JP2008162927A - Nerve cell-protecting agent, medicinal composition containing the same, cosmetic composition and food - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a new nerve cell-protecting agent having high nerve cell-protecting activities and excellent safetiness. <P>SOLUTION: The nerve cell-protecting agent contains a rosemary extract as an active ingredient. The nerve cell-protecting agent has cell protrusion-elongating activities and acetylcholine release-promoting activities on the nerve cell, and additionally can achieve high safetiness. The medicinal composition obtained by mixing the nerve cell-protecting agent with a pharmacologically acceptable additive, the cosmetic composition and the food obtained by mixing the composition with a food raw material are also provided. <P>COPYRIGHT: (C)2008,JPO&INPIT

Description

  The present invention relates to a nerve cell protective agent. More specifically, the present invention relates to a nerve cell protective agent extracted from rosemary, a pharmaceutical composition containing the same, and food.

  Modern society is full of stress, and we are stressed every day by all of our social and natural environments, such as human relationships, commuting on a crowded train, traffic jams, heat and cold, and noise.

  “Stress” generally refers to such a mental and physical burden or situation, but in a broader sense, the living body is stable against external stimuli (homeostasis or homeostasis). Can be defined as a reaction that attempts to maintain On the other hand, stimuli from the external environment are called “stressers” and include a wide range of mental and physical things such as pain and cold, and infections.

  When a living body enters a stress state, it activates the sympathetic nervous system, releases adrenaline and noradrenaline from the adrenal medulla, increases heart rate and blood pressure, and shows a protective response to stressors. It also releases adrenocorticotropic hormone (ACTH) from the pituitary gland and secretes glucocorticoids (adrenocortical hormones) from the adrenal cortex to increase systemic glucose metabolism and blood flow.

  In response to this stress state, we try to reduce (relax) stress by various methods such as music, sports, massage, aromatherapy, and bathing. In particular, bathing is the most familiar method for obtaining a high relaxing effect by suppressing the excitement of the sympathetic nervous system by making the parasympathetic nervous system dominant.

  However, it is known that when the stress state lasts for a long period of time, a disorder appears in the nerve function so that, for example, the autonomic nervous system is exhausted and a depression or a depression state caused by its functional deterioration is caused. Neuronal impairment caused by such long-term stress is caused by excessive release of glucocorticoids, which causes abnormal neuronal metabolism, leading to abnormal intracellular calcium concentration and increased production of active oxygen. It is thought to be a cause.

  Such neuronal cell death due to stress is particularly prominent in neurons in the brain and further in neurons in the hippocampus region. The death of cranial nerves leads to the breakdown of the neural network constructed by the cells. For example, it contributes to neurological dysfunction such as emotional instability and decreased memory function, and is also involved in various neurological diseases. It is clear that

  For example, in Alzheimer's disease, which is a typical neurodegenerative disease, the involvement of stress called endoplasmic reticulum stress is assumed. The endoplasmic reticulum is the normal folding (folding) of proteins synthesized by ribosomes, that is, a place where sugar chain modifications and three-dimensional structures are formed. Endoplasmic reticulum stress is a state in which folding of this protein is impaired and unfolded protein accumulates in the endoplasmic reticulum. In Alzheimer's disease, it is thought that the long-lasting state triggers neuronal cell death.

  In addition, in myocardial infarction and stroke, hypoxia due to ischemia causes stress and causes neuronal cell death. Neural dysfunctions such as disruption of the neural network and subsequent motor and language dysfunction Is caused.

  Such “stress” at the cell level includes ER stress, hypoxia stress, oxidative stress due to active oxygen, nutrient starvation, heat stress, and the like. In particular, endoplasmic reticulum stress and oxidative stress are said to be deeply involved in neuronal cell death in central neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis.

  As described above, various neurological dysfunctions caused by stress, as well as neuronal cell death, can be effectively prevented, depression and memory function decline, emotional instability, Alzheimer's disease, Parkinson's disease, muscle atrophic side In order to treat or prevent nervous system diseases such as cord sclerosis, various drugs having a nerve cell protective function have been developed.

  As a drug having such a nerve cell protecting function, Patent Document 1 discloses a nerve nerve protecting agent for central nerves containing donepezil hydrochloride, and a preventive and / or therapeutic agent for nerve cell damage in the central nervous system. ing. Donepezil hydrochloride is a substance that increases the amount of acetylcholine in the brain by reversibly inhibiting acetylcholinesterase, an enzyme that degrades acetylcholine, and activates the cholinergic nervous system in the brain. This substance is widely used as a therapeutic agent for Alzheimer's disease.

Patent Document 2 discloses a nerve cell protective agent containing fucoxanthin as an active ingredient. Since this nerve cell protective agent contains fucoxanthin contained in brown algae such as seaweed that has been used as a food material since ancient times, it is considered to have high safety.
No. 2004-110444 JP 2001-335480 A

  As described above, the present invention has high neuroprotective activity and is safe in view of the situation where development of nerve cell protective agents has been actively conducted for the purpose of treating or preventing neurological dysfunction and nervous system diseases. It is a main object to provide a novel neuronal cell protective agent that is superior to the above.

  In order to solve the above problems, the present inventor has searched for various natural products, and the extract of rosemary (Rosmarinus of ficinalis), a typical western herb belonging to the Labiatae plant, has a neuron-protecting action. As a result, the present invention has been completed.

  That is, this invention provides the nerve cell protective agent which uses a rosemary extract as an active ingredient.

  This nerve cell protective agent also has a cell process elongation action and an acetylcholine release promoting action on nerve cells.

  A nerve cell protective agent containing rosemary extract as an active ingredient can be mixed with a pharmacologically acceptable additive to obtain a pharmaceutical composition and a cosmetic composition. It can also be mixed with food ingredients to make food.

  These pharmaceutical compositions, cosmetic compositions and foods have the following advantages.

  Since the nerve cell protective agent according to the present invention is a plant-derived component, the pharmaceutical composition is highly likely to be continuously applied over a long period of time, and is highly likely to have few side effects. In addition, for example, the possibility of preventing the onset of a nervous system disease such as Alzheimer's disease by applying a nerve cell protective agent according to the present invention continuously for a long time as a cosmetic, health supplement, etc. There is. In addition, even when a neurological disease has already developed, it may be possible to suppress the progression of the disease state by applying it continuously for a long period of time.

  According to the present invention, a novel nerve cell protective agent having high nerve function protecting activity is provided. Further, the nerve cell protective agent is likely to be excellent in safety.

  Rosemary is a highly safe plant that has been used as a Western herb since ancient times for a wide range of uses such as medicinal, fragrance and cooking. Carnosic acid, which is considered to have an action of improving memory, and is one of rosemary extract components, has an effect of promoting the production of nerve growth factor (NGF) that plays an important role in maintaining nerve cells. It is known that there is.

  The present inventor has clarified that an extract from rosemary has a cell stress inhibitory effect, a cell process elongation action and an acetylcholine release promoting action on nerve cells, and has a novel nerve cell protective action according to the present invention. A neuron protective agent was completed.

  That is, in the present invention, the neuroprotective action includes “inhibition action of cell stress on nerve cells”, “cell process elongation action”, and “acetylcholine release promoting action”. Each will be described below.

  First, the “cell stress-inhibiting action” refers to an action of suppressing or alleviating the stress response of cells that have undergone cell stress such as endoplasmic reticulum stress, oxidative stress, hypoxic stress, nutrient starvation, and heat stress.

  When a cell is subjected to cell stress, the cell expresses a group of proteins collectively called stress proteins. As an example, there is “heat shock protein (hereinafter referred to as HSP)” whose expression is induced in response to heat stress.

  HSP refers to a group of proteins having a molecular weight of tens of thousands to about 150,000, and is classified into families such as HSP47 (molecular weight of about 47,000) and HSP70 (about 70,000) according to molecular weight. HSP has a function called a molecular chaperone, and assists with protein folding, refolding (refolding) of denatured proteins, transport to and degradation of intracellular organelles, and abnormal proteins into cells subjected to heat stress. It prevents the accumulation of denatured proteins and preserves the function of organelles. Therefore, the expression induction of HSP can be regarded as an index of heat stress on cells.

  Inhibition of cell stress can protect neurons from cell death due to stress, and can prevent or treat the onset of neurological dysfunction or neurodegenerative disease by preventing the breakdown of the neural network due to neuronal cell death It seems possible.

  Next, the “cell process elongation action” can be referred to as an action of promoting plasticity of nerve cells.

  Nerve cells build up a neural network by extending their cell processes. A junction between a cell process and a cell process is called a synapse, and a nerve cell transmits information via a neurotransmitter in the synapse.

  Nerve cells continually elongate cell processes (neural cell plasticity) to reconstruct a neural network, control information transmission, and control neural functions such as emotional expression and memory. Therefore, if the extension of neurites can be promoted, it becomes possible to promote the reconstruction of the neural network that has been broken by the death of nerve cells, thereby improving and improving the nerve function.

  The “acetylcholine release promoting action” is an action of promoting the release of acetylcholine at the synapse. Acetylcholine is one of the neurotransmitters along with glutamic acid, aspartic acid, γ-aminobutyric acid (GABA), glycine, serotonin, dopamine, noradrenaline and the like. Nerve cells that release acetylcholine are called cholinergic nerves, and in the central nervous system, they are projected from the basal part of the forebrain to the cerebral cortex and hippocampus, from the piers of the brainstem and from the outer dorsal capping part to the cerebrum. It is responsible for the projection to the cortex. In the peripheral nervous system, acetylcholine is secreted at the nerve endings of the primary sympathetic nerve, the primary and secondary nerves of the parasympathetic nerve, and the motor nerve.

  Information transmission by acetylcholine is related to the function of memory learning, motor nerve, autonomic nerve (sympathetic and parasympathetic nerve) function, and when abnormality occurs in information transmission by acetylcholine, these functions are impaired and cause various diseases. It becomes.

  For example, there are Alzheimer's disease, dementia, anxiety, autism, depression, Huntington's disease, Parkinson's disease and the like as diseases caused by insufficient or imbalance of acetylcholine in the synaptic cleft. In addition, amyotrophic lateral sclerosis is caused by a decrease in acetylcholine uptake into neurons.

  Thus, since the decrease in acetylcholine is directly involved in the impairment of neuronal function, drugs that promote the release of acetylcholine are central nervous functions such as Alzheimer's disease, dementia, myasthenia gravis, and amyotrophic lateral sclerosis. Used as a remedy for reduction. The above-mentioned donepezil hydrochloride is a substance that increases the amount of acetylcholine in the brain and activates the cholinergic nervous system in the brain, and is widely used as a therapeutic agent for Alzheimer's disease. In addition, a drug that promotes the release of acetylcholine can also be used as a drug that improves neurotransmission disorders in the autonomic nervous system, in order to obtain a relaxing effect by making the parasympathetic nervous system dominant over the sympathetic nervous system It can also be applied as a drug.

  Hereinafter, the suitable form is demonstrated. In addition, embodiment described below shows an example of typical embodiment of this invention, and, thereby, the range of this invention is not interpreted narrowly.

  The nerve cell protective agent according to the present invention can be obtained by extracting whole rosemary plants using various solvents. Here, the whole plant of rosemary means that any part of leaves, flowers, stems and roots can be used. Moreover, these may be used in a raw state, or a dried product may be used. As an extraction solvent, an organic solvent such as methanol, ethanol, propanol, butanol, propylene glycol, 1,3-butylene glycol, glycerin, acetone, methyl ethyl ketone, ethyl acetate, ethers, chloroform, and dichloromethane, and water can be used. it can. Among these, in the present invention, methanol, ethanol, ethyl acetate or a combination of these solvents and water is preferable, and in view of safety in vivo that toxicity is low, ethanol or a mixed solvent of water and ethanol is used. Further preferred. As a suitable extraction method, the whole dried rosemary plant can be obtained by immersing it in 70% ethanol for one week and then removing insolubles using a microfilter having a pore size of 0.45 μm.

  The nerve cell protecting agent according to the present invention can be processed into an appropriate form such as a pharmaceutical composition, a cosmetic composition, and a food.

  When processed into a pharmaceutical composition or a cosmetic composition, a nerve cell protecting agent and a pharmacologically acceptable additive are mixed. Examples of additives 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, polyvinyl pyrrolidone, flavoring agent, Sweeteners and combinations thereof are mentioned. In addition, general cosmetic raw materials such as oils, alcohols, humectants, ultraviolet absorption, fragrances, antioxidants, pigments and the like can also be contained. Furthermore, it is good also as a mixture with another chemical | medical agent as needed.

  The nerve cell protecting agent and the pharmaceutical composition may be used for either oral administration or parenteral administration. The dosage form is not particularly limited, and it is produced in an appropriate dosage form according to the Japanese Pharmacopoeia. Specifically, when it is intended for oral administration, it is produced in a dosage form such as a capsule, a tablet, a powder or a sustained release agent. When intended for parenteral administration, it is produced in dosage forms such as injections and infusions. In addition, the cosmetic composition is a lotion, emulsion, gel, cream, ointment, and more specifically, a makeup whitening makeup such as a makeup base lotion, makeup base cream, liquid, cream or ointment type foundation. It can also be provided as a whitening body cosmetic such as an up cosmetic, a sunscreen lotion, a sunscreen cosmetic such as a sunscreen cream, a hand cream, a leg cream, or a body lotion.

  When processed into food, a neuronal cell protective agent and a suitable food ingredient are mixed. This suitable food ingredient is generally one that can be used as a food material. Examples include flours such as rice, wheat, corn, potatoes, sweet potatoes, soybeans, kelp, wakame, tengusa; chickenpox; lactose; glucose; fructose; sucrose; mannitol; and combinations thereof. Furthermore, spices, colorants, sweeteners, edible oils, vitamins and the like may be added. These suitable food ingredients are used alone or in combination. Furthermore, you may add water as needed and process it into a desired shape. In this way, health functional foods (including specific health functional foods, nutritional functional foods, and beverages), so-called health foods (including beverages), and feed can be obtained. These foods can also be fed to animals as feed.

<Extraction of acetylcholine release promoter from rosemary>
Neurons used in the following examples are obtained by immersing 100 g of dried rosemary whole plant in 1000 ml of 70% ethanol at room temperature for 1 week, and then removing insolubles using a microfilter having a pore size of 0.45 μm. A cytoprotective agent (hereinafter also referred to as rosemary extract) was obtained. This rosemary extract was dried under reduced pressure at 50 ° C. with a rotary evaporator to obtain a slightly brownish-powder powder (hereinafter also referred to as “rosemary extract dried product”). The yield was 1.4%.

<Confirmation of inhibitory action of cell stress using PC12 cells>
PC12 cells derived from rat adrenal medulla are known to elongate neurite-like cell processes by treatment with nerve growth factor (NGF) and differentiate into cells that exhibit neuron-like morphology. Yes. These neuron-like differentiated cells form synapse-like intercellular junctions with elongated cell processes and express various markers specific to neuronal cells. Used in the experiment. Acetylcholinesterase (AchE) described later is also known as a marker for such neural differentiation of PC12 cells.

  PC12 cells were used to measure the promoter activity of the HSP47 gene after heat stress loading in the presence and absence of the neuronal protective agent according to the present invention. As described above, since the induction of HSP expression can be regarded as an index of heat stress on the cell, activation of the HSP47 gene promoter means the stress state of the cell.

  First, a DNA vector containing a recombinant gene in which the lacZ gene sequence was connected downstream of the promoter sequence of the rat HSP47 gene was prepared. Next, this DNA vector was used for transformation (transformation) by a conventional method to prepare PC12 cells having a recombinant gene (hereinafter referred to as transformed PC12 cells). When heat stress is applied to transformed PC12 cells, the lacZ gene and its gene product, β-galactosidase, are expressed by activation of the HSP47 gene promoter. Therefore, β-galactosidase activity is an indicator of the stress state of the cell.

  Transformed PC12 cells were cultured in DMEM (Dulbecos Modified Eagle's Medium) supplemented with 5% fetal bovine serum at 37 ° C. under 5% CO 2 and treated with NGF (Sigma) to differentiate into neuronal cells. It was. After this neuron-like cell was cultured at 42 ° C. for 1.5 hours and subjected to heat stress, the neuronal cell protective agent obtained in Example 1 was treated with 100-fold dilution or 10,000-fold dilution (NGF (+ ) Rosmarinus group). As a control group, nerve-like cells (NGF (+) group) to which only a solvent in which a nerve cell protecting agent was dissolved were added were used. After further culturing at 37 ° C. for 3 hours, the cells were washed with a phosphate buffer (PBS), the cell lysate was collected, 4-MUG serving as a substrate for β-galactosidase was added, and the fluorescence intensity was measured (excitation) The activity of β-galactosidase was measured at a wavelength of 365 nm and an emission wavelength of 450 nm.

  The results are shown in FIG. The β-galactosidase activity was shown as a relative value with the activity in the NGF (+) group as 100%.

  In nerve-like cells treated with a 10,000-fold dilution of the neuron protective agent according to the present invention, β-galactosidase activity was suppressed to about 50% compared to the control group. Inhibition of β-galactosidase activity means a decrease in the activity of the HSP47 gene promoter, indicating that the stress response to heat stress in nerve-like cells has been alleviated. It should be noted that no significant change was observed in the stress response of the neuronal cells treated with the neuron protective agent at a 100-fold dilution compared to the control group.

  As described above, from the results of Example 2, it was shown that the nerve cell protective agent according to the present invention exerts a cell stress inhibitory effect on nerve cells at an appropriate treatment concentration.

<Confirmation of cell projection extension action using PC12 cells>
PC12 cells were cultured in DMEM (Dulbecos Modified Eagle's Medium) supplemented with 5% fetal bovine serum at 37 ° C. under 5% CO 2 and treated with NGF (Sigma) to differentiate into neuronal cells. At this time, simultaneously with NGF treatment, the neuronal cell protective agent obtained in Example 1 was treated with 1,000-fold dilution (NGF (+) Rosmarinus group). For the control group, cells treated only with NGF (NGF (+) group) and cells added only with a solvent in which NGF and a neuron protective agent were dissolved (NGF (−) group) were used. After culturing for 24 hours, the cell morphology of each experimental group was observed.

  The results are shown in FIG.

  In the NGF (−) group, differentiation into nerve-like cells is not induced, so there is no change in cell morphology, and the cells remain circular. On the other hand, in the NGF (+) group, the cell processes are elongated to form a spindle shape, which shows a neuron-like morphology. Furthermore, cell process elongation became more prominent by the treatment with the neuronal cell protective agent according to the present invention (see NGF (+) Rosmarinus group).

  Next, the effect of the neuron protective agent according to the invention on the phosphorylation state of ERK1 / 2 was examined. It is known that neurite outgrowth of PC12 cells by NGF treatment involves a MAP kinase cascade and is accompanied by phosphorylation of ERK1 / 2 belonging to the MAP kinase cascade.

  In addition to the NGF (+) group and the NGF (−) group described above, NGF and neuroprotective agent (1,000 times, 300 times, 100 times) were obtained for the Rosmarinus group treated with the neuroprotective agent according to the present invention alone. Proteins were extracted from cells 8 hours after the treatment (double dilution) by a conventional method, separated by SDS-PAGE, blotted on a membrane, and antibodies (Sigma) that recognize ERK1 / 2 and phosphorylation (p-ERK1 / 2) Western blotting was performed.

  The results are shown in FIG.

  In the NGF (+) group and the Rosmarinus group, a significant increase in p-ERK1 / 2 was observed, confirming that activation of the MAP kinase cascade occurred in both groups. Moreover, phosphorylation of ERK1 / 2 in the Rosmarinus group was enhanced depending on the concentration of the neuronal protective agent.

  This indicates that the neuron protective agent according to the present invention has an action of activating the MAP kinase cascade alone. Furthermore, it was presumed that the present neuronal cell protective agent enhances and promotes the neurite outgrowth action of NGF expressed through the activation of the cascade by this MAP kinase cascade activation action.

  As described above, from the results of Example 3, it was shown that the nerve cell protective agent according to the present invention has a cell projection extension action.

<Confirmation of acetylcholine release promoting action using PC12 cells>
The acetylcholinesterase activity was measured in the cells of each of the NGF (+) Rosmarinus group, NGF (+) group, and NGF (−) group of Example 3. Acetylcholinesterase (AchE) is known to be activated when the amount of acetylcholine released to the synapse is increased. Therefore, an increase in the activity of acetylcholinesterase means an increase in released acetylcholine. Regarding the relationship between increased activity of acetylcholinesterase and increase in released acetylcholine, various documents (eg, Ultrasound-induced enhancement of ACh, ADhE and GABA in fetal brain tissue of mouse. Suneetha, N., Kumar, RP, Ultrasound In Medicine & Biology. Vol. 19: 411-413 (1993)).

  Acetylcholinesterase activity was measured by the following method. After seeding 5000 cells / well of PC12 cells in a 96-well plate and culturing for 24 hours under the above-mentioned culture conditions, the neuronal cell protective agent obtained in Example 1 was treated by ˜fold dilution. After further culturing for 48 hours, NGF was treated (NGF (+) Rosmarinus group). After culturing for 24 hours, the cells were washed with PBS to obtain a cell lysate. For the control group, cells treated only with NGF (NGF (+) group) and cells added only with a solvent in which NGF and a neuron protective agent were dissolved (NGF (−) group) were used. 20 μl of Acetylthiocholine iodide (5.6 mM) and 20 μl of 7-diethylamino-3 (4′-maleimylyl-phenyl) -4-methylcoumarin (0.4 mM) were added to the cell lysate, and the fluorescence intensity was measured (excitation wavelength: 365 nm, The activity of acetylcholinesterase was measured using an emission wavelength of 450 nm. The results are shown in FIG. The acetylcholinesterase activity was shown as a relative value with the activity in the NGF (+) group as 100%.

  Compared with the NGF (+) group, the acetylcholinesterase activity in the NGF (+) Rosmarinus group was 118%, indicating a significant increase. This indicates that in the NGF (+) Rosmarinus group, acetylcholine released from nerve-like cells is significantly increased by the treatment with the neuronal cell protective agent according to the present invention.

  Therefore, the results of Example 4 showed that the nerve cell protective agent according to the present invention has an acetylcholine release promoting action.

  Next, formulation examples of pharmaceutical compositions containing the nerve cell protecting agent of the present invention will be described in detail. According to the formulation shown in Table 1, an ointment (formulation example) was prepared as an example of a pharmaceutical composition containing a rosemary extract.

  Next, formulation examples of cosmetics containing the nerve cell protecting agent of the present invention will be described in detail. According to the formulation shown in Table 2, a lotion containing a rosemary extract (formulation example) was prepared.

Moreover, the emulsion (formulation example) containing a rosemary extract was prepared according to the composition shown in Table 3.

(Note 1) “Lipidure-PMB” manufactured by NOF Corporation

  Next, the formulation example of the foodstuff containing the nerve cell protective agent of this invention is demonstrated in detail. According to the composition shown in Table 4, tune gum (formulation example) containing a dried rosemary extract was prepared.

Moreover, according to the composition shown in Tables 5 and 6, cookies and soft drinks (formulation examples) each containing a dried rosemary extract were prepared.

  Next, formulation examples of the bath preparation containing the nerve cell protecting agent of the present invention will be described in detail. According to the formulation shown in Table 7, a bath preparation (formulation example) containing a rosemary extract was prepared.

  The neuroprotective agent comprising the rosemary extract according to the present invention as an active ingredient treats nervous system diseases such as depression, decreased memory function, emotional instability, Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. Or it can utilize suitably as a pharmaceutical composition for prevention, a cosmetic composition, a foodstuff, etc.

  In addition, these pharmaceutical compositions, cosmetic compositions, and foods can be used to obtain a relaxing effect by making the parasympathetic nervous system superior to the sympathetic nervous system. In particular, since the cosmetic composition is a plant extract component, it has excellent skin functionality and can be widely applied to sensitive skin.

It is a figure explaining the cell stress inhibitory effect of the nerve cell protective agent which concerns on this invention. It is a figure explaining the cell process extension effect | action of the nerve cell protective agent which concerns on this invention. It is a figure which shows activation of the MAP kinase cascade by the neuron protective agent which concerns on this invention. It is a figure explaining the acetylcholine release acceleration | stimulation effect | action of the nerve cell protective agent which concerns on this invention.

Claims (6)

  A nerve cell protective agent comprising rosemary extract as an active ingredient.   2. The nerve cell protective agent according to claim 1, which has a cell process elongation action on nerve cells.   3. The nerve cell protective agent according to claim 1 or 2, which has an action of promoting the release of acetylcholine on nerve cells.   A pharmaceutical composition comprising the nerve cell protective agent according to any one of claims 1 to 3 and a pharmacologically acceptable additive.   A cosmetic composition comprising the nerve cell protecting agent according to any one of claims 1 to 3 and a pharmacologically acceptable additive.   The foodstuff containing the nerve cell protective agent and food raw material as described in any one of Claim 1 to 3.