Compositions containing sesamol compounds and their applications

Abstract

This invention discloses compositions containing sesamol compounds and their applications. The compositions include at least two of sesamol, sesamol dimer, and sesamin glucoside. This invention uses specific compounds from sesamol and its analogues, derivatives, and metabolites as the main active ingredients, resulting in compositions that exhibit synergistic effects, significantly enhancing physiological activities such as controlling body fat, regulating intestinal flora, maintaining blood lipids / blood sugar / blood pressure, protecting the liver, controlling appetite, anti-oxidation, and anti-aging. Furthermore, all components in this composition are derived from pure natural plant-based foods, with no toxic side effects; and the preparation method is simple and easy to operate, making it suitable for preparing related health foods, pharmaceuticals, feed, and feed additives, with promising application prospects.

Description

Technical Field

[0001] This invention relates to the fields of health food and biomedicine, and more specifically, to compositions containing sesaminoid compounds and their applications. Background Technology

[0002] Sesame seeds are rich in nutrients, with an average oil content of over 50%, mainly composed of unsaturated oleic and linoleic acids; the protein content is over 20%, containing a variety of essential amino acids. Sesame seeds are often roasted and used in daily cooking and as a garnish for pastries. In addition, sesame seeds are also processed into various food products such as black sesame paste, sesame flakes, sesame candy, sesame sauce, sesame kernels, and sesame protein powder.

[0003] Sesame seeds are not only rich in nutrients but also exhibit significant nutritional and health benefits. Due to their various effects, such as nourishing the liver and kidneys, promoting bowel movements, and beautifying hair and complexion, black sesame seeds and sesame oil have been included in the Pharmacopoeia, and (black and white) sesame seeds were managed as food and medicine homologous substances as early as 2002. The bioactivity of sesame seeds has also been recognized by countries such as the United States, the United Kingdom, and Japan, and has subsequently been included in their national pharmacopoeias.

[0004] Patent CN202410911892.4 discloses that sesamol can significantly improve inflammation and organic damage caused by intrahepatic bile accumulation and alleviate symptoms related to cholestatic liver disease; CN202410782013.2 discloses that sesamol has a protective effect against extraintestinal pathogenic Escherichia coli infection; CN201910111754.7 discloses the application of sulfonyl sesamol derivatives and their preparation methods, agricultural insecticides, and control of agricultural pests; CN201880066935.6 discloses a composition for relieving hangovers containing conjugates of sesamol and peptides as active ingredients. Current research includes numerous studies on the structural identification and active structure design of sesamol and its analogues, derivatives, and metabolites, as well as studies on the in vitro and in vivo antioxidant, antibacterial, and anti-inflammatory effects of sesamol and its analogues, derivatives, and metabolites. However, systematic reports on the structure-activity relationship and dose-effect relationship of these compounds, and the rational combination and scientific compatibility of compounds in pharmaceuticals, functional foods, and feed additives are lacking.

[0005] In view of this, the present invention is proposed. Summary of the Invention

[0006] The purpose of this invention is to provide a composition containing sesaminoids and its applications. Experiments have shown that this composition can synergistically improve the effects of controlling body fat, regulating intestinal flora, maintaining blood lipids / blood sugar / blood pressure, protecting the liver, controlling appetite, anti-oxidation and anti-aging.

[0007] This invention is implemented as follows:

[0008] In a first aspect, the present invention provides a composition containing sesamol compounds, comprising at least one of sesamol (CAS: 533-31-3) or its analogues, derivatives and metabolites;

[0009] Among them, analogues of sesamol include: 1,2,4-phenylpyrogallol, 2-methoxyhydroquinone, larch resin alcohol and 6-Nitro-1,3-benzodioxole-5-methano; derivatives of sesamol include: sesamol benzoate, sesamol dimer, sesamol sulfate and sesamol glucoside; metabolites of sesamol include: Sesamolactol.

[0010] Secondly, the present invention provides the use of the above composition in the preparation of products for controlling body weight and suppressing appetite.

[0011] Thirdly, the present invention provides the use of the above composition in the preparation of products for maintaining intestinal health.

[0012] Fourthly, the present invention provides the use of the above composition in the preparation of a medicament for improving insulin resistance and lowering blood sugar.

[0013] Fifthly, the present invention provides the application of the above composition in the preparation of products that lower body fat and blood lipids.

[0014] In a sixth aspect, the present invention provides the use of the above composition in the preparation of products that improve liver damage.

[0015] In a seventh aspect, the present invention provides the use of the above composition in the preparation of products for maintaining blood pressure.

[0016] Eighthly, the present invention provides the use of the above-described composition in the preparation of antioxidant and / or anti-aging products.

[0017] The present invention has the following beneficial effects:

[0018] This invention uses specific compounds from sesamol and its analogues, derivatives, and metabolites as the main active ingredients, enabling the obtained composition to produce a synergistic effect and significantly enhance physiological activities such as controlling body fat, regulating intestinal flora, maintaining blood lipids / blood sugar / blood pressure, protecting the liver, controlling appetite, anti-oxidation, and anti-aging. Furthermore, all components in this composition are derived from pure natural plant-based foods, with no toxic side effects; and the preparation method is simple and easy to operate, making it suitable for preparing related foods, pharmaceuticals, feeds, and feed additives, with promising application prospects. Attached Figure Description

[0019] To more clearly illustrate the technical solutions of the embodiments of the present invention, the accompanying drawings used in the embodiments will be briefly introduced below. It should be understood that the following drawings only show some embodiments of the present invention and should not be regarded as a limitation on the scope. For those skilled in the art, other related drawings can be obtained based on these drawings without creative effort.

[0020] Figure 1 The structural formula of sesamol;

[0021] Figure 2 The structural formula of sesamol benzoate is shown.

[0022] Figure 3 The structural formula is 5,5'-bi-1,3-benzodioxacyclopentene-6,6'-diol;

[0023] Figure 4 The structural formula of benzo[d][1,3]dioxane-5-yl acetate;

[0024] Figure 5 The structural formula is 6-(2,4-dimethoxyphenyl)-4-morpholinylmethyl)-1,3-benzodioxanol-5-ol;

[0025] Figure 6 The structural formula is 1,2,4-pyrogallol;

[0026] Figure 7 The structural formula of 2-methoxyhydroquinone;

[0027] Figure 8 The structural formula of sesamol sulfate ester;

[0028] Figure 9 The structural formula of sesamol glucoside is shown.

[0029] Figure 10 The structural formula of larch resin alcohol;

[0030] Figure 11 For Samin's structural formula;

[0031] Figure 12 The structural formula of podophyllin;

[0032] Figure 13 The structural formula is 6-nitro-1,3-benzodioxane-5-methanol;

[0033] Figure 14 The structural formula of sesamol glucoside;

[0034] Figure 15 This is the structural formula of sesamin. Detailed Implementation

[0035] To make the objectives, technical solutions, and advantages of the embodiments of the present invention clearer, the technical solutions in the embodiments of the present invention will be clearly and completely described below. Where specific conditions are not specified in the embodiments, conventional conditions or conditions recommended by the manufacturer shall apply. Reagents or instruments whose manufacturers are not specified are all conventional products that can be purchased commercially.

[0036] This invention provides a composition in which the active ingredient is derived from sesamol compounds. In this invention, sesamol compounds refer to sesamol or its analogues, derivatives, and metabolites, which may include: sesamol, sesamol benzoate, 5,5'-bi-1,3-benzodioxol-6,6'-diol, benzo[d][1,3]dioxol-5-yl acetate, sesamol dimer, 6-((2,4-Dimethoxyphenyl)-4-morpholinylmethyl)-1,3-benzodioxol-5-ol (6-(2,4-dimethoxyphenyl)-4-morpholinylmethyl)-1,3-benzodioxol-5-ol), 1,2,4-pyrogallol, 2-methoxyhydroquinone, sesamol sulfate, sesamol glucoside, larch resin alcohol, Samin (a term specific to the art, currently without a corresponding Chinese name), and Matairesinol (a resin of the pine tree). 6-Nitro-1,3-benzodioxole-5-methanol, Sesamolactol glucoside, and Sesamolactol (a term specific to this field, with no corresponding Chinese name).

[0037] The components of the composition of the present invention are selected from at least one of the above-mentioned sesamoid compounds. For example, the composition contains at least one of sesamol, sesamol benzoate, sesamol dimer, 1,2,4-phenylpyrogallol, 2-methoxyhydroquinone, sesamol sulfate, sesamol glucoside, larch resin alcohol, 6-nitro-1,3-benzodioxane-5-methanol, and Sesamolactol.

[0038] The sesame phenolic compounds of the present invention can be derived from sesame oil, sesame leaves, sesame seeds or sesame meal, and can be obtained by using existing preparation methods or by directly using commercially available related products. The present invention does not limit the source or preparation method.

[0039] In this invention, the sesamoid compounds specifically include: sesamol (CAS: 533-31-3), sesamol benzoate (CAS: 16386-46-2), 5,5'-bi-1,3-benzodioxol-6,6'-diol (CAS: 69276-88-6), benzo[d][1,3]dioxol-5-yl acetate (CAS: 326-58-9), and 6-((2,4-Dimethoxyphenyl)-4-morpholinylmethyl)-1,3-benzodioxol-5-ol (CAS: 6-((2,4-Dimethoxyphenyl)-4-morpholinylmethyl)-1,3-benzodioxol-5-ol (CAS: 633-31-3), sesamoid compounds specifically including: sesamol (CAS: 533-31-3), sesamol benzoate (CAS: 16386-46-2), 5,5'-bi-1,3-benzodioxol-6,6'-diol (CAS: 69276-88-6), benzo[d][1,3]dioxol-5- ... 102616-66-0), 1,2,4-Benzenetriol (CAS: 533-73-3), 2-Methoxyhydroquinone (CAS: 824-46-4), sesamol sulfate, sesamol glucuronide, Lariciresinol (CAS: 27003-73-2), Samin (CAS: 166239-82-3), Matairesinol (CAS: 580-72-3), 6-Nitro-1,3-benzodioxole-5-methanol (CAS: 15341-08-9), Sesamol glucoside glucoside and Sesamolactol, whose structures are as follows Figure 1-15 As shown.

[0040] Preferably, the components of the composition of the present invention are selected from at least two of the above-mentioned sesamol compounds. During the experiments, the inventors discovered that although the above compounds have varying degrees of effect in improving the control of body fat, regulating intestinal flora, maintaining blood lipids / blood sugar / blood pressure, protecting the liver, controlling appetite, anti-oxidation, and anti-aging, only some compounds have synergistic potential when combined, such as the combination of sesamol and sesamol dimer; or the combination of sesamol and sesamin glucoside.

[0041] The above-mentioned sesamol compounds exhibit good physiological activity when combined in any two proportions. More preferably, when the composition consists of sesamol and sesamol dimer, the mass ratio is 1.5~8.5: 8.5~1.5; when the composition consists of sesamol and sesamin glucoside, the mass ratio is 1~9: 9~1.

[0042] During the experiments, it was found that the above-mentioned sesamin compounds, used alone or in combination of at least two, can enhance physiological activities in controlling body fat, regulating gut microbiota, maintaining blood lipids / blood sugar / blood pressure, protecting the liver, controlling appetite, anti-oxidation, and anti-aging. Therefore, the compositions of the present invention have multiple applications, such as:

[0043] (1) Control weight or prepare weight control products.

[0044] (2) Suppress appetite or prepare products that suppress appetite; its specific effects include: regulating gastrointestinal hormone peptide levels and reducing food intake.

[0045] (3) Maintaining gut health or preparing products that maintain gut health; its specific effects include: reducing tumor necrosis factor-α and serum lipopolysaccharide levels.

[0046] (4) Improve insulin resistance and lower blood sugar, or prepare drugs that improve insulin resistance and lower blood sugar.

[0047] (5) Lowering lipids or preparing lipid-lowering products; its specific effects include: reducing body fat, epididymal fat, liver fat, groin fat and blood lipids; more specifically, its effects include lowering serum triglycerides, total cholesterol, low-density lipoprotein cholesterol; regulating the expression levels of leptin, adiponectin and liver peroxisome proliferator-activated receptor γ.

[0048] (6) Improve liver damage or prepare products that improve liver damage; its specific effects include: reducing serum aspartate aminotransferase activity.

[0049] (7) To maintain blood pressure or to prepare products for maintaining blood pressure.

[0050] (8) Antioxidant, anti-aging or preparation of antioxidant and anti-aging products; its antioxidant properties specifically include increasing the activity of superoxide dismutase and catalase and reducing the content of malondialdehyde.

[0051] The products mentioned in the above applications include, but are not limited to, health foods, pharmaceuticals, feed, and feed additives.

[0052] The features and performance of the present invention will be further described in detail below with reference to embodiments.

[0053] The sesamol, sesamol benzoate, sesamol dimer, 1,2,4-phenylpyrogallol, 2-methoxyhydroquinone, sesamol sulfate, sesamol glucoside, larch resin alcohol, 6-nitro-1,3-benzodioxane-5-methanol and Sesamolactol used in the embodiments of the present invention were purchased from Aladdin, Shanghai Yuanye Biotechnology Co., Ltd. and Sigma Reagents Co., Ltd.

[0054] Example 1

[0055] This embodiment provides a composition in which the active ingredient is sesamol.

[0056] Example 2

[0057] This embodiment provides a composition in which the active ingredient is sesamol benzoate.

[0058] Example 3

[0059] This embodiment provides a composition in which the active ingredient is sesamol dimer.

[0060] Example 4

[0061] This embodiment provides a composition in which the active ingredient is 1,2,4-phenylpyrogallol.

[0062] Example 5

[0063] This embodiment provides a composition in which the active ingredient is 2-methoxyhydroquinone.

[0064] Example 6

[0065] This embodiment provides a composition in which the active ingredient is sesamol sulfate.

[0066] Example 7

[0067] This embodiment provides a composition in which the active ingredient is sesamol glucoside.

[0068] Example 8

[0069] This embodiment provides a composition in which the active ingredient is larch resin alcohol.

[0070] Example 9

[0071] This embodiment provides a composition in which the active ingredient is 6-nitro-1,3-benzodioxane-5-methanol.

[0072] Example 10

[0073] This embodiment provides a composition in which the active ingredient is Sesamolactol.

[0074] Example 11

[0075] This embodiment provides a composition comprising the following components: sesamol and sesamol dimer, in a mass ratio of 1.5:8.5.

[0076] Example 12

[0077] This embodiment provides a composition comprising the following components: sesamol and sesamol dimer, in a mass ratio of 8.5:1.5.

[0078] Example 13

[0079] This embodiment provides a composition comprising the following components: sesamol and sesamin glucoside in a mass ratio of 1:9.

[0080] Example 14

[0081] This embodiment provides a composition comprising the following components: sesamol and sesamin glucoside in a mass ratio of 9:1.

[0082] Comparative Example 1

[0083] The difference between this comparative example and Example 11 is that the mass ratio of sesamol and sesamol dimer is different, which is 1.5:9.5.

[0084] Comparative Example 2

[0085] The difference between this comparative example and Example 13 is that the mass ratio of sesamol and sesamin glucoside is different, which is 1:10.

[0086] All functional evaluation schemes were implemented in accordance with the "Methods for Functional Testing and Evaluation of Health Foods (2023 Edition)" issued by the National Health Commission.

[0087] Experimental Example 1

[0088] Verify the effects of the compositions of Examples 1-14 and Comparative Examples 1-2 on weight loss, appetite control, and improved gut health:

[0089] High-fat diet mouse model: 4-week-old healthy male C57BL / 6 mice (SPF grade) were used as experimental animals. There were 12 mice in 3 cages in each treatment group. They had free access to food and water. The experimental period was 8 weeks.

[0090] The experimental groups are as follows:

[0091] The control group (CHOW) was fed a standard maintenance diet;

[0092] The high-fat diet model group (HFD) was fed a commercially available high-fat diet (purified high-fat diet with a fat energy ratio of 45%).

[0093] The experimental intervention group was fed a commercially available high-fat diet with the same energy content, and the diet was supplemented with additional samples from Examples 1-14 and Comparative Examples 1-2 at a dose of 1000 mg / kg.

[0094] Mouse model of compound antibiotic treatment: 4-week-old healthy male C57BL / 6 mice (SPF grade) were selected as experimental animals. There were 12 mice in 3 cages in each treatment group. They had free access to food and water. The experimental period was 8 weeks.

[0095] The experimental groups were as follows: The model control group (NCD) was fed a commercially available high-fat diet (purified high-fat diet with a fat energy ratio of 45%) and was provided with normal drinking water. Except for this group, all other groups had drinking water supplemented with compound antibiotics (Abx, penicillin 1 g / L, neomycin 1 g / L, metronidazole 1 g / L, vancomycin 0.5 g / L). The high-fat diet model group (NCD+Abx) was fed a commercially available high-fat diet, and the intervention group was fed a commercially available high-fat diet with the same energy content. The diet was supplemented with Abx at a dose of 1000 mg / kg for Example 1+Abx, Example 2+Abx, Example 3+Abx, Example 4+Abx, Example 5+Abx, Example 6+Abx, Example 7+Abx, Example 8+Abx, Example 9+Abx, Example 10+Abx, Example 11+Abx, Example 12+Abx, Example 13+Abx, Example 14+Abx, Comparative Example 1+Abx, and Comparative Example 2+Abx.

[0096] Biochemical indicators were measured: gastrointestinal hormone peptide (PYY), tumor necrosis factor-α (TNF-α), and serum lipopolysaccharide (LPS) levels were determined using an enzyme-linked immunosorbent assay (ELISA) kit.

[0097] The experimental results are shown in Table 1-2:

[0098] Table 1. Effects of different experimental groups on body weight, appetite, and gut health in a high-fat diet model.

[0099]

[0100] Note: Gastrointestinal hormone peptide (PYY), tumor necrosis factor-α (TNF-α), and lipopolysaccharide (LPS) content. * indicates that compared with NCD or CHOW, * p < 0.05, ** p < 0.01, *** p < 0.001. $ indicates that compared with the HFD group, $ p < 0.05, $$ p < 0.01, $$$ p < 0.001.

[0101] Table 2. Effects of each experimental group on body weight and appetite in the combined antibiotic treatment experiment.

[0102]

[0103] Note: * indicates that compared with NCD or CHOW, * p < 0.05, ** p < 0.01, *** p < 0.001. $ indicates that compared with the HFD group or NCD+Abx group, $ p < 0.05, $$ p < 0.01, $$$ p < 0.001.

[0104] Regarding weight control: The relative weight of the HFD group was 2.55 times that of the CHOW group (p<0.05), indicating the successful establishment of a high-fat diet-induced obesity model. The relative weight of the groups in Examples 1-10 was significantly lower than that of the HFD group, indicating that sesamol and its analogues, derivatives, and metabolites can significantly reduce mouse weight and have the potential to control weight. The relative weight of the same dose of the combination of sesamol and its analogues, derivatives, and metabolites (Examples 11-14) was reduced by 48.54%, 46.30%, 51.21%, and 54.53% respectively compared to the HFD group, and the relative weight was close to that of the CHOW group. The weight control efficacy was significantly better than when these sesamol and its analogues, derivatives, and metabolites were used alone, showing a significant synergistic effect. In contrast, the weight of the comparative groups 1-2 did not change significantly compared to the HFD group, and no significant synergistic effect was observed compared to when these sesamol and its analogues, derivatives, and metabolites were used alone.

[0105] Regarding appetite control: In Examples 1-10, food intake was significantly reduced compared to the HFD group, and serum levels of the appetite-suppressing hormone PYY were significantly increased, indicating that sesamol and its analogues, derivatives, and metabolites can effectively control appetite. Mice in the same dose of the sesamol and its analogues, derivatives, and metabolites combination (Examples 11-14) showed significantly reduced food intake and significantly increased PYY, demonstrating a significant synergistic effect compared to the single components at the same dose. However, in Comparative Examples 1-2, food intake did not change significantly compared to the HFD group, and no significant synergistic effect was observed compared to the use of these sesamol and its analogues, derivatives, and metabolites alone.

[0106] Regarding the improvement of gut health: The relative body weight and food intake of mice in Examples 1-10 were not significantly different compared to the NCD+Abx group, indicating that sesamol and its analogues, derivatives, and metabolites affect mouse body weight and food intake through the gut microbiota. LPS is an extracellular toxin secreted by Gram-negative intestinal bacteria. Due to changes in intestinal pathways, it infiltrates into the host's bloodstream, triggering systemic low-grade inflammation. It is a host endotoxin and an important marker of gut health. Serum LPS and TNF-α levels in Examples 1-10 were significantly lower than in the HFD group, indicating that sesamol and its analogues, derivatives, and metabolites can significantly improve gut microbiota dysbiosis and systemic inflammation caused by a high-fat diet, thus improving gut health. Furthermore, mice with the same dose of the sesamol and its analogues, derivatives, and metabolites combination (Examples 11-14) showed even lower LPS and TNF-α levels, demonstrating a significant synergistic effect. Furthermore, the Bifidobacterium content in Examples 1-10 was significantly increased compared to the HFD group, indicating that sesamol and its analogues, derivatives, and metabolites can significantly improve gut health. The same dose of the sesamol and its analogues, derivatives, and metabolites combination (Examples 11-14) also showed a synergistic effect in improving gut health. These indicators in Comparative Examples 1-2 showed no significant changes compared to the HFD group, and no significant synergistic effect was observed compared to the use of these sesamol and its analogues, derivatives, and metabolites alone.

[0107] Experiment Example 2

[0108] Verify the role of the compositions of Examples 1-14 and Comparative Examples 1-2 in maintaining blood glucose levels and improving insulin resistance:

[0109] High-fat diet mouse model: 4-week-old healthy male C57BL / 6 mice (SPF grade) were used as experimental animals. There were 12 mice in 3 cages in each treatment group. They had free access to food and water. The experimental period was 16 weeks.

[0110] The experimental groups are as follows:

[0111] The control group (NCD) was fed a standard maintenance diet;

[0112] The high-fat diet model group (HFD) was fed a commercially available high-fat diet;

[0113] The intervention group was fed a commercially available high-fat diet with equal energy at 150 mg / kg body weight, administered by gavage daily for Examples 1-14 and Comparative Examples 1-2, with an experimental period of 10 weeks.

[0114] db / db mouse model: Four-week-old healthy male C57BLKS / JGpt mice were used as the normal control group (CON), and were administered the experimental solvent by gavage at a rate of 5 mL / kg body weight daily; other groups used C57BLKS / JGpt mice. dbdb diabetic mice: The diabetic control group (DBDB) was administered the experimental solvent by gavage at 5 mL / kg body weight daily; the metformin positive control group (Met) was administered metformin by gavage at 200 mg / kg body weight daily (200 mg metformin dissolved in 2.5 mL of PEG400 + 2.5 mL of physiological saline); the intervention group was administered metformin by gavage at 150 mg / kg body weight daily. Examples 1-14 and Comparative Examples 1-2 were all fed a high-fat diet, and the experimental period was 10 weeks.

[0115] Glucose tolerance test: At the end of week 15, mice were fasted for 12 hours, followed by intraperitoneal injection of glucose solution (2 g / kg body weight). Blood glucose levels were measured in each mouse at 0, 30, 60, 90, and 120 minutes, and blood glucose change curves were plotted and the area under the blood glucose change curve (AUC) was calculated.

[0116] Biochemical assays: Serum glucose (GLU) and insulin levels were measured using commercially available standard kits or enzyme-linked immunosorbent assay (ELISA) kits. Insulin resistance index: Insulin level × blood glucose concentration / 22.5.

[0117] The results are shown in Table 3:

[0118] Table 3 Effects of each group on blood glucose and insulin resistance

[0119]

[0120] AUC: Area under the glucose tolerance test curve; GLU: Serum glucose level (mM); IRI: Insulin resistance index. * indicates comparison with NCD or CON, * p < 0.05, ** p < 0.01, *** p < 0.001. $ indicates comparison with HFD or DBDB group, $ p < 0.05, $$ p < 0.01, $$$ p < 0.001. # indicates comparison with Met, # p < 0.05, ## p < 0.01, ### p < 0.001.

[0121] In a high-fat diet mouse model (Table 3), AUC, GLU, and IRI in Examples 1-10 were significantly lower than in the HFD group, indicating that sesamol and its analogues, derivatives, and metabolites can effectively reduce HFD-induced hyperglycemia, maintain normal blood glucose levels, and improve insulin resistance. In contrast, mice treated with the same dose of the sesamol and its analogues, derivatives, and metabolites combination (Examples 11-14) showed significantly lower AUC, GLU, and IRI, demonstrating a significant synergistic effect compared to the use of the same dose of sesamol and its analogues, derivatives, and metabolites alone. These indicators in Comparative Examples 1-2 showed no significant changes compared to the HFD group, and no significant synergistic effect was observed compared to the use of these sesamol and its analogues, derivatives, and metabolites alone.

[0122] Based on the above findings, the ability of sesamol and its analogues, derivatives, metabolites, and combinations thereof to maintain blood glucose levels was specifically verified using a diabetic mouse model. As shown in Table 3, the AUC of groups 1-10 was significantly lower than that of the DBDB group, confirming that sesamol and its analogues, derivatives, and metabolites can effectively reduce the elevation of blood glucose levels in DBDB mice and maintain normal blood glucose levels. The AUC of mice treated with the same dose of sesamol and its analogues, derivatives, and metabolites (Examples 11-14) was also significantly reduced, exhibiting a significant synergistic effect in maintaining blood glucose levels compared to when these sesamol and its analogues, derivatives, and metabolites were used alone. The AUC of Comparative Examples 1-2 showed no significant change compared to the HFD group, and no significant synergistic effect was observed compared to when these sesamol and its analogues, derivatives, and metabolites were used alone.

[0123] Experimental Example 3

[0124] The specific methods for verifying the effects of the compositions of Examples 1-14 and Comparative Examples 1-2 on lipid-lowering and liver damage improvement are as follows:

[0125] High-fat diet mice: 4-week-old healthy male C57BL / 6 mice (SPF grade) were selected as experimental animals. There were 12 mice in 3 cages in each treatment group. They had free access to food and water. The experimental period was 10 weeks.

[0126] The experimental groups are as follows:

[0127] The control group (CHOW) was fed a standard maintenance diet;

[0128] The high-fat diet model group (HFD) was fed a commercially available high-fat diet (purified high-fat diet with a fat energy ratio of 45%).

[0129] The experimental intervention group was fed a commercially available high-fat diet with equal energy, supplemented with Examples 1-14 and Comparative Examples 1-2 at a dose of 1500 mg / kg of feed.

[0130] Measurement of body fat and other indicators: After anesthesia, body fat content was measured by in vivo scanning using a digital dual-energy X-ray scanner. After dissection, epididymal fat and inguinal fat were quickly dissected and weighed, and their ratios to fasting body weight were recorded as epididymal fat and inguinal fat, respectively.

[0131] Biochemical index determination: Lipids were extracted from the liver using the Folch method, dried under nitrogen, and the resulting liver lipid samples were weighed and divided by fasting body weight to determine the liver fat content. The lipids were reconstituted in ethanol, and triglyceride (TG) and total cholesterol (TC) levels were determined according to the procedures of commercially available kits. Serum triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDLC), high-density lipoprotein cholesterol (HDLC), serum aspartate aminotransferase (AST) activity, leptin (Lep), and adiponectin (Adi) were measured using commercially available standard kits or enzyme-linked immunosorbent assay (ELISA). Peroxisome proliferator-activated receptor gamma (PPARγ), a ligand-dependent transcription factor, plays an important role in maintaining triglyceride homeostasis, improving fatty liver degeneration, and visceral fat deposition. Its gene expression in the liver and extraction analysis were performed using standard real-time quantitative PCR methods.

[0132] The experimental results are shown in Table 4-5:

[0133] Table 4. Effects of each experimental group on reducing body fat

[0134]

[0135] Note: * indicates comparison with CHOW, * p < 0.05, ** p < 0.01, *** p < 0.001. $ indicates comparison with HFD group, $ p < 0.05, $$ p < 0.01, $$$ p < 0.001.

[0136] Table 5. Effects of each experimental group on lipid-lowering and liver damage.

[0137]

[0138] Note: Triglycerides (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDLC), high-density lipoprotein cholesterol (HDLC, mM), serum aspartate aminotransferase activity (AST), leptin (Lep), adiponectin (Adi). * indicates comparison with CHOW, *p<0.05, **p<0.01, ***p<0.001. $ indicates comparison with HFD group, $p<0.05, $$p<0.01, $$$p<0.001.

[0139] As shown in Table 4, the body fat and epididymal fat content in Examples 1-10 were significantly lower than those in the HFD group, as were liver fat and groin fat. This indicates that sesamol and its analogues, derivatives, and metabolites can significantly reduce body fat content and have the potential to control body fat. However, the same dosage of the sesamol and its analogues, derivatives, and metabolites combination (Examples 11-14) reduced body fat by 55.80%, 51.78%, 50.15%, and 51.65% compared to the HFD group; liver fat by 42.86%, 40.48%, 38.10%, and 40.48%; epididymal fat by 66.77%, 64.67%, 70.42%, and 71.27%; and groin fat by 57.65%, 64.95%, 73.46%, and 73.72%. This indicates that the sesamol and its analogues, derivatives, and metabolites combination can significantly reduce body fat content, control body fat, and has a significant synergistic effect in reducing body fat. The body fat index of Comparative Groups 1-2 was slightly lower than that of the HFD group, and no significant synergistic effect was observed compared with the use of these sesamol and its analogues, derivatives and metabolites alone.

[0140] As shown in Table 5, TG, TC, LDLC, Lep, and Adil levels in Examples 1-10 were significantly lower than those in the HFD group, while the relative expression of PPARγ was significantly higher in all groups. This indicates that these sesamol and its analogues, derivatives, and metabolites can significantly reduce serum TG, TC, and LDLC levels, and control blood lipid levels through key lipid metabolism hormones (Lep and Adil) and PPARγ, with a clear lipid-lowering pathway and mechanism. In Examples 11-14, TG, TC, and LDLC levels were significantly lower than those in the HFD group, showing a significant synergistic effect compared to the use of the same dose of sesamol and its analogues, derivatives, and metabolites alone. In Comparative Examples 1-2, these indicators were slightly lower than those in the HFD group, and no significant synergistic effect was observed compared to the use of these sesamol and its analogues, derivatives, and metabolites alone.

[0141] Experiment Example 4

[0142] The following methods were used to verify the effect of the compositions of Examples 1-14 and Comparative Examples 1-2 in maintaining blood pressure:

[0143] Experimental setup:

[0144] Normal control group (NCD): Wistar Kyoto rats of the same population but without hypertension and with stable blood pressure. Hypertension model group (CON), positive control group, and experimental group: Spontaneously hypertensive rats (SHRs) were selected, with 10 rats in each group. They were fed a normal diet and had free access to food and water. The experimental period was 4 weeks. The hypertension model group was administered physiological saline by gavage at 5 mL / kg body weight daily (CON), the positive control group was administered captopril at 10 mg / kg body weight / day by gavage (CAP), and the dosage of sesamol and its analogues, derivatives, and metabolites in the experimental group was set as follows: 100 mg / kg body weight / day, administered by gavage to Examples 1-14 and Comparative Examples 1-2, respectively.

[0145] Blood pressure measurement: Blood pressure was measured weekly in the tail artery using the BP-2000 rat non-invasive blood pressure detection system.

[0146] The results are shown in Table 6:

[0147] Table 6. Effects of each experimental group on blood pressure in spontaneously hypertensive rats

[0148]

[0149] Note: * indicates comparison with CON, * p < 0.05, ** p < 0.01, *** p < 0.001. $ indicates comparison with CAP, $ p < 0.05, $$ p < 0.01, $$$ p < 0.001.

[0150] As shown in Table 6, the systolic blood pressure of rats in the CAP (positive control group) and Example 1-10 groups decreased by 29.06%, 16.66%, 16.08%, 14.39%, 24.62%, 23.29%, 21.87%, 13.93%, 19.20%, 13.12%, and 13.38% respectively compared with the CON group, while the diastolic blood pressure decreased by 34.89%, 18.31%, 3.40%, 8.39%, 27.59%, 26.50%, 10.07%, 15.44%, 20.07%, 14.82%, and 14.65% respectively compared with the CON group. This indicates that sesamol and its analogues, derivatives, and metabolites all have significant blood pressure-lowering effects. In rats using the same dose of sesamol and its analogues, derivatives, and metabolites (Examples 11-14), systolic blood pressure decreased by 31.71%, 33.08%, 35.10%, and 35.6% compared to the CON group, and was only 8.61%, 6.44%, 3.23%, and 2.42% higher than the NCD group, respectively. Diastolic blood pressure decreased by 47.16%, 48.59%, 47.68%, and 48.95% compared to the CON group, and was only 7.76%, 4.83%, 6.69%, and 4.20% higher than the NCD group, respectively. The effects were significantly better than the blood pressure-lowering abilities of these sesamol and its analogues, derivatives, and metabolites used alone, and remained at levels similar to those of normal rats, indicating that the combination of sesamol and its analogues, derivatives, and metabolites has a significant synergistic blood pressure-lowering effect. The blood pressure indicators in Comparative Examples 1-2 showed no significant changes compared to the CON group, and no significant synergistic effect was observed compared to the use of these sesamol and its analogues, derivatives, and metabolites alone.

[0151] Experimental Example 5

[0152] The specific methods for verifying the antioxidant and anti-aging effects of the compositions of Examples 1-14 and Comparative Examples 1-2 are as follows:

[0153] Experimental Setup: Lifespan is a key indicator for evaluating the anti-aging properties of interventions. The significantly longer lifespan of nematodes compared to the natural aging lifespan indicates effective anti-aging. During the lifespan experiment, synchronized nematodes were randomly selected for each treatment group, with three parallel plates per group and 30 nematodes per plate, marked as day 0. The nematodes were cultured at 20 °C, and their survival was recorded daily. Nematode death and removal criteria: no reaction within 10 seconds after being lightly touched with a platinum wire; nematodes that disappeared or died after crawling out of the culture dish, or whose eggs hatched into cysts within the body, were not included in the data. The concentrations of each treatment group were as follows: The nematode food was untreated and designated as the NCD group; the food containing 5 mg / mL nicotinamide mononucleotide was designated as the NMN group; and the compositions of Examples 1-14 and Comparative Examples 1-2 were added at 1 mM.

[0154] Antioxidant index determination: Superoxide dismutase (SOD) and catalase (CAT) activities, and malondialdehyde (MDA) content were determined strictly in accordance with the kit instructions from Nanjing Jiancheng Biotechnology Co., Ltd.

[0155] The results are shown in Table 7:

[0156] Table 7. Effects of each experimental group on the lifespan and in vivo antioxidant levels of wild-type Caenorhabditis elegans.

[0157]

[0158] Note: Superoxide dismutase (SOD), catalase (MDA) activity, and malondialdehyde (MDA) content. * indicates comparison with NCD, * p < 0.05, ** p < 0.01, *** p < 0.001. $ indicates comparison with NMN, $ p < 0.05, $$ p < 0.01, $$$ p < 0.001.

[0159] As shown in Table 7, the average lifespan of nematodes in the NMN (positive control group) and Example 1-10 groups were 1.32, 1.07, 1.06, 1.10, 1.19, 1.22, 1.25, 1.04, 1.18, 1.19, and 1.04 times that of NCD, respectively. The lifespan extension rate was 31.76%, 7.47%, 5.77%, 9.78%, 19.12%, 22.25%, 24.62%, 4.34%, 18.35%, 18.57%, and 4.34% higher than that of NCD, respectively. This indicates that sesamol and its analogues, derivatives, and metabolites all have significant lifespan extension and anti-aging effects. The average lifespan of nematodes fed the same dose of sesamol and its analogues, derivatives, and metabolites (Examples 11-14) was 1.36, 1.37, 1.42, and 1.41 times that of NCD, respectively, with lifespan extension rates of 35.60%, 37.25%, 41.65%, and 40.55%, respectively. These were significantly higher than the anti-aging effects of these sesamol and its analogues, derivatives, and metabolites used alone, indicating that the combination of sesamol and its analogues, derivatives, and metabolites has a significant synergistic anti-aging effect. The anti-aging indicators in Comparative Examples 1-2 showed no significant changes compared to the NCD group, and no significant synergistic effect was observed compared to the use of these sesamol and its analogues, derivatives, and metabolites alone.

[0160] Correspondingly, the activities of SOD and CAT enzymes in nematodes of NMN (positive control group) and Examples 1-10 were significantly enhanced compared to NCD, while the content of MDA peroxidation product was reduced, indicating that sesamol and its analogues, derivatives, and metabolites significantly improved the antioxidant capacity of nematodes. However, the same dose of the combination of sesamol and its analogues, derivatives, and metabolites (Examples 11-14) showed a significant increase in SOD and CAT enzyme activities and a significant decrease in MDA content compared to NCD, indicating that the combination also significantly improved the antioxidant capacity of nematodes. Furthermore, the improvement in antioxidant capacity of the combination was significantly greater than that of sesamol and its analogues, derivatives, and metabolites used alone, indicating that the combination also has a significant synergistic antioxidant effect. These antioxidant indicators in Comparative Examples 1-2 showed no significant changes compared to the NCD group, and no significant synergistic effect was observed compared to the use of these sesamol and its analogues, derivatives, and metabolites alone.

[0161] The above description is merely a preferred embodiment of the present invention and is not intended to limit the invention. Various modifications and variations can be made to the present invention by those skilled in the art. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the scope of protection of the present invention.

Claims

1. Use of a composition for the manufacture of a product according to any one of (1) to (6), characterized in that The composition consists of sesamol and sesamol dimer, or consists of sesamol and sesaminol glucoside; The product is: (1) health food for maintaining healthy blood sugar level; (2) health food for controlling body fat; (3) health food for maintaining healthy blood lipid level; (4) health food for maintaining healthy blood pressure level; (5) health food for antioxidation; (6) anti-aging medicine; The mass ratio of sesamol and sesamol dimer in the composition is 1.5~8.5: 8.5~1.5; the mass ratio of sesamol and sesaminol glucoside is 1~9: 9~1.

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