CN105521269A - Rose composition for treating Alzheimer disease and application of rose composition - Google Patents
Rose composition for treating Alzheimer disease and application of rose composition Download PDFInfo
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- CN105521269A CN105521269A CN201510944021.3A CN201510944021A CN105521269A CN 105521269 A CN105521269 A CN 105521269A CN 201510944021 A CN201510944021 A CN 201510944021A CN 105521269 A CN105521269 A CN 105521269A
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- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/23—Apiaceae or Umbelliferae (Carrot family), e.g. dill, chervil, coriander or cumin
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Abstract
The invention belongs to the technical field of traditional Chinese medicines and particularly relates to a rose composition for treating the Alzheimer disease and an application of the rose composition. The rose composition contains radix astragali, rhizoma dioscoreae, radix codonopsis, rhizoma anemarrhenae, radix puerariae, radix ophiopogonis, radix angelicae sinensis and flos rosae rugosae. The rose composition has a remarkable treatment effect for a caenorhabditis elegans Alzheimer disease pathological model, can be applied to the preparation of drugs for treating the Alzheimer disease and also can be applied to the preparation of related health products for preventing and assistantly treating the Alzheimer disease.
Description
Technical field
The invention belongs to technical field of Chinese medicines, be specifically related to a kind of Flos Rosae Rugosae compositions and application thereof for the treatment of Alzheimer's disease.
Background technology
Alzheimer's disease (Alzheimer'sMdisease, AD), being a kind of based on the nervous system degenerative disease of Progressive symmetric erythrokeratodermia cognitive disorder and memory impairment, is the modal a kind of form of senile dementia.Feature is shown as clinically with dysmnesia, aphasia, agnosia, the infringement of visual space technical ability, n-back test obstacle and the generalized dementia such as personality and behavior change.In dementia patients, proportion is more than 75%.Along with the aggravation of China's aging degree, AD can become one of principal disease affecting senior health and fitness, and effective prevention and therapy AD becomes the another key subjects of pendulum in face of us.
Amyloid beta deposition (aβ protein) and neurofibrillary tangles are the two large key pathological feature of AD.Modern medicine has carried out years of researches to the pathogenesis of AD, but due to its cause of disease complexity, the pathogenesis of this disease is still indefinite so far, and " A β cascade hypothesis " is current by one of well accepted mechanism of scientific circles.This theory thinks that the A β of abnormal deposition in brain in patients is by a series of cascade reactions such as radical reaction, Mitochondrial oxidative damage and inflammatory reactions; directly or indirect action in neuron and neurogliocyte; finally cause neuronal function abnormal or dead; cause cognitive impairment and amnesia, finally cause dementia.In familial Alzheimer disease disease patient, find that amyloid precursor protein (APP) gene and presenilin genes are undergone mutation, cause A β to become this theory evidence the strongest in the overexpression of brain.Therefore amyloid beta has become the generally acknowledged anti-AD drug targets of screening.
The AD cause of disease is complicated, the course of disease is very long and morbidity link is more, need Long-term taking medicine, anti-Alzheimer disease medicine acetylcholinesteraseinhibitors inhibitors (as galantamine) main at present and N-methyl-D-aspartate receptor (nmda receptor) antagonist (as memantine), but said medicine is expensive, hallucination after taking medicine, misunderstanding, dizziness, headache and the side effect such as tired are remarkable, and can only delay, but can not control or reverse conditions of patients.
And Chinese medicine composition has the feature of various active component, Mutiple Targets, can overcome the weak point of Western medicine to a certain extent, the drug candidates making screening from Chinese medicine composition treasure-house be used for the treatment of AD has a extensive future.
Flos Rosae Rugosae is the Chinese medicine of promoting flow of QI and blood simply, large geneva leather Flos Rosae Rugosae chloroform extract is proved to be the rat embryonic neuronal cell axon growth that can promote In vitro culture, and the neuron axon atrophy (Awaleetal., 2011) suppressing A β (25-35) to cause.This prompting Flos Rosae Rugosae has anti-AD effect.But when inventor is when studying therapeutical effect to Caenorhabditis elegans AD pathological model of rose water decoct, although find that rose water decoct dose-dependant ground slows down the AD pathological characters of Caenorhabditis elegans, the Flos Rosae Rugosae of any concentration all has significant inhibitory action to the hatching of line eggs.Therefore, while Flos Rosae Rugosae anti-AD effect, there is significant toxic action.
Caenorhabditis elegans (Caenorhabditiselegans) is the research platform of a very useful multifunctional drug screening and mechanism of drug action.Its is cheap, easily cultivate; Generation cycle is short, offspring's number is many, can obtain the consistent individuality of a large amount of background simultaneously, ensures experimental repeatability and adopts large sample amount to test, thus get rid of the impact of individual variation; With higher organism high conservative (KalettaandHengartner, 2006) in gene and molecular pathway.It from the bridge being sieved to horizontal medicine in Mice Body at the beginning of the horizontal medicine of cells in vitro and sieving again, is more and more subject to the favor of pharmacy man as one.The arrhythmia medicine that devGen company of the U.S. utilizes humanization nematicide to screen is entered clinical research by FDA approval.
The foundation of humanization Caenorhabditis elegans AD pathological model people source A β 1-42 gene is proceeded to Myosin promoter downstream and reaches by temperature control table, this nematicide strain can at 15 DEG C of normal growths, under being transferred to 25 DEG C of conditions, A β 1-42 expresses and accumulates at its intramuscular, causes nematicide lose motor capacity and benumb.Add test medicine and can delay muscular paralysis phenotype, the percentage ratio that its result accounts for tested nematode population quantity with muscular paralysis nematode population represents.Do not benumb nematicide ratio higher, medicine anti-AD effect is more remarkable.This model is used to anti-AD disease mechanism and anti-AD medicine and material standed for study on mechanism (Link, 1995 already; 2001).
Based on above-mentioned present Research, the present invention now provides a kind of Flos Rosae Rugosae compositions for the treatment of Alzheimer's disease, and described Flos Rosae Rugosae compositions not only has significant anti-AD effect, and plays the toxicity that synergism slows down Flos Rosae Rugosae.The present invention provides the application of this Flos Rosae Rugosae compositions simultaneously.
List of references
KalettaT,HengartnerMO.Findingfunctioninnoveltargets:C.elegansasamodelorganism.NatRevDrugDiscov2006,5:387e398.
LinkCD.Expressionofhumanbeta-amyloidpeptideintransgenicCaenorhabditiselegans.ProcNatlAcadSciUSA1995,92:9368e9372.
LinkCD.Transgenicinvertebratemodelsofage-associatedneurodegenerativediseases.MechAgeingDev2001,122:1639e1649.
AwaleS，TohdaC，TezukaTetal.ProtectiveEffectsofRosadamascenaanditsactiveconstituentonAβ(25–35)-inducedneuriticatrophy.Evidence-BasedComplementaryandAlternativeMedicine2011,doi:10.1093/ecam/nep149.
Summary of the invention
The object of the invention is to provide a kind of Flos Rosae Rugosae compositions for the treatment of Alzheimer's disease, and this Flos Rosae Rugosae compositions has the potentiality for the treatment of Alzheimer's disease.
Another object of the present invention is to provide the application of above-mentioned Flos Rosae Rugosae compositions.
Above-mentioned purpose of the present invention is achieved through the following technical solutions:
Treat a Flos Rosae Rugosae compositions for Alzheimer's disease, described Flos Rosae Rugosae compositions contains the Radix Astragali, Rhizoma Dioscoreae, Radix Codonopsis, the Rhizoma Anemarrhenae, Radix Puerariae, Radix Ophiopogonis, Radix Angelicae Sinensis, Flos Rosae Rugosae.
Treat a Flos Rosae Rugosae compositions for Alzheimer's disease, described Flos Rosae Rugosae compositions contains the crude drug of following weight ratio: the Radix Astragali 15 parts, Rhizoma Dioscoreae 20 parts, Radix Codonopsis 15 parts, the Rhizoma Anemarrhenae 9 parts, Radix Puerariae 10 parts, Radix Ophiopogonis 10 parts, Radix Angelicae Sinensis 12 parts, Flos Rosae Rugosae 4 parts.
Described Flos Rosae Rugosae compositions can be applied in the medicine of preparation treatment Alzheimer's disease.
This Flos Rosae Rugosae compositions is capsule, tablet, granule, powder, oral liquid, pill as the pharmaceutical preparation of active ingredient.
Described Flos Rosae Rugosae compositions can preparation prevention and auxiliary treatment Alzheimer's disease health product in application.
This Flos Rosae Rugosae compositions is capsule, tablet, granule, powder, oral liquid, pill as the health product dosage form of effective ingredient.
Beneficial effect of the present invention:
1, the present invention tests with Caenorhabditis elegans AD pathological model, and result shows: this Flos Rosae Rugosae compositions has significant therapeutic effect to Caenorhabditis elegans AD pathological model tool.Significantly can delay the paralysis phenotype of Caenorhabditis elegans AD pathological model, this Flos Rosae Rugosae compositions is pointed out to have the potentiality for the treatment of Alzheimer's disease, can apply in the medicine of preparation treatment Alzheimer's disease, also can apply in the health product preparing prevention and auxiliary treatment Alzheimer's disease.
2, when Flos Rosae Rugosae is alone, Caenorhabditis elegans AD pathological model tool is had significant therapeutic effect, but, the rose water decocting liquid of high concentration has significant inhibitory action to the growth of Caenorhabditis elegans or even the hatching of line eggs, thus demonstrates the significant toxicity of Flos Rosae Rugosae.Flos Rosae Rugosae compositions provided by the invention, adds by other flavour of a drug the toxicity reducing Flos Rosae Rugosae, can promote Flos Rosae Rugosae consumption simultaneously, thus promotes the drug effect of the anti-AD of Flos Rosae Rugosae.
Below in conjunction with specific embodiment, technical scheme of the present invention is described in further detail, but protection scope of the present invention is not limited to the following stated.
Accompanying drawing explanation
Fig. 1 Flos Rosae Rugosae is to the effect delaying AD Caenorhabditis elegans paralysis
C-blank group, L-rose wate decocting liquid low dose group, dosage group in M-rose wate decocting liquid, H-rose wate decoction high dose group
Fig. 2 Flos Rosae Rugosae compositions is to the effect delaying AD Caenorhabditis elegans paralysis
C-blank group, ZHW-Flos Rosae Rugosae compositions group, DZ1-matched group 1, DZ2-matched group 2, DZ3-matched group 3, DZ4-matched group 4.
Detailed description of the invention
The preparation method of embodiment 1 Flos Rosae Rugosae compositions of the present invention
Take Radix Astragali 15g, Rhizoma Dioscoreae 20g, Radix Codonopsis 15g, Rhizoma Anemarrhenae 9g, Radix Puerariae 10g, Radix Ophiopogonis 10g, Radix Angelicae Sinensis 12g, Flos Rosae Rugosae 4g, add water 395ml, is heated to seethe with excitement and keeps 30 minutes, being settled to 197mL, filtration sterilization, for subsequent use.
Embodiment 2 Flos Rosae Rugosae of the present invention is to the therapeutical effect of AD Caenorhabditis elegans
1. biomaterial
(1) Caenorhabditis elegans CL4176 is purchased from CaenorhabditisGeneticsCenter (CGC); For transgenic strain, express mankind A β at 25 DEG C of temperature-induced lower muscle specifics
1-42, A β
1-42assemble in muscular tissue, finally cause nematicide to be benumbed, the present embodiment adopts C. Elegans Automatic Screening CL4176 strain as the pathological model of the anti-AD medicine of screening.
(2) escherichia coli OP50 (uracil leaky mutant), purchased from CaenorhabditisGeneticsCenter (CGC), as the food of Caenorhabditis elegans.
2. reagent
(1) solid NGM (NematodeGrowthMedium) medium component and making (being upgraded to example with 1):
| Composition | Content |
| NaCl | 3.00g |
| K 2HPO 4 | 2.34g |
| KH 2PO 4 | 17.23g |
| Peptone | 2.50g |
| Agar | 17.00g |
| Supplement H 2O extremely | 1000mL |
After solid NGM culture medium prepares, high-pressure constant temp sterilizing 20min at 121 DEG C, adds 5mg/mL cholesterol 1mL, 1MMgSO under aseptic operating platform
41mL, 1MCaCl
21mL shakes up, and pours sterilized 9cm culture plate while hot into, about 20mL/ plate.Leave standstill and wait for culture medium solidifying, for subsequent use.
(2) M9 formula of liquid
| Composition | Content |
| Na 2HPO 4 | 6.00g |
| KH 2PO 4 | 3.00g |
| NaCl | 5.00g |
| 1M MgSO 4 | 1.00mL |
| Supplement H 2O extremely | 1000mL |
(3) preparation of lysate: 6.4%NaClO solution and 1MNaOH solution 1:1 mixing by volume.
3. the NGM of preparation containing rose wate decocting liquid is dull and stereotyped
The preparation of rose wate decocting liquid:
Flos Rosae Rugosae 4g, add water 100mL, and heated and boiled also keeps 30 minutes, is settled to 50mL, filtration sterilization, for subsequent use, and rose wate decocting liquid concentration is 80mg/mL.
The NGM of configuration containing rose wate decocting liquid is dull and stereotyped:
Get the rose water decocting liquid of acceptable diluent degree, add in NGM culture medium, a kind of rhyme scheme in Chinese operas serving as the prelude to a complete score for voices.
Get rose wate decocting liquid, add in NGM culture medium, after making the final concentration of rose wate decocting liquid in pastille NGM culture dish be scaled crude drug amount, reach 0.4mg/mL, 0.8mg/mL and 1.6mg/mL.Leave standstill and wait for culture medium solidifying.In culture medium, even spread escherichia coli OP50 is as the food of nematicide.
4. implementation step
(1) cultivation of nematicide:
Be connected on by nematicide and scribble on the solid NGM plate of escherichia coli OP50, the incubator being then placed in 16 DEG C is cultivated, and carries out synchronization process when nematicide grows to adult.
(2) nematicide synchronization:
Select containing a large amount of adult and the NGM culture medium having partial line worm's ovum to hatch, with M9 liquid, nematicide is swept away from culture medium, transfer in centrifuge tube, leave standstill and make, at the bottom of nematicide free settling to pipe, to abandon supernatant.How many sight line worm amounts adds lysate in centrifuge tube, whirlpool misfortune agitator vibrates 5-7 minute until nematicide complete rupture time stop vortex, and be sub-packed in 1.5mL centrifuge tube, wash line eggs three times with M9 solution.
(3) experimental group is arranged:
Blank group (C): sterilized water.
Rose wate decocting liquid low dose group (L): in pastille NGM culture dish, the final concentration of rose wate decocting liquid is 0.4mg/mL;
Dosage group (M) in rose wate decocting liquid: in pastille NGM culture dish, the final concentration of rose wate decocting liquid is 0.8mg/mL;
Rose wate decoction high dose group (H): in pastille NGM culture dish, the final concentration of rose wate decocting liquid is 1.6mg/mL.
(4) experimental procedure
The line eggs be sub-packed in after synchronization in centrifuge tube is transferred to and is coated with OP50 and mixes in the NGM culture dish of the rose wate decocting liquid of variable concentrations, blank group is be coated with OP50 and be added with the NGM culture dish with the isopyknic sterilized water of rose wate decocting liquid, each culture dish 60 nematicides, each drug level three culture dishs, as parallel, cultivate 3 days to the L3 phase for 16 DEG C.Wherein, in pastille NGM culture dish, the final concentration of rose wate decocting liquid is 0.4mg/mL, 0.8mg/mL and 1.6mg/mL.
In order to make nematicide express A β, L3 phase nematicide being turned and induces at 25 DEG C, start after 34h to count nematicide paralysis number.Every two hours count once, until all nematicides are all benumbed (when paralysis refers to mechanical stimulus nematode body, nematicide can not move or only have head movement).The results are shown in Figure 1.
(5) experimental result
The vertical coordinate of Fig. 1 represents the percentage ratio that accounts for of Caenorhabditis elegans not having to benumb, and at point at the same time, this value is larger, shows not have the Caenorhabditis elegans ratio of paralysis in this processed group larger, and namely to delay the effect of paralysis stronger for medicine.
Experimental result shows, has therapeutical effect to Caenorhabditis elegans AD pathological model rose wate decocting liquid dose-dependant.But experiment finds simultaneously, no matter the hatching of rose wate decocting liquid to Caenorhabditis elegans worm's ovum of which kind of concentration has inhibitory action, wherein, in rose wate decocting liquid, the rose wate decocting liquid of dosage group (M) and rose wate decoction high dose group (H) has remarkable inhibitory action (table 1) to Caenorhabditis elegans growth.
Table 1 rose wate decocting liquid is on the impact of Caenorhabditis elegans egg hatching number and growing state
Note: different letter means significant difference, P<0.05.
In embodiment 3 Flos Rosae Rugosae compositions between each component synergism to the therapeutical effect of AD Caenorhabditis elegans
(1) experimental group is arranged
Blank group (C): sterilized water
Flos Rosae Rugosae compositions group (ZHW): take Radix Astragali 15g, Rhizoma Dioscoreae 20g, Radix Codonopsis 15g, Rhizoma Anemarrhenae 9g, Radix Puerariae 10g, Radix Ophiopogonis 10g, Radix Angelicae Sinensis 12g, Flos Rosae Rugosae 4g add water 395 parts, be heated to seethe with excitement and keep 30 minutes, be settled to 197mL, filtration sterilization, for subsequent use.
Matched group 1 (DZ1): take Radix Astragali 15g, Rhizoma Dioscoreae 20g, Radix Codonopsis 15g, adds water 395 parts, is heated to seethe with excitement and keeps 30 minutes, being settled to 197mL, filtration sterilization, for subsequent use.
Matched group 2 (DZ2): take Rhizoma Anemarrhenae 9g, Radix Puerariae 10g, Radix Ophiopogonis, 10g, added water 395 parts, was heated to seethe with excitement and kept 30 minutes, being settled to 197mL, filtration sterilization, for subsequent use.
Matched group 3 (DZ3): take Radix Angelicae Sinensis 12g, Flos Rosae Rugosae 4g, adds water 395 parts, is heated to seethe with excitement and keeps 30 minutes, being settled to 197mL, filtration sterilization, for subsequent use.
Matched group 4 (DZ4): take Radix Astragali 15g, Rhizoma Dioscoreae 20g, Radix Codonopsis 15g, Rhizoma Anemarrhenae 9g, Radix Puerariae 10g, Radix Ophiopogonis 10g, Radix Angelicae Sinensis 12g, add water 395mL, is heated to seethe with excitement and keeps 30 minutes, being settled to 197mL, filtration sterilization, for subsequent use.
NGM plate Flos Rosae Rugosae compositions group (ZHW) final concentration of pastille is 12.5 times of dilutions, matched group 1 (DZ1), matched group 2 (DZ2), matched group 3 (DZ3) and matched group 4 (DZ4) are also 12.5 times of dilutions.
(2) other laboratory operating procedures is with embodiment 2.
(3) experimental result
The vertical coordinate of Fig. 2 represents the percentage ratio that accounts for of Caenorhabditis elegans not having to benumb, and at point at the same time, this value is larger, shows not have the Caenorhabditis elegans ratio of paralysis in this processed group larger, and namely to delay the effect of paralysis stronger for medicine.
Table 2 Flos Rosae Rugosae compositions and the side's of tearing open compositions thereof are on the impact of Caenorhabditis elegans egg hatching number and growing state
Note: different letter representative has significant difference P<0.05.
Table 3 Flos Rosae Rugosae and Flos Rosae Rugosae compositions benumb half paralysis time PT to nematicide
50impact
Note: different letter means significant difference, P<0.05.
Experimental result shows, in Flos Rosae Rugosae compositions group (ZHW), Flos Rosae Rugosae plays Main Function to the treatment of AD Caenorhabditis elegans, if only by Radix Angelicae Sinensis and Flos Rosae Rugosae coupling (DZ3), it slows down AD action effect and full side similar (Fig. 2), but can not alleviate Flos Rosae Rugosae toxicity (table 2).In rose wate decocting liquid, shown significant Developing restraint effect because Flos Rosae Rugosae is alone time dosage group (M), other flavour of a drug add Flos Rosae Rugosae compositions (ZHW) the full side display of formation no longer to the beneficial effect (table 2) that growth is inhibited.
In an experiment, only there is the DZ3 of Radix Angelicae Sinensis and Flos Rosae Rugosae also to show the effect with remarkable Developing restraint, in an experiment, observe nematicide individuality tiny (table 2).Also be in the news Radix Ophiopogonis and there is anti-AD effect, but in the present invention containing the anti-AD action effect of DZ2 of Radix Ophiopogonis significantly lower than Flos Rosae Rugosae composition Z HW.The anti-AD action effect zero difference of the ZHW of the present invention anti-AD action effect in full side and Flos Rosae Rugosae, drug effect does not show collaborative (table 3), but toxicity is significantly lower than the rose wate decocting liquid (table 2) of same concentrations.
Proved by above embodiment, Flos Rosae Rugosae compositions provided by the invention has significant therapeutic effect to Caenorhabditis elegans Alzheimer's disease pathological model tool, can apply in the medicine of preparation treatment Alzheimer's disease, also can apply in the relevant healthcare product preparing prevention and auxiliary treatment Alzheimer's disease.
Claims (6)
1. treat a Flos Rosae Rugosae compositions for Alzheimer's disease, it is characterized in that, described Flos Rosae Rugosae compositions contains the Radix Astragali, Rhizoma Dioscoreae, Radix Codonopsis, the Rhizoma Anemarrhenae, Radix Puerariae, Radix Ophiopogonis, Radix Angelicae Sinensis, Flos Rosae Rugosae.
2. a kind of Flos Rosae Rugosae compositions for the treatment of Alzheimer's disease as claimed in claim 1, it is characterized in that, described Flos Rosae Rugosae compositions contains the crude drug of following weight ratio: the Radix Astragali 15 parts, Rhizoma Dioscoreae 20 parts, Radix Codonopsis 15 parts, the Rhizoma Anemarrhenae 9 parts, Radix Puerariae 10 parts, Radix Ophiopogonis 10 parts, Radix Angelicae Sinensis 12 parts, Flos Rosae Rugosae 4 parts.
3. the application of the Flos Rosae Rugosae compositions as described in any one of claim 1-2 in the medicine of preparation treatment Alzheimer's disease.
4. apply as claimed in claim 3, it is characterized in that, this Flos Rosae Rugosae compositions is capsule, tablet, granule, powder, oral liquid, pill as the pharmaceutical preparation of active ingredient.
5. the application of the Flos Rosae Rugosae compositions as described in any one of claim 1-2 in the health product preparing prevention and auxiliary treatment Alzheimer's disease.
6. apply as claimed in claim 5, it is characterized in that, this Flos Rosae Rugosae compositions is capsule, tablet, granule, powder, oral liquid, pill as the health product dosage form of effective ingredient.
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| KR20020015540A (en) * | 2000-08-22 | 2002-02-28 | 김상근 | Food materials for preventing dementia and foods using the same |
| CN104509855A (en) * | 2014-12-13 | 2015-04-15 | 兰州红菌生物技术有限责任公司 | Auxiliary hypoglycemic composition and preparation method thereof |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| KR20020015540A (en) * | 2000-08-22 | 2002-02-28 | 김상근 | Food materials for preventing dementia and foods using the same |
| CN104509855A (en) * | 2014-12-13 | 2015-04-15 | 兰州红菌生物技术有限责任公司 | Auxiliary hypoglycemic composition and preparation method thereof |
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| 候三喜: "《生活方式与老年痴呆防治》", 31 March 2015, 第四军医大学出版社 * |
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