CN115844917A

CN115844917A - Medicinal use of jujuboside A

Info

Publication number: CN115844917A
Application number: CN202310172889.0A
Authority: CN
Inventors: 单磊; 黄雄; 黄晓赟
Original assignee: Guangdong Chuang Yao Lianhe Pharmaceutical Technology Co ltd
Current assignee: Guangdong Chuang Yao Lianhe Pharmaceutical Technology Co ltd
Priority date: 2023-02-24
Filing date: 2023-02-24
Publication date: 2023-03-28

Abstract

The invention provides application of spina date seed saponin A or derivatives thereof in preparing a medicament for preventing or treating a nerve demyelinating disease. The invention also provides a pharmaceutical composition, which comprises the spina date seed saponin A or the derivatives thereof and a pharmaceutically acceptable carrier. The inventor of the invention finds that the spina date seed saponin A can improve, maintain or delay deterioration of myelin sheath diseases and can reduce the effect of demyelination. Therefore, the spina date seed saponin A has important clinical significance and application prospect as a medicine for treating demyelination peripheral nerve diseases.

Description

Medicinal use of jujuboside A

Technical Field

The invention belongs to the technical field of biological medicine, and relates to application of spina date seed saponin A in preparation of a medicine for treating demyelinating diseases.

Background

A demyelinating disease is a disease of the nervous system, which may include diseases affecting the central and peripheral nervous systems. Central nervous system demyelinating diseases including multiple sclerosis, devic's disease, inflammatory nerve demyelinating diseases, central nervous system neuropathies such as caused by vitamin B12 deficiency; bone marrow diseases such as tuberculosis of spinal cord (Tabesdorsalis), leukoencephalopathies such as progressive multifocal leukoencephalopathy, leukodystrophy or combinations thereof. Neurological demyelinating diseases of the peripheral nervous system include Guillain Barre Syndrome (GBS), chronic Inflammatory Demyelinating Polyneuropathy (CIDP), conduction block Multifocal Motor Neuropathy (MMN) and paraproteinemia demyelinating peripheral neuropathy (PDN).

Myelin sheath of neurons in a neurodegenerative disease is damaged, which impairs signal transduction in affected neurons. In turn, a decrease in transduction leads to deficits in sensory, motor, cognitive or other functions depending on the type of nerve affected.

Disclosure of Invention

The invention provides a medicament for preventing or treating a nerve demyelinating disease.

The invention aims to provide application of spina date seed saponin A in preparation of a medicament for treating a nerve demyelinating disease.

The invention also aims to provide a medicine composition which takes the spina date seed saponin A or the pharmaceutically acceptable salt thereof as an active ingredient and is used for treating or preventing various nerve demyelinating diseases.

In a first aspect, the present invention provides the use of jujuboside a or a derivative thereof for the manufacture of a medicament for the prevention or treatment of a demyelinating disease in a nerve.

In the present invention, the jujuboside may be present in different forms, for example, the present invention includes all the variant forms of the compound. In some embodiments, the derivatives of spina date seed saponin include a free acid, a free base, an ester, a prodrug, a pharmaceutically acceptable salt, or a tautomer of spina date seed saponin a.

In some embodiments, the neurodegenerative disease comprises: multiple sclerosis, optic neuritis, idiopathic inflammatory demyelinating diseases, guillain-Barre syndrome, chronic inflammatory demyelinating polyneuropathy, transverse myelitis, barlow's concentric sclerosis, mediocrural myelination, tabes, neuromyelitis optica, progressive multifocal leukoencephalopathy, anti-MAG neuropathy, hereditary motor and sensory neuropathy, tendonoxanthomatosis, and leukodystrophy including adrenoleukodystrophy, adrenomyeloneuropathy, kanawan's disease, evaporative leukopathy, alexander's disease, refsum's disease, pelizaeus-Mezbach disease, metachromatic leukodystrophy, globuloid cell leukodystrophy.

In some embodiments, wherein the neurodegenerative disease is acute inflammatory demyelinating polyneuropathy.

In some embodiments, the spina date seed saponin A or the derivative thereof can relieve symptoms of the nerve demyelination disease, delay the development of the nerve demyelination disease or prolong the recurrence time of the nerve demyelination disease, and effectively protect against demyelination.

In some embodiments, the jujuboside a or a derivative thereof has an effect of protecting demyelination.

The inventor of the invention finds that the spina date seed saponin A has extremely strong NF-kB inhibition activity through the research on the NF-kB inhibition effect of the spina date seed saponin A, carries out animal drug effect experiments on the spina date seed saponin A, and finds that the spina date seed saponin A shows the effects of inhibiting inflammation and effectively protecting the loss of myelin sheath. A therapeutically effective amount of spina date seed saponin A may reduce inflammation, reduce demyelination, reduce axonal loss, and/or reduce neuronal loss. Therefore, the spina date seed saponin A or the derivatives thereof can be developed into the medicine for preventing or treating the nerve demyelinating disease.

In a second aspect, the present invention provides a pharmaceutical composition for preventing or treating a demyelinating disease, the pharmaceutical composition comprising jujuboside a or a derivative thereof, and a pharmaceutically acceptable carrier.

In some embodiments, the derivatives of spina date seed saponins include a free acid, a free base, an ester, a prodrug, a pharmaceutically acceptable salt, or a tautomer of spina date seed saponin a.

In some embodiments, the pharmaceutical composition comprises spina date seed saponin A, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

In some embodiments, the pharmaceutically acceptable carrier comprises one or more of diluents, excipients, fillers, wetting agents, binders, disintegrants, lubricants, conditioning agents, surfactants, and adsorptive carriers.

In some embodiments, the effective amount of the jujuboside a or its derivative in the pharmaceutical composition is 1-95%, such as 1%, 5%, 10%, 20%, 40%, 60%, 80%, 95% or any value therebetween.

The composition of the medicine composition contains the spina date seed saponin A with a therapeutically effective dose or pharmaceutically acceptable salts thereof, and the spina date seed saponin A compound can be used independently in the medicine composition or can be matched with other medicines for use. Wherein the single dose of the pharmaceutical composition contains active ingredient of spina date seed saponin A and the effective content of derivatives thereof in the pharmaceutical composition is 1-95%. The actual dosage level of the active ingredient in the pharmaceutical compositions of this invention may be varied so as to obtain an amount of the active compound which is effective to achieve the desired therapeutic response for a particular patient, composition and mode of administration. The selected dosage level will depend upon the activity of the particular compound, the route of administration, the severity of the condition being treated and the condition and prior medical history of the patient being treated. However, one skilled in the art can start with a lower dose than is required to achieve the desired therapeutic effect and then gradually increase the dose until the desired therapeutic effect is achieved.

The pharmaceutical composition comprises not only spina date seed saponin A or pharmaceutically acceptable salt thereof with a therapeutically effective amount, but also pharmaceutically acceptable carriers, wherein the pharmaceutically acceptable carriers refer to conventional pharmaceutical carriers in the pharmaceutical field, such as: diluents, excipients, and water, etc.; fillers such as starch, sucrose, lactose, microcrystalline cellulose, and the like; binders such as cellulose derivatives, alginates, gelatin, polyvinylpyrrolidone, and the like; humectants such as glycerol; disintegrating agents such as agar, calcium carbonate, sodium bicarbonate, etc.; absorption enhancers such as quaternary ammonium compounds; surfactants such as cetyl alcohol and the like; adsorption carriers such as kaolin and bentonite; lubricants such as talc, calcium stearate, polyethylene glycol, etc., and other adjuvants such as flavoring agents, sweetening agents, etc., may also be added to the composition.

The pharmaceutical composition is any one of the dosage forms in pharmaceutics, including tablets, capsules, soft capsules, gels, oral agents, suspensions, medicinal granules, patches, ointments, pills, powder, injections, infusion solutions, freeze-dried injections, intravenous emulsions, liposome injections, suppositories, sustained-release preparations or controlled-release preparations. Preferred forms are tablets, coated tablets, capsules, granules, oral liquids and injections.

The pharmaceutical compositions of the invention may be administered generally orally, intravenously, subcutaneously, buccally, rectally, dermally, intranasally, tracheally, bronchially, by any other parenteral route, for example by oral or nasal spray or by inhalation.

Various dosage forms of the pharmaceutical composition of the present invention can be prepared according to conventional production methods in the pharmaceutical field, and then prepared into desired dosage forms. The pharmaceutical compositions may be prepared using any of a variety of methods, including but not limited to, conventional mixing, dissolving, granulating, dragee-making, grinding, emulsifying, encapsulating, entrapping, and lyophilizing.

The pharmaceutical compositions of the invention may be used to treat a variety of neurological demyelinating diseases, including diseases affecting the central and peripheral nervous systems. Such as: neurological demyelinating diseases include: multiple sclerosis, optic neuritis, idiopathic inflammatory demyelinating diseases, guillain-Barre syndrome, chronic inflammatory demyelinating polyneuropathy, transverse myelitis, barlow's concentric sclerosis, mediocrural myelination, tabes, neuromyelitis optica, progressive multifocal leukoencephalopathy, anti-MAG neuropathy, hereditary motor and sensory neuropathy, tendonoxanthomatosis, and leukodystrophy including adrenoleukodystrophy, adrenomyeloneuropathy, carnanwan disease, effaceous leukopathy, alexander disease, refsum disease and Pelizaeus-Merzbach disease, metachromatic leukodystrophy, globuloid cell leukodystrophy.

The invention also provides a method of preventing or treating a demyelinating disease in a subject, the method comprising administering to the subject in need thereof a therapeutically effective amount of jujuboside a or a derivative thereof.

In some embodiments, the method comprises administering to a subject in need thereof a therapeutically effective amount of jujuboside a or a pharmaceutically acceptable salt thereof.

The methods of the invention include treatment of mammals. Mammals include humans.

The invention provides a spina date seed saponin A or a derivative thereof with effective treatment amount. A "therapeutically effective amount" is synonymous with a "therapeutically effective dose" and, when used in the treatment of a neurodegenerative disease, refers to the dose of a compound, composition or combination necessary to achieve the desired therapeutic effect, including doses sufficient to alleviate symptoms or to bring a patient into clinical remission. The amount of active ingredient in the compounds, compositions or combinations of the invention for the treatment of a neurodegenerative disease can be varied in order to obtain a suitable dosage.

In addition, where repeated administrations of the compounds or pharmaceutical compositions of the invention are used, the actual effective amount of the compound or pharmaceutical composition of the invention will further depend on factors including, but not limited to, the frequency of administration, the half-life of the compound or pharmaceutical composition of the invention. The large differences in the necessary effective amounts are to be expected in view of the different efficiencies of the various routes of administration. For example, oral administration typically requires higher dosage levels than administration by intravenous injection.

Administration can be single dose or cumulative (continuous administration) and can be readily determined by one skilled in the art. For example, treatment of a neurodegenerative disease may include a single administration of an effective dose of a compound or pharmaceutical composition of the invention. Alternatively, treating a neurodegenerative disease may comprise administering an effective dose of a compound or pharmaceutical composition of the invention multiple times over a period of time, e.g., daily, every few days, weekly, monthly, or yearly.

The inventor of the invention finds that the spina date seed saponin A can improve, maintain or delay the deterioration of myelin sheath diseases and reduce the effect of demyelination through experiments. Therefore, the spina date seed saponin A has important clinical significance and application prospect as a medicine for treating demyelination peripheral nerve diseases.

Drawings

FIG. 1 shows inhibition of jujuboside A targeting NF-kB signaling pathway based on reporter gene.

FIG. 2 shows the results of experiments on proliferation of MNC from rat lymph nodes stimulated by SAPONIN A with different antigens.

FIG. 3 shows the effect of jujuboside A on TNF- α, IFN- γ and IL-10 content in experimental autoimmune neuritis model.

FIG. 4 shows the effect of spina date seed saponin A on pathological sections of sciatic nerve in an experimental autoimmune neuritis model. Wherein A is normal control group, B is ENA group, C is semen Ziziphi Spinosae saponin A group, HE × 400.

FIG. 5 shows the change of MBP myelin sheath marker protein content with time in CPZ-mediated acute demyelination animal models.

FIG. 6 shows the time-dependent changes in the content of two myelin markers PLP and CNPase in CPZ-mediated acute demyelination animal models.

FIG. 7 shows the effect of jujuboside A on GST-pi labeling and BDNF expression in CPZ-mediated acute demyelination animal models.

Figure 8 shows the effect of jujuboside a on Myelin Basic Protein (MBP) in an animal model of CPZ-mediated acute demyelination.

In fig. 1-8, P <0.05, P <0.01, P <0.001.

Detailed Description

In order to make the objects, technical solutions and advantages of the present invention more apparent, the present invention is further described in detail with reference to the following embodiments. The specific embodiments described herein are merely illustrative of the invention and do not constitute any limitation on the invention. Moreover, in the following description, descriptions of well-known structures and techniques are omitted so as to not unnecessarily obscure the concepts of the present disclosure. Such structures and techniques are also described in numerous publications.

Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly used in the art to which this invention belongs. For the purpose of explaining the present specification, the following definitions will apply and, where appropriate, terms used in the singular will also include the plural and vice versa.

As used herein, the expressions "a" and "an" include plural references unless the context clearly dictates otherwise. For example, reference to "a cell" includes a plurality of such cells and equivalents thereof known to those skilled in the art, and so forth.

In the application, jujuboside A (jujuubiside A), the molecular formula is C58H94O26, the molecular weight is 1207.36, and the Jujuboside A is a triterpenoid saponin compound contained in Chinese date. The structural formula of the spina date seed saponin A is as follows:

the term "treatment" includes treatment to ameliorate one or more symptoms of a neurological demyelinating disease, or to delay the progression of such a disease, e.g. to prevent or delay demyelination such as peripheral demyelination; it also includes treatments to cure such diseases, to bring the patient into a normal functional state and/or to maintain the patient in a normal functional state or to prolong the time to relapse. Therapeutic uses may include prophylactic uses, preventing, controlling or lessening the severity of the onset of a demyelinating disease in a patient, and treatments that control or lessen the severity of an existing disease. The drug or pharmaceutical composition may be administered prior to the onset of symptoms; administration may also be after the onset of symptoms. It can be administered to a patient who may be at risk of onset of a demyelinating disease.

The following examples and figures are provided to aid in the understanding of the present invention. It is to be understood that these examples and drawings are illustrative of the invention and are not to be construed as limiting in any way. The actual scope of the invention is set forth in the following claims. It is to be understood that any modifications and variations may be made without departing from the spirit of the invention.

The various reagents used in the experiments are commercially available in conventional amounts unless otherwise indicated.

Example 1: inhibition effect of spina date seed saponin A compound on reporter gene-based targeting NF-kB signal pathway

NF-kB-RE-Luci 293 cell strain (Beijing Ongsheng Dai Bio Inc.) growing at logarithmic phase was blown out, and a vial of cell-regulated cell suspension was inoculated into a 96-well cell culture plate at a rate of 1:3, 200. Mu.L per well. Placing at 37 ℃ with 5% CO ₂ After 24h was cultured in the incubator, 100 μ L of medium was discarded per well. TNF-alpha (Kingsry) is not added to the blank group, and PBS with the proportion of 100 mu L and the DMSO of the experimental group is added; adding 50 muL of PBS and 50 muL of 1000ng/mL TNF-alpha stimulation in each hole of the inflammation model group with the same DMSO proportion as that of the experiment group; adding 50 mu of LPDTC solution (Biyunnan company) and 50 mu L of TNF-alpha stimulation of 200ng/mL into each hole of the positive control group; different concentrations of drug solutions and 50 μ L of 200ng/mL TNF-. Alpha.solutions were added to each well of the experimental group (note: TNF-. Alpha.solutions were added 1h after drug addition). After further incubation for 24h, the culture medium was aspirated from each well, gently added with 25. Mu.L PBS, and lysed at-80 ℃ for at least 30min. The plates were removed and thawed at room temperature, substrates Steady-Glo Reagent (Promega Corp.) 25. Mu.L were added per well and lysed in the dark for at least 20 min. Taking the reaction solution 40 mu L to 384 wells in whiteAnd (3) an enzyme label plate, and detecting a chemiluminescence value (RLU) by using an enzyme label instrument, wherein the result is shown in figure 1, and the value represents the expression level of luciferase in each detection sample, thereby indirectly reflecting the activation level of NF-kB.

The results after drug treatment show that the spina date seed saponin A (Baoji chenguangyo) has obvious NF-kB inhibition activity at the concentration of 0.1, 1 and 10 mu m/L and is in a dose-effect relationship.

Example 2: effect of spina date seed Saponin A on Experimental autoimmune neuritis model

The molding method comprises the following steps:

healthy male Lewis rats (southern university of medicine laboratory animal center) with the weight of 220g-280g are randomly divided into 3 groups, each group comprises 10 normal control groups, ENA groups and spina date seed saponin A groups, and the tail root of the ENA group is subcutaneously injected with mixed emulsion of 200 mu L P257-81 polypeptide and Freund's complete adjuvant (MPbio company), weighed every other day and observed the disease. The spina date seed saponin A group is subjected to intraperitoneal injection of 200 mu L of spina date seed saponin A at an amount of 5 mg/kg once every other day from 0 day of immunization, and a normal control group is given PBS with the same volume. The disease degree is divided into 0-10 grade, 0 grade: no abnormality; level 1: the tension of the tail part is reduced, and the tail tip is upwarped; and 2, stage: tail paralysis, loss of righting reflex; and 3, level: loss of righting reflection; 4, level: gait disorder and abnormal posture; and 5, stage: hind limb paresis; and 6, level: moderate paralysis; and 7, stage: severe paralysis of hind limbs; and 8, stage: quadriplegia; and 9, stage: dying; 10 level: and death.

The experimental method comprises the following steps:

lymphocyte proliferation assay: on day 16 of sensitization, 5 rats were randomly selected from each group, and subjected to lymph node mononuclear cell (MNC) isolation and PBS-induced mononuclear cell proliferation assay. The cell suspension was added to a 96-well plate at 200. Mu.L per well, 10. Mu.L of LRPMI 1640 culture medium and PBS were added to each sample per 3 wells, followed by 3H-thymidine culture 16H per well, and finally the culture was collected on a type 49 glass fiber filter paper, dried at 80 ℃ and the filter paper sheet was put into a scintillation cup to which a scintillation fluid was added, and the number of pulses per well per minute (CPM) was measured on a beta liquid scintillation counter (PE Co.).

Sensitization 16 thTian lymph node MNC (2X 10) ⁶ /mL) for 56h, taking the supernatant of the culture solution, and performing content determination of TNF-alpha, IFN-gamma and IL-10 by using a double-antibody sandwich ELISA method.

On day 16 of sensitization, rats were sacrificed, bilateral sciatic nerves were taken, sciatic nerve pathological sections were performed, hematoxylin-eosin (HE) staining was performed, and the area of nerve tissue and the number of inflammatory cells on the sections were measured with an image analysis system in terms of the number of inflammatory cells/mm ² And (4) showing.

The experimental results are as follows:

the normal control group had no disease in rats; the rats in the ENA group begin to attack the disease on day 8, paralysis reaches the peak around day 16, and is gradually relieved after day 18; the seed of wild jujube saponin A group starts to get ill on the 9 th day after sensitization, paralysis reaches the peak around the 19 th day, and gradually relieves after the 21 st day.

The results of experiments on the proliferation of lymph node MNC of rats stimulated by different antigens on the 16 th day of sensitization are shown in figure 2, compared with the ENA group, the spina date seed saponin A group can obviously inhibit the proliferation of mononuclear cells induced by PBS, and the ENA group has no difference with a normal control group.

Sensitized day 16 lymph node MNC (2X 10) ⁶ mL) after 56h of culture, the contents of TNF-alpha, IFN-gamma and IL-10 are shown in figure 3, the levels of TNF-alpha and IFN-gamma in the culture supernatant are obviously lower than those of the ENA group but higher than those of the normal control group, and the IL-10 level has no obvious difference among the groups.

The sciatic nerve pathology results are shown in figure 4: on the 16 th day of sensitization, a normal control group is normal, and rat sciatic nerve HE staining pathological sections of spina date seed saponin A group and ENA group show inflammatory cell infiltration and focal demyelination between nerve tracts and in nerve tracts. The inflammatory cell infiltration of the spina date seed saponin A group is obviously lighter than that of the ENA group (P is less than 0.01).

Example 3: experiment of spina date seed saponin A on CPZ-induced acute demyelination animal model

The experimental method comprises the following steps:

6-8 week old C57Bl/6 male mice (southern medical university laboratory animal center) weighing about 18-20g, SPF grade, were divided into the following 4 groups according to experimental needs: (1) normal control group: feeding conventional feed for 6 weeks and normally drinking water; (2) model group (denoted CPZ group): feeding feed containing 0.2% copper ion chelating agent CPZ (Sigma company) for 6 weeks and drinking water normally; (3) 25 mg/kg wild jujube saponin A group (denoted as wild jujube saponin A25 group): feeding 0.2% CPZ-containing feed for 6 weeks, drinking water normally and administering spina date seed saponin A (25 mg/kg/day) at the end of 3 weeks; (4) 50 mg/kg jujuboside group A (jujuboside group A50): feeding the feed containing 0.2% of CPZ for 6 weeks, drinking water normally, and administering spina date seed saponin A50 mg/kg/day at the end of 3 weeks; the test drug is continuously administered for 3 weeks until the end of the experiment, and the normal control group and model group animals are administered an equal volume of solvent.

The experimental results are as follows:

1. in the model group of CPZ-mediated acute demyelination, a semi-quantitative statistical method for content is adopted to detect the change of the content of three myelin sheath marker proteins, namely MBP, PLP and CNPase, along with time every week. As shown in fig. 5 and fig. 6, the content of three myelin marker proteins, MBP, PLP and CNPase, in the brain of mice decreased significantly with time after animals were fed with CPZ-containing feed, indicating the gradual loss of myelin in CPZ-mediated acute demyelination animal model.

2. After feeding for 6 weeks, the influence of each group on the expression of brain-derived neurotrophic factor (BDNF), mature oligodendrocyte (GST-pi marker) and Myelin Basic Protein (MBP) of the CPZ-mediated acute demyelination animal model is detected. As shown in fig. 7 and 8.

The semi-quantitative statistical result of the average area of Myelin Basic Protein (MBP) shows that myelin lipid loss of model animals is serious after the animals are fed with CPZ-containing feed for 6 weeks, and the group of spina date seed saponin A has the effect of protecting myelin loss.

The number of mature oligodendrocyte OLs (GST-pi mark) is obviously reduced in the model group compared with the normal control group, and the GST-pi positive cells can be increased by administering different doses of spina date seed saponin A groups, wherein P is less than 0.01. The jujuboside A group has dose dependence on the increase of the number of positive cells of GST-pi in a unit area.

Increasing the expression of BDNF can provide nutritional support for the demyelination to combat or reverse demyelination caused by CPZ, and the results show that the group of jujuboside a can significantly up-regulate the expression of BDNF in the acute phase brain.

And (4) experimental conclusion:

the spina date seed saponin A can promote the expression of a myelin loss part OLs (GST-pi marker) and the expression of a neurotrophic factor BDNF in an animal model of CPZ-induced acute myelin loss, and the spina date seed saponin A has obvious effects of resisting and relieving CPZ-mediated acute myelin loss.

As can be seen from the above, the experimental results of examples 1-3 show that the jujuboside A has a strong NF- κ B inhibitory effect, and the jujuboside A can significantly inhibit PBS-induced mononuclear cell proliferation and can effectively protect the demyelination. Therefore, the jujuboside A can be used for preparing the medicine for preventing or treating the demyelinating peripheral neuropathy.

The technical solution of the present invention is not limited to the above-mentioned specific embodiments, and all technical modifications made according to the technical solution of the present invention fall within the protection scope of the present invention.

Claims

1. Use of spina date seed saponin A or its derivative in preparing medicine for preventing or treating nerve demyelinating disease is provided.

2. The use of claim 1, wherein the derivative of spina date seed saponin comprises a free acid, a free base, an ester, a prodrug, a pharmaceutically acceptable salt, or a tautomer of spina date seed saponin A.

3. The use of claim 1, wherein the neurodegenerative disease comprises: multiple sclerosis, optic neuritis, idiopathic inflammatory demyelinating diseases, guillain-Barre syndrome, chronic inflammatory demyelinating polyneuropathy, transverse myelitis, barlow's concentric sclerosis, mediocrural myelination, tabes, neuromyelitis optica, progressive multifocal leukoencephalopathy, anti-MAG neuropathy, hereditary motor and sensory neuropathy, tendonoxanthomatosis, and leukodystrophy including adrenoleukodystrophy, adrenomyeloneuropathy, kanawan's disease, evaporative leukopathy, alexander's disease, refsum's disease, pelizaeus-Mezbach disease, metachromatic leukodystrophy, globuloid cell leukodystrophy.

4. The use according to claim 3, wherein the neurodegenerative disease is acute inflammatory demyelinating polyneuropathy.

5. A pharmaceutical composition for preventing or treating a demyelinating disease of nerves, the pharmaceutical composition comprising spina date seed saponin A or a derivative thereof, and a pharmaceutically acceptable carrier.

6. The pharmaceutical composition of claim 5, wherein the derivative of spina date seed saponin comprises a free acid, a free base, an ester, a prodrug, a pharmaceutically acceptable salt, or a tautomer of spina date seed saponin A.

7. The pharmaceutical composition of claim 5, wherein the pharmaceutical composition comprises spina date seed saponin A or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

8. The pharmaceutical composition of claim 5, wherein the pharmaceutically acceptable carrier comprises one or more of diluents, excipients, fillers, wetting agents, binders, disintegrants, lubricants, conditioning agents, surfactants, and adsorptive carriers.

9. The pharmaceutical composition of claim 5, wherein the pharmaceutical composition is in the form of a tablet, a coated tablet, a granule, a capsule, a soft capsule, a gel, an oral preparation, a suspension, a granule, a patch, an ointment, a pill, a powder, an injection, an infusion solution, a lyophilized injection, an intravenous emulsion, a liposome injection, a suppository, a sustained release preparation or a controlled release preparation.

10. The pharmaceutical composition of claim 5, wherein the effective amount of the spina date seed saponin A or the derivative thereof in the pharmaceutical composition is 1-95%.