CN109223786A - Application of the Dauricine in the drug of preparation treatment Alzheimer's disease mitochondria - Google Patents
Application of the Dauricine in the drug of preparation treatment Alzheimer's disease mitochondria Download PDFInfo
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- CN109223786A CN109223786A CN201811262395.7A CN201811262395A CN109223786A CN 109223786 A CN109223786 A CN 109223786A CN 201811262395 A CN201811262395 A CN 201811262395A CN 109223786 A CN109223786 A CN 109223786A
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- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
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Abstract
The invention discloses application of the Dauricine in the drug of preparation treatment Alzheimer's disease mitochondria, Dauricine raises mitochondrial membrane potential, lowers activity keto concentration in cell, raises Bcl-2 expressing quantity in cell；Dauricine can reduce the paralysis rate of AD model nematode；Dauricine will can be used for developing novel AD therapeutic agent to the protective effect of mitochondrial function；In addition, the Alzheimer's disease cell model that the present invention constructs can be used for the research of AD.
Description
Technical field
The invention belongs to pharmaceutical technology fields more particularly to Dauricine in preparation treatment Alzheimer's disease mitochondria
Application in drug.
Background technique
Alzheimer disease (AD) is called senile dementia, is a kind of central nervous system degeneration；Its insidious onset, disease
Journey is in chronic progressive, is senile dementia one of the most common type type.It is shown according to related data, the country of China Alzheimer
Disease (being commonly called as senile dementia) patient increases at multiple, and 1999 are only 3000000 people, reaches within 2016 9000000 people, and estimation the year two thousand fifty will
Up to 36,000,000 people.Currently, alzheimer's disease is mainly for its possible several pathogenesis, aβ protein abnormal deposition, Tau
Protein hyperphosphorylation, Synaptic dysfunction and neurotransmitter exception and Mitochondrial autophagy dysfunction etc. are treated.Have
Studies have shown that the phenomenon that there are metal ion metabolic disorders in Alzheimer's.Metal ion especially copper ion by
In it as variable valency metal, research shows that it can form compound with free A β 1-42 protein binding, into cell and to thin
Born of the same parents' mitochondria generates oxidative damage.The Cu containing high concentration is found through detection in the amyloid plaques of AD patient's intracerebral aggregation2+,
This is also the region that corresponding intracerebral oxidation stress occur.
Currently, the most commonly used several animal models, i.e. Caenorhabditis elegans in research AD disease in the world, drosophila and
Mouse, Caenorhabditis elegans are easier to carry out nervous function research due to the simplification of its physiological structure.And A β toxic protein is made
For induced oxidation in AD stress an important factor for one of, find that it can be by oxidativestress damage mitochondria in many researchs
Function and the damage for inducing neuron aggravate AD symptom.Therefore nematode model is overexpressed using A β to be studied to relevant
Scholars provide convenience.
Mitochondria is considered having especially important effect in neuron, Major Function include: calcium ion regulation and
Redox, the regulation of synaptic plasticity and the regulation of cell survival and death.Mitochondria loses the adjustment effect of calcium ion
Weighing apparatus can trigger Apoptosis and cell death, and excessive chondriokinesis can be promoted by synaptic damage and neuronal death
AD morbidity.In the progress of neurodegenerative disease, injury of mitochondria can lead to apoptotic neuronal death.Existing research table
Bright, Drug inhibition mitochondria dysfunction can improve the impaired memory function of AD.Therefore, mitochondria dysfunction may be AD
It falls ill potential mechanism of action, protection mitochondrial function is still prevention and the key for slowing down AD morbidity and progress.
Currently, clinical mainly reduce acetylcholine degradation using anticholinesterase, enhance the way of cholinergic neuron
Diameter treats AD.Anticholinesterase is first-line treatment drug, mainly include by FDA authenticate Tacrine, donepezil,
The huperzine of rivastigmine, galanthamine and China SFDA certification.But the drug for treating AD still extremely lacks,
It is badly in need of developing new therapy approach and drug and carrys out better healing alzheimer's disease.
Summary of the invention
Present invention aims to overcome that the shortcomings of the prior art, and Dauricine is provided and treats alzheimer ' in preparation
Application in the drug of silent disease mitochondria, Dauricine raise mitochondrial membrane potential, lower activity keto concentration in cell, and up-regulation is thin
Bcl-2 expressing quantity in born of the same parents plays the effect of protecting Alzheimer's disease mitochondria.
To achieve the above object, the technical scheme adopted by the invention is as follows: Dauricine preparation treat Alzheimer's disease
Application in the drug of mitochondria.
As an improvement of the above technical solution, Dauricine raises mitochondrial membrane potential, lowers activity keto concentration in cell,
Raise Bcl-2 expressing quantity in cell.
Present invention discover that Dauricine can remarkable inhibiting activity oxygen (ROS) generation, restore mitochondrial membrane potential, and raise
Anti-apoptotic protective factors Bcl-2.Oxidative stress refers to generates excessive active oxygen (ROS), the removing beyond body itself in vivo
Ability and the series reaction for leading to vivo oxidation Yu the unbalance mediation of antioxidation.Mitochondria is both what intracellular ROS was generated
The first target organs of main place and ROS attack and damage.Mitochondrial membrane potential (MMP) is the quick of evaluation mitochondrial function
Feel index.Under normal circumstances, Medium Culture proton is pumped into mistress by the proton pump of mitochondrial inner membrane, and cell membrane inner potential is made to compare cell
Low 1.0~the 2.0mV of matter.Normal MMP is the prerequisite for maintaining mitochondria to carry out oxidative phosphorylation, generate atriphos,
The stabilization of MMP is conducive to maintain the normal physiological function of cell.When Apoptosis, in the precellular line of the also non-fragmentation of DNA
Plastochondria has damaged, and form occurs and function changes, wherein especially heavy with the opening of mitochondrial membrane permeability conversion hole (PTP)
It wants.The opening of PTP can cause MMP to decline, Mitochondria dysfunction, outer membrane fracture, and discharge rush antiapoptotic factors
Such as cytochrome c leads to Apoptosis.Therefore, MMP reduction is an important feature of early apoptosis of cells.Bcl-2 albumen
Have the function of extending cells survival time and anti-apoptotic, it is referred to as apoptosis suppressor.Some researches show that anti-apoptotic
Bcl-2 albumen ability change, main cause is the change of film stationkeeping ability.Compared with other cancer proteins, Bcl-2 egg
It is white promote cell survival be because produce prevent Apoptosis mechanism, be not make normal cell proliferation machinery by
The regulation of destruction.Therefore, the protective effect of mitochondrial function will be can be used for developing using Dauricine of the present invention novel
AD therapeutic agent.
In addition, the present invention also provides a kind of for treating the drug for the treatment of Alzheimer's disease mitochondria comprising bat
Pueraria lobota alkali.
It as an improvement of the above technical solution, also include pharmaceutically acceptable auxiliary material.
Auxiliary material of the present invention include at least excipient, adhesive, diluent, surfactant, wetting agent, disintegrating agent or
One of antioxidant.The excipient includes, but is not limited to, ion-exchanger, aluminium, aluminum stearate, lecithin, serum
Albumen, buffer substance, glycine, sorbic acid, potassium sorbate, the partial glyceride mixtures of saturated vegetable fatty acid, water, salt or
Electrolyte, disodium hydrogen phosphate, potassium hydrogen phosphate, sodium chloride, zinc salt, colloidal silicon, magnesium trisilicate, polyvinylpyrrolidone, polypropylene
Sour rouge, wax, polyethylene-polyoxypropylene-blocking condensate, lanolin, sugar, dextrose and saccharose, starch, cellulose and it spread out
Biology, gum powder, malt, gelatin and talcum powder.Described adhesive includes hydroxypropyl cellulose, hydroxypropyl methyl cellulose, hydroxyl
Ethyl cellulose, starch 1500, polyvinylpyrrolidone (polyvinylpyrrolidone) and PVP-VA 64.The diluent includes sweet dew
Alcohol, sorbierite, biphosphate calcium dihydrate, microcrystalline cellulose and powdered cellulose.The surfactant can for yin from
Son, cation or neutral surface active agent, anionic surfactant include NaLS, dodecyl sodium sulfate；Sun
Ionic surface active agent includes benzalkonium chloride and alkyl trimethyl ammonium bromide；Neutral surface active agent include glycerol list olein,
Polyoxyethylene sorbitan fatty acid ester, polyvinyl alcohol and anhydrosorbitol alcohol ester.The wetting agent includes poloxamer, gathers
Ethylene oxide alkyl ether, castor oil derivatives and polyoxyethylene 8 stearate rouge.The disintegrating agent can be several modifications
One of starch, modified cellulosic polymeric or polycarboxylic acids, for example, croscarmellose sodium, Explotab,
Polacrilin potassium and calcium carboxymethylcellulose.Antioxidant is selected from tocopherol, L-AA and its sodium or calcium salt etc..
As an improvement of the above technical solution, the dosage form of drug is tablet, paste, powder, decoction, pill or capsule.
In addition, the present invention also provides a kind of construction method of Alzheimer's disease cell model, first in neuronal cell
App gene is transfected, 150 μM of Cu are added after transfection2+And cultivate 2h.
The beneficial effects of the present invention are: the present invention provides Dauricine in preparation treatment Alzheimer's disease mitochondria
Application in drug, the present invention disclose: Dauricine can inhibit the production of active oxygen in Alzheimer's disease cell model well
It is raw, restore mitochondrial membrane potential, raises anti-apoptotic protective factors Bcl-2；Dauricine is to Alzheimer's disease mitochondrial function
Protective effect will can be used for developing novel AD therapeutic agent；Nematode be research Neuscience generally acknowledged at present both at home and abroad most
Common animal model, wild type N2 nematode of the present invention using the A β GMC101 nematode and control being overexpressed, GMC101
Nematode eventually leads to the paralysis of individual and dead higher, and Dauricine can reduce the paralysis rate of nematode；In addition, the present invention constructs
Alzheimer's disease cell model can be used for the research of AD.
Detailed description of the invention
Fig. 1 shows influence of the Dauricine to Apoptosis；Wherein, in normal group of Fig. 1 a statistics, model group and dosing group
Apoptosis rate, Fig. 1 b show the flow cytometer detection result of normal group, the Apoptosis of model group and dosing group；Normal group indicates
Cu is not added in APPsw cell2+It is handled, model group is that Cu is added in APPsw cell2+It is handled, dosing group is
Cu is added in APPsw cell2+It is handled, is added after processing Dauricine (dauricine, i.e. dau), * indicates P < 0.05；
Fig. 2 shows influence of the Dauricine to mitochondrial membrane potential, active oxygen and Bcl-2；Fig. 2 a is mitochondrial membrane potential
(MMP) testing result figure shows after giving Dauricine (1 μM) that mitochondrial membrane potential is replied with conspicuousness, Dauricine
It can be restored with effective protection mitochondria potential to normal level；Fig. 2 b is reactive oxygen species (ROS) testing result figure, is shown
After giving Dauricine (1 μM), intracellular ROS level is substantially reduced, and Dauricine can inhibit the tired of reactive oxygen species
Product, can be with effective protection cell from the damage of ROS；Fig. 2 c is the testing result figure of intracellular Bcl-2 protein expression level,
Show after giving Dauricine (1 μM), Bcl-2 protein expression level obviously rises；Wherein, * indicates P < 0.05；
Fig. 3 shows influence of the Dauricine to nematode；Wherein, Fig. 3 a shows Dauricine to the shadow of wild type N2 nematode
It rings, influence of Fig. 3 b Dauricine to GMC101 molded line worm；Control expression is added without Dauricine, and the abscissa of Fig. 3 is day
Number, ordinate are paralysis rate.
Specific embodiment
Purposes, technical schemes and advantages in order to better illustrate the present invention, below in conjunction with specific embodiments and the drawings pair
The present invention is described further.
Transfection APP (myloid beta (A4) precursor protein) is led in neuronal cell in elder generation of the present invention
Gene is a kind of routine techniques: transfecting app gene in SH-SY5Y cell, constructs APPsw cell, and combine Cu2+Induction
Neuronal cell constructs Alzheimer's disease cell model.
Influence of the Dauricine to Apoptosis
With the Cu of various concentration2+After handling APPsw cell, the Dauricine detection cell for giving a certain concentration (1 μM) is living
Force value, kit are Japanese colleague's cck8 detection kit；Cu is determined by screening2+Concentration be 150 μM, handle 2h when after be added
Dauricine, as a result, it has been found that Dauricine is best to the repairing effect of APPsw cell.Next 150 μM of Cu are utilized2+Carry out Ah
The building of Er Cihaimo disease cell model, and be added Dauricine processing 48h after carry out Apoptosis flow cytometer detection, detection
Kit is the double transfection reagent boxes of BD company AnnexinV-FITC/PI Apoptosis.
As a result as shown in Figure 1, comparing model group, dosing group cell survival rate is significantly risen, and shows that Dauricine can inhibit
Apoptosis.
Influence of the Dauricine to mitochondrial membrane potential, active oxygen and Bcl-2
1) mitochondrial membrane potential detects: by APPsw cell with 10 × 104A/mL quantity is seeded in 6 orifice plates, with 150 μM
Cu2+Dauricine is added after culture 2h, is carried out after 48h using the mitochondrial membrane potential detection kit of the green skies company in Shanghai
Detection；
2) active oxygen detects: by APPsw cell with 10 × 104A/mL quantity is seeded in 6 orifice plates, with 150 μM of Cu2+
Dauricine is added after culture 2h, removes culture medium after 48h, addition is trained with serum-free after being cleaned with phosphate buffered saline solution
The DCFH-DA probe solution that feeding basigamy is set removes culture medium after being incubated for 30min, uses fluorescence after fresh serum-free media is added
Inverted microscope observation, and fluorescence detection is carried out with fluorescence microplate reader；
3) Bcl-2 is detected: by APPsw cell with 10 × 104A/mL quantity is seeded in 6 orifice plates, with 150 μM of Cu2+Training
Dauricine is added after supporting 2h, cell is collected after 48h, cell pyrolysis liquid is added, sufficiently centrifugation is extracted albumen and boiled after cracking
Boiling denaturation, -80 DEG C of storages, carries out Bcl-2 Protein Detection with the albumen of extraction.
As shown in Fig. 2, the accumulation of active oxygen can be effectively reduced in Dauricine, mitochondrial membrane potential is repaired, and is raised anti-
The expression of antiapoptotic factors Bcl-2；Illustrate that Dauricine can be used for targeted therapy alzheimer's disease mitochondria: oxidative stress damage
Wound and anti-apoptotic.
Dauricine is overexpressed the protective effect of nematode damage to aβ protein
Drug food items configuration method: taking 3g NaCl, 17g agar, and 2.5g peptone is added after 975ml water high pressure and adds while hot
Enter the 1M calcium chloride of 1ml, 1ml 15mg/ml cholesterol solution, the 1mol/ml magnesium sulfate and 25ml kaliumphosphate buffer of 1ml mix
A kind of rhyme scheme in Chinese operas serving as the prelude to a complete score for voices obtains NGM agar plate after even.5-Fluorouracil (100mg/l) and OP50 suspension is added after agar plate is cooling, wherein wrapping
It is stand-by after 37 DEG C of cultivations for 24 hours containing certain density Dauricine (0,1,6.4,64 μM).
The measurement of nematode paralysis rate: by 30 by sodium hypochlorite synchronization process twice under L3 phase growth conditions
GMC101 (is overexpressedAβ protein) and wild type N2 nematode be put into different medicine wares, cultivated in 25 DEG C of constant incubators, daily
The animation of nematode in each NGM agar plate is observed in timing, continues one week, records simultaneously statistical result.
As a result as shown in figure 3, in wild type N2 nematode, the nematode paralysis rate that Dauricine and blank group is added is not present
Significant difference；In GMC101 nematode, after dosing 4d, compared to the blank group, nematode is substantially reduced after Dauricine is added
Paralysis rate；This show Dauricine in AD model have certain therapeutic effect.
Finally, it should be noted that above embodiments protect the present invention to illustrate technical solution of the present invention
The limitation of range, although the invention is described in detail with reference to the preferred embodiments, those skilled in the art should be managed
Solution, can modify to technical solution of the present invention or replace on an equal basis, without departing from technical solution of the present invention essence and
Range.
Claims (6)
1. application of the Dauricine in the drug of preparation treatment Alzheimer's disease mitochondria.
2. application as described in claim 1, which is characterized in that Dauricine raises mitochondrial membrane potential, lowers living in cell
Property oxygen concentration, raise cell in Bcl-2 expressing quantity.
3. a kind of for treating the drug for the treatment of Alzheimer's disease mitochondria, which is characterized in that including Dauricine.
4. drug as claimed in claim 3, which is characterized in that also include pharmaceutically acceptable auxiliary material.
5. drug as claimed in claim 3, which is characterized in that the dosage form of drug be tablet, paste, powder, decoction, pill or
Capsule.
6. a kind of construction method of Alzheimer's disease cell model, which is characterized in that first transfect APP base in neuronal cell
150 μM of Cu are added in cause after transfection2+And cultivate 2h.
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109893527A (en) * | 2018-12-10 | 2019-06-18 | 广州医科大学附属第二医院 | A kind of Src inhibitor and its application |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101961344A (en) * | 2009-07-23 | 2011-02-02 | 山东省生物药物研究院 | Drug composite and application thereof |
| CN104095849A (en) * | 2013-04-02 | 2014-10-15 | 中国医学科学院药物研究所 | Multiple-target effects of isoflavone derivative and its application in improvement of learning and memory |
| US20160106729A1 (en) * | 2014-01-03 | 2016-04-21 | Macau University Of Science And Technology | Group of Alkaloids, the Novel Autophagic Enhancers for Treatment of Cancers and Neurodegenerative Conditions Thereof |
| CN109953990A (en) * | 2017-12-26 | 2019-07-02 | 深圳长元知识产权服务有限公司 | Dauricine and its derivative are preventing or are treating the application in neurodegenerative disease |
-
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- 2018-10-26 CN CN201811262395.7A patent/CN109223786A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101961344A (en) * | 2009-07-23 | 2011-02-02 | 山东省生物药物研究院 | Drug composite and application thereof |
| CN104095849A (en) * | 2013-04-02 | 2014-10-15 | 中国医学科学院药物研究所 | Multiple-target effects of isoflavone derivative and its application in improvement of learning and memory |
| US20160106729A1 (en) * | 2014-01-03 | 2016-04-21 | Macau University Of Science And Technology | Group of Alkaloids, the Novel Autophagic Enhancers for Treatment of Cancers and Neurodegenerative Conditions Thereof |
| CN109953990A (en) * | 2017-12-26 | 2019-07-02 | 深圳长元知识产权服务有限公司 | Dauricine and its derivative are preventing or are treating the application in neurodegenerative disease |
Non-Patent Citations (1)
| Title |
|---|
| 费洪新等: "蝙蝠葛碱对阿尔茨海默病模型小鼠海马的影响", 《时珍国医国药》 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109893527A (en) * | 2018-12-10 | 2019-06-18 | 广州医科大学附属第二医院 | A kind of Src inhibitor and its application |
| CN109893527B (en) * | 2018-12-10 | 2021-08-24 | 广州医科大学附属第二医院 | Src inhibitor and application thereof |
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Application publication date: 20190118 |