CN102499933B - Application of cerebroside B compound - Google Patents
Application of cerebroside B compound Download PDFInfo
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- CN102499933B CN102499933B CN 201110324561 CN201110324561A CN102499933B CN 102499933 B CN102499933 B CN 102499933B CN 201110324561 CN201110324561 CN 201110324561 CN 201110324561 A CN201110324561 A CN 201110324561A CN 102499933 B CN102499933 B CN 102499933B
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- -1 cerebroside B compound Chemical class 0.000 title abstract description 19
- YBSQGNFRWZKFMJ-UHFFFAOYSA-N Cerebroside B Natural products CCCCCCCCCCCCCCC(O)C(=O)NC(C(O)C=CCCC=C(C)CCCCCCCCC)COC1OC(CO)C(O)C(O)C1O YBSQGNFRWZKFMJ-UHFFFAOYSA-N 0.000 title abstract 2
- 201000006474 Brain Ischemia Diseases 0.000 claims abstract description 62
- 206010008118 cerebral infarction Diseases 0.000 claims abstract description 58
- 206010008120 Cerebral ischaemia Diseases 0.000 claims abstract description 50
- 239000003814 drug Substances 0.000 claims abstract description 11
- 208000029028 brain injury Diseases 0.000 claims abstract description 9
- 238000002360 preparation method Methods 0.000 claims description 16
- 150000001875 compounds Chemical class 0.000 claims description 9
- 238000002474 experimental method Methods 0.000 abstract description 27
- 229930183167 cerebroside Natural products 0.000 abstract description 19
- 241001237975 Termitomyces Species 0.000 abstract description 18
- RIZIAUKTHDLMQX-UHFFFAOYSA-N cerebroside D Natural products CCCCCCCCCCCCCCCCC(O)C(=O)NC(C(O)C=CCCC=C(C)CCCCCCCCC)COC1OC(CO)C(O)C(O)C1O RIZIAUKTHDLMQX-UHFFFAOYSA-N 0.000 abstract description 18
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Abstract
The invention discloses the application of cerebroside B which is extracted and prepared from termitomyces in preparing a medicine for treating ischemic brain injury. The application proves that a cerebroside compound has obvious treatment function on ischemic brain injury through pharmacology experiments, can reduce the cerebral infarction area which is caused by cerebral ischemia and relieve the cerebral edema through a blood-brain barrier, reduce the death of nerve cells, and simultaneously promote recovery of movement and cognitive functions after cerebral apoplexy, so the death rate of the cerebral apoplexy is reduced. The application develops the new medicine application of the cerebroside compound, and new therapeutic drugs are provided for treating diseases of the cerebral apoplexy.
Description
(this case is application number: 200910154675.0, name is called a kind of the dividing an application of application of cerebroside compound).
Technical field
The invention belongs to the Natural Medicine Chemistry field.Relate generally to the application of cerebroside compound in preparation treatment Neurons Against Cerebral Ischemia damage medicine of from termitomyces, extracting.
Background technology
Cerebral ischemia diseases is one of clinical modal disease, has the high characteristics of sickness rate, disability rate and case fatality rate, and human health in serious threat.Along with the progressively aging of whole world population, the morbidity of ischemic brain injury has increases trend year by year, but still lacks effectively prevention and treatment measure at home and abroad so far.Axoneure is considered to cause the main cause of apoplexy sequela to the anoxia hypersensitivity that injures and the feature that lacks regeneration capacity.Ischemic brain injury mainly comprises minimizing or the interruption of the full cerebral blood flow that (1) local cerebral vascular occlusion (cerebral infarction) and the reasons such as (2) cardiogenic shock and myocardial infarction cause, and they can both cause the death of neurocyte.Therefore, how to stop or alleviate cerebral ischemia and again the nerve cell death behind the perfusion be the focus of Neuroscience Research and sacred disease pharmaceutical research always.
Termitomyces (
Termitomyces albuminosus) belong to Basidiomycetes, Agaricales, Tricholomataceae, Termitomyces, its ecotype is very special, and with the symbiosis of black wing big termite, sporophore only can be grown on the termitarium, is a kind of wild edible fungus of preciousness.This bacterium is valuable medicinal fungus, is used as medicine with sporophore.Just on the books in the Compendium of Material Medica of Ming Dynasty Li Mingzhen: the effect of " stomach reinforcing is refreshing clearly, controls hemorrhoid "
[1]Reported in literature is arranged, and it has blood fat reducing, antioxidation, antiinflammatory and analgesic activity
[2,3]
Cerebroside chemical compound (cerebrosides) is to be present in animal, plant, fungus and the very low and active very strong endogenous material of a halobiontic class content.It and gangliosides (gangliosides), sphingomyelins (sphingomyelins) consist of sphingolipid chemical compound (sphingolipids) jointly.Brain glycosides and ganglioside belong to glycolipid, and sphingomyelins belongs to phospholipid.They all are comprised of a polar head (D-galactose, glucose, polysaccharide and Phosphorylcholine) and two nonpolar tails (sphingol and derivant thereof and fatty acyl long-chain).
The sphingolipid chemical compound is in 1876 at first, found by German internist J.L.W.Tudichum, he be ethanol extraction from brain through fractional crystallization, then obtain sphingol (called after sphingosine), sugar and fatty acid through hydrolysis.But its structure is illustrated in nineteen forty-seven by Carter.The name of cerebroside chemical compound, ceramide, sphingomyelins all is to continue the then name of Tudichum.Nineteen forty-two, Emst Klenk finds to suffer from amaurosis dementia (amauroticidiocy) the patient brain a kind of acid sphingolipid chemical compound, and he is just with its called after ganglioside, acidic moiety called after neuraminic acid (neuraminic acid) wherein.
Naturally occurring sphingolipid compounds content is very low, and the cerebroside chemical compound is all the more so, though up to the present experienced over one hundred year, the natural cerebroside chemical compound of discovery is also not many.Add its similar, brought very large difficulty to separation and purification.But it is relevant with the signal conduction in human brain diseases and the physiological process that this compounds is thought always.
It is reported that JNGZ-A has the activity that inhibition is in the polymerase of repetition DNA state
[4], anti-inflammatory activity
[5], analgesic effect
[6]JNGZ-B has the activity that inhibition is in the polymerase of repetition DNA state
[4]
Summary of the invention
The object of the present invention is to provide a kind of application of cerebroside compound (JNGZ-A and JNGZ-B) in preparation treatment cerebral ischemia Brain Injury After medicine of from termitomyces, extracting preparation.The mainly application in preparation treatment global brain ischemia and focal brain ischemia medicament.
Cerebroside compound of the present invention is JNGZ-A and JNGZ-B, has following structure:
JNGZ-A
JNGZ-B.
Cerebroside compound of the present invention is realized by following steps:
(1) pulverizes: the termitomyces of drying is crushed to 100～10 orders;
(2) extraction: use the methanol lixiviate, obtain the termitomyces extract; Subsequently extract being carried out solvent with 90% methanol aqueous solution and n-hexane distributes, water and n-butyl alcohol behind 90% the methanol aqueous solution concentrating under reduced pressure that obtains are carried out solvent to be distributed, obtain n-butanol layer solution, n-butanol layer solution is obtained the n-butanol layer sample behind concentrating under reduced pressure;
(3) separation and purification: (solvent system is MeOH:H to the n-butanol layer sample by volume with the ODS opening column
2O=90:10,95:5,100:0) separate; Then, (solvent system is CHCl with Silica gel opening column to contain the sample of target compound (95% aq. MeOH flow point)
3: MeOH=100:0,95:5,90:10,0:100) further separate; At last, the sample (CHCl that contains target compound
3: the MeOH=90:10 flow point) with HPLC [Develosil ODS-10) purification obtains JNGZ-A and B, [solvent system: MeOH/H
2O (98:2), flow velocity: 8 ml/min, detect wavelength: 205 nm].
Methanol leach extraction method in the extracting method of the present invention comprises the lixiviate of concussion method or circumfluence method lixiviate.
Beneficial effect of the present invention is:
(1) the inventive method overcome in the past can not separation and purification because of similar, natural cerebroside chemical compound difficulty, solve extraction from termitomyces, separation and purification and obtained two kinds of cerebroside compounds, quick, easy, the characteristics such as yield is high, purity high (content of JNGZ-A and B is all more than 99.0%) that the inventive method has.
(2) cerebroside compound of the inventive method acquisition, animal pharmacology experiment by system, prove that described JNGZ-A and JNGZ-B have remarkable therapeutical effect to ischemic brain injury, specifically, termitomyces JNGZ-A (JNGZ-A) and termitomyces JNGZ-B (JNGZ-B) lumbar injection can see through blood brain barrier, reduce the cerebral infarct size that cerebral ischemia causes and alleviate cerebral edema, and minimizing nerve cell death, promote simultaneously the recovery of post-stroke motion and cognitive function, reduce the mortality rate of apoplexy.
(3) preparation method of the present invention is reasonable in design, and is easy and simple to handle.And opened up the new medicinal usage of cerebroside compound, for treatment apoplexy disease provides new medicine.
Description of drawings
Fig. 1 JNGZ-A and JNGZ-B can see through the analysis of blood brain barrier nervous system regulation function.
Fig. 2 JNGZ-A and JNGZ-B are to the effect of focal ischemia's property cerebral infarction.
Fig. 3 JNGZ-A and JNGZ-B are to the effect of focal ischemia's associated with hydrocephalus.
Fig. 4 JNGZ-A and JNGZ-B to focal cerebral ischemia after the effect of motor function damage.
Fig. 5 JNGZ-A and JNGZ-B cause the effect of nerve cell death to global brain ischemia.
Fig. 6 JNGZ-A and JNGZ-B to global brain ischemia after the effect of memory injury.
Fig. 7 JNGZ-A and JNGZ-B are on the impact of apoplexy (focal cerebral ischemia) mortality rate.
The specific embodiment
The present invention is described in further detail in conjunction with the accompanying drawings and embodiments.
The method that from termitomyces, prepares JNGZ-A and JNGZ-B, concrete steps are:
(1) pulverizes: the termitomyces sample (1.5 kg) (Yanyuan County, Sichuan Province) of drying is crushed to 100～10 orders;
(2) extraction: the termitomyces after will pulverizing is packed in 15 liters the container, with concussion lixiviate in methanol (7.5 liters) the earthquake device 3 days, obtains termitomyces extract (151.3 g); Subsequently extract is carried out solvent with 90% aq. MeOH and n-hexane and distribute, the concentrated rear water of the 90% aq. MeOH solution that obtains and n-butyl alcohol are carried out the solvent distribution, butanol solution obtains n-butanol layer sample (16.0 g) behind concentrating under reduced pressure;
(3) separation and purification: (solvent system is MeOH:H to the n-butanol layer sample with the ODS opening column
2O=90:10,95:5,100:0) separate; Then, (solvent system is CHCl with Silica gel opening column to contain the sample of target compound (95% aq. MeOH flow point, 1.3 g)
3: MeOH=100:0,95:5,90:10,0:100) further separate; At last, the sample (CHCl that contains target chemical combination
3: MeOH=90:10 flow point, 300 mg) usefulness HPLC purification (ODS-UG-5,98% aq. MeOH,
20 * 250 mm, flow velocity: 39 min) and termitomyces JNGZ-B (63.0 mg, retention time: 55 min) 8 ml/min, detect wavelength: 205 nm) obtain termitomyces JNGZ-A (120.0 mg, retention time:.
JNGZ-A is that the inventor obtained with above-mentioned preparation method purification from the extract of termitomyces first in calendar year 2001, uses the methods such as nuclear magnetic resonance, NMR, mass spectrum and decomposition reaction to determine its chemical constitution
[7]Be found to be the known structure chemical compound by Literature Consult
[8,9]
Embodiment 2
JNGZ-A and the physicochemical characteristics of JNGZ-B and the Qualitative Identification of chemical constitution that embodiment 1 is obtained:
The physicochemical property of JNGZ-A: [α]
25 D+ 4.5 (c 0.46, MeOH); Infrared spectrum (KBr) value: 3371,2921,2853,1643,1536,1468, and 1081 cm-1;
M/z728 (M+H)+; Chemical displacement value: C (150 MHz, DMSO+2% D2O): 173.91,135.08,131.26,131.05,123.61,103.56,77.00,76.63 (76.62, CH-OD), 73.49 (73.46), 71.20 (71.17), 70.81 (70.71), 70.25 (70.20), 68.86,61.33 (61.21), 53.04 (53.00, CH-ND-), 39.90,34.53,32.23,31.36,29.10,28.98,28.74,27.49,27.38,24.61,22.14 15.83, and 13.95.
JNGZ-B: use the chemical constitution of having determined JNGZ-B with the same method of the chemical constitution of definite JNGZ-A, find that difference on JNGZ-B and the A structure (comprising stereochemical structure) only is that B Duoed two methylene than A on aliphatic chain.The physicochemical property of JNGZ-B: [α]
25 D+ 2.0 (c 0.46, MeOH), m/z 756 (M+H)+, infrared spectrum value, chemical displacement value and JNGZ-A are identical.
Embodiment 3
JNGZ-A of the present invention (
JNGZ-A)And JNGZ-B (
JNGZ-B)The animal pharmacology experiment of carrying out is to prove its application in preparation treatment Neurons Against Cerebral Ischemia damage medicine.
Because the nerve injury degree that multi-form cerebral ischemia causes is different.The main pathological manifestations of middle cerebral artery occlusion is infarction and the cerebral edema of the Brain TisXs such as striatum, cerebral cortex and Hippocampus, has very high mortality rate and disability rate.Global brain ischemia is then optionally damaged the axoneure (such as the Hippocampal CA 1 neurocyte) to the anoxia sensitivity, hypomnesis occurs.Therefore; the present invention will adopt respectively classical middle cerebral artery occlusion (middle cerebral artery occlusion; MCAO) operation simulates apoplexy; press from both sides the animal model that global brain ischemia is set up in the operation of closing with vertebral artery and common carotid artery, observe lumbar injection JNGZ-A and JNGZ-B to the protective effect of ischemic brain injury.
JNGZ-A and the JNGZ-B of embodiment 1 preparation have the advantages that be insoluble in water.Therefore, first JNGZ-A and the JNGZ-B that extracts is dissolved in 99.5% ethanol, and then with normal saline mother solution is diluted to treatment desired concn (with the ultimate density that keeps ethanol below 1%), obtain pharmaceutical preparation of the present invention.
Sprague-Dawley (SD) rat (body weight 200 g～250 grams, available from Jiangsu Province's Experimental Animal Center) accept JNGZ-A and JNGZ-B(0.5 mg/kg of body weight) behind the lumbar injection, (breathe: 50～60 beats/mins with the matched group of injecting normal saline, heart rate: 305～400 beats/mins, mean arterial pressure: 90～110 millimetress of mercury) compare and obvious toxic reaction (change of lethargy, manic, breathing/heart rate/blood pressure) and side effect (motor behavior is unusual etc.) all do not occur.
Experiment 1:JNGZ-A and JNGZ-B can see through the analysis that blood brain barrier is regulated nervous function
Experiment main material: Sprague-Dawley (SD) rat (male and female each 10), body weight 200 g～250 grams are available from Jiangsu Province's Experimental Animal Center.
Wherein, full brain is taken out in the intraperitoneal anesthesia of experimental implementation A:10% chloral hydrate, makes hippocampal slices.Transmembrane potential (EPSP) behind the electricity irritation Schaffer collateral side shoot continuous record Hippocampal CA 1 excitatory synapse.The administration time of black horizontal bar: JNGZ-A and JNGZ-B.
Wherein, the intraperitoneal anesthesia of experimental implementation B:10% chloral hydrate, recording electrode according to bregma after 3.8 millimeters, the side is opened 2.3 millimeters, the coordinate that the degree of depth is 3.0 millimeters inserts the CA1 pyramidal cell at hippocampus layer, record neurocyte discharge frequency (Mean frequency is 42.71 ± 5.6 beats/mins).After the basic value stable recording 20 minutes, JNGZ-A and JNGZ-B lumbar injection (5 and 10 micromole), continuous record 1～2 hour.
Experimental result: JNGZ-A and JNGZ-B lumbar injection (0.5 mg/kg of body weight) can see through blood brain barrier fast, can weaken the irritability of Hippocampus CA1 synapse propagation function and reduction neurocyte.
The result is referring to Fig. 1, and Fig. 1-A: expression JNGZ-A and the administration of the direct brain sheet of JNGZ-B are on the impact (the field potential record of brain sheet) of Hippocampal CA 1 nerve synapse transmission; Fig. 1-B: the excitatoty change of Hippocampal CA 1 neurocyte (outside the born of the same parents of body brain, recording) behind expression JNGZ-A and the JNGZ-B lumbar injection, and * and * * represent that respectively P＜0.05 compares with matched group with P＜0.0().
Experiment 2:JNGZ-A and JNGZ-B are to the effect of focal cerebral ischemia (MCAO) cerebral infarction
The experiment main material: kunming mice, body weight 25 g～30 grams are available from Jiangsu Province's Experimental Animal Center.
Experimental implementation: 10 % chloral hydrate intraperitoneal anesthesias, ligation right carotid and external carotid artery, close the internal carotid artery distal end with the bulldog clamp folder, fishing line is inserted the internal carotid artery far-end, implement middle cerebral artery and blocked (middle cerebral artery occlusion is called for short MCAO in the drawings) in 60 minutes, preparation focal cerebral ischemia mouse model (using electric blanket to keep the laboratory animal rectal temperature at 37 ± 0.5 degree).After cerebral ischemia 4 hours, carry out the JNGZ-A lumbar injection by per kilogram of body weight 0.5,1.0 milligrams of dosage, or 0.05,0.5,1.0,5.0 milligram of dosage carries out the JNGZ-B lumbar injection, (interval 8 hours) altogether is administered twice.Take out full brain in 24 hours after the cerebral ischemia, placed-20 degree freezing 10 minutes, do the crown serial section of full brain 2 millimeters thick.After 2% TTC dyeing, carry out the area that image J software processes image is measured respectively every brain sheet infarcted region and non-infarcted region.Calculate the percentage ratio of cerebral infarction volume: (infarcted region volume averaging value/non-ischemia side cerebral hemisphere volume averaging value) * 100%.Each experimental group all is male and female each 4 mice.
Experimental result: 60 minutes middle cerebral artery occlusion causes about 26.8% cerebral infarction (white tissue district area, P＜0.01).JNGZ-A and JNGZ-B treatment can reduce the volume (P＜0.05, P＜0.01) of cerebral infarction effectively, and the prompting cerebroside can alleviate the Neurons Against Cerebral Ischemia infarction.The neuroprotective of JNGZ-A presents the dosage correlation of " U " type, and the neuroprotective of JNGZ-B is typical concentration dependent by contrast.The effect that JNGZ-A and JNGZ-B are described may be by different mechanism.
The result is referring to Fig. 2, and among the figure, ## represents that P＜0.01(compares with sham operated rats); * represent respectively that with * * P＜0.05 compares with the cerebral ischemia group with P＜0.0().
Experiment 3:JNGZ-A and JNGZ-B are to the effect of focal cerebral ischemia (MCAO) associated with hydrocephalus
Experiment main material: with experiment 2.
Experimental implementation: the preparation of cerebral ischemia mouse model is identical with experiment 2.After cerebral ischemia 4 hours, carry out the JNGZ-A lumbar injection by per kilogram of body weight 0.5,1.0 milligrams of dosage, or 0.05,0.5,1.0,5.0 milligram of dosage carries out the JNGZ-B lumbar injection, (interval 8 hours) altogether is administered twice.After the cerebral ischemia 24 hours, fast broken end takes out full brain, adopt dried wetting phase that densimetry is measured about half brain water content, and calculate brain water content according to Elliott formula [(WW-DW)/WW] * 100%, release the degree of cerebral edema.Each experimental group all is male and female each 4 mice.
Experimental result: cerebral ischemia causes the increase (P＜0.05) of brain water content 13.5%, and prompting has the generation of cerebral edema.JNGZ-A and JNGZ-B treatment can reduce the water content (P＜0.05) of cerebral ischemia-reperfusion after the cerebral ischemia.
The result is referring to Fig. 3, and among the figure, # represents that P＜0.05(compares with sham operated rats); * represent that P＜0.05(compares with the cerebral ischemia group).
Experiment 4:JNGZ-A and JNGZ-B are to the effect of motor function damage behind the focal cerebral ischemia (MCAO)
Experiment main material: identical with experiment 2.
Experimental implementation: the preparation of cerebral ischemia mouse model is identical with experiment 2.After the cerebral ischemia 4～8 days, carry out the runner experiment, detect the motor function of mice after the cerebral ischemia.The maximum (top) speed of runner experiment is 30 rev/mins, continues for 200 seconds.Each experimental group all is male and female each 4 mice.
Experimental result: cerebral ischemia can obviously reduce the movement time (P＜0.01) of mice on runner.Movement time (P＜0.05, P＜0.01) after the cerebral ischemia on the runner of JNGZ-A or JNGZ-B treatment energy significant prolongation test mice, the treatment of prompting cerebroside can improve the dyskinesia of post-stroke.
The result is referring to Fig. 4, and among the figure, the movement time of not administration of sham-operation group on runner is as 100%; ## represents that P＜0.01(compares with sham operated rats); * represent respectively that with * * P＜0.05 compares with the cerebral ischemia group with P＜0.01().
Experiment 5:JNGZ-A and JNGZ-B cause the effect of nerve cell death to global brain ischemia (4VO)
Experiment main material: Sprague-Dawley (SD) rat, body weight 200g～250 g is available from Jiangsu Province's Experimental Animal Center.
Experimental implementation: 10% chloral hydrate intraperitoneal anesthesia, the coagulation bilateral vertebral artery, close bilateral common carotid arteries 20 min(four blood vessel blocking methods with arteriole folder folder, be called for short among the figure: 4VO), preparation transience (20 minutes) Induced by Global Cerebral Ischemia in Rats model (spending 37 ± 0.5 with maintenance laboratory animal rectal temperature with electric blanket).Carried out the JS-CB lumbar injection by per kilogram of body weight 0.05,0.5,1 or 5 milligram of dosage in 4 hours after cerebral ischemia, (interval 8 hours) altogether is administered twice.After the cerebral ischemia the 8th day, with 4% paraformaldehyde through the fixing cerebral tissue of left ventricle perfusion.After the paraffin embedding, do the Hippocampus serial section.After 1% Toluidine blue staining, measure the density (cell number in the every mm length of pyramidal layer) of Hippocampal CA 1 survival pyramidal cell.Each experimental group all is male and female each 4 rat.
Experimental result: global brain ischemia caused about 60% neuronal death (P＜0.01) in 20 minutes.JNGZ-A or JNGZ-B treatment can rely on the nerve cell death (P＜0.05, P＜0.01) that ground minimizing cerebral ischemia causes by dosage, the nerve cell death that the prompting cerebroside can stop ischemia to cause after the cerebral ischemia.The neuroprotective of JNGZ-A presents the dosage correlation of " U " type, and the neuroprotective of JNGZ-B is typical concentration dependent by contrast.The effect that further specifies JNGZ-A and JNGZ-B may be by different molecular mechanisms.
The result is referring to Fig. 5, among the figure, and 4VO: four blood vessel blockings (global brain ischemia); ## represents that P＜0.01(compares with sham operated rats); * represent respectively that with * * P＜0.05 compares with the cerebral ischemia group with P＜0.01().
Experiment 6:JNGZ-A and JNGZ-B are to the effect of memory injury after the global brain ischemia (4VO)
Experiment main material: with experiment 5.
Experimental implementation: the preparation of Induced by Global Cerebral Ischemia in Rats model is identical with experiment 5 with JNGZ-A or JNGZ-B administration.Carry out the test of " Morris " water maze in the 3rd～7 day after cerebral ischemia, check the spatial memory function of rat.Going up on the stage incubation period of record rat.Each experimental group all is male and female each 4 rat.
Experimental result: 20 minutes global brain ischemia cause that escape latency prolongs (P＜0.01), and prompting spatial cognition function reduces.JNGZ-A or JNGZ-B treatment can partly reduce the escape latency prolongation (P＜0.05, P＜0.01) that cerebral ischemia causes, and the prompting cerebroside can improve the cognitive decrease of post-stroke.
The result is referring to Fig. 6, and among the figure, ## represents that P＜0.01(compares with sham operated rats); * represent respectively that with * * P＜0.05 compares with the cerebral ischemia group with P＜0.01().
Experiment 7:JNGZ-A and JNGZ-B are on the impact of mortality rate behind the focal cerebral ischemia (MCAO)
Experiment main material: identical with experiment 2.
Experimental implementation: the preparation of cerebral ischemia mouse model is identical with experiment 2.Comprehensively relatively appeal the death of cerebral ischemia animal (MCAO).Each experimental group all is 40 mices.
Experimental result: the mortality rate behind 60 minutes the middle cerebral artery occlusion is up to 60%(P＜0.01).Began to carry out JNGZ-A(0.5 milligram dosage after the cerebral ischemia in 4 hours) or JNGZ-B(1.0 milligram dosage) treatment can reduce the apoplexy mice mortality rate to 20-30%(P＜0.05, P＜0.01).
The result is referring to Fig. 7, and among the figure, ## represents that P＜0.01(compares with sham operated rats); * represent respectively that with * * P＜0.05 compares with the cerebral ischemia group with P＜0.01().
The list of references that the present invention relates to
[1] the 1st edition the 1st printing No. 10 1982:1719-1719. in Tiantan Xili, Chongwen District, Beijing City of Li Ming rare edition grass detailed outline (check and punctuate originally) [M]
[2] Wang Yixin, Yang Guizhi. the experimentation [J] of Di Yong termitomyces effect for reducing blood fat. Chinese clinic study magazine, 2003,8:185 – 186.
[3] Wang Yixin, Di Yong, Yang Guizhi. the antioxidation [J] of termitomyces in hypercholesterolemiain in rats. Chin Prev Med, 2005,6:10-12.
[4] Mizushina Y.;Hanashima L.;Yamaguchi T.
Biochemical and biophysical research communications 1998,249,17-22.
[5] Cheng S.;Wen Z.;Chiou S.
J.Nat.Prod.
2009,72,465-468.
[6] Koyama K.;Akiba M.;Imaizumi T.
Planta Med 2002,68,284-285.
[7] Qi J.; Ojika M.; Sakagami Y.
Bioorganic & Medicinal Chemistry 2001,9, 2171-2177.
[8] Sitrin R. D.; Chan G.; Dingerdissen J.; Debrosse C.; Mehta R.; Roberts G.; Rottschaefer S.; Staiger D.; Valenta J.; Snader K. M.; Stedman R. J.; Hoover J. R. E.
J. Antibiot. 1988, 41, 469-480.
[9].Toledo M. S.; Levery S. B.; Straus A. H.; Suzuki E.; Momany M.; Glushka J., Moulton J. M.; Takahashi H. K.
Biochemistry 1999, 38, 7294-7306。
Claims (1)
1. the application of JNGZ-B chemical compound in preparation treatment cerebral ischemia Brain Injury After medicine, described JNGZ-B chemical compound has following structural formula:
JNGZ-B.
2. the application of a kind of JNGZ-B chemical compound according to claim 1 in preparation treatment cerebral ischemia Brain Injury After medicine is characterized in that this cerebral ischemia is global brain ischemia or focal cerebral ischemia.
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| 张鞍灵等.《脑苷脂B 的结构鉴定》.《西北植物学报》.2001,第21卷(第4期),684-8页. |
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