CN1422861A - Use of saponin - Google Patents

Use of saponin Download PDF

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CN1422861A
CN1422861A CN01142574A CN01142574A CN1422861A CN 1422861 A CN1422861 A CN 1422861A CN 01142574 A CN01142574 A CN 01142574A CN 01142574 A CN01142574 A CN 01142574A CN 1422861 A CN1422861 A CN 1422861A
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receptor
disease
saponin
plant
cholinergic
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张晓�
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Priority to AU2002354334A priority patent/AU2002354334A1/en
Priority to PCT/CN2002/000862 priority patent/WO2003048182A1/en
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07J—STEROIDS
    • C07J9/00—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of more than two carbon atoms, e.g. cholane, cholestane, coprostane
    • 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
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
    • A61P25/16—Anti-Parkinson drugs
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia

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  • General Chemical & Material Sciences (AREA)
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  • Psychiatry (AREA)
  • Hospice & Palliative Care (AREA)
  • Psychology (AREA)
  • Molecular Biology (AREA)
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  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

The present invention provides totle saponins compounds, especially use of totle saponins compounds obtained from plants. In particular, these totle saponins compounds can regulate central cholinergic N receptor, and do not combine with the excited combinative the point of N receptor, and do not affect cholinergic M disease of the central nervous system and schizophrenia, depression or the like relevant with central drug. The present invention provides a pharmaceutical composition for treating the disease relevant with central cholinergic N receptor.

Description

The purposes of saponin
Technical field
The present invention relates to saponin, particularly the purposes of the total saponin that extracts in the plant.Particularly, the present invention relates to the application of saponin in the medicine of preparation treatment and nervus centralis cholinergic n receptor (choline-like, nicotinic acetylcholine receptor) diseases associated.The invention still further relates to the pharmaceutical composition that comprises described saponin.
Background technology
N receptor, claim nicotine-like acetylcholinergic receptor (nicotinic acetylcholine receptor) again, it is a kind of acceptor of maincenter and peripheral cholinergic nerve system, another acceptor in this system is a m receptor, claims toadstool alkali sample acetylcholine receptor (muscarinic acetylcholine receptor) again.Nicotine is that Nicotine (Nicotine) has special affinity to n receptor, and toadstool alkali ( MUscarine) m receptor there is special affinity.Nicotine is the agonist of n receptor, n receptor be activated after it combines, produce the biological function of acceptor.Basic medical research in recent years proves that cholinergic nerve of centrum system, especially n receptor play an important role on brain function, of paramount importance is that it is being learnt, memory, identification, the effect in attention and the personal behavior performance.In addition, n receptor also participates in regulating corticocerebral volume of blood flow.Foregoing for example is described in Paterson, D. and A.Nordlberg, and Neuronal nicotinicreceptors in the human brain, Prog Neurobiol 61 (1): among the 75-111 (2000).
The disease that is caused by central nervous system pathological change has a variety of.Particularly, central nervous system disease mainly is meant various nerve degenerative diseases (neurodegenerative diseases), schizophrenia (schizophrenia), dysthymia disorders (depression), and the central pharmacological dependence is as to dependence of Nicotine or alcohol etc.
Nerve degenerative diseases comprises alzheimer's disease (Alzheimer ' s disease), it is senile dementia, Louis corpusculum disease (Lewy body disease or Dementia with Lewy bodies), vascular dementia (vascular dementia), Parkinson's disease (Parkinson disease), Tu Leiteshi (Tourette) syndromes.The common ground of this class nervus centralis degenerative disease is that the cause of disease is unclear.Though result of study is in recent years found aged, transgenation, protein metabolism disorder, the immune system disorder, cerebral trauma, encephalitis disease (inflammation), poison, even the level of receiving an education is all relevant with the morbidity of these diseases with living habit factors such as (as smokings, excessive drinking etc.).But to each disease, the single tired element of none can become the clear and definite cause of disease.
Schizophrenia and dysthymia disorders are all complicated central nervous system disorderss very of two kinds of not cleer and peaceful clinical manifestations of the cause of disease, but do not belong to nerve degenerative diseases.
The central pharmacological dependence is meant the dependence to addictive drug or material, as to morphine, and the dependence of Cocaine etc.Smoking addiction is owing to the dependence to Nicotine.
In the above-mentioned various diseases with alzheimer's disease be senile dementia the most people pay attention to.Its reason is the first place that the sickness rate of senile dementia comes these diseases.Along with improving constantly of China's national life level and medical condition, the average life span also will prolong, and China is faced with the problem of aging society.Consequent consequence is that the number of suffering from senile dementia disease rolls up, and China will become the maximum country of senile dementia disease number of patients in the world.As not effectively prevention and treatment measure, will bring great burden to family and society.
Yet, owing to also thoroughly do not get the cause of disease of these diseases clear, on clinical treatment, also do not exist at the specific medicament of any disease wherein.
The clinical symptom that very noticeable phenomenon is smoker among alzheimer's disease and the parkinsonian is evident as gently than the non-smoker, and 90% schizophreniac is the heavy smoker.As allowing them stop smoking, their clinical symptom can obviously increase the weight of.This phenomenon may illustrate that smoking is the ego therapy that these patients take, and promptly obtains Nicotine by smoking, and then stimulates the ego therapy of n receptor.From nosetiology, pathology, the result of study that experimental pharmacology and experimental therapeutic obtain confirms foregoing these diseases pathology with pathology, particularly n receptor the cholinergic nerve of centrum system without exception, and substantial connection is arranged.
Particularly; for alzheimer's disease; the interior cholinergic nerve system of alzheimer's disease human brain is impaired to be an outstanding europathology variation of this disease; the activity that shows as choline acetylase (cholineacetyltransferase) descends, by signal transduction system imbalance in the neurone of m receptor mediation etc.Wherein the most outstanding is the variation of n receptor.The variation of n receptor concentrates on and learns, memory, and identification and personal behavior performance have closely-related brain district, as preceding cortex, side cortex, hippocampus etc.The genetic expression of n receptor descends (amount of mRNA descends) in the alzheimer's disease human brain, the proteinic synthetic reduction of receptor subunits, and the binding site of tagged ligand obviously reduces, and receptor-mediated ionic physiological function is obstructed.Because the especially important effect of n receptor on above-mentioned brain function of cholinergic system, the clinical symptom of alzheimer's disease is considered to mainly be caused by cholinergic system degeneration in the brain.Experimentation on animals and people volunteer experiment show that Nicotine itself can improve the clinical symptom of dementia of the Alzheimer type significantly.For example can be referring to Newhouse., P.A., Kelton, M., Nicotinic systems in centralnervous systems disease:degenerative disorders and beyond, Pharm Acta Helv74 (2000) 91-101 and Nordberg, A.PET studies and cholinergic therapy inAlzheimer ' s disease.Rev Neurol (Paris) 155 (Suppl 4): S53-63 (1999).Therefore, the medicine that can believe effective lifting n receptor can be treated Alzheimer's disease.
In addition, following disease is also relevant with n receptor, believes by promoting these diseases that n receptor can be treated or improvement is relevant with n receptor.
Louis corpusculum disease is a kind of dementia, is only second to the most common dementia disease of Alzheimer.N receptor significantly decreases in the different zones of this class patient brain, for example can be referring to Perry E., et al.Nicotinic receptor subtypes in human brain ageing, Alzheimer and Lewy bodydiseases, Eur J Pharmacol 393 (2000) 215-222.
Vascular dementia: though there is not the interior n receptor of experimental data proof vascular dementia human brain that obvious variation is arranged, because n receptor participates in regulating the cortex volume of blood flow, n receptor remains the important target acceptor of the new medicine of development.For example can be referring to Martin-Ruiz C et al., Nicotinic receptors indementia of Alzheimer, Lewy body and vascular types, Acta Neurol Scand Suppl2000; 176:34-41.
With regard to attention deficiency/hyperkinetic syndrome (Attention Deficit/Hyperactivity Disorder, ADHD), because the smoking rate of the adult patient of this type of disease of trouble is very high, therefore prompting has the potential therapeutic action with n receptor specificity bonded Nicotine class medicine to this disease.Nearest acute this active effect on this illness of treatment of double blinding Nicotine clinical trial proof Nicotine.
Though parkinsonian pathology is different with alzheimer's disease with the cause of disease, with alzheimer's disease roughly the same be that n receptor in these patient's brains significantly decreases.And up-to-date clinical experiment result shows that Nicotine can obviously improve the various clinical symptom that comprises motion and recognition function, for example with reference to Belluardo, N., Mudo, G., Blum, M., Fuxe, K., Central nicotinic receptors, neurotrophic factors and neuroprotection, the content described in Behav Brain Res 113 (2000) 21-34.
Schizophreniac's smoking ratio is up to 90%.Experimentation on animals proof P50 reaction (to the experiment of audio stimulation reaction) is relevant with the α 7 hypotype functional defecies of hippocampus low-affinity n receptor.Genetics studies have shown that the change of the 15th pair of α 7 n receptor regulation domains on the karyomit(e) may be a schizoid feature.Up-to-date result of study shows that also the egg mortar content of α 7N acceptor in schizophrenia patient's brain is obviously with low, for example can be referring to Guan, Z.Z., X.Zhang, K.Blennow, and A.Nordberg.Decreased Protein Level of Nicotinic Receptor alpha7 Subunit in theFrontal Cortex from Schizophrenic Brain, Neuroreport 10 (8): 1779-82 (1999).
In addition, combine and disease about Tu Leiteshi, not only a clinical trial certificate Nicotine by the transdermal nicotine patch, can obviously reduce the face spasm.
According to statistics, the smoking rate of patients with depression reaches 46%.The result of a clinical experiment shows dysthymia disorders severe think of person after accepting 4 days Nicotine skin patchs, and its clinical symptom is obviously improved.
The central pharmacological dependence: it is the heavy smoker that alcohol becomes pain person's majority.Experimental results show that alcohol can obviously reduce the expression of n receptor on cell.The amount of the n receptor in alcoholic's brain also is starkly lower than non-alcoholic.In contrast be that n receptor quantity in smoker's brain is apparently higher than the non-smoker.
Therefore, believe that by promoting the active effect for the treatment of or improving above-mentioned disease can be arranged with nicotine specific bonded n receptor.
In sum, influence on development or improve courage maincenter alkali nervous system function, the medicine that particularly can promote n receptor are for prevention with treat these diseases and have clear meaning.In the art, recover the function of cholinergic system neurotransmission by direct or indirect stimulation cholinergic receptor, and the medicine that influences cholinergic system is provided.Particularly, the medicine that directly stimulates cholinergic receptor is the agonist of acceptor, and the medicine of indirect stimulation cholinergic receptor is a cholinesterase inhibitor.
For treating above-mentioned disease, particularly dementia of the Alzheimer type, mainly adopt cholinesterase inhibitor clinically.The mechanism of action of cholinesterase inhibitor is by suppressing cholinesterase, reduce this enzyme to the hydrolysis of vagusstoff and promote the level of vagusstoff, under the stimulation of high-level vagusstoff, the function of impaired cholinergic nerve system, the function that comprises n receptor is improved or recovers.For example with reference to Giacobini, E., Cholinergic Foundations of Alzheimer ' s Disease Therapy, content is described among J.Physiol Paris 92 (1998) 283-287.
Because the vital role of n receptor on the brain physiological function and the substantial connection of above-mentioned each disease and n receptor pathology, in addition with the obvious clinical effect of n receptor specificity bonded Nicotine itself, be that the research and development of target body medicine are subjected to attention more and more widely in recent years with the n receptor to these common central nervous system diseases.But because Nicotine itself has very strong periphery side effect, itself can not become clinical application.
At present, the other several main directions at development prevention and treatment dementia of the Alzheimer type disease drug are Antybody therapies in the world, the inhibitor of specific enzymes (beta-secretase etc.), anti-senescence compounds (oestrogenic hormon etc.).For the other diseases of listing in the present invention except that dementia of the Alzheimer type disease, the medicine that the The experimental results prompting influences n receptor has potential prevention and treatment meaning to these diseases.
But, use the problem that cholinesterase inhibitor or receptor stimulant faced to be: because the acceptor that is stimulated is an acceptor " residual " or " pathology ", therefore these medicines are to treatment of diseases effect (the base line dependent) of " baseline dependency " often, and promptly curative effect of medication is relevant with the lesion degree of the interior cholinergic nerve system of brain with drug toxicity.This gives in selection of clinical drug dose and the control side effect and has brought certain difficulty.
Therefore, wish that obtaining increasing functional cholinergic receptor expresses and the low medicine of side effect.
Summary of the invention
The present inventor has been surprised to find that saponin has the functional cholinergic n receptor quantity of increasing, and the low effect of side effect simultaneously can be used in the medicine for preparing treatment and central cholinergic system n receptor diseases associated.
The purpose of this invention is to provide the application of a kind of saponin in treatment and nervus centralis cholinergic n receptor diseases associated.Described saponin can be the total saponin that extracts from plant, comprises steroidal and triterpenoid saponin, also can be the saponin by being synthesized into.
Another object of the present invention provides the pharmaceutical composition that comprises described saponin and pharmaceutical carrier, is used for the treatment of and nervus centralis cholinergic n receptor diseases associated.
Particularly, the present inventor's current research is the result show, from some herbal medicine as polygala root (Polygala tenuifolia), pseudo-ginseng (Panax notoginseng), the root of bidentate achyranthes (Achyranthes bidentata), Ningpo Yam Rhizome (Achyranthes bidentata), total saponin of wind-weed extractions such as (Anemarrhena asphodeloides) can promote the binding site of cholinergic n receptor significantly, the lifting amplitude but does not influence the binding site of m receptor between 50% to 300%.The contriver finds that also these total saponins do not suppress combining of n receptor and its specific agonist, so the mechanism that their raise n receptor is to raise the machine-processed different of n receptor with Nicotine.
Total saponin of experiment usefulness contains the triterpenoid saponin and the steroid saponin of different amounts respectively.Triterpenoid saponin and steroid saponin have a lot of isomer, and each component contains isomer and is no less than 20.The molecular weight of isomer is about 1000Da.
Because n receptor and study, memory and recognition function and mood have confidential relation, and above-mentioned in addition central nervous system disease is relevant with the variation of n receptor to a great extent, so these plant sapogenin glycoside compositions can be applied in prevention and treat in this class disease.
Also relate to the pharmaceutical composition that is used to prevent and treat central nervous system disease among the present invention, comprising by extract in the plant can specificity rising maincenter sample cholinergic n receptor triterpene or the total saponin of steroidal, perhaps also can using wherein, one or more have the saponin of described chemical structure or its isomer and the pharmaceutical composition that the universal medication carrier is formed.
The present invention does not get rid of the saponin that has above-mentioned plant sapogenin glycoside structure or obtain to have with spline structure through chemosynthesis can improve or treat the central cholinergic system function, and the pharmaceutical composition that particularly has lifting maincenter sample cholinergic n receptor can be used in the disease described in treatment the present invention.
By extracting in the plant or synthesizing the dosage of saponin in pharmaceutical composition that obtains and to carry out choose reasonable according to the disease specific kind and the state of an illness, do not limit here.
Be used for the formulation of medicine of clinical treatment and additive and administering mode according to clinical effectiveness with make things convenient for patient's conventional use-pattern to design, do not limit here.
Embodiment
The saponin that uses among the present invention can be the total saponin that extracts in the plant.Wherein total saponin refers to by all saponins that extract in the kind of plant.
These saponins can adopt document, and for example " (Huang Taikang chief editor, Chinese medicine science and technology press, April in 1994 the 1st edition, Beijing) described method is extracted and obtained in conventional Chinese medicine composition and the pharmacology handbook.
Particularly, can obtain the plant sapogenin glycoside compound by the method that comprises the following steps:
1, water soaks into plant, boils a few hours in the boiling water, gets supernatant and concentrates.
2, with the enriched material of above gained again with after the water dissolution, through stirring postprecipitation.Water-fast lyophobic dust will precipitate, and the supernatant that contains water soluble molecules reclaims, and concentrates once more.
3, the water soluble extract after concentrating is handled for several times with alcohol, and flush away impurity and salt are used to be further purified behind the partially purified water-soluble substances frost drying.
4, the material that above-mentioned ice is done is further isolated the total saponin component that comprises various different saponins through different types of column chromatography method.
5, isolated total saponin component has carried out further analysis with Gilson high pressure liquid chromatograph-Fimigan AQA mass spectrograph.The concrete operations step is, dried sample water-soluble (2mg/ml), get 30 microlitres and inject Merck Chromatith Performance RP-18e chromatography column (4.6x100mm) through automatic sampler, flow velocity 1.5ml/ branch, 10%-80% is the cyanogen gradient elution, result's Unipoint Lc/MSInterface Window software processes.The result further confirms the component in the above-mentioned sample or mainly is triterpene or steroid saponin.
Embodiment
It below is the non-limiting example that the present invention exemplifies technical solution of the present invention.These embodiment have further described and have illustrated the embodiment in the scope of the invention.It should be understood that, the embodiment that provides herein only is used for illustrative purposes, is not to be used for limiting the present invention, under the condition that does not deviate from spirit and scope of the invention, those of ordinary skills can carry out various changes to it, and this is that those of ordinary skills approve.
Embodiment 1
By polygala root, pseudo-ginseng, Ningpo Yam Rhizome, the wind-weed, Radix Panacis Quinquefolii, the root of bidentate achyranthes, teasel root, the total saponin that extracts in the Radix Astragali is to the influence of the n receptor of human neuroblastoma cell strain SH-SY5Y.
1, the SH-SY5Y cell is cultivated in containing the DMEM nutrient solution of 7.5% calf serum.The condition of cell culture incubator is 37 ℃ and 5%CO 2
2, carry out first day of beginning in cell cultures of drug treating.Medicine dissolves the aseptic membrane filtration degerming of (100mg/10ml) back with 0.2 μ m with cell culture fluid.
3, cell is collected after cultivating 4-5 days under the condition that medicine exists and is used to prepare film homogenate.
4, [ 3H] Epibatidine (n receptor ligands specific, than 48Ci/mmol alive, final concentration 3nM) carries out in the homogenate of SH-SY5Y cytolemma in conjunction with experiment, uses Tris-HCl, and the pH7.4 damping fluid, was incubated temperature in 3 hours by 25 ℃.Isolate bound fraction with the GF/C filter membrane then.Radioactivity liquid flashing counting determining on the GF/C filter membrane.Non-specific binding is by (-) nicotine decision of 0.1mM.
5, the result as shown in Table 1.Polygala root wherein, pseudo-ginseng, Ningpo Yam Rhizome, Rhizoma Anemarrhenae total saponins have obvious lifting n receptor [ 3H] effect of epibatidine binding site.
Table one: the total saponin of plant handle to SH-SY5Y cytolemma n receptor [ 3H] influence of epibatidine binding site
The control group treatment group
[ 3H] the Epibatidine binding site [ 3H] the Epibatidine binding site
The total saponin of (fmol/mg albumen) (fmol/mg albumen) polygala root: 20mg/L 158.1 ± 3.6 287.1 ± 8.4100mg/L 66.5 ± 3.6 179.4 ± 8.3 notoginseng total saponins: 10mg/L 158.1 ± 3.6 258.1 ± 12.7 Yam total saponins: 10mg/L 158.1 ± 3.6 262.4.1 ± 8.7100mg/L 158.1 ± 3.6 268.8 ± 10.1 Rhizoma Anemarrhenae total saponins: 100mg/L 44.0 ± 1.1 112.0 ± 7.5 total panaquilons: 100mg/L 44.0 ± 1.1 54.4 ± 2.3 Achyranthes Bidentata Saponins: the 100mg/L 66.5 ± total saponin of 3.6 88.1 ± 4.4 teasel roots: 100mg/L 66.5 ± 3.6 79.1 ± 6.9 total saponins in astragalus: 100mg/L 66.5 ± 3.6 58.8 ± 3.4
Embodiment 2
By polygala root, pseudo-ginseng, Ningpo Yam Rhizome, the wind-weed, Radix Panacis Quinquefolii, the root of bidentate achyranthes, teasel root, the total saponin that extracts in the Radix Astragali is to the influence of the m receptor of human neuroblastoma cell strain SH-SY5Y.
1, the SH-SY5Y cell is cultivated in containing the DMEM nutrient solution of 7.5% calf serum.The condition of cell culture incubator is 37 ℃ and 5%CO 2
2, carry out first day of beginning in cell cultures of drug treating.Medicine dissolves the aseptic membrane filtration degerming of (100mg/10ml) back with 0.2 μ m with cell culture fluid.
3, cell is collected the homogenate of back preparation film after cultivating 4-5 days under the condition that medicine exists.
4, [ 3H] QNB (m receptor ligands specific, than 48Ci/mmol alive, final concentration 1nM) carries out in the homogenate of SH-SY5Y cytolemma in conjunction with experiment, uses Tris-HCl, and the pH7.4 damping fluid, was incubated temperature in 1.5 hours by 25 ℃.Isolate bound fraction with the GF/C filter membrane then.Radioactivity liquid flashing counting determining on the GF/C filter membrane.Non-specific binding is determined by the coromegine (atropine) of 0.1mM.
5, the result as shown in Table 2.These saponins do not have obvious lifting m receptor [ 3H] effect of QNB binding site.
Table two: the total saponin of plant handle to SH-SY5Y cytolemma m receptor [ 3H] influence of QNB binding site
The control group treatment group
[ 3H] the QNB binding site [ 3H] the QNB binding site
The total saponin of (fmol/mg albumen) (fmol/mg albumen) polygala root: 20mg/L 384.8 ± 3.2 367.2 ± 31.8100mg/L 321.1 ± 26.4 162.6 ± 2.6 notoginseng total saponin: 10mg/L 384.8 ± 3.2 379.5 ± 9.1 Yam total saponin: 10mg/L 384.8 ± 3.2 481.5 ± 15.0100mg/L 384.8 ± 3.2 361.5 ± 14.7 Rhizoma Anemarrhenae total saponins: 100mg/L 219.4 ± 9.7 262.0 ± 11.3 total panaquilons: 100mg/L 219.4 ± 9.7 202.7 ± 6.2 Achyranthes Bidentata Saponins: 100mg/L 321.1 ± total saponin of 26.4 299.0 ± 11.7 teasel roots: 100mg/L 321.1 ± 26.4 320.0 ± 8.7 total saponins in astragalus: 100mg/L 321.1 ± 26.4 355.9 ± 23.1
Embodiment 3
By polygala root, pseudo-ginseng, Ningpo Yam Rhizome, the wind-weed, Radix Panacis Quinquefolii, the root of bidentate achyranthes, teasel root, total saponin competition inhibition of extracting in the Radix Astragali [ 3H] the epibatidine specificity combination that homogenate prepares n receptor to rat brain.
1, the homogenate preparation is obtained by the rat brain of removing cerebellum.
2, [ 3H] the total saponin receptors bind of epibatidine/ experiment condition: [ 3H] epibatidine final concentration 0.5nM, use Tris-HCl, the pH7.4 damping fluid, was incubated temperature in 3 hours by 25 ℃.Isolate bound fraction with the GF/C filter membrane then.Radioactivity liquid flashing counting determining on the GF/C filter membrane.Non-specific binding is by (-) nicotine decision of 0.1mM.
3, the result as shown in Table 3.These saponins do not compete inhibition [ 3H] the epibatidine specificity combination that homogenate prepares n receptor to rat brain, indicate them not combine with the agonist binding site of n receptor.
Table three: the total saponin competition of plant suppresses [3H] epibatidine specificity combination that homogenate prepares n receptor to rat brain
[ 3H] the total saponin of percentage contrast 100 ± 1.4 polygala roots of Epibatidine specific binding: 10mg/L 99.7 ± 4.9100mg/L 99.4 ± 1.9 notoginseng total saponins: 10mg/L 105.5 ± 2.3100mg/L 97.6 ± 1.8 Yam total saponins: 10mg/L 99.1 ± 2.2100mg/L 103.5 ± 5.5 Rhizoma Anemarrhenae total saponins: 10mg/L 98.7 ± 3.3100mg/L 96.8 ± 1.0 total panaquilons: 10mg/L 97.7 ± 4.9100mg/L 99.4 ± 4.9 Achyranthes Bidentata Saponins: the total saponin of 10mg/L 102.6 ± 3.2100mg/L 101.2 ± 3.8 teasel roots: 10mg/L 94.7 ± 0.6100mg/L 101.7 ± 4.9 total saponins in astragalus: 10mg/L 97.6 ± 1.8100mg/L 94.7 ± 2.8
Pass through the foregoing description, those of ordinary skill in the art can clearly understand, can improve the expression of n receptor significantly by the total saponin of polygala root, Radix Notoginseng total arasaponins, Yam total saponin and/or Rhizoma Anemarrhenae total saponins among the present invention and seldom or not influence the expression of m receptor, so they are specific to the effect of n receptor.Because these saponins do not suppress combining of specific agonist and n receptor, illustrate that they do not combine with the agonist bonded site of acceptor.
By contrast, it is to cause n receptor to desensitize because Nicotine combine with the agonist binding site of n receptor that Nicotine raises n receptor mechanism, and the receptor biological change-over period of having desensitized is elongated, and the result is the quantity rising of n receptor.
These plant sapogenin glycoside compounds of the present invention are not that with the agonist binding site bonded meaning of n receptor the n receptor that is raised by plant sapogenin glycoside is the acceptor of non-desensitization, have therefore kept its complete biological function.
Plant sapogenin glycoside with above-mentioned functions, the meaning of saponin aspect clinical therapeutics that obtains through organic synthesis be recover or additional central nervous system in impaired n receptor, and then reach the effect of prevention and treatment and the interior n receptor diseases associated of central nervous system.
And above-mentioned disease is to the therapeutic response of Nicotine class medicine " baseline " often.And the rise of the n receptor that is caused by plant sapogenin glycoside changes or recovers to a certain extent the function of n receptor neurotransmission, this means that the direction that pathology " baseline " is become better transforms, the result of Chan Shenging is other direct or indirect curative effect that stimulates the n receptor medicine of raising therefrom, thereby the new application of saponin in preparation treatment and nervus centralis cholinergic diseases associated is provided.

Claims (7)

1. the application of saponin in the medicine of preparation and central cholinergic system n receptor diseases associated.
2. according to the application of claim 1, wherein said saponin is for can extract the total saponin that obtains from plant, and described plant comprises polygala root, pseudo-ginseng, Ningpo Yam Rhizome and the wind-weed.
3. according to the application of claim 1 or 2, wherein said medicine can be used for the treatment of central nervous system disease, comprises the disease of nerve degenerative diseases, schizophrenia, dysthymia disorders and central drug dependence.
4. according to each application among the claim 1-3, wherein said nerve degenerative diseases comprises alzheimer's disease, Louis corpusculum disease, vascular dementia, Parkinson's disease, Tourette's syndrome.
5. pharmaceutical composition that is used for the treatment of with central cholinergic system n receptor diseases associated, described composition comprises one or more saponin and pharmaceutical carrier.
6. according to the pharmaceutical composition of claim 5, wherein said saponin is for extracting the total saponin that obtains from plant.
7. according to the pharmaceutical composition of claim 5 or 6, wherein said saponin is to extract to obtain from the plant that comprises polygala root, pseudo-ginseng, Ningpo Yam Rhizome and the wind-weed.
CN01142574A 2001-12-03 2001-12-03 Use of saponin Pending CN1422861A (en)

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CN01142574A CN1422861A (en) 2001-12-03 2001-12-03 Use of saponin
AU2002354334A AU2002354334A1 (en) 2001-12-03 2002-12-03 Use of totle saponins compounds and a pharmaceutical composition containing totle saponins compounds
PCT/CN2002/000862 WO2003048182A1 (en) 2001-12-03 2002-12-03 Use of totle saponins compounds and a pharmaceutical composition containing totle saponins compounds

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CN01142574A CN1422861A (en) 2001-12-03 2001-12-03 Use of saponin

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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102274296A (en) * 2010-06-13 2011-12-14 首都医科大学 Application of tenuigenin in preparing medicament for preventing or treating parkinson' disease (PD)
CN115915972A (en) * 2020-12-14 2023-04-04 莱特先进生医股份有限公司 Polygala tenuifolia extract for treating attention deficit hyperactivity disorder

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1083819A (en) * 1993-05-11 1994-03-16 富宁制药厂 Notoginseng total saponin medicines and preparation method thereof
CN1131237C (en) * 1997-09-26 2003-12-17 中国人民解放军军事医学科学院放射医学研究所 Usage of steroi saponin for preventing and curing senile dementia and new steroid saponin

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102274296A (en) * 2010-06-13 2011-12-14 首都医科大学 Application of tenuigenin in preparing medicament for preventing or treating parkinson' disease (PD)
CN102274296B (en) * 2010-06-13 2013-05-08 首都医科大学 Application of tenuigenin in preparing medicament for preventing or treating parkinson' disease (PD)
CN115915972A (en) * 2020-12-14 2023-04-04 莱特先进生医股份有限公司 Polygala tenuifolia extract for treating attention deficit hyperactivity disorder

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AU2002354334A1 (en) 2003-06-17

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