Composition for improving memory and preventing, alleviating or treating cognitive impairment, containing orixa japonica extract as active ingredient

Abstract

The present invention relates to a composition for improving memory and preventing, alleviating or treating cognitive impairment, containing an Orixa japonica extract as an active ingredient. The Orixa japonica extract of the present invention has an excellent neuroprotective effect and, in particular, the neuroprotective effect of an Orixa japonica leaf extract is remarkably better than that of an Orixa japonica stem extract, and memory and cognitive function are improved by administering the Orixa japonica leaf extract to an animal model in scopolamine-induced cognitive decline, and thus the present invention can be effectively used as a health functional food for improving memory and cognitive function disorders and as a medicine and a feed additive for preventing, alleviating or treating degenerative brain diseases.

Description

Composition for improving memory and preventing, improving or treating cognitive dysfunction, containing Sangsan extract as an active ingredient

[0001] The present invention relates to a composition for improving memory and preventing, improving or treating cognitive dysfunction, comprising an extract of Sangsan as an active ingredient.

[0002]

[0003] This work was supported by the Ministry of Science and ICT's major projects (Project Number: 1711195903, KSN2411012).

[0004] Advances in medical technology and improved living standards have nearly doubled the average human lifespan over the past half-century, leading to a rapid increase in the proportion of the elderly population relative to the total population. According to 2005 data released by Statistics Korea, the average lifespan in South Korea is 78.5 years, and the proportion of the population aged 65 and older already reached approximately 7% in 2000, demonstrating the country's rapid entry into an aging society. Furthermore, South Korea is projected to become an aged society by 2018 and a super-aged society by 2026, with the elderly population exceeding 20%. And the old-age dependency ratio (population aged 65 and over divided by population aged 15-64), which was 21.3% in 2020, is expected to rise to 35.7% in 2030. If one elderly person was supported for every 8.2 people of working age in 2004, this will mean one elderly person for every 6.8 people in 2010, one elderly person for every 4.7 people in 2020, and one elderly person for every 2.8 people in 2030. This means that the possibility of social burden due to slow economic growth, decreased national competitiveness, and deepening intergenerational conflict is increasing at the national level.

[0005] Reflecting these social outlooks and realities, recent attention has focused on diseases prevalent among the elderly. In particular, the incidence of dementia increases significantly with age, reaching approximately 20% in those aged 75-84 and nearly 50% in those aged 85 and older. Due to the nature of the disease, which requires absolute dependence on the care of others, it has emerged as a significant social concern. Furthermore, the economic losses caused by dementia are significant. Taking into account all factors, including lost work, the social cost of dementia treatment in Korea is estimated at 3.4 to 4.4 trillion won. In the United States, the annual cost of dementia treatment is estimated at approximately 100 to 120 billion dollars. In other words, as society ages, dementia is emerging as one of the greatest health challenges facing humanity in the 21st century. Accordingly, there is a growing demand for the development of functional substances and foods that can prevent and treat cognitive impairment, including dementia.

[0006] Cognitive dysfunction, such as loss of memory and learning ability caused by Alzheimer's disease (AD), a type of senile dementia, is caused by damage to acetylcholinergic neurons in the basal brain. Based on this research, various drugs have been developed that can enhance the function of acetylcholinergic neurons according to various mechanisms of action, such as muscarinic acetylcholine receptor agonists, acetylcholine production promoters, and acetylcholinesterase (AChE) inhibitors. In fact, most of the Alzheimer's disease treatments currently used in each country are acetylcholinesterase inhibitors, such as tacrine and donepezil. Other drugs used include rivastigmine and galatamine.

[0007] The need to develop more effective agents (including health functional food ingredients) to improve cognitive function or memory impairment in degenerative brain diseases is greater than ever. Ultimately, research is needed to develop new agents with multifunctional effects, targeting the neuronal mechanisms underlying dementia development.

[0008] Meanwhile, Sangsan (Orixa japonica Thunb.) is a deciduous broad-leaved shrub in the Rutaceae family, growing to about 2 m tall, with alternate, oblong-ovate leaves. Native to tropical Asia, it grows wild in Japan, India, Vietnam, Nepal, and along the southern coasts of Korea, including Jeju Island. Sangsan is the traditional Korean term for the root of the Korean primrose, which is bitter, pungent, and toxic, and is primarily used to treat dysentery and phlegm. Yellowish-green flowers bloom in April in racemes, and the fruit is a brown, sessile berry that ripens in November. The root is used medicinally, and the wood is used for handicrafts. It grows on mountainsides and is known to be distributed in Jeolla Province in Korea and Japan.

[0009] Prior art related to improving memory or cognitive function impairment includes Korean Patent No. 2224178, which discloses a "composition for improving cognitive ability or memory comprising an extract of the fruit or leaves of the red thorn tree," and Korean Patent Publication No. 2023-0016574, which discloses a "composition for improving memory, preventing or treating cognitive impairment or degenerative brain disease, comprising an extract of Gwalruin as an active ingredient." However, the "composition for improving memory and preventing, improving or treating cognitive dysfunction, comprising an extract of Sangsan as an active ingredient," according to the present invention, has not yet been disclosed.

[0010] The present invention was derived from the above-mentioned needs, and relates to a composition for improving memory and preventing, improving, or treating cognitive dysfunction, comprising an extract of Sangsan as an active ingredient. The Sangsan extract of the present invention has an excellent neuronal cell protection effect, and in particular, the neuronal cell protection effect of Sangsan leaf extract is remarkable compared to that of Sangsan stem extract, and the present invention was completed by confirming that memory and cognitive function were improved by administering Sangsan leaf extract to an animal model of cognitive decline induced by scopolamine.

[0011] In order to solve the above problem, the present invention provides a health functional food composition for improving cognitive function or memory containing an extract of Orixa japonica as an effective ingredient.

[0012] In addition, the present invention provides a pharmaceutical composition for preventing or treating degenerative brain diseases containing an extract of Orixa japonica as an active ingredient.

[0013] In addition, the present invention provides a feed additive for preventing or improving degenerative brain diseases containing an extract of Orixa japonica as an effective ingredient.

[0014] In addition, the present invention provides a herbal medicine composition for preventing or treating degenerative brain diseases containing an extract of Orixa japonica as an active ingredient.

[0015] In addition, the present invention provides a veterinary composition for preventing or treating degenerative brain diseases containing an extract of Orixa japonica as an active ingredient.

[0016] The present invention relates to a composition for improving memory and preventing, improving or treating cognitive dysfunction, comprising a Sangsan extract as an active ingredient. The Sangsan extract of the present invention has an excellent neuron protection effect, and in particular, the neuron protection effect of the Sangsan leaf extract is remarkable compared to that of the Sangsan stem extract, and in an animal model of cognitive decline induced by scopolamine, administration of the Sangsan leaf extract has the effect of improving memory and cognitive function.

[0017] Figure 1 shows the results of confirming the neuroprotective effect of Sangsan leaf extract in mouse-derived hippocampal neurons. (A) Cell viability was confirmed by treating Sangsan leaf extract alone, and (B) Cell viability was confirmed by treating glutamate and Sangsan leaf extract together. ### indicates that the cell viability of the glutamate alone treatment group (-) was statistically significantly decreased compared to the normal group (Con), and p<0.001, and * and *** indicate that the cell viability of the glutamate and 1-50㎍ / ㎖ Sangsan leaf extract treatment group was statistically significantly increased compared to the glutamate alone treatment group (-), and * indicates p<0.05, and *** indicates p<0.001.

[0018] Figure 2 shows the results of comparing the neuroprotective effects of the extracts of the leaves of the perilla plant and the stem of the perilla plant in mouse-derived hippocampal neurons. ### indicates that the cell viability of the glutamate-only treatment group (-) was statistically significantly decreased compared to the normal group (Con), p<0.001; ** and *** indicate that the cell viability of the glutamate and perilla leaf extract or perilla stem extract treatment groups was statistically significantly increased compared to the glutamate-only treatment group (-); ** indicates p<0.01; *** indicates p<0.001; and $$ indicates that the cell viability of the perilla leaf extract treatment group was statistically significantly increased compared to the perilla stem extract, p<0.01.

[0019] Figure 3 shows the results of the Y-maze test to confirm the cognitive function improvement effect according to administration of the Sangsan leaf extract of the present invention in an animal model of cognitive decline induced by scopolamine. Con is a normal group, SCO is a control group administered scopolamine, SCO+Done is a positive control group administered scopolamine and donepezil (1 mg / kg), SCO+Sangsan20 is a group administered scopolamine and the Sangsan leaf extract of the present invention (20 mg / kg), and SCO+Sangsan40 is a group administered scopolamine and the Sangsan leaf extract of the present invention (40 mg / kg). ## indicates that the time spent in the new arm of the control group (SCO) administered with scopolamine was statistically significantly reduced compared to the normal group (Con), p<0.01, and * indicates that the time spent in the new arm of the groups administered with scopolamine and the Sangsan leaf extract of the present invention (SCO+Sangsan20 and SCO+Sangsan40) was statistically significantly increased compared to the control group (SCO) administered with scopolamine, p<0.05.

[0020] Figure 4 shows the results of a novel object recognition test to confirm the effect of administration of Sangsan leaf extract on improving memory and cognitive function in an animal model of cognitive impairment induced by scopolamine. ## indicates that the memory index of the control group (SCO) administered scopolamine was statistically significantly decreased compared to the normal group (Con), and p<0.01, and * indicates that the memory index of the groups administered scopolamine and the Sangsan leaf extract of the present invention (SCO+Sangsan20 and SCO+Sangsan40) was statistically significantly increased compared to the control group (SCO) administered scopolamine, and p<0.05.

[0021] In order to achieve the purpose of the present invention, the present invention provides a health functional food composition for improving cognitive function or memory containing an extract of Orixa japonica as an effective ingredient.

[0022] The above extract of Sangsan is preferably an extract of the leaves or stems of Sangsan, but is not limited thereto.

[0023] The above-mentioned Sangsan extract can be prepared by a method including, but not limited to, the following steps:

[0024] (1) A step of extracting by adding an extraction solvent to Sangsan;

[0025] (2) a step of filtering the extract of step (1); and

[0026] (3) A step of preparing an extract by drying the filtered extract of step (2).

[0027] In the above step (1), the extraction solvent is preferably selected from water, C1 to C4 lower alcohol or a mixture thereof, more preferably methanol, but is not limited thereto.

[0028] In the above manufacturing method, the extraction method may utilize any conventional method known in the art, such as filtration, hot water extraction, immersion extraction, reflux cooling extraction, and ultrasonic extraction. In the above method, the drying in step (3) is preferably, but not limited to, reduced pressure drying, vacuum drying, boiling drying, spray drying, or freeze drying.

[0029] The above composition is preferably manufactured in any one formulation selected from powder, granules, pills, tablets, capsules, candies, syrups, and beverages, but is not limited thereto.

[0030] When the health functional food composition of the present invention is used as a food additive, the above-mentioned Sangsan extract can be added as is or used together with other foods or food ingredients, and can be used appropriately according to a conventional method. The mixing amount of the active ingredient can be appropriately determined depending on its purpose of use (prevention or improvement). Generally, when manufacturing a food or beverage, the composition of the present invention is added in an amount of 15 parts by weight or less, preferably 10 parts by weight or less, based on the raw material. However, in the case of long-term intake for the purpose of health and hygiene or health control, the amount may be below the above range, and since there is no problem in terms of safety, the active ingredient can also be used in an amount above the above range.

[0031] There are no specific restrictions on the types of the above foods. Examples of foods to which the above extract can be added include meat, sausage, bread, chocolate, candy, snacks, confectionery, pizza, ramen, other noodles, gum, dairy products including ice cream, various soups, beverages, tea, drinks, alcoholic beverages, and vitamin complexes, and all health functional foods in the conventional sense are included.

[0032] When the composition of the present invention is used as a health beverage, it may contain various flavoring agents or natural carbohydrates as additional ingredients, as in conventional beverages. The natural carbohydrates mentioned above are monosaccharides such as glucose and fructose, disaccharides such as maltose and sucrose, polysaccharides such as dextrin and cyclodextrin, and sugar alcohols such as xylitol, sorbitol, and erythritol. As a sweetener, a natural sweetener such as thaumarin or stevia extract, or a synthetic sweetener such as saccharin or aspartame can be used. The proportion of the natural carbohydrate is generally about 0.01 to 0.04 g, preferably about 0.02 to 0.03 g, per 100 g of the composition of the present invention. The composition of the present invention may contain various nutrients, vitamins, electrolytes, flavoring agents, coloring agents, pectic acid and its salts, alginic acid and its salts, organic acids, protective colloid thickeners, pH adjusters, stabilizers, preservatives, glycerin, alcohol, carbonating agents used in carbonated beverages, etc. In addition, the composition of the present invention may contain fruit pulp for the production of natural fruit juice, fruit juice drinks, and vegetable drinks. These components may be used independently or in mixtures. The proportion of these additives is not particularly important, but the composition of the present invention is typically selected in the range of 0.01 to 0.1 parts by weight per 100 parts by weight.

[0033] In addition, the present invention provides a pharmaceutical composition for preventing or treating degenerative brain diseases containing an extract of Orixa japonica as an active ingredient.

[0034] The above degenerative brain disease is preferably, but not limited to, Alzheimer's disease, mild cognitive impairment or dementia.

[0035] The pharmaceutical composition according to the present invention can be formulated and used in the form of oral formulations such as capsules, powders, granules, tablets, suspensions, emulsions, syrups, aerosols, external preparations, suppositories, and sterile injection solutions, respectively, according to conventional methods.

[0036] The pharmaceutical composition according to the present invention may further comprise a pharmaceutically acceptable carrier, excipient or diluent.

[0037] Carriers, excipients and diluents that may be included in the pharmaceutical composition of the present invention include various compounds or mixtures including lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia gum, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methyl cellulose, microcrystalline cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil.

[0038] When formulated, they are usually prepared using diluents or excipients such as fillers, bulking agents, binders, wetting agents, disintegrating agents, and surfactants. Solid preparations for oral administration include tablets, pills, powders, granules, and capsules, and these solid preparations are prepared by mixing the pharmaceutical composition with at least one excipient, such as starch, calcium carbonate, sucrose or lactose, gelatin, etc. In addition to simple excipients, lubricants such as magnesium stearate and talc are also used. Liquid preparations for oral administration include suspensions, oral solutions, emulsions, and syrups, and in addition to commonly used simple diluents such as water and liquid paraffin, various excipients such as wetting agents, sweeteners, fragrances, and preservatives may be included. Preparations for parenteral administration include sterile aqueous solutions, non-aqueous solvents, suspensions, emulsions, lyophilized preparations, and suppositories. Non-aqueous solvents and suspending agents can include propylene glycol, polyethylene glycol, vegetable oils such as olive oil, and injectable esters such as ethyl oleate. Suppository bases can include withepsol, macrogol, Tween 61, cocoa butter, laurin butter, and glycerogelatin.

[0039] The appropriate dosage of the pharmaceutical composition of the present invention can be prescribed in various ways depending on factors such as the formulation method, administration method, patient's age, weight, sex, pathological condition, food, administration time, administration route, excretion rate, and reaction sensitivity.

[0040] The pharmaceutical composition of the present invention can be administered orally or parenterally, and in the case of parenteral administration, it can be administered by topical application to the skin, intravenous injection, subcutaneous injection, intramuscular injection, intraperitoneal injection, transdermal administration, etc.

[0041] In addition, the present invention provides a feed additive for preventing or improving degenerative brain diseases containing an extract of Orixa japonica as an effective ingredient.

[0042] The above degenerative brain disease is as described above.

[0043] The feed additive of the present invention corresponds to supplementary feed under the Feed Management Act. The term "feed" in the present invention may mean any natural or artificial diet, meal, etc., or ingredients of the meal, which are intended for or suitable for animals to eat, ingest, and digest. The type of the feed is not particularly limited, and feed commonly used in the relevant technical field may be used. Non-limiting examples of the feed include plant feeds such as grains, roots, fruits, food processing by-products, algae, fibers, pharmaceutical by-products, oils and fats, starches, meal, or grain by-products; and animal feeds such as proteins, inorganic substances, oils and fats, mineral substances, oils and fats, single-cell proteins, zooplankton, or food. These may be used alone or in combination of two or more.

[0044] In addition, the present invention provides a herbal medicine composition for preventing or treating degenerative brain diseases containing an extract of Orixa japonica as an active ingredient.

[0045] The above degenerative brain disease is as described above.

[0046] The herbal medicine composition of the present invention means, but is not limited to, one manufactured according to a herbal medicine prescription.

[0047] In addition, the present invention provides a veterinary composition for preventing or treating degenerative brain diseases containing an extract of Orixa japonica as an active ingredient.

[0048] The above degenerative brain disease is as described above.

[0049] The veterinary composition comprising the extract of the present invention may further comprise suitable excipients and diluents according to conventional methods. Excipients and diluents that may be included in the veterinary composition comprising the extract of the present invention include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia gum, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methyl cellulose, microcrystalline cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate, cetanol, stearyl alcohol, liquid paraffin, sorbitan monostearate, polysorbate 60, methylparaben, propylparaben, and mineral oil.

[0050] The veterinary composition comprising the extract of Sangsan according to the present invention may further include fillers, anticoagulants, lubricants, wetting agents, flavoring agents, emulsifiers, preservatives, etc. The veterinary composition according to the present invention may be formulated using a method well known in the art so as to provide rapid, sustained or delayed release of the active ingredient after administration to an animal, and the formulation may be in the form of a powder, granule, tablet, capsule, suspension, emulsion, solution, syrup, aerosol, soft or hard gelatin capsule, suppository, sterile injection solution, sterile external preparation, etc.

[0051] The veterinary composition according to the present invention may vary depending on the age, sex, and weight of the animal, but may be administered once or several times a day, and the dosage may be increased or decreased depending on the route of administration, severity of the disease, sex, weight, age, etc. Therefore, the above dosage does not limit the scope of the present invention in any way.

[0052]

[0053] Hereinafter, the present invention will be described in detail by examples. However, the following examples are only illustrative of the present invention, and the content of the present invention is not limited to the following examples.

[0054]

[0055] Example 1. Preparation of Sangsan extract

[0056] The stem and leaf extracts of Orixa japonica used in the present invention were purchased from the Korea Plant Extract Bank of the Korea Research Institute of Bioscience and Biotechnology (Daejeon, Korea). Specifically, the stem and leaf of Orixa japonica were collected in Jochon-eup, Jeju-si, Jeju Special Self-Governing Province in 2016, dried in the shade and powdered, and then methanol was added. Extraction was performed using an ultrasonic extractor (SDN-900H, SD-ULTRASONIC CO., LTD) at room temperature (30 cycles, 40 KHz, 1500 W, 15 min treatment, 120 min stand / cycle). Afterwards, filtration (Qualitative Filter No. 100, HYUNDAI MICRO CO., LTD) and drying under reduced pressure to obtain the leaf extract and stem extract of Orixa japonica, respectively.

[0057]

[0058] Example 2. Neuroprotective effect

[0059] The experiment was conducted using a mouse hippocampal neuronal cell line (HT22 cell line) isolated from hippocampal brain tissue, which is closely related to cognitive function. HT22 cells were seeded at 3.0 × 10 in each well of a 96-well plate. 3Cells were seeded at a density of 10 cells / ㎖ and stabilized for 24 hours. The cells were pretreated with various concentrations of Sangsan leaf extract or Sangsan part (leaf, stem) extract and cultured for 24 hours. Next, glutamate (5 mM glutamate), which induces neuronal damage, was treated together with Sangsan extract and reacted for 24 hours. Cell viability was confirmed through an MTT assay. The control group was treated with DMSO.

[0060] All data were analyzed using GraphPad Prism 5, and statistical significance was assessed using ANOVA and Tukey's post hoc test to compare multiple groups. A p value of less than 0.05 was considered statistically significant.

[0061] As a result, it was confirmed that there was no cytotoxicity when treated with the Sangsan leaf extract of the present invention (Fig. 1A), and as shown in Fig. 1B, compared to the normal group (Con), the cell viability was significantly reduced in the glutamate-only treatment group, whereas glutamate-induced cytotoxicity was significantly increased when treated with 1 to 50 μg / ml of Sangsan leaf extract, confirming that the Sangsan leaf extract has an excellent neuronal cell protection effect.

[0062] In addition, as a result of comparing the effects of the Sangsan leaf extract and Sangsan stem extract on glutamate-induced cytotoxicity in brain neurons, it was confirmed that the Sangsan leaf extract had a significantly higher cell viability than the stem extract (Fig. 2).

[0063]

[0064] Example 3. Effect of improving cognitive function

[0065] 1) Animal testing

[0066] To determine the therapeutic effects of the extract of the leaves of the common ginseng (Pseudomonas amurense) on cognitive dysfunction or memory impairment, a cognitive impairment animal model constructed by injection of scopolamine was used. Seven-week-old mice were purchased and stabilized for one week before use in the experiment. The mice were orally administered the extract of the common ginseng (20, 40 mg / kg) dissolved in drinking water for 7 days, followed by co-administration of scopolamine and the common ginseng leaf extract for 7 days (SCO + Pseudomonas amurense 20 and SCO + Pseudomonas amurense 40). The normal group (Con) received drinking water and saline, and the control group (SCO) received drinking water and scopolamine. The positive control group (SCO + Donepezil) was administered 1 mg / kg of donepezil dissolved in drinking water together with scopolamine.

[0067]

[0068] 2) Y-maze test

[0069] To measure the cognitive ability of laboratory animals, a Y-maze experiment was conducted. The Y-maze used in the experiment is made of black plastic and consists of three arms, with the length, height, and width of each arm being 33 cm, 15 cm, and 10 cm. After designating each arm as A, B, and C, one arm of the Y-shaped maze was blocked and the mouse was allowed to freely explore the other two arms for 5 minutes. After 1 hour, the blocked arm was opened to allow the mouse to freely explore, and the time it took for the mouse to enter the newly opened arm was recorded.

[0070] As a result, as disclosed in Fig. 3, the time to enter a new arm was significantly reduced in the control group (SCO) compared to the normal group (Con), and the time to explore a new arm was statistically significantly increased in the groups administered the Sangsan leaf extract of the present invention (SCO+Sangsan20 and SCO+Sangsan40) compared to the control group (SCO).

[0071]

[0072] 3) Novel object recognition test

[0073] To measure memory and cognitive abilities in experimental animals, two identical objects were placed and explored. The next day, one of the objects was replaced with a novel object, and the time spent exploring each object was measured again. Finally, the discrimination index was calculated as [(novel object) - (familiar object) / total time].

[0074] As a result, as disclosed in Fig. 4, the memory index (Discrimination index) was significantly reduced in the control group (SCO) compared to the normal group (Con), but it was confirmed that the memory index was improved in the Sangsan leaf extract administration group (SCO+Sangsan20 and SCO+Sangsan40) of the present invention compared to the control group (SCO).

Claims

1. A health functional food composition for improving cognitive function or memory containing an extract of Orixa japonica as an active ingredient.

2. A health functional food composition for improving cognitive function or memory, characterized in that the Sangsan extract in paragraph 1 is an extract of the leaves or stems of Sangsan.

3. A health functional food composition for improving cognitive function or memory, characterized in that the extraction solvent of the Sangsan extract in paragraph 1 is water, a lower alcohol of C1 to C4, or a mixture thereof.

4. A health functional food composition for improving cognitive function or memory, characterized in that the composition is manufactured in any one formulation selected from powder, granules, pills, tablets, capsules, candy, syrup, and beverage in the first paragraph.

5. A pharmaceutical composition for the prevention or treatment of degenerative brain diseases containing an extract of Orixa japonica as an active ingredient.

6. A pharmaceutical composition for preventing or treating a degenerative brain disease, characterized in that the degenerative brain disease in paragraph 5 is Alzheimer's disease, mild cognitive impairment, or dementia.

7. A pharmaceutical composition for preventing or treating a degenerative brain disease, characterized in that, in addition to the above-mentioned Sangsan extract, it further comprises a pharmaceutically acceptable carrier, excipient or diluent.

8. A pharmaceutical composition for preventing or treating a degenerative brain disease, characterized in that the composition is prepared in any one formulation selected from among capsules, powders, granules, tablets, suspensions, emulsions, syrups, and aerosols in accordance with paragraph 5.

9. Feed additive for the prevention or improvement of degenerative brain diseases containing Orixa japonica extract as an active ingredient.

10. A herbal medicine composition for the prevention or treatment of degenerative brain disease containing an extract of Orixa japonica as an active ingredient.

11. A veterinary composition for the prevention or treatment of degenerative brain diseases containing an extract of Orixa japonica as an active ingredient.

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