CN110123895A - Huajuhong causes the application of response to oxidative stress drug in preparation prevention and treatment cerebral ischemia - Google Patents
Huajuhong causes the application of response to oxidative stress drug in preparation prevention and treatment cerebral ischemia Download PDFInfo
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- CN110123895A CN110123895A CN201910254346.7A CN201910254346A CN110123895A CN 110123895 A CN110123895 A CN 110123895A CN 201910254346 A CN201910254346 A CN 201910254346A CN 110123895 A CN110123895 A CN 110123895A
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- huajuhong
- cerebral ischemia
- oxidative stress
- drug
- cerebral
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/75—Rutaceae (Rue family)
- A61K36/752—Citrus, e.g. lime, orange or lemon
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P39/00—General protective or antinoxious agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
Abstract
The present invention relates to Huajuhongs to prevent and treat the application that cerebral ischemia causes the drug of oxidative stress in preparation, the function of Huajuhong is used for cough due to wind-cold evil, larynx is itched abundant expectoration, dyspepsia is got sick from drinking too much wine, evil of vomitting ruffian is bored, and cerebral arterial thrombosis is a kind of complex disease of polygenes multiple target point many A signal pathways that is related to, oxidative stress and inflammatory reaction are the important mechanisms of cerebral arterial thrombosis morbidity, therefore traditional understanding Huajuhong is not to the preventive and therapeutic effect of cerebral ischemia, but the present invention is it has been investigated that Huajuhong can intervene multiple pathology links of cerebral arterial thrombosis, serum oxidative caused by cerebral arterial thrombosis (abbreviation cerebral ischemia) can be significantly inhibited stress, it can be applied to the drug of response to oxidative stress caused by prevention and treatment cerebral ischemia.
Description
Technical field
The present invention relates to biomedicine technical fields, cause response to oxidative stress medicine more particularly to a kind of prevention and treatment cerebral ischemia
Object.
Background technique
Ischemic cerebrovascular disease is also known as cerebral ischemia diseases, is the most common cranial vascular disease, and seriously affect patient
The disease of health and quality of life, it includes transient ischemic attack, invertibity neurological dysfunction and cerebral infarction.And
When symptoms of cerebral ischemia occurs, often bring response to oxidative stress, oxidative stress refer to body when by various destructive stimulus,
Internal high activity molecule such as active oxygen radical (reactive oxygen species, ROS) and active nitrogen free radical
(reactive nitrogen species, RNS) generates excessive, and degree of oxidation exceeds the removing of oxide, oxidative system and anti-
Oxidative system is unbalance, once this coordination generates disorder and imbalance with dynamic equilibrium, a series of metabolism will be caused to lose
It is often reduced with immune function, forms oxygen radical chain reaction, damage biomembrane and its function, so that forming the transparent venereal disease of cell
Become, fibrosis, large area cellular damage is caused into nerve, tissue, organ equivalent damage, very big to human health damage.
Huajuhong because its with unique stomach invigorating promoting the circulation of qi, preventing phlegm from forming and stopping coughing medicinal effects due to well-known four directions, be a kind of work
Name treatment cough drug, it can also be used to abdominal fullness and distention caused by the taste stagnation of the circulation of vital energy, pain, nausea and vomiting, do not feel like eating card.State
It is inside and outside not reported that Huajuhong can be applied to correlated response caused by prevention and treatment cerebral ischemia.
Summary of the invention
A kind of Huajuhong is provided and is prevented and treated in preparation it is an object of the invention to avoid shortcoming in the prior art
Cerebral ischemia causes the application of response to oxidative stress drug.
The purpose of the present invention is achieved through the following technical solutions:
Application of the Huajuhong in the drug that preparation prevention and treatment cerebral ischemia causes oxidative stress.
Preferably, the Huajuhong is the Exocarpium Citri Rubrum by processing, and concocting method is as follows: when Exocarpium Citri Rubrum summer fruit prematurity
Harvesting removes pericarp in fruit flesh and part, compression moulding re-dry.
Preferably, the Huajuhong is the Exocarpium Citri Rubrum fruit for being grown in Maoming City Huazhou City.
Beneficial effects of the present invention:
In existing understanding, the function of Huajuhong (also known as " Exocarpium Citri Grandis ") is used for cough due to wind-cold evil, and larynx is itched abundant expectoration, and dyspepsia gets sick from drinking too much wine, vomits
Jailbird is bored, cerebral arterial thrombosis be it is a kind of be related to the complex disease of polygenes multiple target point many A signal pathways, oxidative stress and
Inflammatory reaction is the important mechanisms of cerebral arterial thrombosis morbidity, traditional understanding Huajuhong not to the preventive and therapeutic effect of cerebral ischemia,
But the present invention can significantly inhibit ischemic it has been investigated that Huajuhong can intervene multiple pathology links of cerebral arterial thrombosis
Serum oxidative caused by cerebral apoplexy (abbreviation cerebral ischemia) stress, thus can be applied to response to oxidative stress caused by prevention and treatment cerebral ischemia
Drug.
Detailed description of the invention
Using attached drawing, the present invention will be further described, but the content in attached drawing does not constitute any limitation of the invention.
Fig. 1 is different group rat blood serum nadph oxidases (NOX), lipid peroxidation product (4-HNE), protein carbonyl
Change (protein carbonyl), DNA oxidation product (8-OHdG), antioxidase HO-1 and NQO-1 contain spirogram.
Specific embodiment
The invention will be further described with the following Examples.
Experiment: Huajuhong causes the effect in oxidative stress in prevention and treatment cerebral ischemia
1.1. test sample and reference substance
1.1 test sample
Title: Huajuhong
Supplier: Huazhou Li Feng Exocarpium Citri Grandis Investment Co., Ltd
Character: this product is yellow powder
Usage and dosage: daily 3~9g.
Storage: sealing is protected from light
Place of retention: China Medical Sciences Academy Medical Plants Institute's pharmacological toxicology center
Remaining test article treating method: after keeping sample, remaining test sample returns to client
1.2 negative control
Title: 0.9% sodium chloride injection
Source: Shangdong Hualu Pharmaceutical Co., Ltd.
Lot number: G16092904
Preservation condition: room temperature
1.3 test samples are prepared
1.3.1 preparation method
With normal saline at required concentration.
Prepare frequency
Test matching while using.
2. test material
2.1 trial drugs and dose design
Huajuhong raw medicine, Huajuhong water extract, the test of Huajuhong alcohol extract respectively set 1 dosage group, are 0.9g/kg.
Enteric coated aspirin (is produced) by Bayer HealthCare Co, and test sets 1 dosage group as 10mg/kg(clinical equivalent agent
Amount)
Wherein,
Huajuhong raw medicine is that the finished product for the commercial type that Huazhou Li Feng Exocarpium Citri Grandis Investment Co., Ltd cooks is polished into powder.
The extraction of Huajuhong water is that Huajuhong original absorbent gauze encases, and is obtained with 95 degree of boiled water or more of soakings.
Huajuhong alcohol extract is filtering acquisition after Huajuhong original medicinal alcohol or the immersion of other alcohols solvents.
Reagent and instrument
The 4-0 filament nylon line of first polysiloxane coated is purchased from the dense Science and Technology Ltd. of West Beijing；Tetrazole red (TTC) is purchased from
Sigma；ELISA kit is purchased from Beijing Yi Kebaide Co., Ltd；Electronic balance is purchased from Mei Teletuo benefit instrument (Shanghai)
Co., Ltd；Microplate reader agrees (Shanghai) company purchased from Supreme Being.
Animal and rearing conditions
3.3.1 experimental animal
Healthy male SD rat (weight 280-300g) is provided by Beijing dimension experimental animal company, tonneau China, and licensing number is
The capital SCXK() 2016-0006.
Rearing conditions
Experimental animal carries out animal feeding in China Medical Sciences Academy Medical Plants Institute's animal center.Animal facility is held
Barrier environment standard is held in continuation of insurance.The control range of main environment index: 20~26 DEG C of room temperature, temperature difference per day≤4 DEG C.Relative humidity
40~70%.15 time/hour of minimum air changes, optical illumination: dark=12h, bright=12h.It raises in base box, 5, every box,
Its cultured space meets the minimum space needed for experimental animal in National Standard of the People's Republic of China GB14925-2010
Regulation.All animals carry out feeding management by the qualified personnel of training, keep animal diet followed activity in entire breeding process
Freely.
Quarantine and domestication process
After experimental animal enters animal house, the animal quarantine phase is 3~5 days.In quarantine observation drinking water for animals, ingests and be good for
Health situation, and whether there is disease and intimations of mortality.Healthy animal fur is smooth, be quick on the draw, secretion without exception etc..Hair
What incumbent abnormal phenomenon all needs to report to thematic responsible person and clinical veterinarian, confirms under animal doctor's guidance, through thematic responsible person, pick
It is replaced except ill animal, with healthy animal.Confirm that animal health is disease-free, can use.After Animal adaptability is raised 1 week
It can be tested.
4. test method
4.1 animal packets and drug-treated
4.1.1 animal packet
72 male SD rats are randomly divided into 6 groups, every group 12, are respectively as follows:
1. sham-operation group (Sham)
Arteria cerebri media embolism Reperfu- sion 2. (MCAO/R) model group
Aspirin 3. (ASA, 10mg/kg, clinical equivalent dosage) group
Huajuhong raw medicine 4. (ECG, 0.9g/kg, crude drug amount 9g/d) group
Huajuhong water extract 5. (AE-ECG, 0.9g/kg, crude drug amount 16.5g/d) group
Huajuhong alcohol extract 6. (EE-ECG, 0.9g/kg, crude drug amount 24.5g/d) group
4.1.2 drug-treated
Huajuhong raw medicine, Huajuhong water extract, Huajuhong alcohol extract, aspirin are in MCAO operation the last week stomach-filling
Administration, sham-operation group and MCAO/R the model group rats then isometric physiological saline of stomach-filling.
Cerebral ischemia re-pouring injured (MCAO/R) model
Cerebral ischemia re-pouring injured (MCAO/R) model is made using line brush.Surgical procedure strict aseptic technique, chief surgical
Process is as follows: 4% chloraldurate (10mL/kg) intraperitoneal injection of anesthesia rat isolates arteria carotis communis (CCA), external carotid artery
(ECA) and internal carotid (ICA) arteria carotis communis, is closed with arteriole folder folder, with the branch of bipolar coagulation coagulation external carotid artery.Trip
From external carotid artery trunk, away from ligation at 3~4 mm of arteria carotis communis bifurcated.Temporarily folder closes internal carotid, eye scissors to arteriole folder
External carotid artery is cut into an osculum, the 4-0 filament nylon line of first polysiloxane coated is inserted into, makes a call to a turpentine in external carotid artery clip
To block the blood reflux of internal carotid, the arteriole folder of internal carotid is removed, nylon wire is touched and enters internal carotid, reach cranium
Interior arteria cerebri anterior blocks the opening of arteria cerebri media (MCA), insertion depth about 18-22mm.Remove the fine motion of arteria carotis communis
Arteries and veins folder, layer-by-layer suture subcutaneous tissue and skin after disinfection, Yu Shuhou 2h slowly extract nylon wire out and carry out Reperfu- sion for 24 hours.Sham-operation
For group in addition to being not inserted into nylon wire, remaining operation is identical as model group.The rectal temperature dimension of all rats in the entire experiment process
It holds at 37 DEG C.
Oxidative stress Indexs measure
All rats are taken, serum is taken after abdominal aortic blood 5mL, 3000rpm centrifugation 10min, separates cerebral cortex and hippocampus group
It knits, takes supernatant after 3000rpm centrifugation 10min after 10% homogenate.Using ELISA kit detection oxidative stress index NADPH oxidation
Enzyme, 4- Hydroxynonenal (4-HNE), 8- are hydroxylated deoxyguanosine (8-OHdG), protein carbonyl (Protein carbonyl), blood
Heme oxygenase 1(HO-1) and quinone oxidoreductase 1(NQO-1) horizontal.
Data processing
All data are handled by SPSS22.0 for Windows statistical software, and data are with mean ± standard deviation (mean ± SD)
It indicates.It is examined using t and One-way ANOVA is for statistical analysis to continuous data, made two-by-two with least significant difference (LSD)
Compare, withP< 0.05 indicates that difference is statistically significant.
5. experimental result
Huajuhong significantly inhibits models of cerebral ischemia-reperfusion injury rat blood serum oxidative stress
As shown in figure 1 and table 1, compared with sham-operation group, MCAO/R model group rats serum N ADPH oxidizing ferment (NOX), lipid mistake
Oxidation product (4-HNE), protein carbonyl (protein carbonyl), DNA oxidation product (8-OHdG), antioxidase HO-1
With NQO-1 level dramatically increase (P< 0.01)；Compared with MCAO/R model group, aspirin, Huajuhong water extract, alcohol extracting
Object group rat blood serum NOX, 4-HNE, protein carbonyl, 8-OHdG level substantially reduce (P< 0.01), Huajuhong
Raw medicine group rat blood serum NOX, protein carbonyl level substantially reduce (P< 0.01), each administration group rat blood serum
HO-1 and NQO-1 level without significant changes (P >0.05).
The serum oxidative that 1 Huajuhong of table can significantly inhibit MCAO/R rat model stress
Note: ##,P< 0.01 vs sham-operation group；*,P< 0.05 vs MCAO/R model group；*,P< 0.01 vs MCAO/R mould
Type group.
Experiments verify that knowing: compared with MCAO/R model group, aspirin, Huajuhong water extract, alcohol extract group are big
Mouse serum NO level X, 4-HNE, protein carbonyl, 8-OHdG level substantially reduce (P < 0.01), Huajuhong raw medicine group
Rat blood serum NOX, protein carbonyl level substantially reduce (P < 0.01), and Huajuhong is preventing and inhibiting cerebral ischemia
Caused response to oxidative stress has a significant effect.
Finally it should be noted that the above examples are only used to illustrate the technical scheme of the present invention explanation rather than right is wanted
Ask the limitation of protection scope.Those skilled in the art should be appreciated that referring to preferred embodiment and can be to of the invention
Technical solution is modified or replaced equivalently, but belongs to the substantially identical and protection scope of technical solution of the present invention.
Claims (3)
1. application of the Huajuhong in the drug that preparation prevention and treatment cerebral ischemia causes oxidative stress.
2. application of the Huajuhong according to claim 1 in the drug that preparation prevention and treatment cerebral ischemia causes oxidative stress,
It is characterized in that, the Huajuhong is the Huajuhong by processing, concocting method is as follows: Huajuhong summer fruit not at
It is harvested when ripe, removes pericarp in fruit flesh and part, compression moulding re-dry.
3. application of the Huajuhong according to claim 1 in the drug that preparation prevention and treatment cerebral ischemia causes oxidative stress,
It is characterized in that, the Huajuhong is the Exocarpium Citri Rubrum fruit for being grown in Maoming City Huazhou City.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
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| CN201910254346.7A CN110123895A (en) | 2019-03-31 | 2019-03-31 | Huajuhong causes the application of response to oxidative stress drug in preparation prevention and treatment cerebral ischemia |
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| CN201910254346.7A CN110123895A (en) | 2019-03-31 | 2019-03-31 | Huajuhong causes the application of response to oxidative stress drug in preparation prevention and treatment cerebral ischemia |
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Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106389416A (en) * | 2016-11-29 | 2017-02-15 | 徐健 | Medicine for preventing and treating stroke and application |
| CN110420214A (en) * | 2019-03-31 | 2019-11-08 | 李锋 | A kind of prevention and treatment cerebral ischemia causes the drug and its preparation of response to oxidative stress |
-
2019
- 2019-03-31 CN CN201910254346.7A patent/CN110123895A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106389416A (en) * | 2016-11-29 | 2017-02-15 | 徐健 | Medicine for preventing and treating stroke and application |
| CN110420214A (en) * | 2019-03-31 | 2019-11-08 | 李锋 | A kind of prevention and treatment cerebral ischemia causes the drug and its preparation of response to oxidative stress |
Non-Patent Citations (1)
| Title |
|---|
| VAIBHAV GAUR等: "Protective effect of naringin against ischemic reperfusion cerebral injury: Possible neurobehavioral, biochemical and cellular alterations in rat brain", 《EUROPEAN JOURNAL OF PHARMACOLOGY》 * |
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Application publication date: 20190816 |