CN108186637A - A kind of application of isorhynchophylline in the drug with neuroprotection is prepared - Google Patents
A kind of application of isorhynchophylline in the drug with neuroprotection is prepared Download PDFInfo
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- CN108186637A CN108186637A CN201810022687.7A CN201810022687A CN108186637A CN 108186637 A CN108186637 A CN 108186637A CN 201810022687 A CN201810022687 A CN 201810022687A CN 108186637 A CN108186637 A CN 108186637A
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- drug
- isorhynchophylline
- neuroprotection
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- 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
- A61K31/438—The ring being spiro-condensed with carbocyclic or heterocyclic ring systems
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Abstract
The present invention provides a kind of application of isorhynchophylline in the drug with neuroprotection is prepared; drug provided by the invention with neuroprotection; toxic effects of the neurotoxin MPTP to dopaminergic neuron can effectively be saved; there is protective effect to dopaminergic neuron; antihypertensive effect, the effect of extension blood vessel and the effect of reducing heart rate common compared to isorhynchophylline; the present invention develops a kind of new application of isorhynchophylline, and the neuropharmacology for further Study of Traditional Chinese Medicine material uncaria provides theoretical foundation and experiment basis；Further, isorhynchophylline is that the exploitation for the treatment of anti-parkinson drug, anti-depression drug, treatment Alzheimer disease drugs provides new thinking and possibility；Especially as the drug for the treatment of Parkinson's disease, effect is especially prominent.
Description
Technical field
The invention belongs to field of natural medicinal chemistry, are related to a kind of isorhynchophylline and are preparing the medicine with neuroprotection
Application in object.
Background technology
Uncaria is the evergreen liana of Rubiaceae wild gambier, climbs up by holding on to shape shrub, and stem branch square column type is very thin hairless, leaf papery
It is oval, capitulum.Uncaria is used as medicine with the stem branch of buckle, it has The flat liver of heat-clearing, dispelling wind and relieving convulsion effect, modern pharmacology reality
It tests and also confirms that uncaria has antihypertensive effect, therefore with very high medical value.Before research shows that uncaria decoction, ethyl alcohol extraction
Object, Rhomotoxine mitrinermine, no matter to anesthetized animal or not anesthetized animal, intact animal or hypertension animal, no matter also quiet
Arteries and veins injection or gastric infusion have antihypertensive effect.In addition to this uncaria also there is calm and anticonvulsant action, rhynchophyllin can have
Effect inhibits the drug effects such as the breathing of the frog and mouse and the effect of diminution pupil.Wherein, the following institute of isorhynchophylline structure in rhynchophyllin
Show：
Monoamine oxidase (monoamine oxidase, MAO) is naturally occurring a kind of enzyme in human body, is catalyzed monoamine
The enzyme of substance oxidative deamination.Human body is included there are two types of monoamine oxidase：Monoamine oxidase A and monoamine oxidase B.Monoamine oxygen
Change enzyme A to be mainly distributed in catecholaminergic neuron；Monoamine oxidase B is mainly distributed on serotoninergic neuron, histamine
In serotonergic neuron and Deiter's cells, both hypotypes all can inactivate monoamine neurotransmitter.And monoamine oxidase
Inhibitor then can by inhibiting the oxidation activity to Monoamines of monoamine oxidase, so as to reach mitigation or eliminate by
Monoamines caused by a variety of causes reduce or the excessively high caused disease of activity of monoamine oxidase, and act on monoamine oxidase
Drug then have treatment depression, Parkinson's disease, the effect of Alzheimer disease.At present, some researches show that isorhynchophylline energy
It is substantially reduced the activity of MAO-A.
Therefore, the new application of isorhynchophylline how is further developed, this has the medicine exploitation of relevant disease
Significance.
Invention content
The purpose of the present invention is to provide a kind of application of isorhynchophylline in the drug with neuroprotection is prepared.
To reach the invention purpose, the present invention uses following technical scheme：
The present invention provides a kind of application of isorhynchophylline in the drug with neuroprotection is prepared.
In the present invention, isorhynchophylline can effectively save neurotoxin MPTP and the toxicity of dopaminergic neuron is made
With, have protective effect to dopaminergic neuron, the antihypertensive effect common compared to isorhynchophylline, extend blood vessel effect and subtract
The effect of slow heart rate, the present invention develop a kind of new application of isorhynchophylline, are the neural medicine of further Study of Traditional Chinese Medicine material uncaria
Reason provides theoretical foundation and experiment basis.
Further, isorhynchophylline can effectively invert the death of dopaminergic neuron, and dopaminergic neuron is played
Good protective effect is carried for treatment anti-parkinson drug, anti-depression drug, the exploitation for the treatment of Alzheimer disease drugs
New thinking and possibility are supplied, especially as the drug for the treatment of Parkinson's disease, effect is more prominent.
Preferably, the drug with neuroprotection is the drug for treating Alzheimer disease.
Preferably, the drug with neuroprotection is the drug for treating depression.
Preferably, the drug with neuroprotection is the drug for treating Parkinson's disease.
Preferably, the drug with neuroprotection is that norepinephrine and/or serotonin are expressed
There is the drug of agonistic effects.
In the present invention, the drug with neuroprotection can significantly increase norepinephrine and/or 5- hydroxyl colors
The expression of amine.
Preferably, the drug with neuroprotection is the drug for acting on monoamine oxidase.
Preferably, the monoamine oxidase includes monoamine oxidase-A and/or monoamine oxidase-B.
Preferably, the monoamine oxidase is monoamine oxidase-A.
In the present invention, the drug with neuroprotection can reduce or inhibit the table of monoamine oxidase MAO-A
Up to activity, neuroprotection has been given play to, and then the possibility for the treatment of Parkinson's disease can be provided.
Preferably, the dosage form of the drug with neuroprotection includes appointing in tablet, capsule or granule
It anticipates a kind of or at least two combinations.
Relative to the prior art, the invention has the advantages that：
Application of the isorhynchophylline provided by the invention in the drug with neuroprotection is prepared, wherein isorhynchophylline
Toxic effects of the neurotoxin MPTP to dopaminergic neuron can be effectively saved, has protection to make to dopaminergic neuron
With the antihypertensive effect common compared to isorhynchophylline extends the effect of blood vessel, the effect of reducing heart rate, and the present invention develops one
The new application of kind isorhynchophylline, the neuropharmacology for further Study of Traditional Chinese Medicine material uncaria provide theoretical foundation and experiment basis.
Application of the isorhynchophylline provided by the invention in the drug with neuroprotection is prepared, has neuroprotection
The drug of effect has good effect in terms for the treatment of Parkinson's disease, Alzheimer disease, depression；Isorhynchophylline can be effective
The death of dopaminergic neuron is inverted, good protective effect is played to dopaminergic neuron, especially as treatment
The drug of Parkinson's disease, effect is especially prominent, and the drug new for exploitation provides new thinking and may.
Description of the drawings
Fig. 1 is control group test chart during the neuroprotection of the embodiment of the present invention 1 is tested.
Fig. 2 is MPTP group test charts during the neuroprotection of the embodiment of the present invention 1 is tested.
Fig. 3 is deprenyl group and MPTP mixing group group test charts during the neuroprotection of the embodiment of the present invention 1 is tested.
Fig. 4 is isorhynchophylline Z2 and MPTP mixing group test chart during the neuroprotection of the embodiment of the present invention 1 is tested.
Specific embodiment
The technical solution further illustrated the present invention below by specific embodiment.Those skilled in the art should be bright
, the embodiment be only to aid in understand the present invention, be not construed as to the present invention concrete restriction.
Embodiment 1
The present embodiment verifies the neuroprotection of isorhynchophylline by following experimental procedure
At dopaminergic neuron specificity toxin MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) 40 μ g/ml
The after fertilization zebrafish embryo of 1-3 days is managed, using the deprenyl (Deprenyl) of 20 μ g/mL as positive control, adds in 20 μM
Isorhynchophylline (being represented with Z2), be that probe does in situ hybridization with dopaminergic neuron specific marker gene dat, measure knot
Fruit.
As a result such as Fig. 1 (control group), Fig. 2 (MPTP groups), Fig. 3 (deprenyl group and MPTP mixing group) and Fig. 4 (different uncarias
Alkali Z2 and MPTP mixing group) shown in.Being compared from figure can be concluded that, Z2 can effectively invert dopamine caused by MPTP
The death of serotonergic neuron.Generally, it is considered that caused by Parkinson's disease is the death because of dopaminergic neuron, and dat is DOPA
The label sets gene of aminergic neuron, therefore the death of Z2 reversion dopaminergic neurons, illustrate isorhynchophylline as pa gold
The medicine of gloomy disease, there is good therapeutic effect.
Embodiment 2
The present embodiment does in situ hybridization detection dopaminergic neuron with dat probes, observes after fertilization by following experiment
Dopamine neuron quantity changes before and after the zebrafish embryo dosing of 3 days.
A, 0.1%PTU is added in into control group embryo and removes depigmentation；
B, MPTP handles embryo 48 hours；
C, positive control medicine Deprenyl and MPTP coprocessing embryo is added in 48 hours；
D, MPTP and Z2 processing embryo.
It is obtained by experiment, the normal expression of A group diencephalon dopaminergic neurons；B group diencephalon dopaminergic neurons are a large amount of
It is dead；C groups dopaminergic neuron is compared with B groups and is considerably increased；There is notable recovery than dopaminergic neuron with C groups,
And the protecting effect of Z2 is more preferable.
It can be concluded that by above-mentioned experiment, isorhynchophylline being capable of dopaminergic nerve caused by effective protection MPTP
The loss of member, isorhynchophylline have excellent neuroprotection.
Due to the neuroprotection of isorhynchophylline, this provides the foundation for the treatment for Parkinson's disease.
Applicant states that the present invention illustrates that the isorhynchophylline of the present invention in preparation there is nerve to protect by above-described embodiment
Application in the drug of shield effect, but the invention is not limited in above-mentioned processing steps, that is, do not mean that the present invention has to rely on
Above-mentioned processing step could be implemented.Person of ordinary skill in the field is it will be clearly understood that any improvement in the present invention, to this hair
The equivalence replacement of bright selected raw material and the addition of auxiliary element, the selection of concrete mode etc. all fall within the protection model of the present invention
Enclose within the open scope.
Claims (9)
1. a kind of application of isorhynchophylline in the drug with neuroprotection is prepared.
2. application according to claim 1, which is characterized in that the drug with neuroprotection is for treating
The drug of Alzheimer disease.
3. application according to claim 1 or 2, which is characterized in that the drug with neuroprotection be for
Treat the drug of depression.
4. application according to any one of claim 1-3, which is characterized in that the drug with neuroprotection
To be used to treat the drug of Parkinson's disease.
5. according to the application described in any one of claim 1-4, which is characterized in that the drug with neuroprotection
To there is the drug of agonistic effects for norepinephrine and/or serotonin expression.
6. application according to any one of claims 1-5, which is characterized in that the drug with neuroprotection
To act on the drug of monoamine oxidase.
7. application according to claim 6, which is characterized in that the monoamine oxidase include monoamine oxidase-A and/or
Monoamine oxidase-B.
8. the application described according to claim 6 or 7, which is characterized in that the monoamine oxidase is monoamine oxidase-A.
9. according to the application described in any one of claim 1-8, which is characterized in that the drug with neuroprotection
Dosage form include tablet, capsule or granule in any one or at least two combination.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810022687.7A CN108186637A (en) | 2018-01-10 | 2018-01-10 | A kind of application of isorhynchophylline in the drug with neuroprotection is prepared |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810022687.7A CN108186637A (en) | 2018-01-10 | 2018-01-10 | A kind of application of isorhynchophylline in the drug with neuroprotection is prepared |
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| CN108186637A true CN108186637A (en) | 2018-06-22 |
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| CN201810022687.7A Pending CN108186637A (en) | 2018-01-10 | 2018-01-10 | A kind of application of isorhynchophylline in the drug with neuroprotection is prepared |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114404412A (en) * | 2022-03-03 | 2022-04-29 | 中国人民解放军军事科学院军事医学研究院 | Application of uncaria active compound in preparation of medicine for preventing and/or treating mental disorder diseases |
| CN116077563A (en) * | 2022-11-25 | 2023-05-09 | 黑龙江儒泰科技发展有限责任公司 | Traditional Chinese medicine composition for treating liver and kidney deficiency type depression and preparation method thereof |
-
2018
- 2018-01-10 CN CN201810022687.7A patent/CN108186637A/en active Pending
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114404412A (en) * | 2022-03-03 | 2022-04-29 | 中国人民解放军军事科学院军事医学研究院 | Application of uncaria active compound in preparation of medicine for preventing and/or treating mental disorder diseases |
| CN114404412B (en) * | 2022-03-03 | 2023-09-05 | 中国人民解放军军事科学院军事医学研究院 | Application of uncaria active compound in preparing medicament for preventing and/or treating mental disorder diseases |
| CN116077563A (en) * | 2022-11-25 | 2023-05-09 | 黑龙江儒泰科技发展有限责任公司 | Traditional Chinese medicine composition for treating liver and kidney deficiency type depression and preparation method thereof |
| CN116077563B (en) * | 2022-11-25 | 2023-10-10 | 黑龙江儒泰科技发展有限责任公司 | Traditional Chinese medicine composition for treating liver and kidney deficiency type depression and preparation method thereof |
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Application publication date: 20180622 |