vascular smooth muscle cell proliferation and loose important step that sinapic acid choline ester. suppresses the interior stream of outer calcium, points out it to have the periphery hypotensive effect.Because intracellular Ca2+ raises and to cause calcium overload is the neurocyte dead final path of degenerating, the inhibitory action that the PC12 intracellular Ca2+ that sinapic acid choline ester. causes KCl and Glu raises points out it protective effect to be arranged to axoneure.And from experimental result, the inhibitory action that the PC12 intracellular Ca2+ that sinapic acid choline ester. causes Glu raises is better than KCl is caused the inhibition that interior calcium raises, and shows that its effect of blocking receptor dependent form calcium channel is better than the blocking-up to voltage dependent form calcium channel.So sinapic acid choline ester. is particularly useful for hypertensive alzheimer disease patient.
Claims (4)
1, sinapic acid choline ester. flows the application in the medicine in the calcium at preparation acetylcholine esterase inhibition activity medicine and/or outside suppressing.
2, in the application of claim 1, acetylcholinesteraseinhibitors inhibitors is to prevent and treat the alzheimer disease medicine.
3, in the application of claim 1, sinapic acid choline ester. is treated with the application in hypertensive alzheimer disease patient's medicine in preparation.
4, prevent and treat the alzheimer disease compositions, it is characterized in that containing sinapic acid choline ester..
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| CN103153323A (en) * | 2010-09-17 | 2013-06-12 | 韩国食品研究院 | Composition for promoting memory and learning ability |
| CN105732402A (en) * | 2016-03-07 | 2016-07-06 | 大连大学 | Method for preparing sinapine thiocyanate from rapeseed cakes and application |
| CN106045866A (en) * | 2016-07-05 | 2016-10-26 | 大连大学 | Synthesis and application of sinapine chlorate |
| CN113599407A (en) * | 2021-07-21 | 2021-11-05 | 上海应用技术大学 | White mustard seed extract and preparation method and application thereof |
| CN115089655A (en) * | 2022-05-12 | 2022-09-23 | 北京宜生堂医药科技研究有限公司 | Traditional Chinese medicine composition for treating Alzheimer's disease, extract, preparation method and application |
-
2004
- 2004-09-20 CN CN 200410064690 patent/CN1259045C/en not_active Expired - Fee Related
Cited By (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102146045A (en) * | 2010-02-08 | 2011-08-10 | 大连大学 | Method for preparing sinapine |
| CN103153323A (en) * | 2010-09-17 | 2013-06-12 | 韩国食品研究院 | Composition for promoting memory and learning ability |
| US20130171278A1 (en) * | 2010-09-17 | 2013-07-04 | Korea Food Research Institute | Composition for promoting memory and learning ability |
| CN103153323B (en) * | 2010-09-17 | 2015-08-26 | 韩国食品研究院 | Memory and learning capacity enhancing compositions |
| CN105732402A (en) * | 2016-03-07 | 2016-07-06 | 大连大学 | Method for preparing sinapine thiocyanate from rapeseed cakes and application |
| CN106045866A (en) * | 2016-07-05 | 2016-10-26 | 大连大学 | Synthesis and application of sinapine chlorate |
| CN113599407A (en) * | 2021-07-21 | 2021-11-05 | 上海应用技术大学 | White mustard seed extract and preparation method and application thereof |
| CN115089655A (en) * | 2022-05-12 | 2022-09-23 | 北京宜生堂医药科技研究有限公司 | Traditional Chinese medicine composition for treating Alzheimer's disease, extract, preparation method and application |
| CN115089655B (en) * | 2022-05-12 | 2023-09-08 | 北京宜生堂医药科技研究有限公司 | Traditional Chinese medicine composition for treating Alzheimer's disease, extract, preparation method and application |
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| CN1259045C (en) | 2006-06-14 |
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