Modified protein-reducing agent and method for producing the same

Abstract

To provide: a modified protein-reducing agent that is safe and can be taken at a daily dosage or used as a functional food, and that makes it possible to reduce the amount of modified protein in a body; and a method for producing the modified protein-reducing agent.SOLUTION: A modified protein-reducing agent according to the present invention contains an above-ground portion of sesame (Sesamum indicum) or an extract thereof as an active ingredient. A method for producing a modified protein-reducing agent according to the present invention includes the steps of sowing and growing seeds of sesame (Sesamum indicum) and collecting the above-ground portion of the grown sesame.SELECTED DRAWING: None

Description

[Technical field]

[0001] The present invention relates to an agent for reducing denatured proteins that is safe, can be taken daily, and can be used as a health food, and is capable of reducing denatured proteins in the body, and a method for producing the same. [Background technology]

[0002] Aging, overeating, and poor diet can lead to excess glucose in the blood, which causes the glycation of intracellular and extracellular proteins that are the basis of the components of each tissue in the body, resulting in the production and accumulation of denatured proteins. In addition, advanced glycation end products (AGEs) are contained in animal fat foods that are cooked by heat, particularly by deep-frying, baking, and sauteing. In addition, some artificial sweeteners that are widely used in soft drinks and confectionery are said to produce advanced glycation end products more quickly than glucose. These denatured proteins are highly toxic and are considered to be causative agents of aging. For example, not only do they cause dull skin, wrinkles, and senile spots in appearance, but they also reduce supple movement and cause the decline and deterioration of each tissue's function. In addition, advanced glycation end products accumulate in blood vessels, causing myocardial infarction and cerebral infarction, and accumulate in bones, causing osteoporosis, and accumulate in the eyes, causing cataracts, thus affecting the health of the entire body (Patent Documents 1-8, Non-Patent Documents 1-7). Hemoglobin A1c, which is used to diagnose diabetes, is also a type of advanced glycation end product.

[0003] Although there have been many reports on the relationship between human diseases and advanced glycation end products, inhibition of the formation of advanced glycation end products, and natural products that break down advanced glycation end products, there are no safe and inexpensive medicines or natural products that show a specific improving effect when ingested by humans. Since denatured proteins are thought to accumulate in the body in extremely small amounts due to lifestyle habits, etc., it would be even more desirable if there were a safe drug that could be ingested every day.

[0004] Sesame has long been known as a nutritious food and is also used as a herbal medicine. Sesame oil is also extracted from the seeds due to their high oil content. Sesamin, which is contained in sesame, is said to have various physiological activities, such as antioxidant effects, cholesterol absorption inhibition, and anticancer effects.

[0005] As for sesame, the seeds are mainly used for food and research, and little is known about the physiological activity of the above-ground parts other than the seeds, such as the leaves. The oldest Chinese pharmacological book, the Shennong Bencao Jing, contains a description of the efficacy of sesame leaves along with the seeds, and a similar description can be found in the Food Materia Medica, published during the Yuan Dynasty, but the nutritional physiology and medical evaluation of sesame when ingested by humans is unknown. Even today, sesame thinnings are eaten in West Africa, and young leaves are also used as an ingredient, such as being added to soup.

[0006] For example, there is a report on the radical scavenging activity of sesame seed sprouts four days after germination (Non-Patent Document 8). However, there are no reports on the physiological activity of above-ground parts five days or more after germination. [Prior art documents] [Patent documents]

[0007] [Patent Document 1] International Publication No. 2014 / 126199 Brochure [Patent Document 2] JP 2017-195855 A [Patent Document 3] JP 2019-1725 A [Patent Document 4] JP 2020-143034 A [Patent Document 5] JP 2020-152672 A [Patent Document 6] JP 2020-188689 A [Patent Document 7] JP 2020-193182 A [Patent Document 8] Patent Publication No. 2021-49 [Non-patent literature]

[0008] [Non-Patent Document 1] Satoru Goto et al., Experimental Medicine, 16, 2324-2331 (1998) [Non-Patent Document 2] ED Schleicher et al., The Journal Clinical Investigation, 99, 457-468 (1997) [Non-Patent Document 3] Katrien HJGaens et al., Arteriosclerosis, Thrombosis, and Vascular Biology, 34, 1199-1208 (2014) [Non-Patent Document 4] N Breusing and T Grune,Biological,Chemistry,389,203-209(2008) [Non-Patent Document 5] K Ishizaki et al., Glycative Stress Research, 7, 22-28 (2020) [Non-Patent Document 6] M Yagi et al., Glycative Stress Research, 8, 156-161 (2021) [Non-Patent Document 7] Masao Watanabe, Pharmaceutical Journal, 140, 1335-1341 (2020) [Non-Patent Document 8] Kinuko Ishiyama et al., Journal of the Japanese Society for Food Science and Technology, 53, 8-16 (2006) Summary of the Invention [Problem to be solved by the invention]

[0009] As described above, denatured proteins such as advanced glycation end products cause various disorders and diseases in the body, and various components that are believed to have a reducing effect are being researched. However, no component is known that is safe enough to be taken regularly and that can actually reduce denatured proteins in the body when administered to humans. Therefore, an object of the present invention is to provide a denatured protein reducer that is safe, can be taken daily, and can be used as a health food, and is capable of reducing denatured proteins in the body, and a method for producing the same. [Means for solving the problem]

[0010] The present inventors have conducted extensive research to solve the above problems, and as a result have found that the above-ground parts of sesame, which are safe for consumption, contain components that can effectively reduce denatured proteins in the body, thereby completing the present invention. The present invention will now be described.

[0011] [1] An agent for reducing denatured protein, comprising the above-ground parts of sesame (Sesamum indicum) or an extract thereof as an active ingredient. [2] The agent for reducing a denatured protein according to [1] above, wherein the denatured protein is an advanced glycation end product. [3] The agent for reducing a denatured protein according to [1] above, wherein the denatured protein is a protein multimer. [4] A method for producing a denatured protein reducing agent, comprising: Sowing and growing sesame (Sesamum indicum) seeds; A method comprising the step of harvesting the above-ground parts of grown sesame. [5] The method according to [4] above, wherein the above-ground part of sesame is harvested when one or more buds are visible and before flowering. [6] The method according to [4] or [5], further comprising a step of extracting the active ingredient from the above-ground parts of sesame using a solvent. [7] The method according to [6], wherein the solvent is an alcohol-based solvent. Effect of the Invention

[0012] The active ingredient of the denatured protein reducing agent of the present invention is contained in the aboveground part of sesame, which is also used for food, so it is safe and can be taken regularly every day. In addition, the denatured protein reducing agent of the present invention can actually reduce denatured protein by administering it to subjects who are particularly concerned about the accumulation of denatured protein. Therefore, the present invention is industrially very excellent as a health food that contributes to people's regular health. [Brief description of the drawings]

[0013] [Figure 1] FIG. 1 is a photograph of an SDS-PAGE gel in which the inhibitory effect of the hot water extract of the above-ground parts of sesame according to the present invention on the glycation cross-linking reaction of lysozyme was evaluated. [Diagram 2] FIG. 2 is a photograph of an SDS-PAGE gel in which the inhibitory effect of the alcoholic water extract of the above-ground parts of sesame according to the present invention on the glycation cross-linking reaction of lysozyme was evaluated. [Diagram 3] FIG. 3 is a graph showing the inhibitory effect of the aqueous extract of the above-ground parts of sesame according to the present invention on the glycation cross-linking reaction of lysozyme. [Figure 4] FIG. 4 is a graph showing the inhibitory effect of the aqueous extract of the aerial parts of sesame according to the present invention on a crosslinking reaction. [Diagram 5] FIG. 5 is a graph showing the activating effect of the aqueous extract of the above-ground parts of sesame according to the present invention on oxidative protease that degrades denatured proteins. [Figure 6] FIG. 6 is a graph showing the effect of the dried powder of sesame above-ground parts according to the present invention in reducing advanced glycation endproducts in subjects with high accumulation of advanced glycation endproducts. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0014] The denatured protein reducing agent according to the present invention contains the above-ground parts of sesame (Sesamum indicum) or an extract thereof as an active ingredient. In the present disclosure, the active ingredient refers to a component that has a denatured protein reducing effect among the components contained in the denatured protein reducing agent according to the present invention, in other words, the denatured protein reducing agent according to the present invention contains the above-ground parts of sesame or an extract thereof in an amount that exerts a denatured protein reducing effect. Specifically, without being particularly limited, for example, the ratio of the above-ground parts of sesame or an extract thereof in the denatured protein reducing agent according to the present invention can be 10% by mass or more and 100% by mass or less.

[0015] Sesame (Sesamum indicum) is an annual plant of the Sesamum genus of the Pedaliaceae family, and it is said that there are about 3,000 species, based on the differences in the shape of the seeds, such as size and color. The type of sesame is not particularly limited, but the inventor has experimentally confirmed that Sa Mong Nan Net Thae and Sesame Zou have an excellent effect of reducing denatured proteins.

[0016] Sa Mong Nan Net Thae is a small black sesame that has been cultivated in a specific area of ​​Myanmar for a long time and is also known by the product name "Goma Kurohachi (registered trademark)". The seeds of Sa Mong Nan Net Thae are very similar in weight and appearance to the seeds of the registered lignan sesame (Registration No.: 19697, Application No.: 20790, Type of agricultural, forestry and fishery plant: Sesamum indicum L., Variety name: ITCFA2001; Registration No.: 19698, Application No.: 20791, Type of agricultural, forestry and fishery plant: Sesamum indicum L., Variety name: ITCFA2002), but the inventors have clarified through genome analysis that the two varieties are evolutionarily different, with large insertions and deletions of sequences between the two genomes. The difference in the genomes of Goma Kurohachi and lignan sesame can be verified by PCR.

[0017] Gomazou is a high-lignan variety that can be cultivated in Japan and was selected from the progeny of the high-yielding white sesame line Toyama016 and the tropical germplasm line H65 native to southern China, which has high sesamin and sesamolin contents.

[0018] The above-ground part refers to the part that is not underground and can be seen above ground when sesame seeds are sown and grown. The above-ground part of sesame can be obtained by cutting and removing the underground part from grown sesame.

[0019] The above-ground part of sesame is preferably from a plant having, for example, two or more true leaves. The above-ground part of sesame is preferably harvested before fully ripe seeds are set. Also, plants with a plant height of 50 cm or more, plants with one or more buds but before flowering, plants before one or more flowers are seen, etc. can be harvested. The period from sowing to harvesting can be adjusted appropriately, and can be, for example, one month or more, preferably two months or more or 2.5 months or more, and can be 3.5 months or less, preferably three months or less.

[0020] The above-ground parts of sesame may be used as is, or may be subjected to one or more treatments selected from washing with water, drying, crushing, hydrolysis, and extraction. Examples of hydrolysis treatment include treatment at 25±5°C and humidity of 90% or more for 1 hour to 5 hours, or rotation in a drum followed by heating to stop hydrolysis. Hydrolysis treatment may reduce bitterness.

[0021] The form of the active ingredient of the agent for reducing denatured protein according to the present invention is not particularly limited, and examples thereof include liquid, paste, and powder. Powders include coarse powders, micro powders, and nano-micro powders.

[0022] The form of the denatured protein reducing agent according to the present invention is not particularly limited, and examples thereof include solid, gel, and liquid forms. More specifically, examples thereof include powders, fine granules, granules, tablets, coated tablets, capsules, lozenges, and liquid forms. The denatured protein reducing agent according to the present invention may contain additives other than the active ingredient depending on the dosage form. Examples of additives include excipients, binders, lubricants, disintegrants, emulsifiers, stabilizers, absorption promoters, differentiation agents, and preservatives. The amount of each additive is not particularly limited and may be appropriately adjusted.

[0023] The agent for reducing a denatured protein according to the present invention can be produced, for example, by a method including the following steps.

[0024] 1. Sesame seeding and growing process In this process, sesame seeds are sown and grown. This process may be carried out in accordance with the usual method of growing sesame. For example, sesame seeds may be sown from mid-May to mid-June in Japan after the maximum temperature exceeds 20°C. Specifically, holes are made about 1 cm deep, 5-6 seeds are placed in each hole, then the holes are covered with soil and watered thoroughly. When the plants have 1-2 true leaves, poorly growing plants are thinned out so that there are about 3 plants in each hole, when there are 3-4 true leaves, there are 2 plants, and when there are 5-6 true leaves, there is 1 plant.

[0025] 2. Sesame seed harvesting process In this step, the above-ground parts of the grown sesame seeds are harvested. Specifically, the above-ground parts are separated from the underground parts of the grown sesame seeds. The harvesting time and post-processing are as described above.

[0026] 3.Extraction process In this process, the active ingredient is extracted from the above-ground part of sesame using a solvent. This process may or may not be performed, but by performing the extraction, it is possible to further enhance the effect of the active ingredient in reducing denatured proteins.

[0027] The solvent used for extraction in this step is not particularly limited and may be appropriately selected, but from the viewpoint of safety, for example, an aqueous solvent may be mentioned. The aqueous solvent refers to water, a mixed solvent of water and a water-soluble organic solvent, or a water-soluble organic solvent. The ratio of the water-soluble organic solvent in the mixed solvent may be appropriately adjusted, but for example, it may be 50% by mass or more, preferably 60% by mass or more or 65% by mass or more, and more preferably 70% by mass or more. Examples of the water-soluble organic solvent include alcohol-based solvents such as methanol and ethanol; ether-based solvents such as tetrahydrofuran; amide-based solvents such as dimethylformamide and dimethylacetamide; and sulfoxide-based solvents such as dimethylsulfoxide. From the viewpoint of relatively little harm to the human body, ethanol is suitable as the water-soluble organic solvent. In addition, the type of water is not particularly limited, and purified water, distilled water, pure water, tap water, etc. may be used without any particular restriction.

[0028] The extraction conditions in this step are not particularly limited, and a conventional method can be used. For example, about 5 mL to 100 mL of solvent is added per 1 g of the aboveground part of sesame, and extraction is performed for about 30 minutes to 10 hours. The extraction temperature is also not particularly limited, and extraction may be performed at room temperature, extraction may be performed at or below the boiling point of the solvent, or heating to reflux. For example, when water is used as the solvent, heating may be performed at 60°C to 100°C.

[0029] After extraction, general post-treatment may be carried out. For example, solids may be removed from the mixture after extraction by filtration or centrifugation. Furthermore, the obtained solution may be distilled, concentrated, or dried. Examples of drying methods include heat drying, vacuum drying, freeze drying, and spray drying. In addition, the active ingredient may be further purified by chromatography or the like.

[0030] The amount of the denatured protein reducing agent according to the present invention should be appropriately adjusted depending on whether it is preventive use or therapeutic use, the severity of the patient, other conditions, age, sex, etc., and is not particularly limited. For example, the denatured protein reducing agent according to the present invention can be used at 10 mg or more per day in solid content when taken orally, and at 100 mg or more when used externally. Since the denatured protein reducing agent according to the present invention is very safe, the upper limit of the amount of use is not particularly limited, but for example, it can be 2 g or less per day in solid content when taken or 5 g or less when used externally. In addition, the number of times per day can be about 1 time or more and 5 times or less.

[0031] The denatured protein reducing agent according to the present invention can be administered not only to humans but also to animals other than humans. Examples of animals to which the agent can be administered other than humans include livestock such as horses, cows, pigs, sheep, goats, camels, and llamas; sports animals such as racehorses; pet animals such as dogs and cats; laboratory animals such as mice, rats, guinea pigs, and rabbits; poultry such as chickens, ducks, turkeys, and ostriches; and seafood such as farmed fish.

[0032] The denatured protein reducing agent according to the present invention has an extremely excellent effect of reducing denatured proteins. Specifically, it exhibits actions such as suppressing glycation and multimerization of proteins, decomposing denatured proteins once formed, and activating enzymes that degrade denatured proteins. Therefore, the denatured protein reducing agent according to the present invention is effective in preventing and treating diseases and symptoms involving protein denaturation. Examples of such diseases and symptoms include wrinkles, age spots, dullness, and sagging skin; diabetic complications such as cataracts, arteriosclerosis, and renal dysfunction; aging such as memory disorders and dementia; and cancer. EXAMPLES

[0033] The present invention will be described in more detail below with reference to examples. However, the present invention is not limited to the following examples, and it is possible to carry out the present invention by making appropriate modifications within the scope of the above and below-mentioned aims, and all of these modifications are included in the technical scope of the present invention.

[0034] Example 1 Small black sesame seeds, which have been cultivated for a long time in a specific region of Myanmar and are locally called Sa Mong Nan Net Thae (hereinafter abbreviated as "SMNNT"), were sown, and after about three months, when buds were visible, the underground parts were cut and removed from the aboveground parts, and dried at 37°C for 72 hours. The obtained dried aboveground parts of SMNNT were pulverized using a hammer mill.

[0035] Example 2 2 g of the dried SMNNT aerial part powder of Example 1 was mixed with 40 mL of water and heated at 80° C. for 1 hour. The mixture was then filtered and centrifuged to remove the solids, yielding an extract. 5 mL of the resulting extract was taken and heated at 105° C. for 1 hour to remove the solvent, and the amount of solids was measured.

[0036] Example 3 An extract was obtained and the solid content was measured in the same manner as in Example 2, except that 70% ethanol water was used instead of water and heating was performed at 50° C. for 4 hours.

[0037] Example 4 A powder of the above-ground parts of sesame was obtained in the same manner as in Example 1, except that "Gomazo", a variety of sesame, was used instead of SMNNT.

[0038] Example 5 An extract was obtained in the same manner as in Example 2, except that the powder of the above-ground parts of the sesame plant in Example 4 was used, and the solid content was measured.

[0039] Example 6 An extract was obtained in the same manner as in Example 3, except that the powder of the above-ground parts of the sesame plant in Example 4 was used, and the solid content was measured.

[0040] Example 7: Genomic Analysis The seeds of SMNNT are very similar to the so-called lignan sesame seeds in terms of the number of seeds per gram and the color tone. Therefore, DNA was prepared from both and genome analysis was performed. The number of bases in the sesame genome is known to be about 270 million bases, and in our genome analysis, we obtained sequence data that was about 55 times the number of bases in the sesame genome per variety, which means that we analyzed any genome region 55 times. Therefore, probabilistically, all genome regions were covered, and it can be determined that misreadings were corrected by the analysis program. As a result of genome analysis, it became clear that SMNNT and lignan sesame are evolutionarily different varieties, as large sequence insertions and deletions were observed between the genomes of SMNNT and lignan sesame. From the obtained analysis data, it is possible to verify the genome differences between SMNNT and lignan sesame by PCR.

[0041] Test Example 1: Evaluation of the inhibitory effect on AGEs protein cross-link formation The inhibitory effect on AGEs protein cross-link formation was evaluated with reference to the method described in Perera HKI et al., Asian J.Med.Sci.,6(1),28-33(2015). Specifically, 0.1 mol / L phosphate buffer (pH 7.4), each extract, lysozyme as a protein, and fructose as a sugar were mixed and incubated at 60°C for 40 hours. The concentrations of lysozyme and fructose were adjusted to 5 mg / mL and 0.5 mol / L, respectively. The amount of each extract added was adjusted based on the solid content so that the solid content concentration was as shown in Figures 1 and 2. In addition, as a control, the extraction solvent was added instead of the extract, and aminoguanine was added as a positive control. For comparison, a reaction solution was obtained in the same manner without adding fructose. The obtained lysozyme saccharification reaction solution, distilled water, and 2-mercaptoethanol sample solution were mixed at a volume ratio of 5:5:2 and reacted. The crosslinking reaction was then stopped by heating at 95°C for 5 minutes, and after cooling, SDS-PAGE electrophoresis was performed according to a conventional method. The gel concentration was 4-20% and the current value was 20 mA. After electrophoresis, the lysozyme band was stained with CBB and decolorized with methanol-acetic acid. The results are shown in Figures 1 and 2. The molecular weight of the lysozyme monomer is 13.1 kDa, the molecular weight of the dimer is 25.8 kDa, and the molecular weight of the trimer is 40.5 kDa. In addition, in Figures 1 and 2, "Fru" represents fructose, and "AG" represents aminoguanine. The explanation of the lanes in Figure 1 is shown in Table 1, and the explanation of the lanes in Figure 2 is shown in Table 2.

[0042] [Table 1]

[0043] [Table 2]

[0044] As shown in Figures 1 and 2, lysozyme is saccharified by fructose, and is further dimerized by 2-mercaptoethanol, and trimer formation is also observed. On the other hand, the formation of dimers is inhibited by SMNNT and the extract from the aerial parts of Sesame Seed. The trimer is hardly observed.

[0045] Next, the photographed images of each gel were processed using the image processing software "ImageJ," and the intensities of the bands corresponding to the protein dimer and trimer were quantified, and the cross-linking inhibition rate was calculated using the following formula. The results are shown in Figure 3. Cross-linking inhibition rate (%) = [{(band intensity with extract and fructose added) - (band intensity with extract and no fructose added)} / {(band intensity with solvent and fructose added) - (band intensity with solvent and no fructose added)}] x 100 As shown in the results in Figure 3, all of the extracts according to the present invention effectively inhibited protein cross-linking compared to the positive control aminoguanine, and in particular, the 70% ethanol extract showed a stronger cross-linking inhibitory effect than the hot water extract. Also, the 70% ethanol extract derived from the aerial parts of SMNNT showed a stronger cross-linking inhibitory effect than the extract from the aerial parts of Sesame Seed. Furthermore, the cross-linking inhibitory effect of the extract derived from the aerial parts of SMNNT was stronger than that of the positive control aminoguanine.

[0046] Test Example 2: Evaluation of AGEs cross-linking cleavage activity The cleavage activity of the formed AGEs interprotein crosslinks by the aerial parts of SMNNT was evaluated with reference to Vasan S et al., Nature, 382, ​​275-278 (1996). Specifically, the extract of the aboveground part of SMNNT in Example 3, or N-phenacylthiazolium bromide (PTB) as a positive control, 10 mmol / L 1-phenyl-1,2-propanedione (PPD), and 0.2 mol / L phosphate buffer (pH 7.4) were mixed in a ratio of extract solids:PPD:phosphate buffer = 5:1:4 (mass ratio) and reacted at 37°C for 8 hours (n=3).When a substance having an action of cleaving protein-protein crosslinks is included in the reaction system, PPD is decomposed to produce benzoic acid as shown in the following reaction formula.

[0047] [ka]

[0048] The reaction was then stopped by adding 0.7 mol / L hydrochloric acid. The reaction solution was centrifuged, and the amount of benzoic acid in the supernatant was analyzed by HPLC, and the AGEs cross-link cleavage rate was calculated using the following formula. Three experiments were performed. The results are shown in Figure 4. AGEs cross-link cleavage rate (%) = [(amount of benzoic acid in sample solution - amount of benzoic acid in control solution) / amount of PPD used in reaction] x 100 As shown in the results in FIG. 4, it was demonstrated that the extract from the aerial parts of SMNNT has a stronger AGEs cross-linking activity than PPD, which is the positive control.

[0049] Test Example 3: Evaluation of oxidative protease activation Glycated and oxidized damaged proteins are degraded by oxidative protease (hereinafter abbreviated as "OPH"). Therefore, we used acylaminoacid releasing enzyme (manufactured by Takara Bio Inc., hereinafter abbreviated as "AARE") and N-acetyl-L-alanine-p-nitroanilide (manufactured by Bachem, hereinafter abbreviated as "AAPA") as a substrate to evaluate the activation of oxidative protease. The extract of Example 2 or Example 3 was mixed so that the concentrations of 0.1 mol / L Tris-HCl (pH 7.4), 2 mmol / L AAPA, 1 mU / mL AARE, and extracted solids were as shown in FIG. 5. 250 μL of the resulting mixture was incubated at 37° C. for 60 minutes, and the amount of liberated p-nitroanilide (hereinafter abbreviated as "pNA") was measured by absorbance at 405 nm using a spectrophotometer. As a control, distilled water was used instead of the extract. Based on the obtained measured values, the OPH activation rate was calculated by the following formula. The results are shown in FIG. 5. OPH activation rate (%) = [(optical density 60 minutes after the start of reaction - optical density immediately after the start of reaction) / (optical density 60 minutes after the start of reaction of control - optical density immediately after the start of reaction of control)] x 100 As shown in the results in Figure 5, it was revealed that the extract from the aerial parts of SMNNT strongly enhances the activity of oxidative protease that breaks down AGEs.

[0050] Test Example 4: Clinical Trial A placebo-controlled, randomized, single-blind, parallel-group comparative study to verify the effect on accumulation of denatured proteins in human skin was conducted in compliance with the Ministry of Education, Culture, Sports, Science and Technology, the Ministry of Health, Labor and Welfare, and the Ministry of Economy, Trade and Industry Notification No. 1, "Ethical Guidelines for Life Science and Medical Research Involving Human Subjects" (issued on March 23, 2021). A total of 57 subjects were randomly selected based on gender, age, etc., and the AGE age of the skin before ingestion was measured using an AGE Scanner (Diagnoptics Technologies). From the evening of the day in question, subjects were asked to consume 1.5 g of the powder of the above-ground parts of SMNNT from Example 1 twice a day, in the morning and at night, for six months. Measurements were performed once a month, and the test was performed without any special instructions regarding other dietary content or lifestyle habits. The placebo group was asked to consume molokheiya powder instead of the above-ground parts of SMNNT powder, and measurements were performed in the same manner. The average AGE age measured by the AGE Scanner for subjects in their 20s was 19.5 ± 6.5 years, with the difference between the age at which AGEs were first measured and their actual age being within 10 years. For subjects in their 40s, the average was 42.7 ± 4.2 years, with the difference between the age at which AGEs were first measured and their actual age also being within 10 years, so there was not much difference from their actual age. However, there was a large variation in the 50s, with the average being 52.9 ± 4.0, but there were subjects with a difference of about 20 to 30 years between the age at which AGEs were first measured and their actual age. It is believed that abnormal accumulation of AGEs is related to lifestyle habits, particularly diet, that continue for long periods of time, such as 15 or 20 years. In subjects in their 20s to 40s whose AGEs age at the start of the study was insufficient, and no significant effect was observed in the placebo group. However, in seven subjects aged 54 to 76 whose AGEs age at the start of the study was over 70 years old, as measured by the AGEs Scanner, the average AGEs age at the start of the study was 78.4±3.4 years, but after just six months of consuming UPS powder of selected SMNNT, it dropped to 69.6±5.3 years, confirming a downward trend. The results are shown in Figure 6.

Claims

1. A denatured protein decomposition agent characterized by containing the leaves of Sa Mong Nan Net Thae or an extract thereof as an active ingredient.

2. The agent for degrading a denatured protein according to claim 1, wherein the denatured protein is an advanced glycation end product.

3. The agent for decomposing a denatured protein according to claim 1, wherein the denatured protein is a protein multimer.

4. A method for producing a denatured protein degrading agent, comprising the steps of: sowing and growing seeds of Sa Mong Nan Net Thae; and The method comprises the step of harvesting leaves of grown Sa Mong Nan Net Thae.

5. 5. The method according to claim 4, wherein the above-ground part of sesame is harvested when one or more buds are visible and before flowering.

6. 5. The method of claim 4, further comprising the step of extracting the active ingredient from the leaves of Sa Mong Nan Net Thae using a solvent.

7. The method according to claim 6, wherein the solvent is an alcohol-based solvent.

Images