CN102138953A - Application of chorispora bungeana or extract thereof in preparation of medicaments for preventing and treating cardiovascular and cerebrovascular diseases - Google Patents

Application of chorispora bungeana or extract thereof in preparation of medicaments for preventing and treating cardiovascular and cerebrovascular diseases Download PDF

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CN102138953A
CN102138953A CN2010101173781A CN201010117378A CN102138953A CN 102138953 A CN102138953 A CN 102138953A CN 2010101173781 A CN2010101173781 A CN 2010101173781A CN 201010117378 A CN201010117378 A CN 201010117378A CN 102138953 A CN102138953 A CN 102138953A
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extract
chorispora bungeana
chorispora
bungeana
cerebral
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CN102138953B (en
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孙雅煊
安黎哲
刘婷
王东晖
盛红梅
张华�
向云
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Lanzhou University
Cold and Arid Regions Environmental and Engineering Research Institute of CAS
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Lanzhou University
Cold and Arid Regions Environmental and Engineering Research Institute of CAS
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Abstract

The invention belongs to the technical field of medicines, and provides application of chorispora bungeana or an extract thereof in the preparation of medicaments for preventing and treating cardiovascular and cerebrovascular diseases. The extract of the chorispora bungeana comprises a water extract and an alcohol extract of the chorispora bungean. Studies indicate that the chorispora bungeana or the extract thereof has the obvious effects of resisting cerebral ischemia, cerebral anoxia, cerebral thrombosis and vascular dementia in human bodies, has small side effect and can be taken for a long term.

Description

The application in preparation control cardiovascular and cerebrovascular diseases medicament of Chorispora bungeana or its extract
Technical field
The invention belongs to medical technical field, be specifically related to the preparation of Chorispora bungeana extract, the application in preparation control cardiovascular and cerebrovascular diseases medicament of Chorispora bungeana or its extract.
Background technology
Cardiovascular and cerebrovascular disease is in the world today mankind to be threatened one of maximum disease, and its M ﹠ M surpasses cancer and leaps to the first in the world.The data of ministry of Health of China announcement in 2008 shows that cardiovascular and cerebrovascular disease mortality rate height ranks first in the general mortality rate of Chinese population, and urbanite's deaths from heart disease rate is 19.65%, and the cerebrovascular disease mortality rate is 19.62%.Wherein, have the cerebrovascular disease of " sickness rate height, disability rate height, mortality rate height, relapse rate height; complication is many " characteristics,, still can have cerebrovascular disease survivor life more than half not take care of oneself fully even adopt most advanced, the most perfect treatment means.At present, the cerebrovascular disease medicament treatment comprises antioxidation, antiinflammatory, anticoagulation, antiplatelet aggregation and thromboembolism treatment etc.But the most of pathways of drug action that has gone on the market is single, and therefore unsatisfactory curative effect, even cause the aggravation of the state of an illness seeks the direction that can useful effect becomes current development in the medicine of a plurality of Pathophysiology links.
Chorispora bungeana (Chorispora bungeana Fisch.et Mey.) is the perennial alpine periglacial plant of Cruciferae, mainly is distributed on the subalpine meadow, grassland, gravel matter hillside at height above sea level 2600~4000m place, Xinjiang.Abominable living environment has brought up the effect of Chorispora bungeana uniqueness, but (Ah Yi tells your antiperspirant not see the research of its preparation method of extract of bibliographical information and treating cerebral ischemia, Tan Dunyan, Li Zhijun, Deng. the structure of Chorispora bungeana nutrition organs and environmental relation research [J]. Xinjiang Agricultural Univ's journal, 1998,21 (4): 273-277; Han Yan, Li Zhengyan, Yue Xiule, etc. the real-time quantitative analysis [J] that the clone of Chorispora bungeana iron transporter gene coded sequence and resistance thereof are expressed. Chinese biological chemistry and molecular biosciences journal, 2008,24 (6): 549-555; Zhang Lijing. the clone of Chorispora bungeana ferritin gene CbFer, expression and anti-oxidation function analysis [D] thereof. Lanzhou: Lanzhou University, 2006).
Summary of the invention
The invention provides the new purposes of Chorispora bungeana or its extract, be that Chorispora bungeana or its extract are used to prepare the application that prevents and treats cardiovascular and cerebrovascular diseases medicament, application especially for preparation control cerebrovascular disease medicament can be used for the prevention and the treatment of cerebral thrombosis, cerebral ischemia, cerebral embolism, the multiple cerebrovascular disease of vascular dementia.The invention provides a kind of pharmaceutical composition that comprises Chorispora bungeana or its extract and conventional pharmaceutical carrier, it is characterized in that described pharmaceutical composition is the preparation that adopts the oral or non-oral route mode administration that the conventional formulation prepared forms.
The invention provides the method for prevention or treatment cardiovascular and cerebrovascular disease, comprise to the cardiovascular and cerebrovascular disease patient giving Chorispora bungeana or its extract or pharmaceutical composition noted earlier.
Chorispora bungeana provided by the invention or its extract can prolonged application, and have tangible prevention or improve the effect of heart and brain damage, non-evident effect, cheap.
The Chorispora bungeana extract that adopts various distinct methods preparations is to not influence of purposes of the present invention.
The specific embodiment
Cardiovascular and cerebrovascular disease is the general designation of cardiovascular diseases and cerebrovascular, ischemic or hemorrhage take place by the heart due to hyperlipemia, hyperlipidemia, atherosclerosis, thrombosis, the hypertension etc., brain and body tissue in general reference, comprise coronary heart disease, angina pectoris, myocardial ischemia, cerebral ischemia, cerebral hemorrhage, cerebral anoxia, cerebral embolism, brain dementia etc.
The invention provides the application in the medicine of preparation control cardiovascular and cerebrovascular disease of Chorispora bungeana or its extract, particularly Chorispora bungeana or its extract application in preparation control cerebrovascular disease medicament is including, but not limited to cerebrovascular disease such as cerebral ischemia, cerebral anoxia, cerebral thrombosis, vascular dementia.
After gathered on the gravel hillside near the Chorispora bungeana plant can from height above sea level be the Tianshan Mountains of 3700~4000m 7~August of every year, transport laboratory back together with earth in carton on the sunny side, the water spray maintenance is moistening in the way.The high about 3~10cm of plant, by white pubescence, underground have a thick fleshy tap root, butt has axial root stock, the leaf majority, and base is given birth to, drastic crack is to totally cleaving, the blade ellipse, (Ah Yi tells your antiperspirant, Tan Dunyan to pinniform, Li Zhijun, Deng. the structure of Chorispora bungeana nutrition organs and environmental relation research [J]. Xinjiang Agricultural Univ's journal, 1998,21 (4): 273-277).
The Chorispora bungeana extract can prepare in the following manner:
(1) gets fresh Chorispora bungeana Herb, clean the removal of impurity, use pulverizer to pulverize, put in the 1000ml round-bottomed flask, add 4 times of about 1h of water logging bubble of medical material weight, heat decocts, and extracts three times, each 1.5h, filter (with 80 order nylon cloth) merging filtrate, the centrifugal 10min of 3000rpm, get supernatant concentration, lyophilization becomes dry extract promptly to get the Chorispora bungeana water extract.
(2) get fresh Chorispora bungeana Herb, clean the removal of impurity, oven dry, the use pulverizer is pulverized, and puts in the 1000ml round-bottomed flask, adds 4 times of about 1h of water logging bubble of medical material weight, heat decocts, extract three times, each 1.5h filters (with 80 order nylon cloth), merging filtrate, the centrifugal 10min of 3000rpm gets supernatant concentration, and lyophilization becomes dry extract promptly to get the Chorispora bungeana water extract.
(3) get fresh Chorispora bungeana Herb, clean the removal of impurity, use pulverizer to pulverize, put in the 1000ml round-bottomed flask, the about 1h of 60%~80% (v/v) soak with ethanol that adds 4 times of weight of medical material, reflux, extract, 3 times, each 1h filters (with 80 order nylon cloth), merging filtrate, the centrifugal 10min of 3000rpm gets supernatant concentration, and lyophilization becomes dry extract promptly to get the Chorispora bungeana ethanol extract.
(4) get fresh Chorispora bungeana Herb, clean the removal of impurity, oven dry, the use pulverizer is pulverized, put in the 1000ml round-bottomed flask, add the about 1h of 60%~80% (v/v) soak with ethanol of 4 times of weight of medical material, reflux, extract, 3 times, each 1h, filter (with 80 order nylon cloth) merging filtrate, the centrifugal 10min of 3000rpm, get supernatant concentration, lyophilization becomes dry extract promptly to get the Chorispora bungeana ethanol extract.
Chorispora bungeana of the present invention or its extract can be according to clinical needs, add corresponding pharmaceutical carrier, exist with dosage forms such as tablet, pill, granule, capsule, suspension, solution, syrup, injection, cream, ointment, gel, spray, chewing agent or patches.
Chorispora bungeana of the present invention or its extract can adopt oral or non-oral way medication, the preferred oral administering mode according to clinical needs.
When Chorispora bungeana of the present invention or its extract formulation adopt the oral way medication, the preferred 0.05-50g/ people of human dosage/day (being equivalent to the crude drug amount), wherein 0.5-25g/ people/day (being equivalent to the crude drug amount) more preferably, most preferably be 2.5-5g/ people/day (being equivalent to the crude drug amount).
The present invention will be described below in conjunction with experimental example, but the present invention is not limited to this embodiment.
The preparation of embodiment 1 Chorispora bungeana extract
Annual 7~August be from height above sea level near Tianshan Mountains of 3700~4000m on the sunny side the gravel hillside gather the Chorispora bungeana plant, in carton, transport laboratory back together with earth, water spray keeps moistening in the way.Get the fresh Chorispora bungeana Herb of 80g, clean the removal of impurity, use pulverizer to pulverize, put in the 1000ml round-bottomed flask, add 4 times of about 1h of water logging bubble of medical material weight, heat decocts, and extracts three times, each 1.5h, filter (with 80 order nylon cloth) merging filtrate, the centrifugal 10min of 3000rpm, get supernatant concentration, lyophilization becomes dry extract promptly to get 1.7g Chorispora bungeana water extract.
The preparation of embodiment 2 Chorispora bungeana extracts
Annual 7~August be from height above sea level near Tianshan Mountains of 3700~4000m on the sunny side the gravel hillside gather the Chorispora bungeana plant, in carton, transport laboratory back together with earth, water spray keeps moistening in the way.Get the fresh Chorispora bungeana Herb of 80g, clean the removal of impurity, oven dry, the use pulverizer is pulverized, and puts in the 1000ml round-bottomed flask, adds 4 times of about 1h of water logging bubble of medical material weight, heat decocts, extract three times, each 1.5h filters (with 80 order nylon cloth), merging filtrate, the centrifugal 10min of 3000rpm gets supernatant concentration, and lyophilization becomes dry extract promptly to get 6.9g Chorispora bungeana water extract.
The preparation of embodiment 3 Chorispora bungeana extracts
Annual 7~August be from height above sea level near Tianshan Mountains of 3700~4000m on the sunny side the gravel hillside gather the Chorispora bungeana plant, in carton, transport laboratory back together with earth, water spray keeps moistening in the way.Get the fresh Chorispora bungeana Herb of 80g, clean the removal of impurity, use pulverizer to pulverize, put in the 1000ml round-bottomed flask, the about 1h of 60%~80% (v/v) soak with ethanol that adds 4 times of weight of medical material, reflux, extract, 3 times, each 1h filters (with 80 order nylon cloth), merging filtrate, the centrifugal 10min of 3000rpm gets supernatant concentration, and lyophilization becomes dry extract promptly to get 1.9g Chorispora bungeana ethanol extract.
The preparation of embodiment 4 Chorispora bungeana extracts
Annual 7~August be from height above sea level near Tianshan Mountains of 3700~4000m on the sunny side the gravel hillside gather the Chorispora bungeana plant, in carton, transport laboratory back together with earth, water spray keeps moistening in the way.Get the fresh Chorispora bungeana Herb of 80g, clean the removal of impurity, oven dry, the use pulverizer is pulverized, put in the 1000ml round-bottomed flask, add the about 1h of 60%~80% (v/v) soak with ethanol of 4 times of weight of medical material, reflux, extract, 3 times, each 1h, filter (with 80 order nylon cloth) merging filtrate, the centrifugal 10min of 3000rpm, get supernatant concentration, lyophilization becomes dry extract promptly to get 7.3g Chorispora bungeana ethanol extract.
The anti-cerebral thrombosis research of embodiment 5 Chorispora bungeana extracts
1. material and method
1.1 laboratory animal: the healthy adult male Wistar rat, the SPF/VAF level, body weight 250~300g is provided by Beijing Vital River Experimental Animals Technology Co., Ltd., licence numbering: SCXK (capital) 2007-0001.Using unity and coherence in writing health food Function detection center SPF level experimental animal room in the Beijing Union University before the experiment conforms a week.
1.2 reagent: Chorispora bungeana extract: in above-mentioned preparation embodiment, prepare; NAOXINTONG JIAONANG: Xianyang Buchang Pharmaceutical Co., Ltd.
1.3 instrument: AR-2140 type ten thousand/electronic balance: prunus mume (sieb.) sieb.et zucc. Teller-Tuo benefit Instr Ltd..
1.4 laboratory animal grouping and administration
Extracting male Wistar rat is divided into 5 groups at random: model group, Chorispora bungeana (being equivalent to crude drug amount 5,2.5,1.25g/kg) group, NAOXINTONG JIAONANG (0.324g/kg) group, 24 every group, gastric infusion 14d before the art, every day 1 time.Model group is irritated stomach and is given the solvent distilled water in contrast.
1.5 thrombosis experiment
With 10% chloral hydrate (350mg/kg, ip) anesthetized rat.Animal heat is maintained 37 ℃.It is fixing to allow animal lie on the back, and cuts skin and subcutaneous tissue along cervical midline.Operating microscope separates right carotid and left side external jugular vein down.Intubate is carried out at two ends, behind the formation rat neck artery-vein bypass 15min, takes out No. 4 silk thread, weighs after removing floating blood on the filter paper, promptly obtains wet weight of thrombus.The back thrombosis of will weighing places drying baker, at 60 ℃, takes out behind the dry 4h and weighs, and is the thrombosis dry weight.
1.6 statistical procedures
Experimental result is all represented with x ± s, adopts one factor analysis of variance to organize a significance relatively, relatively adopts the t check between sample average. *Expression P<0.05 shows that administration group and model group relatively have significant difference; *Expression P<0.01 shows that administration group and model group relatively have utmost point significant difference.
2. result
2.1 the Chorispora bungeana extract is to the influence of rat neck arteriovenous thrombus weight
Table 1 Chorispora bungeana extract to the influence of rat neck arteriovenous thrombus weight (x ± s, n=8)
The thrombus weight of Chorispora bungeana extract group is starkly lower than model group, shows that the Chorispora bungeana extract has anti-cerebral thrombosis effect.
Figure GSA00000023739600051
Annotate: compare with model group, *Expression P<0.05 *Expression P<0.01
The research of embodiment 6 Chorispora bungeana extract anti-cerebral ischemias
1. material and method
1.1 laboratory animal: the healthy adult male Wistar rat, the SPF/VAF level, body weight 200~250g is provided by Beijing Vital River Experimental Animals Technology Co., Ltd., licence numbering: SCXK (capital) 2007-0001.Using unity and coherence in writing health food Function detection center SPF level experimental animal room in the Beijing Union University before the experiment conforms a week.
1.2 reagent: Chorispora bungeana: in above-mentioned preparation embodiment, prepare; NAOXINTONG JIAONANG: Xianyang Buchang Pharmaceutical Co., Ltd; APC (Aspirin Phenacetin and Caffeine): Hubei Pharmaceutical Co., Ltd.; Chloral hydrate: Tianjin recovery fine chemistry industry institute; Red tetrazolium (2,3,5-triphenyltetrazolium, TTC): Sigma company; MDA, MPO, SOD, Coomassie brilliant blue test kit: bio-engineering research institute is built up in Nanjing; TT, FB test kit: U.S. Pacific Ocean company.
1.3 instrument: AR-2140 type ten thousand/electronic balance: prunus mume (sieb.) sieb.et zucc. Teller-Tuo benefit Instr Ltd.; Electric-heated thermostatic water bath: mayor of Beijing bearing instruments and meters company; TGL 16M centrifuge: the triumphant scientific instrument company limited that reaches in Hunan; MH-2 micro oscillator: its woods Bel instrument Manufacturing Co., Ltd of Haimen, Jiangsu; DY89-II type electric driven glass refiner: NingBo XinZhi Biology Science Co., Ltd; The desk-top drying baker of WG-2003: south, Huiyang electric experimental facilities factory; Microplate reader: U.S. Thermo company; ACL Advance automatic coagulation analyzer: U.S. Beckman Coulter Inc..
1.4 animal grouping and administration
Extracting male Wistar rat is divided into 6 groups at random: sham operated rats, model group, Chorispora bungeana (being equivalent to crude drug amount 5,2.5,1.25g/kg) group, NAOXINTONG JIAONANG (0.324g/kg) group, 24 every group, gastric infusion, every day 1 time.1h after the 5d administration implements operation.
1.5Wistar the making of focal cerebral ischemia in rats model
Rat is with chloral hydrate 350mg/kg, intraperitoneal injection of anesthesia, it is fixing to lie on the back, the neck median incision, expose successively and separate left carotid (Common carotid artery, CCA), internal carotid artery (Internalcarotid artery, ICA), external carotid artery (External carotid artery, ECA).Close common carotid artery and internal carotid artery with bulldog clamp folder, ligation external carotid artery distal end is opened an osculum on external carotid artery, and the head end circle is blunt and insert internal carotid artery through the fishing line that poly-D-lysine is handled, and inserts length and is about 18~20mm in crotch.Ligation internal carotid artery and common carotid artery, fixing fishing line, skin suture (fishing line is reserved a little in external).Behind the ischemia 2h, fixing rat, with fishing line pull out to neck, the external carotid artery crotch, realize perfusion again.Sham operated rats is only separated three prongs, not inaccessible middle cerebral artery.
1.6 function of nervous system's defective scoring
Model group and each medication group rat do function of nervous system's defective scoring, and standards of grading are:
1) carries the rat tail and observe forelimb flexing situation.Stretch to ground as bilateral forelimb symmetry, count 0 fen; As the offside wrist song of performing the operation, count 1 fen; As the offside elbow flexing of performing the operation, count 2 fens; As the offside shoulder inward turning of performing the operation, count 3 fens; As the existing wrist elbow of the offside of performing the operation flexing has the shoulder inward turning again, counts 4 fens.2) rat is placed on the level ground, push away both shoulders respectively, check resistance to side shifting.As bilateral resistance equity and strong, count 0 fen; Slightly descend as resistance when the operation offside promotes rat, count 1 fen; Descend as resistance moderate when the operation offside promotes animal, count 2 fens; Descend as resistance severe when the operation offside promotes rat, count 3 fens.3) the two forelimbs of rat are placed on the wire netting, observe the muscular tension of forelimb.As bilateral muscle of anterior limb tension force equity and strong, count 0 fen; As slightly descending, count 1 fen to operation offside muscle of anterior limb tension force; As descending, count 2 fens to operation offside muscle of anterior limb tension force moderate; As descending, count 3 fens to operation offside muscle of anterior limb tension force severe; 4) rat has and does not stop counting 1 fen to the operation offside person of turn-taking.According to above standard scoring, full marks are 11 minutes, and mark is high more, shows that the rat delayed ischemic neurological deficits is serious more.
1.7 the cerebral infarction scope is measured
Adopt the TTC staining to measure the cerebral infarction scope.Animal broken end back is taken out complete brain rapidly, and the crown brain sheet that is cut into 2mm is hatched 30min in (with the phosphate buffered saline(PBS) preparation) 37 ℃ of water-baths in 2%TTC solution.Infarction tissue is white in color, and normal surrounding tissue is rose.Fixing in 10% neutral formalin solution then.Every brain sheet tow sides are scanned, obtain infarcted region and non-infarcted region area with the image analysis software integration.
1.8 the mensuration of brain water content
After ischemia 2h pours into 22h again, the rapid broken end of mice is got brain, survey brain water content with dried wet method, on ice cube, get brain rapidly, the cerebral tissue that takes out is placed in the culture dish that the moistening qualitative filter paper of normal saline is arranged in, in case water evaporates, the while is removed the pia mater encephali and the sludged blood on brain cortex surface fast.Accurately take by weighing brain weight with one thousandth sky chessboard, place 100 ℃ of baking oven 24h then after, weigh once more, be relative water content with (1-dry weight/weight in wet base) * 100%.
1.9 coagulation function is measured
After pouring into 22h again, postcava is got blood 3ml, measures thrombin time of blood plasma (TT) and fibrinogen content (FB) with ACL Advance automatic coagulation analyzer.
1.10 cerebral tissue MDA content, MPO and SOD determination of activity
Rat is sacrificed by decapitation after cerebral ischemia 2h pours into 22h again, gets brain on ice pan fast.Weigh, add ice-cold normal saline, make 10% brain tissue homogenate by 1: 9 (W/V).Homogenate with the centrifugal 10min of 3000r/min, is got supernatant, preserve to be measured at-70 ℃ of ultra cold storage freezers.Press the test kit description and measure MDA content, MPO activity and SOD activity.Protein content determination adopts the Coomassie brilliant blue method.
1.11 statistical procedures
Experimental result is all represented with x ± s, adopts one factor analysis of variance to organize a significance relatively, relatively adopts the t check between sample average. *Expression P<0.05 shows that administration group and model group relatively have significant difference; *Expression P<0.01 shows that administration group and model group relatively have utmost point significant difference.
2 results
2.1 the Chorispora bungeana extract is to the influence of rat function of nervous system defective, cerebral infarction scope, brain water content
The result is as shown in table 2, compare with sham operated rats, the defective scoring of model group function of nervous system, cerebral infarction scope and brain water content obviously increase, the Chorispora bungeana extract is dose dependent ground and reduces function of nervous system's defective scoring, reduce the cerebral infarction scope, alleviate cerebral edema, show that Chorispora bungeana has the anti-cerebral ischemia reperfusion injury and protect.
Table 2 Chorispora bungeana extract to the influence of rat function of nervous system defective, cerebral infarction scope, brain water content (x ± s, n=8)
Figure GSA00000023739600071
Compare with model group, *Expression P<0.05 *Expression P<0.01
2.2 the Chorispora bungeana extract is to the influence of rat coagulation function
Ischemia 2h pours into 22h again can cause that the rat plasma thrombin time shortens significantly, and fibrinogen content raises significantly.Compare with model group, Chorispora bungeana can prolong thrombin time of blood plasma significantly, reduces fibrinogen content, shows that the Chorispora bungeana treating cerebral ischemia is relevant with anticoagulant active.
Table 3 Chorispora bungeana extract to the influence of rat coagulation function (x ± s, n=8)
Figure GSA00000023739600072
Figure GSA00000023739600081
Compare with model group, *Expression P<0.05 *Expression P<0.01
2.3 the Chorispora bungeana extract is to the influence of the MPO of rat cerebral tissue, SOD activity and MDA content
As shown in table 3, the Chorispora bungeana extract has inhibitory action significantly to the active reduction of Ischemia and Reperfusion in vivo in Rats hindbrain tissue SOD, simultaneously, can reduce the active and MDA content of MPO effectively, shows that its treating cerebral ischemia and its antiinflammatory, antioxidant activity are relevant.
Table 4 Chorispora bungeana extract to the influence of the MPO of rat cerebral tissue, SOD activity and MDA content (x ± s, n=8)
Compare with model group, *Expression P<0.05 *Expression P<0.01
The anti-cerebral anoxia research of embodiment 7 Chorispora bungeana extracts
1. material and method
1.1 laboratory animal: the healthy adult male ICR mouse, the SPF/VAF level, body weight 18~22g is provided by Beijing Vital River Experimental Animals Technology Co., Ltd., licence numbering: SCXK (capital) 2007-0001.Using unity and coherence in writing health food Function detection center SPF level experimental animal room in the Beijing Union University before the experiment conforms a week.
1.2 reagent: Chorispora bungeana: in above-mentioned preparation embodiment, prepare; NAOXINTONG JIAONANG: Xianyang Buchang Pharmaceutical Co., Ltd; Sodium nitrite, Xi'an chemical reagent factory.
1.3 instrument: AR-2140 type ten thousand/electronic balance: prunus mume (sieb.) sieb.et zucc. Teller-Tuo benefit Instr Ltd..
1.4 acute cerebral ischemia anoxia experiment
Get fasting 12h, tried 40 of ICR mices, be divided into model group at random, Chorispora bungeana (being equivalent to crude drug amount 5,2.5,1.25g/kg) group, NAOXINTONG JIAONANG (0.324g/kg) group, 8 every group.Behind the mouse peritoneal drug administration by injection 2h, each treated animal by broken end only, immediately by manual time-keeping, is noted down time and the mouth breathing number of times of each treated animal broken end back to the respiratory arrest from cervical region.
The survival experiment 1.5 sodium nitrite poisons
Get fasting 12h, tried 40 of ICR mices, be divided into model group at random, Chorispora bungeana (being equivalent to crude drug amount 5,2.5,1.25g/kg) group, NAOXINTONG JIAONANG (0.324g/kg) group, 8 every group.Behind the mouse peritoneal drug administration by injection 2h, each organizes mice by 240mg/kg dosage lumbar injection sodium nitrite (concentration is 24mg/ml), is index with the respiratory arrest, writes down the mice time-to-live respectively.
1.6 statistical procedures
Experimental result is all represented with x ± s, adopts one factor analysis of variance to organize a significance relatively, relatively adopts the t check between sample average. *Expression P<0.05 shows that administration group and model group relatively have significant difference; *Expression P<0.01 shows that administration group and model group relatively have utmost point significant difference.
2 results
2.1 the Chorispora bungeana extract is to the influence of chmice acute cerebral hypoxia ischemia time
Can significant prolongation break end mouth breathing time and the sodium nitrite of caused global brain ischemia mice of Chorispora bungeana extract causes death the mice time-to-live, increase the frequency of respiration after mice breaks end, show that the Chorispora bungeana extract can reduce the brain oxygen consumption, improve the utilization rate of cerebral tissue oxygen.
Table 5 Chorispora bungeana extract to the influence of chmice acute cerebral hypoxia ischemia time (x ± s, n=8)
Compare with negative control group, *Expression P<0.05 *Expression P<0.01
2.2 the Chorispora bungeana extract is to the influence of poisoning time-to-live of mice sodium nitrite
Table 6 Chorispora bungeana extract to the mice sodium nitrite poison the time-to-live influence (x ± s, n=8)
Figure GSA00000023739600092
Compare with negative control group, *Expression P<0.05 *Expression P<0.01
The anti-angiogenic dementia research of embodiment 8 Chorispora bungeana extracts
1. material and method
1.1 laboratory animal: healthy adult male ICR mouse, the cleaning level, body weight 18~20g, provide by Beijing Vital River Experimental Animals Technology Co., Ltd., use unity and coherence in writing health food Function detection center SPF level experimental animal room in the Beijing Union University, Beijing Union University before the experiment and conform a week.
1.2 reagent: Chorispora bungeana: in above-mentioned preparation embodiment, prepare; NAOXINTONG JIAONANG: Xianyang Buchang Pharmaceutical Co., Ltd
1.3 instrument: water maze: Anhui Province Huaibei Zhenghua Biological Instrument Co., Ltd.; Mice is kept away dark instrument: institute of Materia Medica,Chinese Academy of Medical Sciences.
1.4 set up vascular dementia model
24h fasting before the ICR mice art is freely drunk water.With 4% chloral hydrate (400mg/kg, ip) anesthesia.It is fixing that postanesthetic mice is lain on the back, the cervical region preserved skin, and sterilization skin cuts skin along cervical midline, separates the left and right side common carotid artery, closes blood vessel with the bulldog clamp folder, blocking-up bilateral common carotid arteries blood flow 30min.Remove bulldog clamp and pour into again, skin suture.Sham operated rats will not be pressed from both sides and be closed blood vessel, and all the other steps are the same.After pouring into 2h again, gastric infusion under the mice waking state, dosage is the same, continuous irrigation stomach 25d.
1.5 mice water maze laboratory
Before the experiment, give water filling in the water maze, the depth of water there was not 23~25 ℃ of platform 2cm water temperatures.The training the 1d mice be placed in 10s on the platform, make it be familiar with safety island, then with mice in order the head put into water from 4 quadrants successively towards tank, timing 2min, mice find platform and stop 10s thereon after, timing stops automatically.5d removes platform, and the swimming starting point of mice is 2 quadrantal points away from platform, and the platform number of times is worn in the incubation period of mice platform and record in the record 2min.
1.6 mice is kept away dark experiment
Mice is put into darkroom dorsad, bright chamber, can be shocked by electricity when mice enters into darkroom four-footed contact copper grid, its normal reaction is for withdrawing from the darkroom at once.During the 1st day adaptive training, the record mice enters the number of times in darkroom and the time that enters camera bellows the 1st time in 3min; Behind the adaptive training, open supply unit, mice is put into bright chamber and darkroom dorsad, mice enters darkroom contact copper grid and is shocked by electricity, and mice is taken out immediately.Experiment once more behind the 24h, the time that the interior mice of observation 3min enters camera bellows first is incubation period, the number of times that mice enters camera bellows is an errors number.
1.7 statistical procedures
Experimental result is all represented with x ± s, adopts one factor analysis of variance to organize a significance relatively, relatively adopts the t check between sample average. *Expression P<0.05 shows that administration group and model group relatively have significant difference; *Expression P<0.01 shows that administration group and model group relatively have utmost point significant difference.
2. result
2.1 the Chorispora bungeana extract is to mice water maze laboratory escape latency and the influence of wearing the platform number of times
The display model group mice water maze escape latency time increases as a result, wears the platform number of times and reduces, and learning and memory function is badly damaged.The Chorispora bungeana extract significantly reduces the water maze escape latency time, increases to wear the platform number of times, relatively has significant difference with model group.
Table 7 Chorispora bungeana extract to mice water maze laboratory escape latency and wear the platform number of times influence (x ± s, n=8)
Compare with model group, *Expression P<0.05 *Expression P<0.01
2.2 the Chorispora bungeana extract is kept away the influence that dark experiment keeps away dark incubation period and wears the case number of times to mice
Compare with sham operated rats, passive the keeping away of model group mice significantly shortened dark incubation period, keeps away secretly to wear the case number of times and obviously increase.Chorispora bungeana extract doses dependency ground increases that mice is passive keeps away dark incubation period, reduces to keep away and secretly wears the case number of times.
Table 8 Chorispora bungeana extract to mice keep away dark experiment keep away dark incubation period and wear the case number of times influence (x ± s, n=8)
Figure GSA00000023739600112
Compare with model group, *Expression P<0.05 *Expression P<0.01
The safety evaluatio of embodiment 9 Chorispora bungeana extracts
1. material and method
1.1 laboratory animal: healthy adult ICR mice, cleaning level, body weight 18~22g, male and female half and half; Healthy adult W istar rat, the cleaning level, body weight 250~300g, male and female half and half, provide by Beijing Vital River Experimental Animals Technology Co., Ltd., use unity and coherence in writing health food Function detection center SPF level experimental animal room in the Beijing Union University before the experiment and conform a week.
1.2 reagent: Chorispora bungeana: in above-mentioned preparation embodiment, prepare;
1.3 method: 30 of mices, get 10 at random as normal control, irritate the stomach distilled water every day; Surplus and irritate stomach 20 every days and give Chorispora bungeana extract (being equivalent to crude drug amount 20g/kg), 2 weeks of continuous irrigation stomach, observe the mice general state every day, food-intake is weighed.Took off cervical vertebra execution mice in 24 hours after the last administration, dissect its internal organs outward appearance of back perusal and change situation.
Took off cervical vertebra execution animal in 24 hours after the administration, dissect its internal organs outward appearance of back perusal and change situation.
2. result
The result shows, gives Chorispora bungeana extract 20g/kg (being equivalent to 16 times of minimum effective doses) continuous two weeks of mice, the mice general state, and food ration, body weight and internal organs show no obvious abnormalities.

Claims (10)

1. Chorispora bungeana or its extract application in preparation prevention or treatment cardiovascular and cerebrovascular diseases medicament.
2. purposes according to claim 1 is characterized in that the application in preparation prevention or treatment cerebrovascular disease medicament of Chorispora bungeana or its extract.
3. according to claim 1,2 described purposes, it is characterized in that described cerebrovascular disease is cerebral ischemia, cerebral anoxia, cerebral thrombosis or vascular dementia.
4. purposes according to claim 1 is characterized in that described Chorispora bungeana extract is the Chorispora bungeana water extract.
5. purposes according to claim 1 is characterized in that described Chorispora bungeana extract is the Chorispora bungeana ethanol extract.
6. purposes according to claim 3, it is characterized in that described Chorispora bungeana water extract prepares in the following manner: a part of getting Chorispora bungeana Herb or Herb, the use pulverizer is pulverized, and soaks, and heating decocts, extract 3 times, filter, merging filtrate, centrifugal, get supernatant concentration, lyophilization becomes dry extract promptly to get the Chorispora bungeana water extract.
7. purposes according to claim 4, it is characterized in that described Chorispora bungeana ethanol extract prepares in the following manner: get the Chorispora bungeana Herb, the use pulverizer is pulverized, add soak with ethanol, reflux, extract, 3 times is filtered, merging filtrate, centrifugal, get supernatant concentration, lyophilization becomes dry extract promptly to get the Chorispora bungeana ethanol extract.
8. a pharmaceutical composition is characterized in that described pharmaceutical composition comprises Chorispora bungeana or Chorispora bungeana extract and conventional pharmaceutical carrier.
9. pharmaceutical composition according to claim 7 is characterized in that described pharmaceutical composition is the preparation that adopts the oral or non-oral route mode administration that the conventional formulation prepared forms.
10. the method for preventing or treating cardiovascular and cerebrovascular disease comprises to the cardiovascular and cerebrovascular disease patient giving Chorispora bungeana or its extract.
CN 201010117378 2010-02-01 2010-02-01 Application of chorispora bungeana or extract thereof in preparation of medicaments for preventing and treating cardiovascular and cerebrovascular diseases Expired - Fee Related CN102138953B (en)

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102232986A (en) * 2010-04-21 2011-11-09 中国科学院寒区旱区环境与工程研究所 Use of Chorispora bungeana or extract thereof in preparation of medicines for preventing and treating liver diseases

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
李争艳等: "低温条件下高山离子芥SA的产生及NO对SA质量分数的影响", 《兰州大学学报(自然科学版)》 *

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102232986A (en) * 2010-04-21 2011-11-09 中国科学院寒区旱区环境与工程研究所 Use of Chorispora bungeana or extract thereof in preparation of medicines for preventing and treating liver diseases

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