Medicinal and edible mixed wine formula for regulating metabolic syndrome based on multiple targets

Abstract

The invention relates to the technical field of traditional Chinese medicines, and discloses a medicinal and edible mixed wine formula based on multi-target regulation of metabolic syndrome, and the mixed wine formula comprises the following components in parts by weight: 15-20 parts of radix puerariae; 8-12 parts of gastrodia elata; 10 to 15 parts of roxburgh rose; 12 to 15 parts of poria cocos; the raw materials are used as formula components, and the formula proportion is adjusted and optimized according to the characteristics of the raw materials, so that the effectiveness of each raw material is exerted to the greatest extent in the preparation process, and network pharmacological analysis reveals that the formula passes through key targets of ALB, AKT1, ACTB, TP53 and INS and meanwhile regulates and controls the action mechanism of PI3K-Akt and AMPK signal channels. A three-time gradient extraction process is innovatively established, and a precision filtration technology is combined, so that the extraction rate of active ingredients in the raw materials is improved, and finally animal experiments prove that the traditional Chinese medicine composition has a regulating effect on metabolic syndromes, and has a wide application prospect. Therefore, the innovative medicinal and edible compound wine with clear action mechanism, advanced process and controllable quality is provided for the field of traditional Chinese medicines.

Description

Technical Field

[0001] The present invention relates to the technical field of traditional Chinese medicine, and specifically to a formula of medicated diet and homologous wine based on multi-target regulation of metabolic syndrome. Background Art

[0002] Metabolic syndrome is a group of metabolic disorder syndromes mainly characterized by central obesity, hypertension, abnormal blood glucose and lipid disorders. With the change of lifestyle, its incidence rate increases year by year and has become an important problem threatening human health. In the field of medicated diet and homologous wine preparation, the following main problems exist:

[0003] First of all, the efficacy of existing prepared wines is mainly based on traditional cognition and lacks modern pharmacological verification. Although some studies have shown that certain single medicated diet and homologous raw materials have the effect of regulating metabolism, the mechanism of action and targets of compound prepared wines are still unclear.

[0004] Secondly, in terms of the preparation process, the traditional process has the following deficiencies: the extraction process parameters are not clear, resulting in a low extraction rate of active ingredients; the process repeatability is poor, and the quality fluctuates greatly between batches; the quality standard is imperfect, and it is difficult to ensure the product stability.

[0005] Furthermore, in terms of formula design, most are empirical compatibility, lacking scientific theoretical guidance; the synergistic effect has not been fully verified; the ratio optimization lacks objective basis.

[0006] Finally, the preparation methods of existing health wines are not only complex in process but also high in cost, and the mechanism of action has not been clarified. Another prepared wine has a simple formula, but no systematic efficacy evaluation has been carried out. These problems seriously restrict the application of medicated diet and homologous wines in the prevention and treatment of metabolic diseases. Therefore, developing a compound prepared wine based on modern pharmacological research with clear mechanism of action and targets, and optimizing its preparation process and formula design is of great significance for improving the application of medicated diet and homologous wines in the prevention and treatment of metabolic diseases. Summary of the Invention

[0007] (1) Technical Problems to be Solved

[0008] In view of the deficiencies of the prior art, the present invention provides a formula of medicated diet and homologous wine based on multi-target regulation of metabolic syndrome, which has the advantages of a compound prepared wine with a clear mechanism of action and targets and high product stability, and solves the problems that the mechanism of action and targets of existing prepared wines are still unclear and the product stability is low.

[0009] (2) Technical Solutions

[0010] To achieve the above-mentioned purpose, the present invention provides the following technical scheme: a formula of a medicinal and edible wine based on multi-target regulation of metabolic syndrome, wherein the formula of the wine is calculated by weight as follows: 15-20 parts of Pueraria root; 8-12 parts of Gastrodia elata; 10-15 parts of Rosa roxburghii; 12-15 parts of Poria cocos; and 10-12 parts of Honeysuckle.

[0011] Preferably, the formula of the prepared liquor is as follows by weight: 19 parts of Pueraria root; 12 parts of Gastrodia elata; 13 parts of Rosa roxburghii; 12 parts of Poria cocos; and 12 parts of Honeysuckle.

[0012] Preferably, the formula of the prepared liquor is as follows by weight: 16 parts of Pueraria root; 9 parts of Gastrodia elata; 10 parts of Rosa roxburghii; 15 parts of Poria cocos; and 11 parts of Honeysuckle.

[0013] Preferably, the prepared alcoholic beverage is prepared according to its formula weight, comprising the following steps:

[0014] Step 1: Pretreatment of raw materials: Wash and slice the kudzu root, gastrodia elata, roxburghii, tuckahoe, and honeysuckle in the formula weight proportions, put them into a tray, and dry them in an oven at 50-60°C for 1-2 hours until the water content is ≤13%;

[0015] Step 2, loading and three extractions: the pretreated raw materials are mixed and placed in a multifunctional extraction tank, and reflux extraction is performed with pure water as solvent, and three extractions under different conditions are performed to obtain three extracts respectively, and finally the extracts are combined;

[0016] Step 3: Reduce pressure and concentrate: put the combined extract into a reduced pressure concentration tank, set the temperature of the reduced pressure concentration tank to 50-60°C, control the vacuum degree between -0.055MPa and -0.06MPa, and concentrate until the relative density of the concentrated extract is 1.10-1.15kg / m 3 When in between, stop the device;

[0017] Step 4: Preparation and blending: select 50-65 degree edible alcohol as the base wine, mix the concentrated extract with the base wine in a ratio of 1:5 to obtain a mixed solution, add citric acid, and adjust the pH of the mixed solution to between 5.0 and 6.0;

[0018] Step 5, filtration and filling: The mixed liquid is filtered through a coarse filter with a pore size of 100-200 microns, and the liquid after coarse filtration is finely filtered through 0.45μm and 0.22μm microporous filter membranes in turn. After fine filtration, the finished product of the prepared liquor is obtained, and finally aseptic filling, sealing and labeling are carried out.

[0019] Preferably, the Pueraria root is selected from rhizomes that are more than 3 years old, and the starch content is ≥ 60%; the Gastrodia elata is selected from tubers that are more than 1 year old, and the gastrodin content is ≥ 0.5%.

[0020] Preferably, the Rosa roxburghii fruits selected are mature fruits with a vitamin C content of ≥ 2000 mg / 100 g.

[0021] Preferably, the Poria cocos selected is the sclerotium over 3 years old with a polysaccharide content of ≥ 25%; the Lonicera japonica selected is the newly blossomed flower buds with a chlorogenic acid content of ≥ 1.5%.

[0022] Preferably, the raw material pretreatment parameters in Step 1 are: rinsing with running water for 3 - 5 times; the slice thickness is 2 - 3 mm.

[0023] Preferably, the process of the three - time extraction in Step 2 is as follows:

[0024] S2.1, the first extraction: According to the liquid - to - solid ratio of 8:1, calculate and add pure water to the raw materials. Set the heating temperature of the extraction tank at 90 - 95 °C, and carry out reflux extraction for 1.5 - 2.0 hours. After the extraction is completed, through the filtration system of the extraction tank, separate the extract from the solid residue, and collect the first extract;

[0025] S2.2, the second extraction: Leave the solid residue after the first extraction in the tank. According to the liquid - to - solid ratio of 6:1, calculate and add pure water to the raw materials. Set the heating temperature of the extraction tank at 85 - 90 °C, and carry out reflux extraction for 1.0 - 1.5 hours. After the extraction is completed, through the filtration system of the extraction tank, separate the extract from the solid residue, and collect the second extract;

[0026] S2.3, the third extraction: Leave the solid residue after the second extraction in the tank. According to the liquid - to - solid ratio of 4:1, calculate and add pure water to the raw materials. Set the heating temperature of the extraction tank at 80 - 85 °C, and carry out reflux extraction for 1.0 hour. After the extraction is completed, through the filtration system of the extraction tank, separate the extract from the solid residue, and collect the second extract.

[0027] Preferably, the blending temperature in Step 4 is 20 ± 2 °C.

[0028] Compared with the prior art, the present invention provides a formula of a medicated and edible homologous blended wine based on multi - target regulation of metabolic syndrome, and has the following beneficial effects:

[0029] 1. The present invention uses 15-20 parts of kudzu root, 8-12 parts of gastrodia elata, 10-15 parts of rosa roxbunghii tratt, 12-15 parts of poria cocos, and 10-12 parts of honeysuckle flower. These raw materials are used as formula components, and the formula ratio is adjusted and optimized according to the characteristics of the raw materials, so as to maximize the effectiveness of each raw material in the preparation process. Then, through network pharmacology analysis, it is revealed that this formula acts on key targets such as ALB, AKT1, ACTB, TP53, and INS, and simultaneously regulates the action mechanisms of PI3K-Akt and AMPK signaling pathways. Combined with the three-gradient extraction process and the addition of precision filtration technology, the extraction rate of active ingredients in the raw materials is increased. Through animal experiments, it is confirmed that the present invention has a regulatory effect on metabolic syndrome, thus providing an innovative food-medicine homologous blended wine with clear action mechanism, advanced technology, and controllable quality in the field of traditional Chinese medicine.

[0030] 2. The present invention establishes a three-gradient extraction process, adopts the reflux extraction method, and uses pure water as a solvent for extraction under three different conditions. The temperature and time parameters are adjusted for each extraction, which can more comprehensively extract the effective ingredients in the raw materials. This stepped extraction method can not only improve the extraction efficiency but also avoid the pollution problems caused by organic solvents, making the entire extraction process safer and more reliable, thereby increasing the yield of effective ingredients. At the same time, a technology combining coarse filtration and fine filtration is adopted. Coarse filtration removes larger particles and impurities, while fine filtration can remove most bacteria and microparticles, which can not only ensure the clarity of the blended wine but also disinfect the blended wine. And during the blending process, the temperature and material-liquid ratio of the blending process are optimized, and edible alcohol with a degree of 50-65 is selected as the base wine, which can not only ensure the taste of the wine but also provide a certain anti-corrosion effect. The concentrated extract is mixed with the base wine at a ratio of 1:5. Such a ratio can not only ensure the flavor and efficacy of the final product but also improve the stability of the final blended wine. Description of the Drawings

[0031] Figure 1 It is the process flow chart of the preparation of the food-medicine homologous blended wine of the present invention;

[0032] Figure 2 It is the Venn diagram of the drug of the present invention and the targets of metabolic syndrome;

[0033] Figure 3 It is the traditional Chinese medicine-active ingredient-target network diagram of the present invention;

[0034] Figure 4 It is the PPI protein interaction network diagram of the present invention;

[0035] Figure 5 It is the result diagram of the KEGG pathway enrichment analysis of the present invention;

[0036] Figure 6 It is the influence of the blended wine of the present invention on the blood glucose index of rats;

[0037] Figure 7 The effect of the prepared wine of the present invention on the blood lipid index of rats;

[0038] Figure 8 This is a temperature-time curve diagram of the three extraction processes of the present invention. DETAILED DESCRIPTION

[0039] The following will be combined with the drawings in the embodiments of the present invention to clearly and completely describe the technical solutions in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0040] See also Figure 1 - Figure 8 , a formula for a medicinal and edible wine based on multi-target regulation of metabolic syndrome. The formula of the wine and its effects are as follows by weight: 15-20 parts of Pueraria lobata: has the effects of lowering blood sugar and improving insulin sensitivity; 8-12 parts of Gastrodia elata: has the effects of regulating blood pressure and improving microcirculation; 10-15 parts of Rosa roxburghii: has the effects of anti-oxidation and regulating blood lipids; 12-15 parts of Poria cocos: has the effects of promoting diuresis and reducing swelling, and regulating metabolism; 10-12 parts of Honeysuckle: has the effects of anti-inflammatory and improving pancreatic islet function.

[0041] Specifically, the formula for preparing the wine is as follows by weight: 19 parts of Pueraria root; 12 parts of Gastrodia elata; 13 parts of Rosa roxburghii; 12 parts of Poria cocos; and 12 parts of Honeysuckle.

[0042] Specifically, the formula for preparing the wine is calculated by weight as follows: 16 parts of Pueraria root; 9 parts of Gastrodia elata; 10 parts of Rosa roxburghii; 15 parts of Poria cocos; and 11 parts of Honeysuckle.

[0043] Specifically, the prepared liquor is prepared according to the weight of its formula, including the following steps:

[0044] Step 1, raw material pretreatment: Pueraria root, Gastrodia elata, Rosa roxburghii, Poria cocos, and honeysuckle in the formula weight parts are washed and sliced, and then placed in a tray. The impurities and dirt on the surface are removed by washing. Slicing helps to improve the drying efficiency. Dry in an oven at a temperature of 50-60°C for 1-2 hours to a moisture content of ≤13%. Drying at this temperature can effectively prevent the damage of high temperature to the active ingredients, and ensure that the raw materials are dried evenly, which is convenient for subsequent extraction;

[0045] Step 2: Loading and Three - time Extraction: The pre - treated raw materials are mixed and put into a multi - functional extraction tank. The reflux extraction method is adopted. The reflux extraction method can improve the utilization rate of the solvent and make the extraction more thorough. Using pure water as the solvent can avoid the pollution problems that may be brought by organic solvents, and is safer and more reliable. Three extractions under different conditions are carried out to obtain the extraction solutions for three times respectively. Finally, the extraction solutions are combined. By adjusting the extraction conditions (such as temperature, time, etc.), the active ingredients in the raw materials can be more comprehensively extracted, and the extraction solutions for three times are obtained respectively. Finally, the extraction solutions are combined, which improves the extraction efficiency and output;

[0046] Step 3: Vacuum Concentration: The combined extraction solution is put into a vacuum concentration tank. The temperature of the vacuum concentration tank is set at 50 - 60 °C. Concentration is carried out at a lower temperature to reduce the loss of heat - sensitive components. The vacuum degree is controlled between - 0.055 MPa and - 0.06 MPa for concentration until the relative density of the concentrated extraction solution is between 1.10 - 1.15 kg / m 3 At this time, stop the equipment to ensure the stable quality of the concentrated solution;

[0047] Step 4: Preparation and Blending: Select edible alcohol with a degree of 50 - 65 as the base liquor. Selecting this degree of edible alcohol as the base liquor can not only ensure the taste of the wine but also provide a certain anti - corrosion effect. The concentrated extraction solution and the base liquor are mixed at a ratio of 1:5. Such a ratio can ensure the flavor and medicinal effect of the final product to obtain a mixed solution. Add citric acid to adjust the pH of the mixed solution to between 5.0 - 6.0, which helps to improve the taste and enhance the stability of the product;

[0048] Step 5: Filtration and Filling: The mixed solution passes through a coarse filter with a pore size of 100 - 200 microns for coarse filtration to remove larger particles and impurities and improve the purity of the product. The liquid after coarse filtration is successively subjected to fine filtration through 0.45 μm and 0.22 μm microporous membranes (the 0.45 μm membrane can remove most microorganisms and fine particles, while the 0.22 μm membrane further ensures sterility, removing almost all bacteria and microparticles to ensure the sterility and clarity of the product). After fine filtration, the finished blended wine is obtained. Finally, it is aseptically filled, sealed, and labeled (after fine filtration, the finished blended wine is obtained. Finally, it is aseptically filled, sealed, and labeled to ensure the quality and safety of the product).

[0049] The advantages are as follows: The innovation of the preparation process is to establish a three-stage gradient extraction process. By adopting the reflux extraction method and using pure water as the solvent for extraction under three different conditions, the temperature and time parameters are adjusted for each extraction, enabling a more comprehensive extraction of the active ingredients in the raw materials. This stepped extraction method can not only improve the extraction efficiency but also avoid the pollution problems caused by organic solvents, making the entire extraction process safer and more reliable, thereby increasing the yield of active ingredients. At the same time, a technology combining coarse filtration and fine filtration is adopted. Coarse filtration removes larger particles and impurities, while fine filtration can remove most bacteria and microparticles, which can not only ensure the clarity of the blended wine but also disinfect the blended wine. Moreover, during the blending process, the temperature and the ratio of liquid to material of the blending process are optimized, and edible alcohol with a degree of 50-65 is selected as the base wine, which can not only ensure the taste of the wine but also provide a certain antiseptic effect. The concentrated extract is mixed with the base wine at a ratio of 1:5. Such a ratio can not only ensure the flavor and medicinal effect of the final product but also enhance the stability of the final blended wine.

[0050] Specifically, Pueraria lobata with a rhizome over 3 years old is selected, and the starch content is ≥60%; Gastrodia elata with a tuber over 1 year old is selected, and the gastrodin content is ≥0.5%.

[0051] Specifically, Rosa roxburghii with mature fruits is selected, and the vitamin C content is ≥2000 mg / 100 g.

[0052] Specifically, Poria cocos with a sclerotium over 3 years old is selected, and the polysaccharide content is ≥25%; Lonicera japonica with newly blooming flower buds is selected, and the chlorogenic acid content is ≥1.5%.

[0053] Specifically, the parameters for raw material pretreatment in Step 1 are: rinsing with running water 3-5 times; the slice thickness is 2-3 mm.

[0054] Specifically, the process of the three extractions in Step 2 is as follows:

[0055] S2.1, the first extraction: According to the liquid-to-material ratio of 8:1, calculate and add pure water to the raw materials, set the heating temperature of the extraction tank at 90-95°C, and perform reflux extraction for 1.5-2.0 hours. After the extraction is completed, separate the extract from the solid residue through the filtration system of the extraction tank, and collect the first extract;

[0056] S2.2, the second extraction: Leave the solid residue after the first extraction in the tank, calculate and add pure water to the raw materials according to the liquid-to-material ratio of 6:1, set the heating temperature of the extraction tank at 85-90°C, and perform reflux extraction for 1.0-1.5 hours. After the extraction is completed, separate the extract from the solid residue through the filtration system of the extraction tank, and collect the second extract;

[0057] S2.3, Third extraction: Leave the solid residue after the second extraction in the tank. Calculate and add pure water to the raw materials according to the liquid-to-solid ratio of 4:1. Set the heating temperature of the extraction tank to 80 - 85 °C and perform reflux extraction for 1.0 hour. After the extraction is completed, separate the extract from the solid residue through the filtration system of the extraction tank and collect the second extract.

[0058] Specifically, the blending temperature in step four is 20 ± 2 °C.

[0059] Example 1: Establishment of the preparation process

[0060] 1. Raw material pretreatment

[0061] 1.1 Raw material selection criteria: For Pueraria lobata, select rhizomes over 3 years old with a starch content ≥ 60%; for Gastrodia elata, select tubers over 1 year old with a gastrodin content ≥ 0.5%; for Rosa roxburghii Tratt, select ripe fruits with a vitamin C content ≥ 2000 mg / 100 g; for Poria cocos, select sclerotia over 3 years old with a polysaccharide content ≥ 25%; for Lonicera japonica Thunb., select newly blooming flower buds with a chlorogenic acid content ≥ 1.5%.

[0062] 1.2 Pretreatment process:

[0063] Washing: Rinse with running water 3 times;

[0064] Slicing: Thickness 2 - 3 mm;

[0065] Drying: Temperature 50 °C, water content ≤ 13%.

[0066] 2. Extraction process (see Figure 1 )

[0067] 2.1 First extraction:

[0068] Temperature: 90 - 95 °C;

[0069] Time: 1.5 - 2 hours;

[0070] Liquid-to-solid ratio: 8:1;

[0071] Extraction method: Reflux extraction.

[0072] 2.2 Second extraction:

[0073] Temperature: 85 - 90 °C;

[0074] Time: 1 - 1.5 hours;

[0075] Liquid-to-solid ratio: 6:1;

[0076] Extraction method: Reflux extraction.

[0077] 2.3 Third extraction:

[0078] Temperature: 80 - 85 °C;

[0079] Time: 1 hour;

[0080] Liquid - to - material ratio: 4:1;

[0081] Extraction method: reflux extraction.

[0082] III. Concentration process

[0083] 3.1 Concentration conditions:

[0084] Temperature: 50 - 60 °C;

[0085] Vacuum degree: - 0.06 MPa;

[0086] End - point control: relative density 1.10 - 1.15.

[0087] 4. Formulation process

[0088] 4.1 Requirements for base liquor:

[0089] Alcohol content: 50 - 65 degrees;

[0090] Sensory requirements: colorless and transparent, odorless;

[0091] Hygiene requirements: comply with national food safety standards.

[0092] 4.2 Formulation parameters:

[0093] Ratio of concentrated liquid to base liquor: 1:5;

[0094] Blending temperature: 20 ± 2 °C;

[0095] pH adjustment: 5.0 - 6.0.

[0096] Example 2: Conduct network pharmacology analysis

[0097] 1 Network pharmacology analysis

[0098] 1.1 Screening of active ingredients Use the TCMSP database (Traditional Chinese Medicine Systems Pharmacology Database) to screen the active ingredients of the five - flavor raw materials:

[0099] Screening criteria: oral bioavailability (OB) ≥ 30%, drug likeness (DL) ≥ 0.18;

[0100] Screening results: Rosa roxburghii Tratt: 3 active ingredients, 93 targets; Gastrodia elata Blume: 9 active ingredients, 318 targets; Pueraria lobata (Willd.) Ohwi: 4 active ingredients, 58 targets; Poria cocos (Schw.) Wolf: 6 active ingredients, 18 targets; Lonicera japonica Thunb.: 17 active ingredients, 199 targets;

[0101] 1.2 Through Venn diagram analysis (as Figure 2 shown), 100 common targets of drugs - diseases were obtained.

[0102] Construct a traditional Chinese medicine - active ingredient - target network for the action network (as Figure 3 shown):

[0103] Number of nodes: 132 (5 traditional Chinese medicines, 27 active ingredients, 100 targets), Number of edges: 386, Network density: 0.45;

[0104] 2. PPI protein - protein interaction network (see Figure 4 );

[0105] 2.1 Sources of disease targets:

[0106] - GeneCards database: Relevance score≥30.0

[0107] - TTD database

[0108] - Disgenet database

[0109] 2.2 Target analysis results:

[0110] Common targets: 100

[0111] Key targets (sorted by Degree value): ALB(89), AKT1(76), ACTB(72), TP53(68), INS(65), TNF(62), IL6(58), IL1B(55), HIF1A(52), ESR1(49)

[0112] Pathway enrichment analysis (see Figure 5 )

[0113] 3.1 Enrichment of biological processes (GO - BP):

[0114] Regulation of inflammatory response

[0115] Oxidative stress response

[0116] Glucose metabolic process

[0117] Regulation of lipid metabolism

[0118] 3.2 KEGG pathway enrichment:

[0119] PI3K-Akt signaling pathway (P < 0.001);

[0120] AMPK signaling pathway (P < 0.001);

[0121] Insulin signaling pathway (P < 0.01);

[0122] TNF signaling pathway (P < 0.01);

[0123] HIF-1 signaling pathway (P < 0.01).

[0124] Example 3: Establishment of quality standards

[0125] Physical and chemical indexes

[0126] 1.1 Basic indexes:

[0127] Alcohol content: 38% - 42% vol;

[0128] Total acid: ≤1.0 g / L;

[0129] pH value: 5.0 - 6.0;

[0130] Total solids: ≥2.0 g / L

[0131] Turbidity: ≤12 NTU;

[0132] 1.2 Determination of active ingredient content (HPLC-MS / MS method):

[0133] Puerarin: ≥2.5 mg / mL;

[0134] Gastrodin: ≥1.2 mg / mL;

[0135] Vitamin C: ≥0.5 mg / mL;

[0136] Pachymic acid: ≥1.0 mg / mL;

[0137] Chlorogenic acid: ≥1.3 mg / mL.

[0138] Table 1 Verification of active ingredient content (n = 6)

[0139]

[0140]

[0141] Example 4: Efficacy verification

[0142] Experimental animals and grouping

[0143] 1.1 Experimental animals:

[0144] - 60 SPF-grade male SD rats;

[0145] - Body weight: 200 ± 20 g;

[0146] - Age: 8 weeks old;

[0147] 1.2 Grouping (n = 12):

[0148] - Normal control group: Normal diet;

[0149] - Model control group: High-fat diet;

[0150] - Low-dose group: 2 ml / kg / d;

[0151] Medium-dose group: 4 ml / kg / d;

[0152] - High-dose group: 8 ml / kg / d

[0153] 2. Experimental methods

[0154] 2.1 Establishment of metabolic syndrome model:

[0155] - Feed composition: 10% lard + 2% cholesterol + 88% basal feed;

[0156] - Modeling time: 8 weeks;

[0157] - Environmental conditions: Temperature 23 ± 2 °C, relative humidity 55 ± 5%, 12 h light-dark cycle; 2.2 Administration plan:

[0158] - Administration route: Gavage;

[0159] - Administration time: 9:00 every day;

[0160] - Administration cycle: 4 weeks;

[0161] - Administration volume: 1 ml / 100 g body weight;

[0162] 3. Detection indexes and results

[0163] 3.1 Blood glucose indexes: (See Figure 6 )

[0164] - Fasting plasma glucose (FPG);

[0165] - 2-hour postprandial plasma glucose (2hPG);

[0166] - Glycated hemoglobin (HbA1c);

[0167] - Insulin sensitivity index (ISI);

[0168] 3.2 Blood lipid indexes: (See Figure 7 )

[0169] - Total cholesterol (TC);

[0170] - Triglyceride (TG);

[0171] - High - density lipoprotein cholesterol (HDL - C);

[0172] - Low - density lipoprotein cholesterol (LDL - C);

[0173] Table 2 Comparison of blood glucose indexes of rats in each group (Mean±SD, n = 12)

[0174]

[0175] Table 3 Comparison of blood lipid indexes of rats in each group (Mean±SD, n = 12)

[0176]

[0177] Example 5: Process optimization verification Extraction process optimization (as Figure 8 shown) 1.1 Influence of temperature: The extraction rate is the highest in the range of 85 - 95°C; too high temperature will cause degradation of active ingredients; too low temperature affects the extraction efficiency; 1.2 Influence of time:

[0178] The first extraction is best at 1.5 - 2 hours; the second extraction is best at 1 - 1.5 hours; the third extraction takes 1 hour; 1.3 Influence of liquid - to - material ratio:

[0179] The first is best at 8:1;

[0180] The second is best at 6:1;

[0181] The third is best at 4:1;

[0182] Example 6: Stability study

[0183] 1. Accelerated test

[0184] 1.1 Test conditions:

[0185] - Temperature: 40±2°C;

[0186] - Relative humidity: 75%±5%;

[0187] - Time: 6 months;

[0188] - Sampling time points: 0, 1, 2, 3, 4, 5, 6 months;

[0189] Table 4 Changes in active ingredient content during 6 - month accelerated test (mg / mL)

[0190]

[0191] 1.2 Test results:

[0192] - The physicochemical indexes are stable;

[0193] - The content decline of the active ingredients does not exceed 5%;

[0194] - The microbial indexes meet the requirements;

[0195] - The sensory properties show no obvious changes;

[0196] 2. Long-term stability test

[0197] 2.1 Test conditions:

[0198] - Temperature: 25 ± 2 °C;

[0199] - Relative humidity: 60% ± 10%;

[0200] - Time: 12 months;

[0201] - Sampling time points: 0, 3, 6, 9, 12 months;

[0202] 2.2 Test items:

[0203] a) Physicochemical indexes:

[0204] Alcohol content, pH value, total acid, total solids;

[0205] b) Active ingredients:

[0206] Puerarin, gastrodin, vitamin C, pachymic acid, chlorogenic acid; c) Microbial indexes:

[0207] Total bacterial count, coliform group, molds and yeasts;

[0208] Example 7: Safety evaluation;

[0209] Acute toxicity test

[0210] Experimental animals: ICR mice;

[0211] Maximum gavage dose: 15 g / kg;

[0212] Observation time: 14 days;

[0213] Result: LD50 > 15 g / kg, belonging to the practically non-toxic level;

[0214] Long-term toxicity test

[0215] 2.1 Test scheme:

[0216] Animals: SD rats;

[0217] Doses: low, medium, high dose groups;

[0218] Administration time: 90 days;

[0219] Observation indicators: general condition, blood routine, biochemical indicators, tissue pathology;

[0220] 2.2 Results:

[0221] No obvious toxic reaction was observed, and all biochemical indicators were within the normal range. No abnormality was found in the histopathological examination.

[0222] Example 8: Mechanism of action research

[0223] KEGG pathway enrichment analysis (as Figure 5 shown)

[0224] 1.1 Significantly enriched pathways:

[0225] PI3K-Akt signaling pathway (P < 0.001);

[0226] AMPK signaling pathway (P < 0.001);

[0227] Insulin signaling pathway (P < 0.01);

[0228] TNF signaling pathway (P < 0.01);

[0229] HIF-1 signaling pathway (P < 0.01);

[0230] 1.2 Verification of key pathways: Detection of key protein expression by Western blot:

[0231] The p-AKT / AKT ratio increased significantly (P < 0.01);

[0232] The p-AMPK / AMPK ratio increased significantly (P < 0.01);

[0233] The expression of TNF-α decreased significantly (P < 0.01);

[0234] Table 5 Results of Western blot quantitative analysis (Mean±SD, n = 3)

[0235] Protein expression ratio Normal group Model group Low-dose group Medium-dose group High-dose group p-AKT / AKT 1.00±0.08 0.42±0.05** 0.65±0.06* 0.82±0.07** 0.93±0.08** p-AMPK / AMPK 1.00±0.09 0.38±0.04** 0.58±0.05* 0.75±0.06** 0.89±0.07** TNF-α / β-actin 1.00±0.07 2.85±0.21** 2.15±0.18* 1.65±0.14** 1.28±0.11**

[0236] Molecular docking verification

[0237] 2.1 Docking software: AutoDock Vina

[0238] 2.2 Docking results:

[0239] The binding energy of puerarin to AKT1 was -8.2 kcal / mol;

[0240] The binding energy of gastrodin with AMPK is -7.8 kcal / mol;

[0241] The binding energy of chlorogenic acid with TNF-α is -7.5 kcal / mol.

[0242] The advantages are as follows: In the present invention, 15-20 parts of kudzu root, 8-12 parts of gastrodia elata, 10-15 parts of rosa roxburghii tratt, 12-15 parts of poria cocos, and 10-12 parts of honeysuckle flower are used as the formula components, and the formula ratio is adjusted and optimized according to the characteristics of the raw materials, so that the effectiveness of each raw material is maximized in the preparation process. Then, through network pharmacology analysis, it is revealed that the formula acts on key targets such as ALB, AKT1, ACTB, TP53, and INS, and simultaneously regulates the action mechanisms of the PI3K-Akt and AMPK signaling pathways. Combined with the three-step gradient extraction process and the addition of a precision filtration technology, the extraction rate of the active ingredients in the raw materials is increased. Animal experiments confirm that the present invention has a regulatory effect on metabolic syndrome, thus providing an innovative medicated dietetic wine with a clear action mechanism, advanced technology, and controllable quality in the field of traditional Chinese medicine.

[0243] Although the embodiments of the present invention have been shown and described, it will be understood by those of ordinary skill in the art that various changes, modifications, substitutions, and variations can be made to these embodiments without departing from the principles and spirit of the present invention, and the scope of the present invention is defined by the appended claims and their equivalents.

Claims

1. A formula for a medicinal and edible wine based on multi-target regulation of metabolic syndrome, characterized in that: The formula of the prepared liquor is calculated by weight as follows: 15-20 parts of Pueraria root; 8-12 parts of Gastrodia elata; 10-15 parts of Rosa roxburghii; 12-15 parts of Poria cocos; and 10-12 parts of Honeysuckle.

2. The formula of a medicinal and edible wine based on multi-target regulation of metabolic syndrome according to claim 1, characterized in that: The formula of the prepared wine is calculated by weight as follows: 19 parts of Pueraria root; 12 parts of Gastrodia elata; 13 parts of Rosa roxburghii; 12 parts of Poria cocos; and 12 parts of Honeysuckle.

3. The formula of a medicinal and edible wine based on multi-target regulation of metabolic syndrome according to claim 1, characterized in that: The formula of the prepared wine is calculated by weight: 16 parts of Pueraria root; 9 parts of Gastrodia elata; 10 servings of sea buckthorn; 15 parts of Poria cocos; 11 parts of Flos Honeysuckle.

4. The formula of a medicinal and edible wine based on multi-target regulation of metabolic syndrome according to claim 1, characterized in that: The prepared liquor is prepared according to the weight proportion of the formula, comprising the following steps: Step 1: Pretreatment of raw materials: Wash and slice the kudzu root, gastrodia elata, roxburghii, tuckahoe, and honeysuckle in the formula weight proportions, put them into a tray, and dry them in an oven at 50-60°C for 1-2 hours until the water content is ≤13%; Step 2, loading and three extractions: the pretreated raw materials are mixed and placed in a multifunctional extraction tank, and reflux extraction is performed with pure water as solvent, and three extractions under different conditions are performed to obtain three extracts respectively, and finally the extracts are combined; Step 3: Reduce pressure and concentrate: put the combined extract into a reduced pressure concentration tank, set the temperature of the reduced pressure concentration tank to 50-60°C, control the vacuum degree between -0.055MPa and -0.06MPa, and concentrate until the relative density of the concentrated extract is 1.10-1.15kg / m 3 When in between, stop the device; Step 4: Preparation and blending: select 50-65 degree edible alcohol as the base wine, mix the concentrated extract with the base wine in a ratio of 1:5 to obtain a mixed solution, add citric acid, and adjust the pH of the mixed solution to between 5.0 and 6.0; Step 5, filtration and filling: The mixed liquid is filtered through a coarse filter with a pore size of 100-200 microns, and the liquid after coarse filtration is finely filtered through 0.45μm and 0.22μm microporous filter membranes in turn. After fine filtration, the finished product of the prepared liquor is obtained, and finally aseptic filling, sealing and labeling are carried out.

5. The formula of a medicinal and edible wine based on multi-target regulation of metabolic syndrome according to claim 4, characterized in that: The Pueraria root is selected from rhizomes that are more than 3 years old, and the starch content is ≥60%; the Gastrodia elata is selected from tubers that are more than 1 year old, and the gastrodin content is ≥0.5%.

6. The formula of a medicinal and edible wine based on multi-target regulation of metabolic syndrome according to claim 4, characterized in that: The roxburghii roxburghii is selected from mature fruits, and the vitamin C content is ≥2000mg / 100g.

7. The formula of a medicinal and edible wine based on multi-target regulation of metabolic syndrome according to claim 4, characterized in that: The Poria cocos is selected from sclerotia over 3 years old, with a polysaccharide content of ≥25%; the honeysuckle is selected from newly blooming buds, with a chlorogenic acid content of ≥1.5%.

8. The formula of a medicinal and edible wine based on multi-target regulation of metabolic syndrome according to claim 4, characterized in that: The raw material pretreatment parameters in step 1 are: rinsing with running water 3-5 times; and the slice thickness is 2-3 mm.

9. The formula of a medicinal and edible wine based on multi-target regulation of metabolic syndrome according to claim 4, characterized in that: The process of three extractions in step 2 is: S2.1, first extraction: according to the ratio of liquid to material 8:1, calculate and add pure water to the raw material, set the heating temperature of the extraction tank to 90-95°C, and perform reflux extraction for 1.5-2.0 hours. After the extraction is completed, the extraction liquid is separated from the solid residue through the filtration system of the extraction tank, and the first extraction liquid is collected; S2.2, second extraction: the solid residue after the first extraction is left in the tank, pure water is calculated and added to the raw material according to the ratio of liquid to material of 6:1, the heating temperature of the extraction tank is set to 85-90°C, and reflux extraction is performed for 1.0-1.5 hours. After the extraction is completed, the extraction liquid is separated from the solid residue through the filtration system of the extraction tank, and the second extraction liquid is collected; S2.3, third extraction: keep the solid residue after the second extraction in the tank, calculate and add pure water to the raw material according to the ratio of liquid to material 4:1, set the heating temperature of the extraction tank to 80-85℃, and perform reflux extraction for 1.0 hour. After the extraction is completed, separate the extract from the solid residue through the filtration system of the extraction tank, and collect the second extract.

10. The formula of a medicinal and edible wine for regulating metabolic syndrome based on multiple targets according to claim 1, characterized in that: The mixing temperature in step 4 is 20±2°C.

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