CN106389410A - Application of piperlonguminine in preparation of drugs for treating Parkinson's disease - Google Patents
Application of piperlonguminine in preparation of drugs for treating Parkinson's disease Download PDFInfo
- Publication number
- CN106389410A CN106389410A CN201611090915.1A CN201611090915A CN106389410A CN 106389410 A CN106389410 A CN 106389410A CN 201611090915 A CN201611090915 A CN 201611090915A CN 106389410 A CN106389410 A CN 106389410A
- Authority
- CN
- China
- Prior art keywords
- cell
- roots
- grass
- medicine
- rotenone
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Classifications
-
- 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
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/357—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having two or more oxygen atoms in the same ring, e.g. crown ethers, guanadrel
- A61K31/36—Compounds containing methylenedioxyphenyl groups, e.g. sesamin
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention relates to the field of medicines, in particular to pharmaceutical new application of piperlonguminine. The pharmaceutical new application of the piperlonguminine is application in preparation of drugs with at least one function of 1 treating a central nervous system disease, 2 treating a rotenone induced Parkinson's disease model, 3 inhibiting cell apoptosis and 4 relieving dopamine neuron damage or protecting a dopaminergic neuron. The experiments prove that the piperlonguminine can inhibit cell apoptosis and protect the dopaminergic neuron so as to treat the central nervous system disease.
Description
Technical field
The present invention relates to drug world is and in particular to the bright peaceful alkali of the Bi roots of grass treats answering in Parkinsonian medicine in preparation
With.
Background technology
Parkinson's (Parkinson ' s disease, PD) are clinically one of modal nerve degenerative diseases, its
Main clinical manifestation is that static tremor, myotonia, bradykinesia and posture are unstable, and causes the main cause of these symptoms to exist
After involving central nervous system in the PD middle and later periods, disease optionally damages substantia nigra of midbrain dopaminergic neuron, leads to black substance
Dopaminergic neuron progressive denaturation lacks, thus leading to range of motion and non-motor symptoms.
Along with population in the world aging, the population incidence of disease of PD is in obvious ascendant trend.Epidemiological study is shown in
Chinese over-65s crowd's Parkinson's incidence of disease is close to 2%, and along with high disability rate, this drastically influence elderly population
The general level of the health and quality of life.Because the PD cause of disease is complicated and mechanism of causing a disease is unclear, therefore its treatment means also more has
Limit.The means of PD mainly have at present：Drug therapy, operative treatment, cell transplantation, transgenic technology etc., and circular for confirmation medical science
(evidence based medicine EBM) evidence shows, current drug therapy is still the most commonly used and maximally efficient controlling
Treatment method.EBM evidence shows that the choice drug of clinical treatment PD is still the Madopar with levodopa as main component, and it is main
Mechanism is to supplement the deficiency of dopamine and produce therapeutic action, substantially remains a kind of alternative medicine of property of suiting the medicine to the illness, but controls
Treatment has many limitation in itself, because L-dopa can enter the 1% of the amount deficiency taking dose of central nervous system, in a large number
The metabolism in periphery for the L-dopa can produce many drug side-effects, and due to this medicine can only symptomatic treatment to improve disease
Shape, the prognosis for patient is not obviously improved, the treatment means therefore remaining a kind of taking stopgap measures and not effecting a permanent cure, should with this medicine
With the prolongation of time and the increasing of dosage, its therapeutic action is less and less, and toxicity is increasing simultaneously.Therefore research and develop one
Kind there is more preferable curative effect and the medicine of more low toxicity side effect is strategic point problem to be solved in basis and clinic.
In recent years, to Chinese Traditional Medicine open and access, there are Research Prospects increasingly, numerous studies confirm Chinese Traditional Medicine
Can be by protecting nigral cell, improving neurotransmitter content, suppress the effects such as response to oxidative stress, reduction excitatory toxicity to reach
To the Parkinsonian purpose for the treatment of, and compared with Western medicine, Traditional Chinese Medicine medicine has relatively low toxic and side effect.
The Bi roots of grass is a kind of Piperaceae pepper platymiscium, its be dried maturescent fruit ear be in, cover, Tibetan medicine's Generally used, taste
Pungent, property is hot, be clinically used for treat stomach abdomen crymodynia, poor appetite, indigestion, kidney tremble with fear, tremble with fear the symptom such as rush down, vomit.Contain in the Bi roots of grass
There are abundant alkaloid, amide-type, lignanoids, the compound of terpene, sterols and other class, wherein alkaloid and amide-type
About 35 kinds, the wherein bright peaceful alkali of the Bi roots of grass is one of main monomer component in the Bi roots of grass.The bright peaceful alkali of the Bi roots of grass is have not been reported at present in document
Correlative study in terms of the treatment in the Parkinson disease model that rotenone induces of medicine monomer.
Content of the invention
It is an object of the invention to provide a kind of new medicine use of the bright peaceful alkali of the Bi roots of grass.
At least one of the new medicine use of the bright peaceful alkali of the Bi roots of grass provided by the present invention is that it has following 1) -4 in preparation)
Application in the medicine of function：(please examine and state herein, and guarantee to cover all of scope)
1) treat central nervous system disease；
2) Parkinson disease model for the treatment of rotenone induction；
3) inhibited apoptosis；
4) mitigate dopamine neuron to damage.
In above-mentioned application, described central nervous system disease concretely Parkinson's.
The present invention also provide a kind of comprise the bright peaceful alkali of the Bi roots of grass there are following 1) -4) at least one of function medicine system
Agent：
1) treat central nervous system disease；
2) Parkinson disease model for the treatment of rotenone induction；
3) inhibited apoptosis；
4) mitigate dopamine neuron to damage.
Said medicine preparation can be made into various forms of oral formulations, including：Capsule, tablet, granule, powder, ball
Agent, pill, sustained-release preparation, oral liquid, mixture and syrup.The medicine of above-mentioned various formulation all can be according to pharmaceutical field
Conventional method preparation.
With rotenone (Rotenone) damage model, that is, 100nM rotenone processes SK-N-SH clone and primary to the present invention
The cell model that neuron is formed is cell model.
Experiment proves：Add Rotenone (final concentration 100nM) 2 hours, add the bright peaceful alkali (final concentration 100nM) of the Bi roots of grass afterwards
Co-culture 24h with Rotenone.Cell viability is detected by the method for MTT, LDH, the result display bright peaceful alkali of the Bi roots of grass can be notable
Alleviate the cell viability decline that Rotenone causes；Cell mortality is detected by the method that PI/Hochest dyes, result shows
Show that the bright peaceful alkali of the Bi roots of grass can significantly alleviate the cell mortality rising that Rotenone causes；Caspase 3, Caspase 9 are lived
Power is detected, the result display bright peaceful alkali of the Bi roots of grass can significantly alleviate Apoptosis.
In order to further determine that the bright peaceful alkali of the Bi roots of grass pass through inhibited apoptosis thus to rotenone induction Parkinson's mould
Type plays therapeutic action, and the present invention adopts rotenone oral administration C57BL mouse animal model.
Above-mentioned modelling is to be administered orally, by 10mg/kg rotenone, the model being formed 6 weeks.Bi Ba Mingning alkali treatment group be
After rotenone is administered orally 6 weeks, treated within 4 weeks with 2mg/kg and 4mg/kg oral administration respectively.
Experiment proves：C57BL mouse is carried out with behaviouristics detection, the result display bright peaceful alkali of the Bi roots of grass can significantly alleviate trifoliate jewelvine
The Parkinson disease mice dyskinesia of ketone induction and hyposphresia, depressed non-motor symptoms；In corpus straitum and
Midbrain, is exempted to dopaminergic neuron Specific marker tyrosine hydroxylase (Tyrosine hydroxylase, TH)
Epidemic disease histochemical stain and the detection of protein immunoblot method, result shows that the bright peaceful alkali of the Bi roots of grass can resist the mould of rotenone induction
Type mouse TH positive neuron disappearance and the minimizing of nerve endings；By the method for efficient liquid phase (HPLC) to corpus straitum DOPA
Amine content is detected, result shows, the model mice striatal dopamine that the bright peaceful alkali of the Bi roots of grass can slow down rotenone induction contains
The decline of amount；Model mice brain tissue is carried out with Caspase 3, Caspase 9 viability examination, the result display bright peaceful alkali of the Bi roots of grass can
To alleviate the Apoptosis of rotenone induction.
Above-mentioned experiment shows, the bright peaceful alkali of the Bi roots of grass can protect dopaminergic neuron with inhibited apoptosis, thus treating
Central nervous system disease.
Brief description
Fig. 1 is the protective effect of the cell viability detecting the bright peaceful alkali pair of the Bi roots of grass on SK-N-SH cell and primary neuron.
It is illustrated as rotenone and processes 2h, treated using the bright peaceful alkali PLG of the 100nM Bi roots of grass, after co-culturing 24h, by MTT, LDH method
The cell viability of detection different pharmaceutical treatment group and cytotoxicity.
Fig. 2 is on SK-N-SH cell and primary neuron, detects each group cell mortality.It is illustrated as rotenone to process
2h, is treated using the bright peaceful alkali PLG of the 100nM Bi roots of grass, after co-culturing 24h, cell is carried out with PI/Hochest dyeing, PI dye is dead
Cell is redness, and Hochest dye total cell is blueness, and the value of statistics red/blue can be used to assess cell mortality.
Fig. 3 is on C57BL mouse, detects the non-athletic behavior such as mouse movement behavior and sense of smell, depression.It is illustrated as
After C57BL mouse rotenone 10mg/kg is administered orally 6 weeks, the bright peaceful alkali PLG of the oral Bi roots of grass carries out treating 4 weeks, and dosage is respectively 2mg/kg
And 4mg/kg.Afterwards mouse is carried out with transfer rod detection, the motor behavior of pole-climbing check and evaluation mouse, olfactometry, syrup preference is tried
Test detection to assess the non-athletic behavior of mouse.
Fig. 4 is corpus straitum and midbrain detection TH positive neuron and its tip taking C57BL mouse.It is illustrated as C57BL little
After mouse rotenone 10mg/kg is administered orally 6 weeks, the bright peaceful alkali PLG of the oral Bi roots of grass carries out treating 4 weeks, dosage respectively 2mg/kg and 4mg/
kg.Take mouse striaturn and midbrain, detect that TH positive neuron and nerve endings contain by the method for immunohistochemical staining
Amount.
Fig. 5 is corpus straitum and the midbrain detection TH protein content taking C57BL mouse.It is illustrated as C57BL mouse rotenone
After 10mg/kg is administered orally 6 weeks, the bright peaceful alkali PLG of the oral Bi roots of grass carries out treating 4 weeks, dosage respectively 2mg/kg and 4mg/kg.Take mouse
Corpus straitum and midbrain, detect TH protein level by the method for western blot.
Fig. 6 is to take C57BL mouse corpus straitum detection DOPAMINE CONTENT IN RABBIT.It is illustrated as C57BL mouse rotenone 10mg/kg to be administered orally
After 6 weeks, the bright peaceful alkali PLG of the oral Bi roots of grass carries out treating 4 weeks, and dosage is respectively 2mg/kg and 4mg/kg.Take mouse striaturn, pass through
The method detection DOPAMINE CONTENT IN RABBIT of efficient liquid phase.
Fig. 7 is detection Level of Apoptosis on SK-N-SH cell and primary neuron.It is illustrated as rotenone and process 2h,
Treated using the bright peaceful alkali PLG of the 100nM Bi roots of grass, after co-culturing 24h, collect cell by using caspase-3 and
Caspase-9 viability detection kit detection cell caspase-3 and caspase-9 vigor, thus assess Level of Apoptosis.
Fig. 8 is to take C57BL mouse midbrain, detection Caspase 3, Caspase 9 vigor.It is illustrated as C57BL mouse trifoliate jewelvine
After ketone 10mg/kg is administered orally 6 weeks, the bright peaceful alkali PLG of the oral Bi roots of grass carries out treating 4 weeks, dosage respectively 2mg/kg and 4mg/kg.Take little
Mouse midbrain, is lived using caspase-3 and caspase-9 viability detection kit detection cell caspase-3 and caspase-9
Power, thus assess Level of Apoptosis.
Specific embodiment
Below by specific embodiment, the present invention will be described, but the invention is not limited in this.
Experimental technique used in following embodiments if no special instructions, is conventional method；Institute in following embodiments
Reagent, biomaterial etc., if no special instructions, all commercially obtain.
Used in following embodiments, clone is as follows：
SH-SY5Y clone：People's dopaminergic nerve blastoma cell (ATCC, this room is frozen) (American Type
Culture Collection) article No. CRL-2266TM；
SPF level SD tire mouse：The SD tire mouse of gestational age 13.5d, purchased from Beijing animal used as test company of dimension tonneau China.
Test method in following embodiments is as follows：
1. the mensure (mtt assay) of cell viability
(1) use trypsin digestion and cell；
(2) fully blow and beat cell with suction pipe so as to from wall, be prepared into single cell suspension；
(3) or using white blood cell count(WBC) plate cell is counted；
(4) according to 2-3 × 104The density in/hole, the single cell suspension of SK-N-SH is added to 96 orifice plates by the cell volley of rifle fire
In, prepared with carrying out MTT experiment；
(5) individual group is carried out after respective handling, to each hole add MTT (5mg/ml) 10 μ l, 37 DEG C, 5%CO2Incubator continues
Continuous culture 4h；
(6) inhale and abandon culture medium, every hole adds 100 μ l DMSO, vibrate 10 minutes, so that particle is completely dissolved；
(7) orifice plate is placed in ELIASA, reads the absorbance at 490nm wavelength, statistics mapping.
2. lactic dehydrogenase release rate assay (LDH method)
(1) adjustment cell concentration plants the corresponding orifice plate in 96 orifice plates according to experimental design.1‐1.5×104Individual cell/
Hole, every hole 50 μ l；
(2) after cell attachment, every hole adds assay medium50 μ l afterwards to wash cell 2 times with assay medium；
(3) take medicine stoste to be measured to be diluted to the concentration of experimental design, add respective concentration in each experimental design hole
Medicine 50 μ l；
(4) 37 DEG C, 5%CO2Incubation 12 hours；
(5) Rotenone 100nM is added to continue incubation 24 hours；
(6) add lysis solution 5 μ l reaction 15min in high control group；
(7) every hole adds 100 μ l reaction mixture (now to join 250 μ l catalyst+11.25ml dye
Solution) room temperature reaction 30min, lucifuge；
(8) every hole adds 50 μ l stop solution terminating reactions；
(9) ELIASA 490nm reads absorbance analysis.
3.PI/Hochest dyes
(1) cell takes out in incubator, is inhaled with Pasteur pipe and abandon culture medium in aseptic super-clean bench；
(2) with PBS liquid washed cell, to remove residual media and serum composition, inhale and abandon PBS liquid；
(3) add the 0.5ml cell dissociation buffer of 37 DEG C of preheating in blake bottle so as to fully and cells contacting, inhale to abandon and disappear
Change liquid, observation of cell under inverted microscope, treat that cell process bounces back, cell space starts to become bowlder, adds 1ml DMEM immediately, with end
Only pancreatin digestion；
(4) fully blow and beat cell with suction pipe so as to from wall, be prepared into single cell suspension；
(5) according to cell density, cell is inoculated in 96 orifice plates, 37 DEG C of incubations；
(6) reach 70% to cell density, rotenone group adds the every hole of 100nM Rotenone 100 μ l, PLG group and CSA
Group is treated after Rotenone process for two hours, and 37 DEG C are incubated 24 hours；
(7) inhale and abandon culture medium, dilute PI with culture medium, hochest to 10 μM/ml, every hole adds 100 μ l, is incubated 30 minutes,
Using the detection of high intension analysis system.
4. SABC step：
(1) animal is fixed through perfusion, takes brain immediately, successively puts in 4% paraformaldehyde solution containing 20%, 30% sucrose
After fix 4 DEG C overnight；
(2) frozen section, 40 μm, section is put in 0.01M PBST liquid (pH7.2-7.5) and is waited to contaminate；
(3) cut into slices and embathe three times in 0.01M PBST liquid, 5min；
(4) cut into slices into 1N hydrochloric acid, antigen retrieval 30min, room temperature；
(5) cut into slices and embathe three 10min into PBST；
(6) cut into slices and eliminate the active 10min of endogenous peroxydase into 3%H2O2；
(7) cut into slices and embathe three times into PBST, each 10min；
(8) cut into slices and close 1h, room temperature (suppression unspecific staining) into 5% normal sheep serum, abandon serum, section is unclear
Wash, directly enter an anti-TH (0.01M PBST dilution) of suitable dilution, 4 DEG C of incubation is overnight；
(9) cut into slices and embathe three times into PBST, each 5min；
(10) cut into slices into 1:Anti- (the 0.01M PBST dilution) 2-3h of the II of 300 biotin labelings, room temperature；
(11) cut into slices and embathe three times into PBST, each 5min；
(12) cut into slices into 1:The strepto- avidin III of 300 horseradish enzyme marks resists (0.01M PBST dilution) 2-3h, room temperature；
(13) cut into slices and embathe three times into PBST, each 5min；
(14) cut into slices into DAB colour developing, 5-10min, room temperature；
(15) cut into slices into flowing water, fully embathe；
(16) cut into slices and mount piece in 0.01M PB liquid, spontaneously dry；
(17) the up dehydration of section, transparent, sealing.
The bright peaceful alkali PLG of embodiment 1, the Bi roots of grass suppresses the cellular damage of rotenone induction.
1st, primary neuronal cell vigor is detected by the method for MTT.
Mtt assay is a kind of method of detection cell survival and growth.Its Cleaning Principle is the amber in living cells mitochondria
Acidohydrogenase can make exogenous MTT be reduced to water-insoluble bluish violet crystallization first a ceremonial jade-ladle, used in libation (Formazan) and be deposited in cell,
And dead cell no this function.Dimethyl sulfoxide (DMSO) (DMSO) can dissolve the first a ceremonial jade-ladle, used in libation in cell, with enzyme-linked immunosorbent assay instrument in 540nm ripple
Strong point measures its absorbance value, can indirectly reflect living cells quantity.In the range of certain cell number, MTT crystallization formed amount with
Cell number is directly proportional, and that is, light absorption value is bigger, and its activity is stronger.
2nd, primary neuronal cell toxicity is detected by the method for LDH.
LDH (lactic dehydrogenase) is stable cytoplasm enzyme, exists in all of cell, is released quickly against when after birth damages
In cell culture fluid.LDH activity passes through two enzymic catalytic reactions：LDH Oxidation of Lactic salt generates acetonate, then acetonate
React with tetrazolium salts INT and generate first (formazan) crystallization.Increase in nutrient solution for first (formazan) crystallization content, with cracking
Cell number increase directly related.First (formazan) crystalline dye is water-soluble, can be with spectrophotometer in 500nm wavelength
Detection.By detecting the activity of LDH in cells and supernatant, can determine whether that this analysis of degree of cell damage is sensitive, convenient, smart
Really it is adaptable to many plant cytotoxicity analysis.
3rd, the primary neuronal cell death rate is detected by the method that PI/Hochest dyes.
Hochest33342 is a kind of blue specific dye being combined with cell DNA, can penetrate living cells film, therefore energy
Mark living cells and dead cell.And PI dyestuff is to enter in the complete cell of cell membrane, that is, living cells is to PI (iodate third
Pyridine) dyestuff is refused to contaminate, and non-viable non-apoptotic cell is i.e. damaged in early stage due to film integrality, can be sent red fluorescence by PI dyeing.
According to these characteristics, it is often used in detection cell death ratio with the double dyeing of PI/Hoechst.Its ratio is bigger, shows cell
The death rate is higher.
4th, experimental result
After primary neuron 2h at 100nM rotenone, treated with the bright peaceful alkali PLG of the 100nM Bi roots of grass, be more jointly incubated
24h, after carry out MTT cell viability detection and LDH cytotoxicity detection.Experimental result shows, primary nerve after rotenone process
The cell viability of unit all substantially reduces and cytotoxicity substantially increases, and PLG treatment group then has clear improvement.
On primary neuron, the method using the double dye of PI/Hochest have detected cell mortality, and PI can contaminate extremely thin
Born of the same parents, take on a red color, and Hochest can contaminate total cell number, au bleu, calculate red/blue and can obtain cell mortality.Result shows
Show, after rotenone processes cell, cell mortality substantially increases, and all have improvement after PLG treatment.
The bright peaceful alkali PLG of embodiment 2, the Bi roots of grass alleviates the behaviouristics obstacle of Parkinson disease mice of rotenone induction and many
Bar amine lacks
1st, the Parkinson's being induced by transfer rod detection, pole-climbing detection, olfactometry, syrup preference check and evaluation rotenone
The behaviouristics of model mice
Turn-club test and Grasping clubglass test are usually used in detecting the mouse movement coordination ability and anti-fatigue ability.Transfer rod instrument is tested
Animal is placed on coarse cylinder and avoids landing, after rotating cylinder, if animal landing is got off, will stop following corresponding
Sensor simultaneously records result automatically.Grasping clubglass test is the baton round of an a diameter of 2.5cm to be fixed on a long 60cm, slightly
The rod top of 1cm, rod is wrapped with gauze to be prevented from skidding.Mouse is positioned over rod top, record mouse is from rod top
Return to the time on ground.Time is shorter, represents that the mouse movement coordination ability is stronger.
Food embedded experiment is usually used in mouse olfactometry.Mouse is taken food 14h before carrying out olfactometry, during detection, will
1mm3Food buries at 0.5cm under the mouse cage bedding and padding to be detected, and mouse is put into mouse cage central authorities to be detected, and record mouse is from putting into
Mouse cage is to the time finding food.The search of food time is shorter, represents that mouse sense of smell ability is better.
The experiment of syrup preference is usually used in detecting that mouse is depressed.During experiment, two bottles of water are put in mouse cage, one bottle is from the beginning
Water, another bottle is 1% sucrose water, voluntarily drinks 1h by mouse, and the other amount of drinking of two bottles of moisture of record, calculates SP value=sugar afterwards
The water yield/(syrup amount+pure water amount) * 100%, SP value is less, represents that mouse Degree of Depression increases.
2nd, striatal dopamine levels are detected by the method for efficient liquid phase
Take rapidly brain tissue after removing mouse broken end, separate striatum, for detecting DA content.During mensure, accurately claim
Take brain weight, by mass volume ratio 1:19 19 times of sample treatment liquid (500ml water+14.35ml perchloric acid+5.5ml of addition
200 μ g/ml DHBA+90mg EDTA), the tissue homogenate of homogenate preparation on ice 5%, 4 DEG C of centrifugation 20min of 12000r/min,
Take supernatant to cross 0.22 μm of filter membrane to be used for detecting.
3rd, midbrain and striatal TH positive neuron and nerve endings are detected by the method for SABC
SABC, is applied immunology general principle antigen-antibody reaction, and that is, antigen is combined with antibody specificity
Principle, histocyte endoantigen is determined by the chromogenic reagent that chemical reaction makes labelled antibody, it is carried out position, fixed
Property and the research of relative quantification.In this experiment, by SABC, mouse midbrain and corpus straitum TH are dyeed, to assess midbrain and
Striatal dopaminergic neuron and nerve endings content.
4th, experimental result
This animal used as test is C57BL mouse, and rotenone qf oral administration dosage is 10mg/kg, is administered six weeks, carries out every two weeks
Behaviouristics detection.Behaviouristics result shows, after rotenone is processed, mouse body weight reduces compared with control group, and motion energy
Power declines, depressed, the symptom such as hyposphresia.
Mouse rotenone oral administration, after six weeks, is administered orally and is treated to the bright peaceful alkali PLG of the Bi roots of grass, and dosage is 2mg/kg,
4mg/kg, is administered 4 weeks.Carry out a behaviouristics detection every two weeks.And after PLG treatment, treatment group mouse relatively damage group motion barrier
Hinder, hyposphresia, depression all has different degrees of alleviation.
By the method for efficient liquid phase, mouse Striatal Dopamine Content is detected, result shows damage group mouse
DA content substantially reduces compared with control group, and PLG treatment group makes moderate progress.
TH dyeing is carried out by the method for SABC to corpus straitum and two positions of substantia nigra of midbrain, result shows rotenone
After process, Mice brain tissues line body and black substance position TH level substantially reduce compared with control group, and PLG treatment has clear improvement.
Claims (9)
1. application in the medicine of preparation treatment central nervous system disease for the bright peaceful alkali of the Bi roots of grass.
2. application according to claim 1, described central nervous system disease is Parkinson's.
3. the application in the medicine of the Parkinson disease model in preparation treatment rotenone induction for the bright peaceful alkali of the Bi roots of grass.
4. application in the medicine preparing inhibited apoptosis for the bright peaceful alkali of the Bi roots of grass.
5. the bright peaceful alkali of the Bi roots of grass mitigates the application in the medicine that dopamine neuron damages in preparation.
6. a kind of medicine treating central nervous system disease, it comprises the bright peaceful alkali of the Bi roots of grass.
7. a kind of medicine of the Parkinson disease model treating rotenone induction, it comprises the bright peaceful alkali of the Bi roots of grass.
8. a kind of medicine of inhibited apoptosis, it comprises the bright peaceful alkali of the Bi roots of grass.
9. a kind of medicine mitigating dopamine neuron damage, it comprises the bright peaceful alkali of the Bi roots of grass.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201611090915.1A CN106389410A (en) | 2016-12-01 | 2016-12-01 | Application of piperlonguminine in preparation of drugs for treating Parkinson's disease |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201611090915.1A CN106389410A (en) | 2016-12-01 | 2016-12-01 | Application of piperlonguminine in preparation of drugs for treating Parkinson's disease |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN106389410A true CN106389410A (en) | 2017-02-15 |
Family
ID=58084291
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201611090915.1A Pending CN106389410A (en) | 2016-12-01 | 2016-12-01 | Application of piperlonguminine in preparation of drugs for treating Parkinson's disease |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN106389410A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112675221A (en) * | 2021-01-05 | 2021-04-20 | 首都医科大学 | Application of long pepper total alkaloids and piperine in preparation of adjuvant therapy medicines for Parkinson's disease |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101791336A (en) * | 2010-04-08 | 2010-08-04 | 首都医科大学 | Extract from long pepper and preparation method and application thereof |
-
2016
- 2016-12-01 CN CN201611090915.1A patent/CN106389410A/en active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101791336A (en) * | 2010-04-08 | 2010-08-04 | 首都医科大学 | Extract from long pepper and preparation method and application thereof |
Non-Patent Citations (5)
| Title |
|---|
| 《BRAIN RESEARCH》 * |
| 《JOURNAL OF CHROMATOGRAPHY B》 * |
| 《PHARMACEUTICAL BIOLOGY》 * |
| HAO WANG等: "Protection effect of piperine and piperlonguminine from Piper longum L. alkaloids against rotenone-induced neuronal injury", 《BRAIN RESEARCH》 * |
| WEI YANG等: "Neuroprotective effects of piperine on the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced Parkinson"s disease mouse model", 《INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE》 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112675221A (en) * | 2021-01-05 | 2021-04-20 | 首都医科大学 | Application of long pepper total alkaloids and piperine in preparation of adjuvant therapy medicines for Parkinson's disease |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Limón et al. | Neuroprotective effect of alpha-asarone on spatial memory and nitric oxide levels in rats injected with amyloid-β (25–35) | |
| Guo et al. | Therapeutic time window and underlying therapeutic mechanism of breviscapine injection against cerebral ischemia/reperfusion injury in rats | |
| Wang et al. | Protection effect of piperine and piperlonguminine from Piper longum L. alkaloids against rotenone-induced neuronal injury | |
| CN102961375B (en) | AMPK (Adenosine Monophosphate Activated Protein Kinase) activating agent and application thereof in preparation of medicaments for treating diabetes mellitus and/or diabetic complication | |
| Lin et al. | β-Sitosterol protects against myocardial ischemia/reperfusion injury via targeting PPARγ/NF-κB signalling | |
| Sohn et al. | The anti-inflammatory and antifibrosis effects of anthocyanin extracted from black soybean on a Peyronie disease rat model | |
| KR20070008089A (en) | Pharmaceutical composition for the prevention and treatment of liver disease comprising a lonicera caerulea l. var. edulis extract | |
| KR100539627B1 (en) | Remedies for allergic diseases and process for producing the same | |
| CN106389410A (en) | Application of piperlonguminine in preparation of drugs for treating Parkinson's disease | |
| CN112933117A (en) | Medicine for preventing and/or treating Parkinson's disease and application thereof | |
| US11638736B2 (en) | Compositions for preventing or treating diseases or disorders associated with neuro-inflammation, neuro-apoptosis, or neuro- oxidative damage and uses thereof | |
| CN105497059B (en) | A kind of Herba Dendrobii extract and the compound of iron and the preparation method and application thereof | |
| CN102716142A (en) | Application of icariin to preparation of medicine for treating parkinsonism | |
| CN101361728B (en) | Salvianolic acid A injection and preparation method thereof | |
| CN109289009A (en) | A kind of Chinese medicine composition and its preparation method and application | |
| CN102727499A (en) | Application of compound 6-furfurylaminopurine in preparations of anti-vascular dementia drugs | |
| CN112007058A (en) | Application of oroxylum indicum as antioxidant stress injury agent | |
| CN107213160A (en) | Applications of the NADPH in agonist drug causes mitochondrial toxicity | |
| TWI359669B (en) | ||
| WO2017121333A1 (en) | Use of cistanche tubulosa extract and isoacteoside in protection of muscles | |
| WO2017020861A1 (en) | Application of polygonum capitatum composition in resisting helicobacter pylori | |
| JP2023536957A (en) | Allergen preparation | |
| CN111494379A (en) | Application of piperine in improving early olfactory disorder of Parkinson's disease | |
| WO2016131320A1 (en) | Use of nadph in preparing medicines for treatment of heart diseases | |
| WO2004006946A1 (en) | Composition comprising the crude extract of the fruit of morus alba l having neuro-protective activity |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| RJ01 | Rejection of invention patent application after publication | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20170215 |