JP5394701B2 - Nerve cell activator - Google Patents

Description

The present invention comprises a nerve cell activator having a nerve nerve growth factor (beta nerve growth factor, hereinafter abbreviated as “NGF”) production promoting activity, an NGF-like activity and an NGF action enhancing activity, and the nerve cell activator. More specifically, it relates to pharmaceutical compositions , and more specifically, it is effective in preventing aging of the nervous system, preventing progression of neurological disorders, or improving central nervous system disorders and peripheral neuropathies. The present invention relates to a highly safe nerve cell activator containing an oxide.

  With the shift to an aging society, senile dementia tends to increase and is becoming a social problem. Many diseases that cause senile dementia are known, and are classified into dementia due to cerebral organopathy, dementia associated with organ diseases other than brain, and dementia due to physical disease due to stress. In addition, dementia due to cerebral organopathy is classified into cerebrovascular dementia and Alzheimer type dementia depending on the cause.

  Currently, cerebral vasodilators are known to have some effect on cerebrovascular dementia, but the cause of Alzheimer-type dementia is still unknown, and acetylcholine Although degrading enzyme inhibitors are also on the market, they cannot be said to be sufficient in terms of the sustained effect. Therefore, it is desired to develop pharmaceuticals and foods useful for dementia due to cerebral organopathy, particularly Alzheimer-type dementia.

  In recent years, it has been found that neurotrophic factors such as NGF secreted from nerve cells have an excellent effect on neurodegenerative diseases. NGF is an important and necessary factor for nerve tissue growth and function maintenance. NGF is also essential for maturation, differentiation, and maintenance of sensory and sympathetic nerves in peripheral nerves and large cell cholinergic neurons in the central nervous system, and has the effect of preventing neuronal degeneration during brain injury. Show.

  NGF is a protein that promotes embryonic perception and sympathetic ganglion neuron differentiation and growth in the peripheral nervous system and promotes neurite outgrowth, and for mature sympathetic neurons to survive and maintain function throughout life It is known to be an essential protein. For example, when an NGF antibody is continuously administered to young animals to neutralize the physiological activity of NGF, remarkable atrophy of sympathetic ganglia and death of ganglion neurons have been observed (Non-patent Document 1). 2). This phenomenon is irreversible and proves the importance of the physiological role of NGF. In addition, applied research on the action of NGF has been conducted, and it has been clarified that NGF is also effective for regeneration of nerve axons (Non-patent Document 3).

  On the other hand, the importance of NGF in the central nervous system is also known, for example, by administering NGF into the ventricle of rats that have cut off the nerve tracts that project from the septum to the hippocampus. Nerve cell degeneration and loss are suppressed (Non-Patent Documents 4 and 5), learning and memory ability of old rats are improved by intracerebroventricular administration of NGF (Non-Patent Document 6), after brain ischemia It has been reported that delayed cell death of hippocampal pyramidal cells is suppressed by pre-administration of NGF (Non-patent Document 7).

As a result, increasing NGF levels in vivo can cause central dysfunction and spinal cord disorders such as Alzheimer-type dementia and cerebrovascular dementia, peripheral nerve damage, diabetic neuropathy, and amyotrophic lateral sclerosis. It is thought to be useful for the treatment of peripheral dysfunction such as symptom.
However, NGF is a protein having a molecular weight of 13,000 as a monomer and 26,000 as a dimer, and cannot pass through the blood brain barrier. Therefore, for example, for the treatment of central dysfunction, intraventricular administration is required. Furthermore, large-scale preparation of NGF is difficult. Thus, there are many problems in using NGF itself, and it is very difficult to use NGF itself.

  Therefore, since NGF is an indispensable factor for the survival of nerve cells, a search for a substance that promotes the production of NGF has been carried out for the purpose of preventing or treating the progression of nerve diseases and nerve cell disorders. As a result, catecholamines (Non-patent Document 8), cholinergic agonists (Patent Document 1), cinnamic acid amide compounds (Patent Document 2), benzoquinone derivatives (Non-patent Document 9), and propentophilin (non-patent documents) Patent Document 10) reports that NGF production is promoted. In addition, fibroblast growth factor, platelet-derived growth factor, transforming growth factor alpha and beta, epidermal growth factor In addition, so-called cell growth factors such as insulin-like growth factor have been recognized to promote NGF production (Non-patent Document 11).

  However, from the viewpoint of achieving prevention or progression prevention of the above-mentioned diseases on a daily basis, it is desirable to have a rich dietary experience and take a composition derived from food having NGF production promoting action.

  Food-derived substances or extracts that promote NGF production include crushed or extracted from hops or ashitaba (Patent Document 3), rosemary-derived carnosic acid (Patent Document 4), green tea-derived theanine (patent Document 5), fucoidan derived from gagome kombu (patent document 6), protamine (patent document 7) and the like are known.

  In addition, as a substance or extract derived from mushrooms, there are many reports on Yamabushitake extract (Patent Document 8), and other Beech Hallitake extract (Non-patent Document 12), Kinugasatake extract (Patent Document 9), and Keroji extract. (Patent Document 10), Shakashimeji Extract (Patent Document 11) and the like are known.

  On the other hand, there are also reports of food-derived low-molecular components that mimic the function of NGF and promote neurite extension. The plant-derived extract described in Patent Document 12 is a polyalkoxyflavonoid derived from a Citrus family, and Patent Document 13 discloses a neurite elongation agent containing rosemary or sage-derived carnosic acid.

  Patent Document 14 discloses a nerve growth factor action enhancer containing an isothiocyanate compound that is a spicy component peculiar to cruciferous plants. Although this nerve growth factor action enhancer alone does not show neurite extension action, it enhances neurite extension action of NGF in the presence of NGF.

  Use of the food-derived composition as described above is useful in that it can prevent unwanted side effects on the living body. However, these compositions have the problem that the effect is not always sufficient in addition to the fact that the supply of raw materials is not always stable.

  Nerve cell activator that has NGF production promoting action and NGF-like activity, that is, neurite outgrowth action is not known except carnosic acid, and other food materials having both actions equal to or higher than carnosic acid Ingredients present in are required.

On the other hand, ergosterol peroxide (EPO) is an oxysterol type ceteroid known to exist widely in mushrooms, yeasts, lichens, sponges and the like. Recent research reports that EPO has immunosuppression, anti-atherosclerosis, apoptosis induction, anti-inflammatory action (Non-patent Document 13) and osteoclast differentiation / proliferation inhibitory action (Patent Document 15). ing. However, it was not known at all that EPO has a nerve activation effect.
R. Levi-Montalcina et al., Physiological Review, 48, 534-569, 1968 H. Thoenen et al., Physiological Review, 60, 1284-1335, 1980 Rich et al., Experimental Neurology, 105, 162-170, 1989 F. Hefti, Journal of Ncuroscience, 6, 2155-2162, 1986: LFKromer, Science, 235, 214-216, 1987 LR Williams et al., Proceedings of National Academy of Sciences USA 83, 9231-9235, 1986 W. Fisher et al., Nature, 329, 65-68, 1987 Shigeno et al., History of Medicine, Vol.145, 579-580, 1988 Y. Furukawa et al., Journal of Biological Chemistry, 261, 6039-6047, 1986 JP-A-63-83020 JP-A-2-104568 R. Takeuchi et al., FEBS Letter, 261, 63-66, 1990 I. Shinoda et al., Biochemical Pharmacology, 39, 1813-1816, 1990. Shinoda et al., Biochemistry, 62, 835, 1990 Table 2003-006037 JP 2001-233835 A JP 7-173059 A No. 2000-062785 JP-A-5-51325 JP-A-7-70168 Okuyama S, Terashima T, Kawamura Y, YokogoshiH, Nutr Neurosci. 7, 741-47, 2004 JP-A-9-020714 JP 11-269125 A JP 2007-137878 A JP 2002-60340 A JP 2007-230945 A JP 2006-16362 A Joo-Sang Lee et al., Biol. Pharm. Bull., 31, 949-954, 200 JP 2008-127378 A

  As mentioned above, among food-derived ingredients, neurotrophic factor-like substances that substitute for the action of NGF, neurotrophic factor production-promoting substances that promote the synthesis and release of neurotrophic factors such as NGF, and neurotrophic factors In general, the action of a compound that enhances the action of is weak and the supply is not always easy. This invention is made | formed in view of the said situation, and makes it a subject to provide the nerve cell activator which consists of a compound distributed widely in foodstuffs and said nerve cell activation effect | action high.

  As a result of searching for ingredients having a high nerve cell activation action in food materials, the present inventors have found that ergosterol peroxide, particularly ergosterol peroxide (EPO), widely present in fungi such as mushrooms and yeasts. Was found to have high neuronal cell activation activity such as neurotrophic factor-like activity, neurotrophic factor production promoting activity, and neurotrophic factor action enhancing activity, leading to the completion of the present invention.

That is, the present invention

  The gist of the present invention is a nerve cell activator characterized by containing ergosterol peroxide as an active ingredient.

Another gist of the present invention is a pharmaceutical composition characterized by containing the above-described nerve cell activator.

  According to the present invention, by using ergosterol peroxide present in dietary mushrooms and yeast as a pharmaceutical composition or food composition, it is possible to prevent aging of the nervous system and prevent or improve the progression of neurological disorders. I can expect. That is, it promotes the survival and functional maintenance of nerve cells to prevent or ameliorate aging of the nervous system, and for damaged nerve cells, prevents their own metamorphic loss and prevents the progression of nerve damage. Can be improved.

  The ergosterol peroxide represented by the above formula (1) provided by the present invention is characterized by containing ergosterol peroxide or a derivative thereof. Ergosterol peroxide can also be separated and purified from white pickled bamboo, for example, as described in the examples herein, but is not necessarily limited to white picked bamboo, and any moss, yeast, Molds and the like can be used as an extraction source.

As for moss, Amanita mushrooms such as shiitake, matsutake, hon-shimeji, eringi, enokitake, shironamemutake, nameko, chanametsutake, etc. A medicinal candy such as semi-bamboo is exemplified, but it is not limited thereto as long as it contains a high amount of EPO. These moss may be natural or artificially cultivated. In addition to fruit bodies, mycelia obtained by liquid culture can be used as a source.

Examples of yeasts include Saccharomyces and Schizosaccharomyces such as baker's yeast and liquor yeast. These yeasts can be prepared in large quantities by liquid culture.

Examples of molds include molds used in food production such as Aspergillus or blue mold.
These molds can also be prepared in large quantities by liquid culture.

  In order to extract ergosterol peroxide from these extraction materials, a solvent may be added to the above materials, but it is preferable to add a solvent to the crushed material after crushing the dried material if possible. Examples of extraction solvents include alcohols such as water, methanol, ethanol, isopropyl alcohol, n-butyl alcohol, tert-butyl alcohol, and amyl alcohol, ketones such as acetone and methyl ethyl ketone, and esters such as methyl acetate and ethyl acetate. A solvent can be used. A mixture of these solvents at an arbitrary ratio may be used as the extraction solvent. Especially, when using with respect to a foodstuff, water and ethanol are desirable, and in order to raise extraction efficiency, it is also possible to use an enzyme, various surfactant, etc. in the range which does not impair the effect of this invention. Further, in addition to using a solvent as described above, it is also possible to use a supercritical extraction method that has been attracting attention in recent years.

  The ratio of the extraction solvent to the extraction raw material can be appropriately determined without any particular limitation. Moreover, extraction time, temperature, etc. can also be determined suitably.

  After the extraction, the mixture of the crushed material and the solvent may be solid-liquid separated by a known method, and only the extract may be recovered. Examples of the solid-liquid separation method include, but are not limited to, centrifugal separation, filter press, and suction filtration.

  If necessary, an extract containing ergosterol peroxide can be obtained by dehydrating the extract using a dehydrating agent such as anhydrous sodium sulfate and then distilling off the solvent. The extract thus obtained can be further fractionated and fractionated as appropriate by column chromatography such as liquid chromatography, extraction, fractional precipitation and the like. In this way, the fraction with increased purity can be used instead of the extract. The fraction may be further purified and isolated by any method such as liquid-liquid distribution method, chromatography method, molecular distillation, rectification and the like.

  Ergosterol peroxide can also be synthesized by photosensitizing reaction of ergosterol under an oxygen stream (Nature, 216, 397, 1967).

  The ergosterol peroxide of the present invention can be prepared by derivatizing the hydroxyl group at the 3-position of the ergosterol peroxide obtained as described above.

Derivatives include esterified products of C ₁ to C ₈ fatty acids that may form a branched or ring such as acetic acid, propionic acid, butyric acid, etc., monosaccharides such as glucose, mannose, galactose, oligos such as lactose, maltose, etc. Glycosides with saccharides can be raised, but the derivatives are not necessarily limited to these derivatives as long as the neurostimulatory action of ergosterol peroxide is not lost.

  The ergosterol peroxide obtained as described above becomes the nerve cell activator of the present invention as it is or by adding other components as necessary.

  As other components contained in the nerve cell activator of the present invention, it can be mixed as long as it does not reduce the neurite activation activity, for example, conventionally used surfactants, solvents, It can be mixed with additives such as thickeners, stabilizers, preservatives, antioxidants, flavorings and the like.

  The nerve cell activator contains ergosterol peroxide as an active ingredient. The content of the active ingredient may vary depending on the age, weight, etc. of the subject to be ingested, but is preferably contained so that it can be taken in an amount of 0.1 to 1000 mg / kg per adult day in terms of ergosterol peroxide, Furthermore, 1-100 mg / kg is preferable and 5-50 mg / kg is the most preferable.

  The pharmaceutical composition of the present invention contains the above nerve cell activator. The content of the nerve cell activator may vary depending on the age, weight, etc. of the subject to be ingested, but it should be 0.1 to 1000 mg / kg per day for adults in terms of ergosterol peroxide. 1 to 100 mg / kg is more preferable, and 5 to 50 mg / kg is most preferable.

  Various additives contained in the pharmaceutical composition of the present invention include surfactants, excipients, colorants, preservatives, coating aids, and combinations thereof. These additives are not particularly limited as long as they are additives in normal pharmaceutical production, and more specific examples include lactose, dextrin, sucrose, mannitol, corn starch, sorbitol, crystalline cellulose, polyvinylpyrrolidone, dextrin, and methylcellulose. , Carboxymethylcellulose salt, stearic acid and its salts, additives such as talc, and combinations thereof. Furthermore, spices, sweeteners and the like may be added. Furthermore, you may add another chemical | medical agent, a food ground material, and a food extract as needed.

  The dosage form of the pharmaceutical composition is not particularly limited, and the pharmaceutical composition is produced in an appropriate dosage form according to the Japanese Pharmacopoeia. Specifically, it is produced in dosage forms such as capsules, tablets, powders, sustained-release agents.

When the nerve cell activator of the present invention is added to food or drink, the content of the nerve cell activator may vary depending on the age, weight, etc. of the subject to be ingested, but per adult day in terms of ergosterol peroxide The content is preferably 0.1 to 1000 mg / kg, more preferably 1 to 100 mg / kg, and most preferably 5 to 50 mg / kg.

  Other materials that can be mixed with foods and drinks containing the nerve cell activator of the present invention include those that can be generally used as food materials. Examples include polysaccharides obtained from rice, wheat, corn, potato, kelp, proteins obtained from soybeans and dairy products, animal raw materials, glucose, lactose, fructose, sucrose, mannitol, xylitol, various oligosaccharides, etc. Examples include saccharides, as well as combinations thereof. Furthermore, spices, colorants, sweeteners, acidulants, edible oils, vitamins and other food crushed products, food extracts and the like may be added. These suitable materials and additives are used alone or in combination. Furthermore, you may process to a desired shape by adding water as needed.

  Specific examples of food and drink include confectionery (gum, candy, caramel, chocolate, cookies, snack confectionery, jelly, gummy, tablet confectionery, etc.), noodles (soba, udon, ramen, etc.), dairy products (milk, ice cream, Yogurt, etc.), seasonings (miso, soy sauce, etc.), soups, beverages (juice, coffee, tea, tea, carbonated drinks, sports drinks, etc.) and general foods and health foods (tablets, capsules, etc.), nutrition Supplementary foods (such as energy drinks) can be mentioned, but are not limited thereto. Moreover, you may add the nerve cell activator of this invention to an instant foodstuff. For example, a nerve cell activator spray-dried or freeze-dried together with powdered cellulose can be easily contained in a food or drink by making it into a powder, granule, tablet or solution.

  Hereinafter, the present invention will be described more specifically with reference to examples. However, the scope of the present invention is not limited to the following examples.

Example 1: Isolation and structure determination of neuronal cell activator from white pickle bamboo (production of NGF by human glioblastoma)
Prepared so that the final concentration is 12.5 × 10 ⁴ cells / ml in EMEM medium containing 10% FBS (fetal bovine serum), 110 mg / ml sodium pyruvate, 1% NEAA (non-essential amino acid solution: Invitrogen Corporation) The human glioblastoma (glioblastoma) T98G cell (RIKEN) suspension was inoculated into each well of a 24-well multiplate and cultured for 3 days. Thereafter, the medium was replaced with an Opti-MEM medium containing 5 mg / ml BSA (bovine serum albumin), and further cultured for 4 days. The medium was changed again, a predetermined amount of each test sample was added, and further cultured for 7 days. The culture supernatant was collected and the amount of NGF was measured.

[Measurement of NGF in culture supernatant]
NGF was measured using “Beta NGF, Human, DuoSet Kit” manufactured by R & D Systems. 100 μl of mouse anti-human beta NGF antibody solution as a Capture Antibody was dispensed into each well in a 96-well multiplate made of polystyrene and allowed to stand overnight at room temperature. After removing the antibody that was not adsorbed on the microplate, each well was washed three times with Wash Buffer (PBS containing 0.05% Tween20). 300 μl of Reagent Diluent (PBS containing 1% BSA) was added to each well and blocked at room temperature for 1 hour or longer, and each well was washed 3 times with Wash Buffer (PBS containing 0.05% Tween20).

  100 μl of human recombinant beta NGF solution as a standard solution or each culture supernatant obtained by the above experiment was dispensed into each well and allowed to stand at room temperature for 2 hours, and then the standard solution or culture supernatant was removed. Further, each hole was washed three times. Dispense 100 μl of sheep anti-human beta NGF antibody solution as Detection Antibody into each well, leave it at room temperature for 2 hours, add 100 μl of peroxidase from horseradish to each well, leave it in the dark for 20 minutes at room temperature. Each well was washed 3 times with Wash Buffer (PBS containing 0.05% Tween20). 100 μl each of Substrate Solution (mixed solution of hydrogen peroxide and tetramethylbenzidine) was added to each hole and allowed to react at room temperature for 20 minutes. 50 μl of 2N sulfuric acid was added as Stop Solution, and the absorbance at 450/540 nm was immediately measured with an absorptiometer, and the amount of NGF was calculated from the standard curve.

[Artificial cultivation of Shironametsumutake]
Artificial cultivation of Shironametsumutake was carried out as follows. 150 g of beech sawdust (Arai Shoten Co., Ltd.), 30 g of Huma (Toyohashi Feed Co., Ltd.) and 350 g of tap water were added to a culture bottle made of 850 cc polypropylene (Chikuma Kasei Co., Ltd.) and mixed well. This medium was autoclaved at 105 ° C. for 60 minutes, then at 120 ° C. for 45 minutes, allowed to cool, and then cultivated in PDA medium (potato dextrose agar medium) (Nissui Co., Ltd.) (patent biological deposit center accession number: P -21287) inoculum. The culture was performed under dark conditions of 23 ° C. and humidity of 55 ± 5% until the mycelium apparently spread on the culture medium, and the culture was further matured for 10 days. As a fruit body primordial generation treatment, humus was aseptically covered with a surface of the culture medium about 10 mm (about 50 g) in a clean bench, and further cultured for 15 days. Then, it culture | cultivated until the fruit body was formed on condition of illumination intensity 20 lux, temperature 20 degreeC, and humidity 90%.
About 100 g of white pickled bamboo shoot per culture bottle was obtained.

[Isolation of NGF production promoting fraction]
The fruit bodies of the white pickled bamboo cultivated as described above were dried with hot air at 80 ° C. and crushed with a blender with a rotary blade to obtain a powder of 1 mm or less. 1 L of methanol was added to 87.0 g of this dried white bamboo shoot powder, and immersion extraction was performed at room temperature for 3 weeks. The residue obtained by concentrating the filtrate under reduced pressure was separated with water-ethyl acetate, and the ethyl acetate layer was dried and concentrated under reduced pressure to obtain 13.6 g of a white pickled bamboo extract. Subsequently, the obtained white rammedum extract was fractionated by silica gel chromatography (developing solvent: hexane / ethyl acetate / methanol = 1/0/0 to 0/0/1 gradient). Among the fractions, the fraction in which NGF production promoting activity was observed compared with the control was concentrated under reduced pressure to obtain 147.5 mg of NGF production promoting fraction.

[Structural analysis]
The structural analysis of the NGF production-promoting fraction obtained from Shironametsumutake was performed. Mass spectrometry (E
I-MS), m / z 428 (molecular weight), m / z 410 (dehydration peak), m / z 396
(Deoxygenation peak) was observed. In addition, as a result of elemental analysis by millimass, C ₂₈ H ₄₄ 0 ₃
It became clear that it has the composition formula of From this, the unsaturation number 7 is calculated.

From the number of protons and the number of methyl groups in the one-dimensional proton NMR spectrum and the results of mass spectrometry, this substance was predicted to be a triterpene or steroidal series. It was found that there were two pairs of double bonds, one set (δ 5.15 ppm) was a transformer type and the other set (δ 6.35 ppm) was a cis type. Further, when this compound was acetylated and NMR was measured, the δ 3.90 ppm multiplet shifted to δ 5.00 ppm by a low magnetic field, and thus it was proved that the peak at δ 3.90 ppm was hydrogen at the base of the secondary hydroxyl group. It was. One-dimensional Carbon-NMR revealed that there were 2 methyl groups bonded to the quaternary carbon and 4 methyl groups bonded to methine. It shows a carbon that is attributable to the following (CDC1 _3, room temperature, 125.76Hz). Chemical Shift (ppm): 30.10 (1C), 34.68 (2C), 66.43 (3C), 39.33 (4C), 82.13 (5C), 135.18 (6C), 130. 73 (7C), 79.39 (8C), 51.08 (9C), 36.94 (10C), 20.61 (11C), 36.91 (12C), 44.54 (13C), 51.67 (14C), 23.38 (15C), 28.62 (16C), 56.19 (17C), 12.85 (18C), 18.15 (19C), 39.70 (20C), 20.85 ( 21C), 135.40 (22C), 132.30 (23C), 42.75 (24C), 33.04 (25C), 19.92 (26C), 19.62 (27C), 17.54 (28C) ).

Furthermore, the mass and NMR spectra were completely consistent with the compound prepared by photosensitization reaction of ergosterol under an oxygen stream.

  From the above results, the NGF production-promoting substance obtained from Shironametsumutake is a scientifically known scientific name (22E) -5α, 8α-epidioxygergosta-6,22-diene-3β-ol (ergosterol peroxide, R = H in chemical formula 1). It was estimated. This substance is presumed that ergosterol was oxidized in vivo either enzymatically or non-enzymatically.

Example 2: Neurotrophic factor-like activity and neurotrophic factor action-enhancing activity of ergosterol peroxide [culture of rat pheochromocytoma cells]
Rat pheochromocytoma PC12 cells (RIKEN) suspended in DMEM medium containing 5% FBS (fetal bovine serum) and 5% HS (horse serum) at a final concentration of 24 holes coated with poly-D-lysine Each well of the multiplate was inoculated at 0.5 × 10 ⁴ cells / well and cultured for 1 day. The culture medium was changed, each test sample was added to a predetermined concentration, and further cultured for 2 days. Then, 10 wells were randomly photographed under magnification in each well (magnification: 200 times).

[Measurement of cell differentiation rate]
The number of cells in each visual field and the number of differentiated cells (cells with extended neurites longer than the major axis of the cell body) were counted, and the cell differentiation rate (number of differentiated cells / total number of cells) was calculated. The results are shown in FIG. From Examples 1 and 2, it can be seen that ergosterol peroxide (EPO) has a nerve cell activation action having both NGF production promoting activity, NGF-like activity, and NGF action enhancing activity.

Example 3 Comparison of Neurostimulatory Action with Carnosic Acid According to the methods of Examples 1 and 2, the neurostimulatory action of three compounds of EPO, acetylated EPO and carnosic acid was compared (10 μM each). As shown in FIG. 2, EPO and acetylated EPO exhibited stronger NGF production promoting action and PC12 cell differentiation promoting action (NGF-like activity) than carnosic acid.

It is a figure which shows the PC12 cell differentiation promotion effect of ergosterol peroxide. It is the figure which compared the NGF production promotion effect and PC12 cell differentiation promotion effect of ergosterol peroxide and carnosic acid.

Claims (2)

  A nerve cell activator comprising ergosterol peroxide as an active ingredient. A pharmaceutical composition for preventing nervous system aging, preventing progression of neuropathy, or improving central nervous system disorder or peripheral neuropathy , comprising the nerve cell activator according to claim 1.