Classifications

• • A—HUMAN NECESSITIES
  • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
  • A23L—FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES, NOT OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF
  • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
  • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
  • A61K36/18—Magnoliophyta (angiosperms)
  • A61K36/88—Liliopsida (monocotyledons)
  • A61K36/899—Poaceae or Gramineae (Grass family), e.g. bamboo, corn or sugar cane
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P25/00—Drugs for disorders of the nervous system
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P25/00—Drugs for disorders of the nervous system
  • A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P3/00—Drugs for disorders of the metabolism
  • A61P3/06—Antihyperlipidemics

Definitions

• the present invention relates to a composition for improving neuroinflammation, a composition for improving brain function, a composition for improving lipid metabolism, a composition for adjusting the composition ratio of intestinal microflora, and the use of plant charcoal.
• Diabetes is a disease in which a state of hyperglycemia continues. Diabetes is broadly divided into type 1 diabetes, which is caused by a lack or deficiency of insulin to absorb blood sugar, and type 2 diabetes, which is caused by insulin resistance. 90-95% of diabetic patients in Japan have type 2 diabetes. In addition to genetic factors, type 2 diabetes is also thought to be related to lifestyle habits such as overeating and lack of exercise.
• Type 2 diabetes can be improved or prevented from worsening by reviewing lifestyle habits or using medication.
• complications such as diabetic retinopathy, diabetic nephropathy, and diabetic neuropathy can occur, and in some cases, dialysis or amputation of limbs may be necessary.
• Non-Patent Document 1 reports that the intestinal microbiota of type 1 and type 2 diabetes patients has a decreased number of bacteria of the Firmicutes phylum and a decreased number of bacteria of the Bacteroidetes phylum.
• Non-Patent Document 2 reports that the intestinal microbiota of type 2 diabetes patients has a decreased number of bacteria of the Proteobacteria phylum.
• Non-Patent Document 3 reports that the intestinal microbiota of type 1 diabetes patients has a decreased number of bacteria of the Verrucomicrobia phylum and Actinobacteria phylum.
• Patent Document 1 discloses a functional food for improving obesity that contains a charcoal composition such as bamboo charcoal or binchotan charcoal. Patent Document 1 also describes that the intestinal bacterial flora is maintained at a healthy composition by ingesting the functional food.
• charcoal, bamboo charcoal, and other charcoal have high adsorption properties, they have long been used for decontaminating oral toxins and treating renal failure.
• the present invention has been made in consideration of the above-mentioned circumstances, and aims to provide a composition for improving neuroinflammation, a composition for improving brain function, a composition for improving lipid metabolism, and a composition for adjusting the composition ratio of intestinal microflora, based on the new functions of plant charcoal.
• the present invention also provides the use of plant charcoal for the production of a composition for improving neuroinflammation, etc.
• composition for improving neuroinflammation comprises: Contains vegetable charcoal.
• composition for improving brain function comprises: Contains vegetable charcoal.
• the lipid metabolism improving composition according to the third aspect of the present invention comprises: Contains vegetable charcoal.
• a composition for adjusting the composition ratio of intestinal microflora comprises: Contains vegetable charcoal, It is intended to increase the ratio of Firmicutes/Bacteroidetes in the intestinal flora.
• a composition for adjusting the composition ratio of intestinal microflora comprises: Contains vegetable charcoal, It is intended to increase the proportion of Proteobacteria in the intestinal flora.
• a composition for adjusting the composition ratio of intestinal flora comprises: Contains vegetable charcoal, It is intended to increase the proportion of Actinobacteria in the intestinal flora.
• the use according to the seventh aspect of the present invention comprises: Use of plant charcoal for the manufacture of a composition for improving neuroinflammation.
• the use according to the eighth aspect of the present invention comprises: Use of plant charcoal for the manufacture of a composition for improving brain function.
• the use according to the ninth aspect of the present invention comprises: Use of plant charcoal for producing a composition for improving lipid metabolism.
• the use according to the tenth aspect of the present invention comprises:
• the present invention relates to use of plant charcoal for the manufacture of a composition for adjusting the composition ratio of intestinal flora, in order to increase the ratio of Firmicutes/Bacteroidetes in the intestinal flora.
• the use according to the eleventh aspect of the present invention comprises:
• the present invention relates to use of plant charcoal for the manufacture of a composition for adjusting the composition ratio of intestinal flora in order to increase the proportion of Proteobacteria in the intestinal flora.
• the use according to the twelfth aspect of the present invention comprises:
• the present invention relates to use of plant charcoal for producing a composition for adjusting the composition ratio of intestinal flora in order to increase the proportion of Actinobacteria in the intestinal flora.
• the present invention provides a composition for improving neuroinflammation, a composition for improving brain function, a composition for improving lipid metabolism, and a composition for adjusting the composition ratio of intestinal flora, all based on the new functions of plant charcoal.
• FIG. 2 is a diagram showing the ratio of the number of bacteria in the phylum Firmicutes to the number of bacteria in the phylum Bacteroidetes in the intestinal bacterial flora of rats in Example 2.
• FIG. 1 shows the proportion of Verrucomicrobia bacteria in the intestinal flora of rats in a normal control group (group I) and a diabetic model control group (group II) according to Example 2. This figure shows the proportion of Verrucomicrobia bacteria in the intestinal bacterial flora of rats in the diabetic model control group, the low-temperature treated bamboo charcoal administration group (Group III), and the high-temperature treated bamboo charcoal administration group (Group IV) in Example 2.
• FIG. 1 shows the proportion of Verrucomicrobia bacteria in the intestinal bacterial flora of rats in a normal control group (group I) and a diabetic model control group (group II) according to Example 2.
• This figure shows the proportion of Verrucomicrobia bacteria in the intestinal bacterial flora of rats in the diabetic model control group, the low-
• FIG. 1 shows the proportion of bacteria in the Proteobacteria phylum in the intestinal flora of rats in Example 2.
• FIG. 1 shows the proportion of bacteria of the phylum Actinobacteria in the intestinal flora of rats in Example 2.
• FIG. 13 is a diagram showing an image of rat liver tissue according to Example 3.
• FIG. 13 is a diagram showing the area of liver tissue stained with Oil Red in a rat in Example 3.
• FIG. 13 is a graph showing the concentration of IL-1 ⁇ in plasma of rats according to Example 4.
• FIG. 13 is a graph showing the concentration of IL-1 ⁇ in splenic tissue of rats according to Example 4.
• FIG. 13 is a graph showing the concentration of IL-1 ⁇ in the intestinal tissue of rats according to Example 4.
• FIG. 13 is a graph showing the concentration of IL-1 ⁇ in liver tissue of rats according to Example 4.
• FIG. 13 shows immunostained intestinal epithelial cells of a rat according to Example 4.
• FIG. 9 shows the relative fluorescence intensity of inducible nitric oxide synthase (iNOS) obtained from FIG. 8.
• FIG. 13 is a diagram showing the ratio of iNOS-positive nerve cells in the hippocampal tissue of rats according to Example 4.
• FIG. 13 shows images of immunostained intestinal epithelium of a rat according to Example 5.
• FIG. 12 shows the relative fluorescence intensity of adiponectin obtained from FIG. 11.
• FIG. 13 shows images of rat hippocampus immunostained for brain-derived neurotrophic factor (BDNF) and adiponectin according to Example 5.
• BDNF brain-derived neurotrophic factor
• FIG. 14 shows the relative fluorescence intensity of BDNF obtained from FIG. 13.
• FIG. 14 shows the relative fluorescence intensity of adiponectin obtained from FIG. 13.
• FIG. 13 is a graph showing adiponectin concentrations in plasma of rats according to Example 5.
• FIG. 13 is a graph showing the amount of adiponectin in liver tissue of rats according to Example 5.
• FIG. 13 shows images of the rat hippocampus immunostained for Iba-1 and GFAP (glial fibrillary acidic protein) in Example 5.
• FIG. 17 shows the percentage of GFAP-positive astrocytes obtained from FIG. 16.
• FIG. 17 shows the percentage of Iba-1 positive microglial cells obtained from FIG. 16.
• FIG. 16 shows the percentage of Iba-1 positive microglial cells obtained from FIG. 16.
• FIG. 13 is a diagram showing blood concentrations of total cholesterol (T-CHO) in rats according to Example 6.
• FIG. 13 is a diagram showing blood levels of LDL-cholesterol (LDL-C) in rats according to Example 6.
• FIG. 13 is a diagram showing blood concentrations of neutral fat (TG) in rats according to Example 6.
• FIG. 13 is a diagram showing the blood concentration of alanine aminotransferase (ALT) in rats according to Example 6.
• FIG. 13 is a diagram showing the blood concentration of indoxyl sulfate in rats according to Example 6.
• FIG. 13 shows a tube before and after centrifugation of a sample containing coconut charcoal in Example 7.
• FIG. 13 shows a tube before and after centrifugation of a sample containing pine charcoal according to Example 7.
• FIG. 13 is a graph showing absorbance for quantifying endotoxin in Example 8.
• 13A and 13B are electron microscope images of low-temperature treated bamboo charcoal, high-temperature treated bamboo charcoal, pine charcoal, and coconut
• the composition according to the present embodiment includes vegetable charcoal.
• the vegetable charcoal can be obtained by a known method.
• the type of plant is not particularly limited, and any type and any part can be used.
• the plant may be a plant immediately after harvest, or a plant several days after harvest.
• Examples of vegetable charcoal include bamboo charcoal, pine charcoal, binchotan charcoal, plum charcoal, plum seed charcoal, birch charcoal, maple charcoal, etc., as well as activated carbon such as coconut charcoal produced from coconut shells.
• the vegetable charcoal is bamboo charcoal.
• bamboo charcoal there is no limitation on the type of bamboo, and any plant belonging to the family Poaceae, subfamily Bambusa may be used. Not only one type of bamboo but also multiple types of bamboo may be used. Examples of bamboo include Madake (Phyllostachys bambusoides), Moso bamboo (Phyllostachys heterocycla f. pubescence), Hachiku (Phyllostachys nigra), Hoteichiku (Phyllostachys aurea), Kikkouchiku (Phyllostachys heterocycla f. heterocycla), Horaichiku (Bambusa multiple) and so on.
• bamboo charcoal is obtained by heat-treating bamboo.
• the bamboo is maintained at 200 to 2000°C, 250 to 1500°C, 300 to 1300°C, or 400 to 1200°C.
• the heat treatment temperature is preferably 500°C.
• the heat treatment may be performed in an air atmosphere, or in an atmosphere with relatively little air by supplying argon gas or the like, or in a vacuum. It is particularly preferable to heat the bamboo in a state similar to steaming under a vacuum.
• the heat treatment time is appropriately set, but is 60 to 120 minutes, 70 to 110 minutes, 80 to 100 minutes, or 85 to 95 minutes.
• the bamboo charcoal obtained by the heat treatment is cooled to room temperature by a known method. If the heat treatment is performed under a vacuum, it may be cooled under a vacuum.
• the bamboo Before the heat treatment, the bamboo may be divided, cut or crushed into pieces of a size that is easy to heat treat, or after the heat treatment, the bamboo may be divided, cut or crushed.
• the composition according to this embodiment is produced by a known method and contains vegetable charcoal.
• the composition contains, for example, 0.1 to 99% by weight, 1 to 50% by weight, and preferably 1 to 20% by weight of vegetable charcoal as an active ingredient.
• the bamboo charcoal contained in the composition as an active ingredient has at least the effects of improving neuroinflammation, improving brain function, improving lipid metabolism, and adjusting the composition ratio of intestinal flora. More specifically, with regard to the effect of improving neuroinflammation, bamboo charcoal suppresses inflammation of nerve cells in the brain, particularly in the hippocampus. Furthermore, bamboo charcoal suppresses neuroinflammation in the hippocampus, i.e., the abnormal activity of microglial cells and astrocytes. With regard to the effect of improving brain function, bamboo charcoal increases the expression of BDNF (Brain-Derived Neurotrophic Factor) in the hippocampus. BDNF is a neurogenesis factor and memory enhancing factor.
• BDNF Brain-Derived Neurotrophic Factor
• bamboo charcoal significantly reduces the fat content in the liver. Furthermore, bamboo charcoal lowers total cholesterol, neutral fats, and LDL-cholesterol in the blood. In terms of adjusting the composition ratio of the intestinal flora, bamboo charcoal increases the ratio of Firmicutes/Bacteroidetes, the proportion of Proteobacteria, and the proportion of Actinobacteria in the intestinal flora. Furthermore, as shown in the examples below, bamboo charcoal has an anti-inflammatory effect by suppressing inflammatory cytokines.
• the Firmicutes/Bacteroidetes ratio refers to the number of bacteria belonging to the Firmicutes phylum:the number of bacteria belonging to the Bacteroidetes phylum.
• the ratio of Proteobacteria and the ratio of Actinobacteria refer to the ratio of the number of bacteria belonging to the Proteobacteria phylum and the ratio of the number of bacteria belonging to the Actinobacteria phylum, respectively, to the number of bacteria constituting the intestinal flora.
• bamboo charcoal and coconut charcoal adsorb phenol red and endotoxin. Therefore, not only bamboo charcoal, but also vegetable charcoal made from other plants has the various effects of bamboo charcoal mentioned above.
• the composition according to this embodiment can be used as a composition for improving neuroinflammation, a composition for improving brain function, a composition for improving lipid metabolism, a composition for adjusting the composition ratio of intestinal flora, and an anti-inflammatory composition.
• the composition according to this embodiment may be, for example, an oral composition or pharmaceutical composition such as a supplement, a food composition, a food or drink, a functional food, or a food additive.
• the form of the supplement is not particularly limited, and may be any form such as a tablet, a powder, a granule, a capsule, a sugar-coated tablet, a film, a lozenge, a chewable tablet, a solution, an emulsion, a suspension, or the like.
• the supplement may contain any component that is normally used as a supplement.
• “Functional food” refers to food or beverages taken for the purpose of maintaining health, and includes foods with health functions such as foods for specified health uses, foods with functional claims, foods with nutrient functions, health foods, and nutritional supplements.
• foods with health functions such as foods for specified health uses or foods with nutrient functions are preferred.
• various additives used in foods specifically colorants, preservatives, thickening stabilizers, antioxidants, bleaching agents, antibacterial and antifungal agents, acidulants, sweeteners, seasonings, emulsifiers, strengthening agents, manufacturing agents, fragrances, etc. may be added to the oral composition.
• Functional foods may be either foods or beverages, and are not particularly limited as long as they can be taken orally.
• functional foods include beverages, confectioneries, processed grain products, paste products, dairy products, seasonings, etc.
• beverages include nutritional drinks, soft drinks, black tea, green tea, etc.
• confectioneries include candy, cookies, tablets, chewing gum, jelly, etc.
• processed grain products include noodles, bread, cooked rice, biscuits, etc.
• paste products include sausages, ham, kamaboko, etc.
• dairy products include butter, yogurt, etc.
• the oral composition may be added to food as a food additive.
• the food additive may be a paste, gel, powder, liquid, suspension, emulsion, granule, etc., so as to be easily added to food.
• the oral composition may contain water, vitamins, minerals, organic acids, organic bases, fruit juice, flavors, functional ingredients, food additives, etc.
• the oral composition can be manufactured by known methods.
• the oral composition may be contained in one or more containers so that the daily intake is the above-mentioned amount, and in this case, preferably one container contains one day's worth of the oral composition.
• the oral composition is provided in a form that can be distinguished from other products as a product in that it contains vegetable charcoal and is used for the above-mentioned purposes.
• a product in that it contains vegetable charcoal and is used for the above-mentioned purposes.
• at least one of the packaging, instructions, and promotional materials for the oral composition product indicates that it has the various effects described above.
• the pharmaceutical composition is not particularly limited, but may be, for example, a liquid, tablet, granule, fine granule, powder, tablet, capsule, etc.
• the pharmaceutical composition may be an injection, oral preparation, rectal suppository, vaginal suppository, nasal absorbent, transdermal absorbent, pulmonary absorbent, oral absorbent, etc.
• the pharmaceutical composition preferably contains a pharmacologically acceptable carrier.
• the pharmacologically acceptable carrier is various organic carrier substances or inorganic carrier substances.
• the pharmacologically acceptable carrier is, for example, an excipient, lubricant, binder, and disintegrant in a solid preparation, or a solvent, dissolution aid, suspending agent, isotonicity agent, buffer, soothing agent, etc. in a liquid preparation.
• additives such as preservatives, antioxidants, colorants, and sweeteners can also be used as necessary.
• excipients include lactose, sucrose, D-mannitol, starch, crystalline cellulose, and light anhydrous silicic acid.
• lubricants include magnesium stearate, calcium stearate, talc, and colloidal silica.
• binders include crystalline cellulose, sucrose, D-mannitol, dextrin, hydroxypropyl cellulose, hydroxypropylmethylcellulose, and polyvinylpyrrolidone.
• disintegrants include starch, carboxymethylcellulose, carboxymethylcellulose calcium, croscarmellose sodium, and carboxymethylstarch sodium.
• Solvents include, for example, water for injection, alcohol, propylene glycol, macrogol, etc.
• Solubilizing agents include, for example, polyethylene glycol, propylene glycol, D-mannitol, benzyl benzoate, ethanol, trisaminomethane, cholesterol, triethanolamine, sodium carbonate, sodium citrate, etc.
• Suspending agents include surfactants, hydrophilic polymers, etc., for example, stearyl triethanolamine, sodium lauryl sulfate, lauryl aminopropionic acid, lecithin, benzalkonium chloride, benzethonium chloride, glycerin monostearate, polyvinyl alcohol, polyvinylpyrrolidone, sodium carboxymethylcellulose, methylcellulose, hydroxymethylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, etc.
• surfactants for example, stearyl triethanolamine, sodium lauryl sulfate, lauryl aminopropionic acid, lecithin, benzalkonium chloride, benzethonium chloride, glycerin monostearate, polyvinyl alcohol, polyvinylpyrrolidone, sodium carboxymethylcellulose, methylcellulose, hydroxymethylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, etc.
• Isotonicity agents include, for example, sodium chloride, glycerin, D-mannitol, etc.
• Buffers include, for example, buffer solutions of phosphates, acetates, carbonates, citrates, etc.
• Soothing agents include, for example, benzyl alcohol, etc.
• Preservatives include, for example, paraoxybenzoic acid esters, chlorobutanol, benzyl alcohol, phenethyl alcohol, dehydroacetic acid, sorbic acid, etc.
• Antioxidants include, for example, sulfites, ascorbic acid, etc.
• FIG. 1 shows the ratio of the number of bacteria in the phylum Firmicutes to the number of bacteria in the phylum Bacteroidetes in the intestinal flora of rats in groups I to IV.
• the ratio of the number of bacteria in the phylum Firmicutes to the number of bacteria in the phylum Bacteroidetes was significantly lower in group II compared to group I. Furthermore, the ratio was significantly higher in groups III and IV compared to group II. This indicates that administration of bamboo charcoal increases the ratio in the intestinal flora of the diabetic model. It was also shown that low-temperature treated bamboo charcoal is more effective at increasing the ratio than high-temperature treated bamboo charcoal.
• the number of Lactobacillales bacteria increased with the ingestion of low-temperature treated bamboo charcoal.
• the number of Bifidobacteria bacteria increased with the ingestion of high-temperature treated bamboo charcoal.
• Bifidobacteria are reduced in diabetic patients, and selectively increasing them is known to have an antidiabetic effect (Cani, P.D., et al., Selective increases of bifidobacteria in gut microflora improve high-fat-diet-induced diabetes in mice through a mechanism associated with endotoxaemia., Diabetologia, 2007, 50:2374-2383).
• Clostridiales bacteria were reduced by both low-temperature and high-temperature treated bamboo charcoal intake.
• Example 3 Changes in liver fat content by ingesting bamboo charcoal After the administration period in Example 2, three rats from each of groups I to IV were subjected to oil red staining of liver tissue, and the stained area was measured.
• FIG. 5 shows images of liver tissues from rats in groups I to IV stained with Oil Red.
• Figure 6 shows the area of liver tissue stained with Oil Red per 10 6 ⁇ m2 of liver tissue. As shown in Figures 5 and 6, the stained area and staining density were larger and deeper in liver tissues from group II than in group I, indicating significantly more fat accumulation. The stained area of liver tissues from groups III and IV was significantly smaller than that of group I. This suggests that administration of bamboo charcoal can reduce fat in liver tissues of diabetic models.
• Example 4 Changes in inflammatory markers by ingesting bamboo charcoal After the administration period in Example 2, the concentrations of interleukin-1 ⁇ (IL-1 ⁇ ) in plasma, spleen tissue and cytoplasmic tissue of rats in groups I to IV were measured (BMS630, Invitrogen). In addition, the expression of iNOS (inducible nitric oxide synthase) in intestinal epithelial cells and hippocampal tissue neurons (NeuN positive cells) was analyzed by immunostaining. Insulin resistance in type 2 diabetes is thought to be related to inflammatory cytokines, and both IL-1 ⁇ and iNOS are inflammatory markers.
• IL-1 ⁇ interleukin-1 ⁇
• iNOS inducible nitric oxide synthase
• bamboo charcoal can reduce inflammation in plasma, spleen tissue, intestinal tissue, intestinal epithelial cells, and neurons in hippocampal tissue. It is suggested that the anti-inflammatory effect of bamboo charcoal is related to its anti-diabetic effect.
• Example 5 Changes in adiponectin, brain-derived neurotrophic factor, and brain neuroinflammation by ingestion of bamboo charcoal
• the rats of groups I to IV after the administration period were subjected to expression analysis of adiponectin and BDNF in intestinal epithelial cells, brain hippocampal tissue, plasma, and liver tissue.
• Adiponectin is a hormone secreted from fat cells, and is an antidiabetic hormone that enhances insulin resistance and suppresses inflammation.
• Adiponectin is known to be low in type 2 diabetes patients, and it is said that the higher the concentration of adiponectin in the blood, the lower the risk of developing type 2 diabetes.
• adiponectin is said to have the effect of preventing hypertension and arteriosclerosis.
• BDNF is known to be reduced, particularly in diabetic patients, among neurotrophic factors, and it has been suggested that the reduced vascular protective function promotes complications such as diabetic retinopathy.
• An anti-adiponectin antibody (MA1-054, manufactured by Invitrogen) was used to detect adiponectin.
• An anti-BDNF antibody (ANT-006, manufactured by Alomone Labs) was used to detect BDNF.
• Figure 13 shows images of the hippocampus immunostained for BDNF and adiponectin in rats from groups I to IV.
• group II the expression levels of BDNF and adiponectin were also significantly lower in the hippocampus compared to group I.
• the expression levels of BDNF and adiponectin were significantly higher in groups III and IV compared to group II, indicating that administration of bamboo charcoal increases the expression levels of BDNF and adiponectin in the hippocampus of diabetic models.
• Figures 15A and 15B show the adiponectin concentration in plasma and the amount of adiponectin in liver tissue, respectively.
• the adiponectin concentration in plasma and the amount of adiponectin in liver tissue were significantly decreased compared to group I, but were significantly increased in groups III and IV.
• Low molecular weight adiponectin is known to pass through the blood-brain barrier (Schon, M., et al., Effects of running on adiponectin, insulin and cytokines in cerebrospinal fluid in healthy young individuals., Sci. Rep., 2019, 9:1959), and it has been suggested that increasing intestinal adiponectin by bamboo charcoal increases brain adiponectin.
• Figure 16 shows images of the hippocampus immunostained for Iba-1 and GFAP from rats in groups I to IV.
• GFAP is an intermediate filament protein and a marker that is specifically expressed in astroglia (astrocytes).
• Figures 17A and 17B show the percentages of GFAP-positive astrocytes and Iba-1-positive microglial cells, respectively, in Figure 16.
• group II showed a higher percentage of neuroinflammation in the hippocampus, i.e., astrocytes and microglial cells, and abnormal activity. Meanwhile, compared to group II, abnormal neuroinflammation activity was significantly suppressed in groups III and IV.
• BDNF memory enhancing and neurogenesis factor
• Example 6 Changes in blood biochemical indices After the administration period in Example 2, blood samples were taken from the rats in groups I to IV, and the blood biochemical indices were measured by requesting Oriental Yeast Co., Ltd.
• (result) 18A, 18B, and 18C show the blood levels of T-CHO, LDL-C, and TG in rats of each group, respectively.
• T-CHO was statistically significantly decreased in groups III and IV compared to group II.
• LDL-C and TG were significantly decreased in group III compared to group II.
• Figures 19A and 19B show the blood concentrations of ALT and indoxyl sulfate in rats in each group, respectively.
• ALT a marker for fatty liver
• Indoxyl sulfate a uremic substance
• bamboo charcoal intake reduced blood T-CHO, TG, LDL-C, and ALT, indicating that lipid metabolism disorders and fatty liver associated with diabetes were significantly improved. The mechanism behind this is thought to be that adiponectin, which increased with bamboo charcoal intake, reduced systemic inflammation.
• Example 7 Phenol red removal test The removal effect of phenol red in the medium by pine charcoal and coconut charcoal was evaluated.
• Pine charcoal is made by carbonizing dried red pine logs and pulverizing them (particle size: average 300 mesh or less, Ina Akamatsu Myotan (trademark) powder, manufactured by Sumi Plus Lab Co., Ltd.).
• Coconut charcoal is made by carbonizing dried coconut shells, activating them, sterilizing them, and pulverizing them (particle size: average 300 mesh or less, functional coconut shell activated carbon powder, manufactured by Sumi Plus Lab Co., Ltd.).
• a given amount of pine charcoal or coconut charcoal was mixed into the DMEM medium containing 0.03% by weight of phenol red in the tube, and the tube was rotated at 4°C for 36 hours. The sample was then centrifuged at 10,000 rpm for 10 minutes.
• Example 8 Endotoxin Removal Test The endotoxin removal effect of the high-temperature and low-temperature treated bamboo charcoal used in Example 1, and the pine charcoal and coconut charcoal used in Example 7 was evaluated using the Pierce Chromogenic Endotoxin Quant Kit (A39552, Thermo Scientific). Endotoxin was dissolved in toxin-free water at a concentration of 0.5 U/ml. The endotoxin solution was mixed with 0.5% or 2% (weight/volume) activated charcoal. After mixing, the tube containing the sample was rotated for 36 hours at 4°C. The sample was then centrifuged at 10,000 rpm for 10 minutes. The resulting supernatant was measured for dye quantification absorbance using an ELISA plate reader with a 405 nm filter lens according to the kit's instructions, and the endotoxin concentration was quantified.
• FIG. 22 shows the absorbance.
• bamboo charcoal treated at high temperature had a better endotoxin removal effect than bamboo charcoal treated at low temperature.
• coconut charcoal showed a strong endotoxin removal effect even at a concentration of 0.5%.
• Pine charcoal showed a higher endotoxin removal effect than bamboo charcoal.
• FIG. 23 shows the electron microscope images. Many small particles were observed in the coconut charcoal, and these small particles had more pores than the other charcoals. The pine charcoal was thinly layered compared to the other charcoals. This suggests that the surface area of the pine charcoal is greater, especially compared to bamboo charcoal. The high-temperature treated bamboo charcoal and the low-temperature treated bamboo charcoal showed relatively larger and less pores than the coconut charcoal.
• the present invention is useful for producing oral compositions, pharmaceutical compositions, etc.

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