A composition containing an extract of silybum marianum, fdp, nr and uses thereof

Abstract

The application provides a composition containing an aqueous extract of Silybum marianum, 1,6-diphosphofructose (FDP) and nicotinamide riboside (NR), and further comprising gamma-aminobutyric acid (GABA). The composition has the effects of anti-inflammation, anti-oxidation, anti-fatigue, liver protection, alcohol elimination, sleep aid, rapid energy supply and anti-aging.

Description

[0001] This application claims priority to Chinese Application No. 202510262631.9, filed on March 5, 2025, entitled “A composition comprising milk thistle extract, FDP, NR and its use thereof”, the entire contents of which are incorporated herein by reference. Technical Field

[0002] This invention belongs to the field of health products and relates to a composition containing milk thistle extract, fructose 1,6-diphosphate (FDP), and nicotinamide ribose (NR). This composition has anti-inflammatory, antioxidant, anti-fatigue, liver-protective, hangover-relieving, sleep-aiding, rapid energy supply, and anti-aging effects. Background Technology

[0003] The liver is one of the most important organs in the human body, performing many vital physiological functions, including metabolism, bile secretion, regulation of blood volume, detoxification, and energy storage. Maintaining good liver function is crucial for overall health. Poor liver function can lead to fatigue, poor sleep quality, insomnia, and excessive dreaming. Sleep problems can impair liver cell repair, further contributing to liver disease.

[0004] Studies have found that more and more modern people are staying up late, which not only burdens the liver but also causes daytime fatigue and lack of energy, as well as difficulty falling asleep at night, further exacerbating the problem and damaging liver health. Therefore, improving sleep quality, reducing daytime fatigue, and repairing liver cells are of great importance.

[0005] Milk thistle (Silybum marianum (L) Gaertn), also known as water pheasant, milk thistle, mouse tendon, and milk thistle seed, has effects such as stabilizing cell membranes, anti-inflammation, anti-cancer, and cardiovascular protection. It is often used for liver damage, hypochondriac pain, and jaundice. Silymarin also has anti-lipid peroxidation, free radical scavenging, antioxidant, and glutathione-enhancing effects. It can protect endothelial cells from oxidative damage by regulating the activity of antioxidant enzymes, reduced glutathione, and protein carbonyl levels. Apigenin (4',5,7-trihydroxyflavone) in milk thistle has therapeutic and sleep-improving effects.

[0006] Fructose-1,6-bisphosphate (FDP) is an intermediate metabolite in glycolysis, which has the effects of regulating enzyme activity, improving cell metabolism and enhancing function. It can improve liver microcirculation and reduce hepatocyte damage. It can provide energy to cells, increase cell membrane stability, and improve cell membrane polarization. As a high-energy matrix, it can provide the energy required for the active transport of metal ions into tissues and cells, thereby improving biological efficacy. Clinically, it is mainly used to improve glucose metabolism and has significant effects such as hypoxia resistance, anti-fatigue, energy provision, inflammation reduction, and improvement of oxidative stress damage.

[0007] Nicotinamide riboside (NR) is a vitamin B3 derivative and a precursor substrate of the noga factor nicotinamide adenine dinucleotide (NAD+). NR promotes energy metabolism and has neuroprotective effects. It can treat non-alcoholic fatty liver disease, improve liver damage caused by decreased NAMPT, and improve lipid metabolism in alcohol-exposed mice. NR intervention can restore the redox state of NAD+ and NADH and enhance the cell activity of hepatocytes.

[0008] Combining milk thistle extract with NR and FDP can synergistically enhance its effects, providing anti-inflammatory, antioxidant, anti-fatigue, liver-protective, hangover-relieving, sleep-aiding, rapid energy supply, and anti-aging benefits. It can also improve sleep quality and relieve symptoms such as dizziness, weakness, and fatigue upon waking. Summary of the Invention

[0009] The purpose of this invention is to provide a composition containing milk thistle extract. This composition has antioxidant, anti-inflammatory, anti-fatigue, liver-protective, hangover-relieving, sleep-aiding, rapid energy supply, and anti-aging effects, and can improve sleep quality and relieve symptoms such as dizziness, weakness, and fatigue after waking up.

[0010] The composition of this invention can also improve sleep, enhance sleep quality, and relieve dizziness, weakness, and fatigue after waking up. It can reduce sleep latency, increase non-rapid eye movement (NREM) sleep time, improve sleep quality, and relieve symptoms such as dizziness, weakness, and fatigue after waking up.

[0011] Compared with existing technologies, the compounds of this invention have the following advantages:

[0012] 1. It has the effects of relieving hangovers and protecting the liver, and can effectively alleviate liver damage caused by alcohol;

[0013] 2. It can improve sleep, enhance sleep quality, and relieve dizziness, weakness, and fatigue upon waking.

[0014] 3. It has better stability and higher bioavailability.

[0015] The composition of this invention is designed for people who stay up late, especially women.

[0016] The present invention provides a composition containing milk thistle extract, which further includes fructose 1,6-bisphosphate (FDP) and nicotinamide ribose (NR).

[0017] In one embodiment, the composition of the present invention contains milk thistle extract in a concentration of ≥50 mg / part, such as 50, 60, 70, 80, 90, 100, 200, 300, 400, 500, 600, 700, 800, 900, or 1000 mg / part.

[0018] In a preferred embodiment, the composition of the present invention contains milk thistle extract at a content of ≥80 mg / part.

[0019] In one embodiment, the composition of the present invention comprises one or more of milk thistle extract, milk thistle extract solid dispersion, milk thistle extract liposomes, milk thistle extract microcapsules, and milk thistle extract inclusion complexes.

[0020] In one embodiment, the composition of the present invention comprises one or more milk thistle extracts, including milk thistle-cyclodextrin inclusion complex, milk thistle-phospholipid complex, and milk thistle-organic polymer solid dispersion.

[0021] In a preferred embodiment, the composition of the present invention comprises a milk thistle extract that is a milk thistle-cyclodextrin inclusion complex.

[0022] In one embodiment, the cyclodextrin in the milk thistle-cyclodextrin inclusion complex of the composition of the present invention is α-cyclodextrin, β-cyclodextrin, or γ-cyclodextrin.

[0023] In a preferred embodiment, the cyclodextrin in the composition of the present invention is γ-cyclodextrin.

[0024] In one embodiment, the composition of the present invention has a molar ratio of milk thistle extract to cyclodextrin of 1-100:1-100. Examples include: 1:100, 2:100, 3:100, 4:100, 5:100, 6:100, 7:100, 8:100, 9:100, 10:100, 1:90:1:80, 1:70, 1:60, 1:50, 1:40, 1:30, 1:20, 1:10, 1:5, 1:4, 1:3, 1:2, 1:1, 2:1, 3:1, 4:1, 5:1, 6:1, 7:1, 8:1, 9:1, 10:1, 15:1, 20:1, 25:1, 30:1, 40:1, 50:1, 100:1.

[0025] In one embodiment, the method for preparing the milk thistle extract specifically includes: (A) separation of milk thistle pericarp and kernel; (B) preparation of crude milk thistle extract; (C) purification of crude extract; and (D) refining of milk thistle extract.

[0026] In one embodiment, the method for preparing the milk thistle-cyclodextrin inclusion complex of the composition of the present invention includes (1) adding milk thistle to ethanol and heating to dissolve until clear to obtain a milk thistle ethanol solution; (2) adding cyclodextrin to water and dissolving to obtain a cyclodextrin solution; (3) mixing the milk thistle ethanol solution and the cyclodextrin solution and continuing to heat the reaction; and (4) drying the reaction system to obtain the product.

[0027] In one embodiment, the dissolution process in step (1) of the above preparation method is carried out by sealing, and further by using a sealed tank.

[0028] In one embodiment, the ratio (weight-volume ratio) of milk thistle to anhydrous ethanol in step (1) of the above preparation method is 1g:10mL-1g:1000mL, for example 1g:50mL, 1g:100mL, 1g:150mL, 1g:200mL, 1g:300mL, 1g:500mL, 1g:800mL, preferably 1g:100mL-1g:500mL.

[0029] In one embodiment, step (1) of the above preparation method uses heating to dissolve the material, and further uses water bath heating to dissolve the material.

[0030] In one embodiment, the heating temperature in step (1) of the above preparation method is 40℃-90℃, and the further heating temperature is 40℃-78℃.

[0031] In one embodiment, the active ingredient of the milk thistle extract in the composition of the present invention includes one or more of silybin A, silybin B, isosilybin A, isosilybin B, silybinine, isosilybinine, silybinin, and taxane.

[0032] In a preferred embodiment, the active ingredient of the milk thistle extract in the composition of the present invention includes at least silybin.

[0033] In one embodiment, the composition of the present invention contains silymarin at a content of 10% or more.

[0034] In a preferred embodiment, the composition of the present invention contains silymarin at a content of 20% or more.

[0035] In a preferred embodiment, the composition of the present invention contains silymarin at a content of 40% or more.

[0036] In a preferred embodiment, the composition of the present invention contains silymarin at a content of 60% or more.

[0037] In a preferred embodiment, the composition of the present invention contains silymarin at a content of 80% or more.

[0038] In a more preferred embodiment, the composition of the present invention contains silymarin at a content of 90% or more.

[0039] In one embodiment, the composition of the present invention includes one or more of FDP magnesium salt, FDP strontium salt, FDP calcium salt, FDP potassium salt, and FDP sodium salt.

[0040] In one embodiment, the composition of the present invention contains FDP at a concentration of ≥100 mg / part, such as 100, 200, 300, 400, 500, 600, 700, 800, 900, or 1000 mg / part.

[0041] In one embodiment, the composition of the present invention contains ≥200 mg / part of FDP.

[0042] In one embodiment, the composition of the present invention contains 200-800 mg / part of FDP.

[0043] In one embodiment, the composition of the present invention contains NR at a content of ≥100 mg / part, such as 100, 200, 300, 400, 500, 600, 700, 800, 900, or 1000 mg / part.

[0044] In one embodiment, the composition of the present invention contains NR at a content of ≥200 mg / part.

[0045] In one embodiment, the composition of the present invention contains NR in a concentration of 100-500 mg / part.

[0046] In one embodiment, the composition of the present invention further includes amino acids.

[0047] Gamma-aminobutyric acid (GABA) is a naturally occurring, non-protein, active amino acid neurotransmitter in the human body. It has neuroprotective effects and can induce sleep, provide sedation and anti-anxiety, improve brain function, and lower blood pressure. Milk thistle combined with GABA can be used to relieve stress and improve sleep.

[0048] In a preferred embodiment, the amino acid in the composition of the present invention is γ-aminobutyric acid (GABA).

[0049] In one embodiment, the composition of the present invention contains GABA at a content of ≥50 mg / part, such as 50, 60, 70, 80, 90, 100, 200, 300, 400, 500, 600, 700, 800, 900, or 1000 mg / part.

[0050] In one embodiment, the composition of the present invention contains 50-300 mg of GABA per serving.

[0051] In a preferred embodiment, the composition of the present invention contains 50-200 mg / part of GABA.

[0052] In one embodiment, the composition of the present invention further includes other plant extracts.

[0053] In one embodiment, the other plant extracts in the composition of the present invention are one or more of the following: Schisandra chinensis extract, Artichoke extract, Licorice root extract, Ginger rhizome extract, Ilex pubescens extract, Ginseng extract, Astragalus membranaceus extract, Rheum palmatum extract, Atractylodes macrocephala extract, Polygonum multiflorum extract, Panax notoginseng extract, Bupleurum chinense extract, Cassia tora extract, Pueraria lobata extract, Bergamot extract, Eucommia ulmoides leaf extract, Ganoderma lucidum extract, Cordyceps sinensis extract, Licorice extract, Brown algae / microalgae extract, Gynostemma pentaphyllum extract, Taraxacum mongolicum extract, Polygonum cuspidatum extract, Andrographis paniculata extract, Chaenomeles speciosa extract, Rice / rice bran extract, Broccoli extract, Hovenia dulcis extract, Coffee berry extract, Phyllanthus emblica extract, Ginkgo biloba extract, Coptis chinensis extract, Scutellaria baicalensis extract, and Rice bran extract.

[0054] In one embodiment, the composition of the present invention contains other plant extracts at a concentration of ≥50 mg / part, such as 50, 55, 60, 65, 70, 75, 80, 90, or 100 mg / part.

[0055] In one embodiment, the active ingredients of the other plant extracts in the composition of the present invention are one or more of polyphenols, polysaccharides, flavonoids, volatile oils, and organic acids.

[0056] In one embodiment, the composition of the present invention comprises one or more of tea polyphenols, tocopherols, tocotrienols, magnolol, tert-butylhydroquinone, anthocyanins, astaxanthin, quercetin, ellagic acid, catechins, proanthocyanidins, rosmarinic acid, curcumin, and resveratrol.

[0057] In one embodiment, the composition of the present invention comprises one or more of sarcosine, creatine, naringin, rosmarinic acid, clove oil, thiotaurine, and boswellic acid.

[0058] In one embodiment, the composition of the present invention comprises one or more of the following polysaccharides: gardenia polysaccharide, L-arabinose, dendrobium polysaccharide, auricularia auricula polysaccharide, D-mannose, D-galactose, astragalus polysaccharide, wolfberry polysaccharide, shiitake mushroom polysaccharide, ginseng polysaccharide, licorice polysaccharide, tremella polysaccharide, kudzu root polysaccharide, mulberry polysaccharide, oat polysaccharide, ophiopogon japonicus polysaccharide, aloe polysaccharide, sophora japonica polysaccharide, β-glucan, α-glucan, β-galactoglucan, L-fucose, D-xylose, D-glucose, and glucuronic acid.

[0059] In one embodiment, the method for preparing the plant extract is selected from enzymatic hydrolysis, water extraction, alcohol extraction, ultrasonic extraction, and supercritical fluid extraction.

[0060] In one embodiment, the method for preparing the plant extract specifically includes: (1) selecting and processing plant raw materials, such as washing, cutting or crushing;

[0061] (2) Active ingredients are extracted using enzymatic hydrolysis, water extraction, alcohol extraction, ultrasonic extraction, and supercritical fluid extraction.

[0062] (3) The extract was separated and purified by methods such as filtration, centrifugation, chromatography, membrane separation and crystallization;

[0063] (4) Concentrate and dry the extract using techniques such as evaporation, freeze drying or spray drying.

[0064] This invention provides a composition containing milk thistle extract, wherein the composition is prepared into a humanly acceptable formulation by adding excipients, including but not limited to tablets, soft capsules, capsules, powders, oral liquids, sprays, solid beverages, and crystals.

[0065] The present invention also provides the use of any of the compositions containing milk thistle extract in anti-fatigue, liver protection, hangover relief, sleep aid, rapid energy supply, and anti-aging.

[0066] The present invention also provides the use of any of the compositions containing milk thistle extract in anti-inflammatory, antioxidant, and anti-aging effects.

[0067] The present invention also provides the use of any of the compositions containing milk thistle extract in anti-fatigue and sleep-aiding purposes.

[0068] The composition of this invention is targeted at people who stay up late; further, it is targeted at women who stay up late.

[0069] This invention provides a composition containing milk thistle extract, which has synergistic effects and possesses anti-inflammatory, antioxidant, anti-fatigue, liver-protective, hangover-relieving, sleep-aiding, rapid energy supply, and anti-aging properties. It can also improve sleep quality and relieve symptoms such as dizziness, weakness, and fatigue after waking up. Attached Figure Description

[0070] Figure 1 The results of mouse liver mass index testing;

[0071] Figure 2 Results of MDA detection in mouse liver;

[0072] Figure 3 Results of TC and TG detection in mouse liver;

[0073] Figure 4 The results of AST and ALT detection in mouse serum;

[0074] Figure 5 The results of TC and TG detection in mouse serum;

[0075] Figure 6 HE staining results for mouse liver;

[0076] Figure 7 The results of oil red staining of mouse liver are shown. Detailed Implementation

[0077] To facilitate understanding by those skilled in the art, the present invention will be further described below with reference to embodiments. The content mentioned in the embodiments is not intended to limit the present invention.

[0078] Example

[0079] Example 1

[0080] The composition was obtained by adding milk thistle extract, NR, and FDP.

[0081] Example 2

[0082] The composition was obtained by adding milk thistle extract, NR, FDP-sodium salt, and GABA.

[0083] Example 3

[0084] The composition was obtained by adding milk thistle-γ-cyclodextrin inclusion complex, NR, FDP-sodium salt, and GABA.

[0085] Example 4

[0086] The composition was obtained by adding milk thistle-γ-cyclodextrin inclusion complex, NR, and FDP-sodium salt.

[0087] Example 5

[0088] The composition was obtained by adding milk thistle-γ-cyclodextrin inclusion complex, NR, FDP-calcium salt, and GABA.

[0089] Example 6

[0090] The composition was obtained by adding milk thistle-γ-cyclodextrin inclusion complex, NR, FDP, and GABA.

[0091] Example 7

[0092] The composition was obtained by adding 80 mg milk thistle-γ-cyclodextrin inclusion complex, 500 mg FDP, 300 mg NR and 100 mg GABA.

[0093] Example 8

[0094] The composition was obtained by adding 100 mg milk thistle-γ-cyclodextrin inclusion complex, 500 mg FDP, 300 mg NR and 100 mg GABA.

[0095] Example 9

[0096] The composition was obtained by adding 400 mg milk thistle-γ-cyclodextrin inclusion complex, 500 mg FDP, 300 mg NR and 100 mg GABA.

[0097] Example 10

[0098] 80 mg of milk thistle-γ-cyclodextrin inclusion complex was mixed with 500 mg of FDP-sodium salt, 300 mg of NR, and 100 mg of GABA. Excipients were added, and the mixture was thoroughly mixed. The mixture was then poured into a capsule mold to prepare capsules. The preparation method involves mixing the milk thistle-γ-cyclodextrin inclusion complex with FDP-sodium salt, NR, and GABA, filling the mixture into capsules, sealing it using dry sealing or wet sealing, and finally packaging the capsules.

[0099] Example 11

[0100] 80 mg of milk thistle-γ-cyclodextrin inclusion complex was mixed with 500 mg of FDP-sodium salt, 200 mg of NR, and 100 mg of GABA, and then excipients such as maltodextrin were added to prepare milk thistle-containing powder strips. The preparation method involves mixing milk thistle-γ-cyclodextrin inclusion complex, FDP-sodium salt, NR, GABA, and other excipients, spray-drying to form a powder, and then filling the powder into strips.

[0101] Example 12

[0102] An oral liquid was prepared by mixing 80 mg of milk thistle-γ-cyclodextrin inclusion complex, 500 mg of FDP-sodium salt, 300 mg of NR, and 150 mg of GABA, and adding appropriate amounts of glycerol, potassium sorbate, and other stabilizers and preservatives. The preparation method involves dissolving the milk thistle-γ-cyclodextrin inclusion complex, FDP-sodium salt, NR, and GABA, mixing thoroughly, adjusting the pH, filtering for sterilization, filling into sterile bottles, and sealing.

[0103] Example 13

[0104] 100 mg of milk thistle-γ-cyclodextrin inclusion complex, 500 mg of FDP-sodium salt, 300 mg of NR, and 100 mg of GABA were mixed, and appropriate amounts of excipients such as calcium bicarbonate and pregelatinized starch were added to prepare tablets. The preparation method includes depackaging, cleaning, sterilizing, and sieving the excipients, mixing them with the milk thistle-γ-cyclodextrin inclusion complex, FDP-sodium salt, NR, and GABA, adding a lubricant, checking the tableting process, and drying to obtain tablets.

[0105] Example 14 Human Trial

[0106] In human trials, volunteers ingested the compositions of the present invention daily (such as those in Examples 5, 6, 7, and 9), and their sleep patterns and daytime fatigue were observed and recorded (Table 1).

[0107] Table 1

[0108] Current fatigue Daytime fatigue Sleep status fatigue after waking up Volunteer 1 I feel less tired and less sleepy. There has been a slight improvement; I am not as tired as before. Falling asleep faster and experiencing longer periods of deep sleep. I woke up feeling well-rested and not tired. Volunteer 2 I feel less tired, less sleepy, and have more energy. There has been a slight improvement; I am not as tired as before. Falling asleep faster I felt more energetic in the morning and less tired than before. Volunteer 3 I feel less tired, less sleepy, and have more energy. Significant improvement, much less fatigue. Falling asleep faster and experiencing longer periods of deep sleep. I felt more energetic in the morning and less tired than before. Volunteer 4 I feel more energetic There has been a slight improvement; I am not as tired as before. Falling asleep faster and experiencing longer periods of deep sleep. I felt more energetic in the morning and less tired than before. Volunteer 5 I feel less tired, less sleepy, more energetic, and have better concentration. Significant improvement, much less fatigue. Falling asleep faster and experiencing longer periods of deep sleep. More focused Volunteer 6 Increased work efficiency and improved concentration Significant improvement, much less fatigue. Falling asleep faster and experiencing longer periods of deep sleep. I woke up feeling well-rested and not tired. Volunteer 7 I felt less tired all day after drinking it. There has been a slight improvement; I am not as tired as before. Falling asleep faster More focused

[0109] Volunteers were divided into three groups: one group ingested the NR+GABA composition daily, another group ingested the milk thistle+FDP composition daily, and the third group ingested the composition of this invention daily. The improvement in their sleep and physical and mental fatigue was observed and recorded (Table 2). / indicates that the indicator was not tested. For example, 8 people improved / 16 people means that there were 16 volunteers with the symptoms, of which 8 people showed improvement after taking the product.

[0110] NR+GABA Milk thistle + FDP Example 6 Improved sleep 8 people improved / 16 people / 11 people improved / 16 people Improvement in deep sleep 10 people improved / 16 people / 12 people improved / 16 people Adverse reactions No adverse reactions / No adverse reactions Improvement in difficulty falling asleep 4 people improved / 7 people / 6 people improved / 7 people Dreams improve the situation 4 people improved / 10 people / 7 people improved / 10 people Improvement of sleep disturbances 6 people improved / 11 people / 9 people improved / 11 people Improvement in the situation of waking up midway 6 people improved / 9 people / 8 people improved / 9 people Improvement in early awakening 0 people improved / 5 people / 4 people improve / 5 people Improvement in morning fatigue 3 people improve / 8 people / 7 people improved / 8 people Improvement in physical fatigue / 15 people improved / 20 people 18 people improved / 20 people Improvement in mental fatigue / 13 people improved / 20 people 15 people improved / 20 people

[0111] Example 15: Construction of a mouse model of alcoholic fatty liver

[0112] 15.1 Experimental Reagents and Consumables

[0113] Experimental animals: 40 SPF-grade male C57 mice, 8 weeks old, weighing 20-22g. Mice were acclimatized for 7 days before the formal experiment. All mice were housed in a clean-grade animal laboratory, with an ambient temperature of 21±2℃, humidity of 30%~70%, 12-hour light and shadow alternation, and free access to food and water.

[0114] Main instruments used in the experiment: Allegra C-34R centrifuge, A-VBL-02 vortex mixer.

[0115] The main reagents and consumables for the experiment were: Red Star Erguotou high-proof liquor.

[0116] 15.2 Experimental Procedures and Results

[0117] 15.2.1 Animal grouping and adaptive feeding

[0118] D1-D7: Animals were acclimatized in an SPF-grade animal facility for 7 days.

[0119] Group Modeling methods Dosage Dosage time G1 - Normal Group / Pure water, 0.2 mL / piece 42d G2-Alcohol Model Group Gavage with alcohol Pure water, 0.2 mL / piece 42d G3-drug group Gavage with alcohol Example 6, 4.5 mL / kg (milk thistle-γ-cyclodextrin inclusion complex 2 mg / mL, NR 7 mg / mL, FDP 11 mg / mL, GABA 2 mg / mL) 42d

[0120] 15.2.2 Alcohol Group Modeling Method

[0121] The model was constructed in two phases. From D8 to D22, the first phase involved administering alcohol at concentrations of (2◦, 5◦, 10◦, 15◦, 20◦, 30◦, 40◦) via gavage for two days at each concentration, for a total of 14 days. From D23 to D39, the second phase began, with the mice administered alcohol at concentrations of (46◦ and 56◦) via gavage for the first eight days, followed by four days of gavage at 52◦ and four days at 56◦. From D40 to D53, the 52◦ and 56◦ concentrations were administered alternately via gavage. Mice were fed a maintenance diet throughout the entire phase.

[0122] On day 40, blood samples were collected from mice in groups G1, G2, and G3 to detect AST and ALT levels after enucleation. Liver tissue was also collected after cervical dislocation to detect MDA levels. Alcohol was administered in the afternoon before tissue collection, and samples were collected approximately 16 hours later. Mice were fasted overnight before tissue collection. The decision to discontinue medication was based on the results.

[0123] Mice in each group underwent enucleation to collect blood samples to detect aspartate aminotransferase (AST), alanine aminotransferase (ALT), total cholesterol (TC), and triglycerides (TG).

[0124] After blood was collected from the mice, the mice were immobilized, their abdominal cavities were opened, and their livers were removed, weighed, and their liver mass index was calculated. Liver mass index = liver mass (g) / body weight (g) × 100%.

[0125] After blood collection, a portion of mouse liver tissue was taken and divided into two parts: the first part was homogenized for the determination of malondialdehyde (MDA), total cholesterol (TC), and triglycerides (TG); the second part was stained with eosin (H&E) and oil red stain.

[0126] The experimental data are expressed as mean ± standard error (Mean ± SEM). All data were processed and statistically analyzed using GraphPadPrism 8.0. The t-test was used to compare the means of two groups, and the ANOVA test was used to compare the means of multiple groups. p < 0.05 was considered statistically significant.

[0127] 15.2.3 Liver quality index results

[0128] Normal liver indices are a direct phenotype of liver function and metabolic health. A significant increase in liver mass and indices induced by continuous gavage with alcohol is a direct indication of alcoholic liver injury. Results are as follows... Figure 1 As shown, the results indicate that after administration of the composition of the present invention, the liver index decreased significantly, meaning that the composition of the present invention has a certain effect in improving alcoholic fatty liver.

[0129] 15.2.4 Liver MDA test results

[0130] The results are as follows Figure 2 As shown, the results indicate that after administration of the composition of the present invention, the MDA level was significantly reduced, indicating that the composition of the present invention has a certain antioxidant capacity and can alleviate lipid peroxidation damage caused by alcohol.

[0131] 15.2.5 Liver TC and TG test results

[0132] Disorders of hepatic lipid metabolism are one of the core pathological features of alcoholic fatty liver disease, with abnormal accumulation of total cholesterol (TC) and triglycerides (TG) in the liver being important markers. Results are as follows... Figure 3 As shown, the results indicate that after administration of the composition of the present invention, the liver TG level of mice was significantly reduced, and the liver TC showed a decreasing trend. That is, the composition of the present invention can improve alcohol-induced liver lipid degeneration by regulating the liver lipid metabolism pathway and reducing the accumulation of cholesterol and triglycerides in the liver.

[0133] 15.2.6 Serum marker test results

[0134] 15.2.6.1 Serum AST and ALT test results

[0135] Changes in serum liver function-related enzymes and lipid metabolism indicators are important biochemical markers reflecting the degree of alcoholic liver injury. Results are as follows: Figure 4 As shown, the results indicate that after administration of the composition of the present invention, the serum AST and ALT levels of mice were significantly reduced, meaning that the composition of the present invention can improve alcohol-induced liver damage.

[0136] 15.2.6.2 Serum TC and TG test results

[0137] Alcoholic liver injury is often accompanied by systemic lipid metabolism disorders, with abnormally elevated serum total cholesterol (TC) and triglyceride (TG) levels being one of its important manifestations. Results as follows... Figure 5 As shown, the results indicate that after administration of the composition of the present invention, the serum TC and TG levels of mice showed a decreasing trend compared with the G2 model group.

[0138] 15.2.7 Liver pathology test results

[0139] 15.2.7.1 Results of HE staining of the liver

[0140] The results of HE staining of liver tissue are as follows Figure 6 As shown, the results indicate that after administration of the composition of the present invention, the pathological changes in mouse liver tissue were significantly improved, the liver lobule structure tended to be intact, the degree of hepatocyte steatosis was significantly reduced, the number and size of lipid droplets decreased, the infiltration range of inflammatory cells was reduced, and necrotic foci basically disappeared. That is, the composition of the present invention has a certain ameliorative effect on alcohol-induced pathological damage to mouse liver tissue.

[0141] 15.2.7.2 Results of liver oil red staining

[0142] Oil Red staining of liver tissue further provided a clearer picture of lipid accumulation in the livers of mice in each group. Results are as follows: Figure 7 As shown, the results indicate that after administration of the composition of the present invention, the number of red lipid droplets in the liver tissue was significantly reduced, the droplet volume was reduced, and they were mainly distributed in the form of small lipid droplets; that is, the composition of the present invention can effectively inhibit alcohol-induced lipid accumulation in the liver and improve the degree of hepatocyte steatosis, indicating that the composition of the present invention also has a certain improving effect on alcohol-induced liver lipid deposition.

[0143] In summary, in the alcohol model group, the composition of this invention significantly reduced the increase in liver mass index caused by alcohol, effectively reduced liver MDA content, improved lipid peroxidation damage, and significantly reduced liver TG levels and serum AST and ALT levels. That is, the composition of this invention has a clear protective effect against alcohol-induced liver injury alone, exerting its effects by reducing oxidative stress, regulating liver lipid metabolism, and improving hepatocyte function, thus showing a certain degree of improvement in alcohol-induced fatty liver.

[0144] It will be understood by those skilled in the art that, unless otherwise defined, all terms used herein (including technical and scientific terms) have the same meaning as commonly understood by one of ordinary skill in the art to which this invention pertains. It should also be understood that terms such as those defined in general dictionaries should be understood to have the same meaning as in the context of the prior art, and should not be interpreted in an idealized or overly formal sense unless specifically defined as herein.

[0145] It should be understood that the above detailed description of the technical solutions of the present invention with reference to preferred embodiments is illustrative and not restrictive. Those skilled in the art can modify the technical solutions described in the embodiments or make equivalent substitutions for some of the technical features based on reading this specification; however, these modifications or substitutions do not cause the essence of the corresponding technical solutions to depart from the spirit and scope of the technical solutions of the embodiments of the present invention.

Claims

1. A composition containing milk thistle extract, further comprising fructose 1,6-bisphosphate (FDP) and nicotinamide ribose (NR).

2. The composition according to claim 1, characterized in that, The milk thistle extract is one or more of the following: milk thistle extract solid dispersion, milk thistle extract liposomes, milk thistle extract microcapsules, and milk thistle extract inclusion complex.

3. The composition according to claim 2, characterized in that, The milk thistle extract is one or more of the following: milk thistle-cyclodextrin inclusion complex, milk thistle-phospholipid complex, and milk thistle-organic polymer solid dispersion.

4. The composition according to claim 3, characterized in that, The cyclodextrin in the milk thistle-cyclodextrin inclusion complex is α-cyclodextrin, β-cyclodextrin, γ-cyclodextrin, and more specifically γ-cyclodextrin.

5. The composition according to claim 3, characterized in that, The molar ratio of milk thistle to cyclodextrin in the milk thistle-cyclodextrin inclusion complex is 1-100:1-100.

6. The composition according to claim 1, characterized in that, The milk thistle extract contains ≥10% silybin.

7. The composition according to claim 1, characterized in that, The FDP includes one or more of FDP magnesium salt, FDP strontium salt, FDP calcium salt, FDP potassium salt, and FDP sodium salt.

8. The composition according to claim 1, characterized in that, The composition also includes an amino acid, and more specifically, the amino acid is γ-aminobutyric acid (GABA).

9. The composition according to any one of claims 1-8, characterized in that, The composition, when combined with excipients, is prepared into one or more of the following: tablets, soft capsules, capsules, powders, oral liquids, sprays, solid beverages, and crystals.

10. The composition according to any one of claims 1-8, and its use in anti-fatigue, liver protection, hangover relief, sleep aid, rapid energy supply, and anti-aging.

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