CN107281206A - Black cohosh root glycosides is preparing the application in preventing and treating senile dementia medicine - Google Patents
Black cohosh root glycosides is preparing the application in preventing and treating senile dementia medicine Download PDFInfo
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Abstract
The invention discloses a kind of medicine for preventing and treating senile dementia, it is that the drug regimen by black cohosh root glycosides or comprising black cohosh root glycosides is prepared from.Through experimental studies have found that, black cohosh root glycosides may protect A β25‑35Damage to SH SY5Y cells, increases the survival of SH SY5Y cells, improves injection D galactolipin joint hippocampal injection A β AD Cognition Function in Rats obstacles.The black cohosh root glycosides of the present invention has definite curative effect to various senile dementias such as preventing and treating Alzheimer disease, vascular dementias.
Description
Technical field
The present invention relates to application of the black cohosh root glycosides in the medicine for preventing and treating senile dementia, health products are prepared, category
Field of medicaments category.
Background technology
Increasingly serious with world population ages, many diseases such as senile dementia relevant with aging etc. has turned into
Today's society seriously threatens the healthy factor of the elderly.The incidence of disease of senile dementia is in continuous ascendant trend, at present should
Disease turns into the fourth-largest cause of disease (being only second to heart disease, tumour and apoplexy) for jeopardizing the elderly's life, as current gerontology
One of the problem of facing the severeest.
Senile dementia mainly includes Alzheimer disease (AD) and vascular dementia (VD), and Alzheimer disease accounts for 60
~70%, vascular dementia accounts for 20~30%.Alzheimer disease（Alzheimer ’s disease, AD）Be it is a kind of with
The degenerative disease of central nervous system based on progressive dementia.Its Clinical symptoms is to remember and other cognition dysfunctions,
Early clinic symptom includes motion, felt or coordination function defect.The main pathological change of AD patient is extracellular amyloid
Albumen precipitation formation senile plaque expelling, the missing of NFT and extensive synapse, inflammation, oxidation are even bad
Extremely.
According to the World Health Organization（WHO）With international Alzheimer disease association（ADI）Statistics, the whole world is with dementia at present
Patient estimate 47,000,000 or so, wherein patients with Alzheimer disease constitutes about 60%-70%.This numeral increases for estimated every 20 years
Long 1 times, i.e., some corner of every 4 seconds earth occurs as soon as a new dull-witted case.Dull-witted illness rate and huge consuming is given
Society and scientific research can also fundamentally treat Alzheimer with huge challenge, but up to the present without a kind of medicine
Disease, researchers are had suffered repeated defeats during the last ten years, are fought repeatedly after suffering repeated defeats.
AD pathogenesis is complicated, at present both at home and abroad still without can treat AD medicine at all, therefore early treatment is to closing again
Will.The medicine listed at present is broadly divided into two kinds, and one kind is anticholinesterase, such as Doneppezil Hydrochloride, Garland
His quick, rivastigmine, huperzine are first-class；Another is excitatory amino acid receptor antagonists, such as memantine.Separately
There are anti-inflammatory, anti-oxidant, anti-cholesterol, anti-beta amyloid class medicine to be used for AD auxiliary treatment.Said medicine can improve in short term
The symptom of AD patient, but advancing of disease can not be alleviated, and resistance is easily formed, adverse reaction is obvious；And traditional Chinese medicine is light in preventing and treating
Degree cognitive disorder and senile dementia have preferable clinical effectiveness, have multipath, the characteristics of too many levels is integrally-regulated, and use
The toxic side effect of natural drug is small.Therefore, the extraction of traditional Chinese medicine monomer or its active principle has very heavy applied to AD preventing and treating
The meaning wanted.
Black cohosh root（black cohoch）It is the perennial wild flower that a class originates in America northeast, also known as total shape class leaf liter
Fiber crops（Original name rattleroot, Cimicifuga racemosa）, ranunculaceae plant is most study most deep medicine in Rattleroot
Use plant.Acrid-sweet flavor, warm-natured, return lung, bladder two are passed through, and deliver cold dispelling effect, and Black Cohosh P.E is clinically used for improving menopause
Afterwards woman vagina atrophy symptom, alleviate perimenopausal syndrome etc..Modern pharmacological research shows that its triterpenoid saponins is treated
Climacteric syndrome safely and effectively, can be widely used in clinic at present as HRT medicine.But so far,
It there are no the relevant report that Black Cohosh P.E prevents and treats senile dementia.Black cohosh root element glycosides (Cimicifugoside), No. CAS is
66176-93-0, molecular formula is C37H54O11, the present inventor further study show that black cohosh root glycosides can significantly improve AD rats recognizes
Know dysfunction, it is very great to preventing and treating senile dementia meaning.
The content of the invention
Drug regimen it is an object of the invention to provide black cohosh root glycosides or comprising black cohosh root glycosides is senile in preparation preventing and treating
Purposes in anti-dementia agent or health products.
The medicine or health products of the present invention for preventing and treating senile dementia, it is characterised in that：Its formulation is pill, particle
Agent, tablet, syrup, mixture, capsule, tincture, medicinal tea, injection.
The medicine or health products of the present invention for preventing and treating senile dementia, it is characterised in that：Can be with any one or one
Plant auxiliary material such as starch, dextrin, lactose, microcrystalline cellulose, HPMC, polyethylene glycol, stearic acid in above pharmacy
The various formulations that magnesium, superfine silica gel powder, xylitol, lactitol, glucose, glycine, mannitol, glycine etc. are mixed.
The medicine or health products of the present invention for preventing and treating senile dementia, it is characterised in that：Preparation can be oral, non-
Enteron aisle, rectum, the form of intranasal administration, can also be made the form of the administrations such as aerosol, inhalant.
The medicine or health products of the present invention for preventing and treating senile dementia, it is characterised in that：Method of administration is preferably oral.
The solid pharmaceutical preparation of oral administration can be tablet, hard capsule, soft capsule, dripping pill, granule, powder,
Pill etc..It can be prepared from according to their customary preparation methods, being used during preparation can be with medicinal auxiliary material.Example
Such as, filler can be used in the preparation process of tablet or capsule（Such as starch, dextrin, sucrose, lactose, calcium sulfate, carbon
Sour calcium, micro- smart cellulose etc.）, binder（Such as methylcellulose, ethyl cellulose, polyvinylpyrrolidone, CMS
Sodium, gelatin, cornstarch etc.）, disintegrant（Such as dry starch, crosslinked carboxymethyl fecula sodium, sodium carboxymethyl starch, low substitution hydroxyl
Propyl cellulose etc.）, lubricant（Such as magnesium stearate, stearic acid, superfine silica gel powder, polyethylene glycol, talcum powder）.Tablet can be with
It is coated according to the method being currently known.Granule also needs to select corresponding flavouring（Such as sucrose, syrupus citri）.Soft capsule
Diluent used includes but is not limited to vegetable oil, mineral oil, propane diols, tween, polyethylene glycol in the preparation of agent（PEG）（200
~8000）In one or more.Suspending agent include but is not limited to cellulose family for example sodium cellulose glycolate, hyetellose,
Ethyl cellulose, hydroxyethylmethylcellulose, hydroxypropylcellulose, methylcellulose, hydroxypropyl methyl cellulose etc.；Gum class is such as
Arabic gum etc.；One or more in other such as carbomers, polyvinyl alcohol.Emulsifying agent includes but is not limited to stearic acid
Sodium, enuatrol, spans（20~80）, Tweens（20~80）, glycerin monostearate, hydroxylated lecithin, diacetyl list it is sweet
One or more in grease, diethylene glycol stearate, orthoformic acid, ethylene glycol monostearate, beeswax.Anti-corrosion used
Agent includes but is not limited to sorbic acid methyl esters, benzoic acid, sorbic acid, methyl p-hydroxybenzoate, Nepal's tortoise beetle ester, Nepal's gold
One or more in ethyl ester, phenmethylol.In the preparation of pill, matrix includes but is not limited to polyethylene glycol（PEG）6000th, gather
Ethylene glycol（PEG）4000th, polyethylene glycol（PEG）1000th, polyethylene glycol（PEG）1500th, odium stearate, glycerin gelatine, stearic acid,
Poloxamer etc.；Condensate liquid includes but is not limited to dimethicone, atoleine, vegetable oil etc..
Oral liquid can be mixture（Oral liquid）, syrup, emulsion, supensoid agent, elixir or suspension, can be with
It is to reconstitute the dry products taken with water or other suitable carriers before its use.These liquid preparations can be according to itself
Prepared by known method, medical additive, such as suspending agent can be used during preparation（Such as cellulose derivative, grape
Sugar/sucrose syrup, sorbitol syrups etc.）, emulsifying agent（Such as Arabic gum, soybean lecithin, lecithin, gelatin, Tweens）, help
Suspension（Such as glycerine, simple syrup, aluminum monostearate vegetable oil, colloid sulfuric acid magnalium）, preservative（Such as benzoic acid, hydroxy benzenes first
Sour methyl esters, nipasol, sorbic acid etc.）.Flavor ameliorating substances, fragrant composition, sweetener etc. can also be added as needed.
The medicine or health products of the present invention for preventing and treating senile dementia, it is characterised in that：The senile dementia is
Alzheimer disease, vascular dementia, Alzheimer disease and vascular dementia and the Mixed dementia one or more deposited.
The medicine or health products of the present invention for preventing and treating senile dementia, it is characterised in that：The senile dementia master
It to be Alzheimer disease.
The Black Cohosh P.E black cohosh root glycosides that the present invention is provided can be also used for preparing food supplement and/or health care
Food, can be prepared into the various formulations of health food, such as tablet, capsule, oral liquid, health drink, health protection tea；
Can be as food additives, applied to food（Such as bread, noodles）, health protection tea, health drink etc..
Embodiment
The invention is further described below by specific embodiment.
Embodiment 1：The neurotoxicity that in vitro study proof black cohosh root glycosides can suppress A β has therapeutic action to AD
1 cell line and reagent
Pheochromocytoma SH-SY5Y cells（Purchased from ATCC）, DMEM/F12, hyclone, MTT, Doneppezil Hydrochloride
（In the U.S., Sigma is bought）, huperzine（Sigma is bought）, black cohosh root glycosides（Sigma is bought）
2. medicine is prepared
1. it is 4ug/ml, 40ug/ml, 400ug/ml that black cohosh root glycosides, which is configured to concentration with tri-distilled water,.
2. A β 25-35 are configured to 100 μm of ol/L with tri-distilled water, filter, packing, and -20 DEG C freeze；It is configured to before use
Required concentration, and it is incubated 7 d at 37 DEG C.
3. positive drug：Doneppezil Hydrochloride and huperzine are dissolved in blank serum, and Doneppezil Hydrochloride compound concentration is 5mg
/ ml, huperzine is 0. 45mg/ml.
3 models are set up
Take the logarithm growth period SH-SY5Y cell, be resuspended after the digestion of the pancreatin of 1mL 0.25%, centrifugation with complete medium, density is
105mL-1, it is inoculated in 96 orifice plates (100 μ L) or 24 orifice plates (1mL).Old nutrient solution is sucked when 80% fusion, new training is added
Nutrient solution, and cell is divided into 15 groups, add A β25-35Cimicifugoside is blackened after 30 μm of ol/L, effect 24h, its concentration is respectively 5ug/
Ml, 50ug/ml, 500ug/ml, 37 DEG C of culture 24h of temperature.
4 neuronal cell viabilities are detected
Every group sets 3 parallel sampleses, takes average.96 orifice plates cultivate the corresponding time respectively, and 20 μ l MTT (concentration are added per hole
For 5 mg/ml), zeroing hole only adds nutrient solution.37 DEG C are continued to cultivate after 4 h, deduct liquid with buckle method, 150 are added per hole
μ l DMSO, 37 DEG C of 10 min of vibration, after purple crystal fully dissolves, put on ELIASA, to filter the nm of wavelength 490, survey
Each hole absorbance value (OD).Then cell survival rate is asked with OD values.
Cell survival rate (%)=experimental group OD/ control group OD × 100%
5 Neuron Apoptosis rates are detected
The double dye methods of Annexin-V/PI use flow cytomery Neuron Apoptosis rate.Collect neuron centrifugation (2000rpm from
Heart 5min)；PBS washing cells secondary (2000rpm centrifuges 5min) collect 1 ~ 5 × 105Cell；Add 500 μ L Binding
Buffer suspension cells；Add after 5 μ L Annexin V-FITC mixings, add 5 μ L Propidium Iodide, mix；Room
Temperature, lucifuge, 5~15min of reaction；Flow cytomery.
6 results
6.1 MTT prompting A β25-35The survival rate of neuron is substantially reduced, black cohosh root glycosides can suppress A β neurotoxicity：
Aβ25-35Concentration be 30 μm of ol/L when, compared with blank control group, model group cells survival rate for (72. 9 ±
3.7), there are obvious decline (P ＜ 0. 01 in %）, illustrate modeling success；Compared with model group, black cohosh root glycosides middle dose group (
87.6 ± 4.9) % and high dose group (91.2 ± 5.3) % cells survival rate significantly rise (P ＜ 0. 001）, say
Bright black cohosh root active principle can suppress A β neurotoxicity.
6.2AV/PI results show that black cohosh root glycosides can reduce A β25-35Caused nerve cell apoptosis, A β25-35Concentration is 30
During μm ol/L, compared with blank control group, significant change occurs in model group cells survival state, apoptosis rate increase is obvious, reachable
More than 40%；Compared with model group, black cohosh root glycosides middle dose group（20.1%）With the apoptosis rate of high dose group（23.5%）Significantly
Reduce (P ＜ 0. 01）, illustrate that black cohosh root glycosides can suppress A β caused nerve cell apoptosis.
7 conclusions
Black cohosh root glycosides can protect A β25-35Damage to SH-SY5Y cells, increases the survival of SH-SY5Y cells.
Embodiment 2：Have shown that black cohosh root glycosides combines hippocampal injection A β to rat skin lower injection D- galactolipins in body research1-42Institute
Cause AD that there is therapeutic action
1 material
1.1 experimental animal
From wister rats, SPF grades, 180 ~ 220g, male, 56
1.2 Experimental agents and reagent
Positive control medicine selects Doneppezil Hydrochloride, is smashed tablet using preceding, and gavage decoction is configured to distilled water
0.45mg/kg•d-1；Huperzine A capsule is configured to gavage decoction with distilled water, and compound concentration is 0.04mg/kg d-1.D- half
Lactose, amyloid-beta 1-42 (A β1-42)（In the U.S., Sigma is bought）, acetylcholinesterase (AChE) kit, courage
Alkali transacetylase (ChAT) kit, SOD active agents box, MDA contents kit, GSH content kits.
1.3 key instrument
Rat stereotaxic apparatus, electronic dental burr, microsyringe, DMS-2 type Morris water maze instrument automatic data collections
And processing system, BH-2 type biomicroscopes, DpxView Pro type computer color vision processing systems, paraffin section device,
Instrument, Image-Pro Plus image analysis systems, high speed are dried in Full automatic closed tissue processor, embedding machine, pathological tissue drift
Freeze refrigerated centrifuge.
2 methods
2.1 packet
Experimental animal standard environment adaptability raise 1 week after, be grouped at random by the body weight principle of correspondence, be divided into blank control group,
Model group, black cohosh root glycosides low dose group (5mg/kg/d), black cohosh root glycosides middle dose group (15mg/kg/d), black cohosh root glycosides high dose
Group (30mg/kg/d), Doneppezil Hydrochloride group (0.45mg/kg/d) and huperzine group（0.02mg/kg•d）, every group 8
2.2 models are set up and are administered
Blank control group:Normal saline is subcutaneously injected, continuous 6 weeks, bilateral hippocampus injected normal saline (1 within the 7th week
It is secondary)
Model group:The mg/kg/d of D- galactolipins 150, continuous 6 weeks, the 7th week bilateral hippocampus injection A β is subcutaneously injected1-42（1 time）5μg
, A β1-42With 0.9% physiological saline solution.
Medicine group：The injection of subcutaneous and bilateral hippocampus is identical with model group
Positive drug group：The injection of subcutaneous and bilateral hippocampus is identical with model group
The whole bilateral hippocampus of experiment is injected 1 time：The wister rat weights pneumoretroperitoneum injection 3.5% for entering experiment the 7th week is hydrated
Chloralization (0.1ml/100g), is then fixed on stereotaxic apparatus, skin of vertex cropping, iodophor disinfection, scope
The cm of diameter 3~4.Scalpel median sagittal scratches scalp, peels off periosteum, exposure bregma (Bergam points), with Bergam points
For the origin of coordinates, with reference to rat brain stereotaxic atlas, parameter is AP-4mm, ML ± 2.0mm, DV-3.0mm, is drilled through with bone drill
Bilateral skull, stereotaxic apparatus guiding under, by micro syringe by total amount be 4 μ L A β1-42（5μg/μL）Solution or
Physiological saline is slowly injected into bilateral hippocampus tissue (per the μ L of side 2), and depth is 4 mm, the μ L/min of speed 0.2, has injected that let the acupuncture needle remain at a certain point 5
min.Inject after medicine or physiological saline, the injection orifice on skull is sealed with bone wax, skin closure and intramuscular injection penicillin.Build
Property after mould according to test medicine is administered.Normal group and model group give isometric distilled water gavage, and one time a day.Respectively
Group mouse stomach carries out Morris water maze laboratories after 8 weeks.
2.3 brain tissue samples are handled
After rat behavior experiment, brain tissue materials are carried out.Broken end quick at low temperature takes full brain, is cleared up with ice-cold normal saline
Bloodstain, is blotted with filter paper, is weighed.Every group randomly select 4 input 4% paraformaldehyde solutions in fix more than 24h (4 DEG C), it
After change rear fixer, after after brain tissue sinking frozen section, or FFPE can be carried out, carry out pathology and SABC dye
Color.Remaining rat is rapidly separated cerebral cortex and hippocampus (being carried out on ice cream) respectively, and each addition 2ml physiological saline (distilled water) is even
Slurry, low-temperature and high-speed centrifuge separates supernatant, is determined for tissue content.
2.5 statistical procedures
The data obtained represents that carrying out data between statistical analysis, group using statistic software SPSS 18.0 compares with mean ± standard deviation
With one-way analysis of variance, examined using LSD, Dunnett ' sC (during heterogeneity of variance), be that difference has conspicuousness meaning with P ＜ 0.05
Justice.Orientation navigation experiment is using the variance analysis of Repeated Measurements, space exploration examination during behaviouristics Morris water mazes are determined
Test and use one-way analysis of variance.
3 experimental results
Black cohosh root glycosides is shown to rat total distance and escape latency result in 3.1Morris water maze laboratories, with blank group ratio
Compared with there were significant difference in the total distance of model group rats, incubation period at the 4th day；Remaining each group does not have significant difference；With model
Group compares, and there were significant difference in the total distance of black cohosh root glycosides middle dose group, incubation period at the 4th day, total road of remaining each dosage group
Journey, incubation period do not have conspicuousness change, are compared with positive drug, and black cohosh root glycosides middle dose group total distance and incubation period are poor without conspicuousness
It is different.
Black cohosh root glycosides is shown to learning and memory in rats capability result in Morris water maze laboratories, with blank control group ratio
Compared with the escape latency of model group significantly extends, and the platform residence time substantially reduces, and spanning platform number of times is substantially reduced, explanation
Modeling success；Compared with model group, black cohosh root glycosides middle dose group escape latency is substantially reduced, and the platform residence time significantly increases
Plus, spanning platform number of times dramatically increases (P ＜ 0. 01）, black cohosh root glycosides high dose group escape latency substantially reduces, and passes through flat
Platform number of times dramatically increases (P ＜ 0. 05）, illustrate that black cohosh root glycosides can improve learning and memory in rats ability；Compared with positive drug,
It is more than Doneppezil Hydrochloride group and huperzine group that black cohosh root glycosides middle dose group passes through target quadrant number of times and platform residence time,
Illustrate that raising effect of the black cohosh root glycosides middle dose group to learning and memory in rats ability is better than positive drug（It is shown in Table 1, table 2, table 3）.
Influence of the black cohosh root glycosides to rat total distance in the Morris water maze laboratories of table 1.
Compared with blank control group,#P ＜ 0.05；Compared * P ＜ 0.05 with model group
Influence of the black cohosh root glycosides to rat escape latency in the Morris water maze laboratories of table 2.
Compared with blank control group,#P ＜ 0.05；Compared * P ＜ 0.05 with model group
Influence of the black cohosh root glycosides to learning and memory in rats ability in the Morris water maze laboratories of table 3.
| Group | Quantity | Escape latency (s) | Target quadrant traversing times | The platform residence time (s) | The target quadrant residence time (s) | Spanning platform number of times |
| Blank control group | 8 | 25.5±2.8 | 4.7±0.5 | 0.8±0.1 | 13.7±1.2 | 1.9±0.3 |
| Model group | 8 | 29.5±3.2# | 4.2±0.3 | 0.4±0.1# | 10.8±1.0 | 1.1±0.2# |
| Black cohosh root glycosides low dose group | 8 | 28.2±3.5* | 4.4±0.3 | 0.8±0.1* | 12.7±1.0 | 1.6±0.3 |
| Black cohosh root glycosides middle dose group | 8 | 26.7±3.7 | 5.2±0.4* | 1.1±0.1* | 14.1±1.3 | 2.2±0.4** |
| Black cohosh root glycosides high dose group | 8 | 25.6±2.7* | 4.6±0.3 | 0.7±0.1 | 11.9±1.2 | 1.9±0.3* |
| Doneppezil Hydrochloride group | 8 | 25.3±2.9* | 4.5±0.4 | 0.7±0.1 | 11.6±1.2 | 1.8±0.3* |
| Huperzine group | 8 | 26.3±3.6 | 4.8±0.5 | 0.6±0.1 | 12.3±1.3 | 1.6±0.4 |
Compared with blank control group,#P ＜ 0.05；Compared * P ＜ 0.05, * * P ＜ 0.01 with model group
3.2 black cohosh root glycosides are to cholinacetyltranslase in rat hippocampus（AchE）And acetylcholinesterase（ChAT）The influence of activity
As a result show, compared with blank control group, the Ach contents of model group are significantly reduced, AchE activity is dramatically increased, ChAT activity is aobvious
Write and reduce；Compared with model group, black cohosh root glycosides low dose group（P ＜ 0.05）, middle dose group（P ＜ 0.01）, high dose group（P ＜
0.05）With positive drug Doneppezil Hydrochloride group（P ＜ 0.05）, huperzine group（P ＜ 0.05）Ach contents dramatically increase, it is black
Cimicifugoside middle dose group（P ＜ 0.01）, high dose group（P ＜ 0.05）With positive drug group（P ＜ 0.001）AchE activity significantly subtract
It is few, black cohosh root glycosides middle dose group（P ＜ 0.05）ChAT activity dramatically increase（It is shown in Table 4）.
Influence of the black cohosh root glycosides of table 4 to Rat hippocampus AchE and ChAT activity
| Group | Dosage mg/kg | Ach（ug/ml） | AchE( U/g) | ChAT( U/g) |
| Blank control group | 188.23±11.22 | 442.35±31.22 | 59.11±6.60 | |
| Model group | 96.37±13.51## | 658.98±55.47## | 42.20±5.58# | |
| Black cohosh root glycosides low dose group | 5.0 | 138.21±13.21* | 550.41±44.17 | 39.99±6.38 |
| Black cohosh root glycosides middle dose group | 15.0 | 187.33±14.49** | 429.21±48.04** | 51.51±8.28* |
| Black cohosh root glycosides high dose group | 30.0 | 154.87±12.09* | 497.21±48.09* | 44.77±11.21 |
| Doneppezil Hydrochloride group | 0.45 | 136.32±13.08* | 427.55±33.18** | 45.63±10.86 |
| Huperzine group | 0.02 | 145.21±11.77* | 374.60±51.01*** | 47.08±7.21 |
Compared with blank control group,#P ＜ 0.05；Compared * P ＜ 0.05, * * P ＜ 0.01 with model group
3.3 black cohosh root glycosides are to AD Rat hippocampus hippocampus person in middle and old age's spots（SP）Influence result show, with blank control group ratio
Compared with SP quantity is dramatically increased in model group hippocampus of mice（P ＜ 0.001）；Compared with model group, black cohosh root glycosides middle dosage（P ＜
0.001）With high dose group（P ＜ 0.01）SP quantity is substantially reduced in rat hippocampus；Compared with positive drug, black cohosh root glycosides middle dosage
SP quantity is fewer than positive drug group in rat hippocampus（It is shown in Table 5）.
Influence of the black cohosh root glycosides of table 5 to Rat hippocampus SP
| Group | Dosage mg/kg | Size of animal | SP quantity（It is individual） |
| Blank control group | 8 | 1.0±0.1 | |
| Model group | 8 | 19.7±4.5### | |
| Black cohosh root glycosides low dose group | 5.0 | 8 | 16.4±4.1 |
| Black cohosh root glycosides middle dose group | 15.0 | 8 | 8.4±3.0*** |
| Black cohosh root glycosides high dose group | 30.0 | 8 | 11.5±2.3** |
| Doneppezil Hydrochloride group | 0.45 | 8 | 12.8±2.9* |
| Huperzine group | 0.02 | 8 | 10.8±2.2** |
Compared with blank control group,###P ＜ 0.001；Compared * * P ＜ 0.01 with model group
3.4 black cohosh root glycosides show and are compared with blank control group to SOD activity, MDA contents, the result of GSH contents in rat hippocampus,
The SOD activity of model group is substantially reduced, MDA contents are dramatically increased, GSH contents are substantially reduced；Compared with model group, black cohosh root glycosides
Low dose group（P ＜ 0.01）Black cohosh root glycosides middle dose group（P ＜ 0.001）With positive drug group（P ＜ 0.01）SOD activity significantly increases
Plus；Black cohosh root glycosides middle dose group（P ＜ 0.05）, high dose group（P ＜ 0.05）With positive drug huperzine group（P ＜ 0.05）MDA
Content is substantially reduced；Black cohosh root glycosides middle dose group（P ＜ 0.01）With positive drug huperzine group（P ＜ 0.05）GSH contents do not have
Substantially reduce；Illustrate that black cohosh root glycosides can improve the oxidation resistance of Rat hippocampus（It is shown in Table 6）
Influence of the black cohosh root glycosides of table 6 to SOD activity, MDA contents, GSH contents in rat hippocampus
| Group | Dosage mg/kg | SOD(U/mgprot) | MDA(nmol/mgprot) | GSH(mg/gprot) |
| Blank control group | 72.28±3.31 | 1.77±0.61 | 8.27±0.84 | |
| Model group | 32.97±2.54# | 3.24±0.78# | 4.06±0.36# | |
| Black cohosh root glycosides low dose group | 5.0 | 88.12±6.94** | 2.54±0.31 | 5.22±0.92 |
| Black cohosh root glycosides middle dose group | 15.0 | 121.48±7.02*** | 2.02±0.33* | 9.18±0.81** |
| Black cohosh root glycosides high dose group | 30.0 | 68.65±5.33 | 1.82±0.13* | 6.56±0.68 |
| Doneppezil Hydrochloride group | 0.45 | 78.28±6.45* | 2.24±0.18 | 7.23±0.95 |
| Huperzine group | 0.02 | 84.35±6.77** | 1.94±0.34* | 7.93±1.03* |
Compared with blank control group,#P ＜ 0.05；Compared * P ＜ 0.05, * * P ＜ 0.01, * * * P ＜ 0.001 with model group
4 conclusions
Black cohosh root glycosides can improve injection of d-galactose joint hippocampal injection A β AD Cognition Function in Rats obstacles；Black cohosh root glycosides can be with
Injection of d-galactose joint hippocampal injection A β AD rat hippocampus area acetylcholine, cholinacetyltranslase is improved, is reduced old
Spot（SP）Occur；Black cohosh root glycosides can improve the oxidation resistance of Rat hippocampus, increase SOD activity, reduction MDA contents,
Increase GSH contents.
The medicine that the present invention treats senile dementia using black cohosh root glycosides as preparing, is carried out using related pharmacology test
Black cohosh root glycosides prevents and treats the pharmacodynamic evaluation of senile dementia, respectively from improvement cholinergic nerve of centrum system, suppression beta-amyloyd egg
(A β) formation and deposition, neuroprotection aspect, illustrate the purposes that albiflorin multipath, Mutiple Targets treat senile dementia in vain.
Claims (8)
1. black cohosh root glycosides or the drug regimen comprising black cohosh root glycosides are preparing prevention or treatment senile dementia medicine or health products
In application, it is characterised in that the black cohosh root glycosides structural formula is
。
2. the medicine of senile dementia or the preparation method of health products are prevented and treated according to claim 1 to 2, it is characterised in that：Its
Formulation is pill, granule, tablet, syrup, mixture, capsule, tincture, medicinal tea, injection.
3. according to claims 1 to 3, it is characterised in that：Can be with auxiliary material in any or more than one pharmacies as formed sediment
Powder, dextrin, lactose, microcrystalline cellulose, HPMC, polyethylene glycol, magnesium stearate, superfine silica gel powder, xylitol, lactose
The various formulations that alcohol, glucose, glycine, mannitol, glycine etc. are mixed.
4. according to Claims 1-4, it is characterised in that：Preparation can be the oral, shape of non-bowel, rectum, intranasal administration
Formula, can also be made the form of the administrations such as aerosol, inhalant.
5. according to claim 1 to 5, it is characterised in that：Method of administration is preferably oral.
6. the black cohosh root glycosides as described in claim 1 to 6 or the drug regimen comprising black cohosh root glycosides are senile silly in preparation preventing and treating
Purposes in slow-witted medicine, health products.
7. according to claim 7, it is characterised in that：The senile dementia be Alzheimer disease, vascular dementia, Ah
Alzheimer's disease and vascular dementia and the Mixed dementia one or more deposited.
8. according to claim 8, it is characterised in that：The senile dementia is mainly Alzheimer disease.
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| Application Number | Priority Date | Filing Date | Title |
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| CN201610189867.5A CN107281206A (en) | 2016-03-30 | 2016-03-30 | Black cohosh root glycosides is preparing the application in preventing and treating senile dementia medicine |
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| CN201610189867.5A CN107281206A (en) | 2016-03-30 | 2016-03-30 | Black cohosh root glycosides is preparing the application in preventing and treating senile dementia medicine |
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Application publication date: 20171024 |