Composition for improving liver metabolism level and use thereof

Abstract

Disclosed in the present invention is a method for improving or modulating the level of liver metabolism, enhancing or maintaining liver function, and improving or preserving liver health in a subject, comprising administering, to the subject, an effective amount of dihydroberberine or a physiologically acceptable salt, acid, or ester thereof. The composition of the present invention can be widely used in nutritional supplements, foods and beverages.

Description

Compositions and uses for improving liver metabolic levels TECHNICAL FIELD

[0001] The present application belongs to the field of biotechnology, and specifically relates to a method for improving or regulating the liver metabolic level of a subject, enhancing or maintaining liver function, and improving or maintaining liver health. BACKGROUND

[0002] Non-alcoholic fatty liver disease (NAFLD) is an important challenge in the field of modern medicine, which is a metabolic liver disease closely related to metabolic syndrome such as obesity, hyperglycemia and hyperlipidemia. The main feature of NAFLD is excessive deposition of fat in liver cells, and its pathogenesis is complex, involving multiple links such as imbalance of fatty acid metabolism, insulin resistance, oxidative stress and inflammatory response. With the development of global economy and changes in lifestyle, the incidence of NAFLD has been increasing year by year, and it has become an important cause of chronic liver disease in developed countries such as Europe and the United States and rich areas in China.

[0003] Dihydroberberine is a bioactive form of berberine (also known as coptis), with higher bioavailability and stronger efficacy. Berberine has a long history of use in traditional medicine in China and India, and in recent years, with the development of modern science, its various pharmacological effects have been gradually revealed. Dihydroberberine is similar in structure to berberine, but its absorption efficiency in the intestinal tract is higher, and it can be absorbed into the blood more quickly through the intestinal wall, thereby exerting stronger pharmacological effects. Through multiple mechanisms such as promoting the expression of glucagon mRNA, increasing the secretion of GLP-1, and up-regulating the expression of glucose transporter Glut 4, dihydroberberine can improve insulin resistance, promote glucose uptake by cells, and reduce blood glucose levels. In addition, it can also inhibit the expression of lipogenesis genes through the AMPK pathway, reduce fat deposition, and improve fat metabolism, thereby alleviating liver steatosis. Dihydroberberine also has good anti-inflammatory and antioxidant effects, which can reduce oxidative stress and inflammatory response in the liver, further protecting the liver from damage.

[0004] As a natural functional raw material, tetrahydrocurcumin is a metabolite of curcumin, with strong anti-inflammatory and antioxidant effects, and has potential application value in the field of dietary supplements. The anti-inflammatory effect of tetrahydrocurcumin can reduce the inflammatory response in the liver, thereby protecting liver cells from damage. At the same time, the antioxidant capacity of tetrahydrocurcumin can effectively scavenge liver free radicals, reducing the damage of oxidative stress to the liver. Tetrahydrocurcumin can alleviate liver steatosis and inflammatory response through its antioxidant and anti-inflammatory effects, and improve liver function. Although the specific mechanism of tetrahydrocurcumin in NAFLD is not completely clear at present, as a potential natural ingredient, it is worth further research and exploration. SUMMARY

[0005] In one aspect, the present application provides a method for improving or modulating liver metabolic level, enhancing or maintaining liver function, improving or maintaining liver health in a subject, the method comprising: administering to the subject an effective amount of dihydroberberine or a physiologically acceptable salt, acid, ester thereof.

[0006] In some embodiments, improving or modulating liver metabolic level, enhancing or maintaining liver function, improving or maintaining liver health in a subject comprises reducing serum and liver aspartate aminotransferase, alanine aminotransferase, alleviating liver cell inflammation and apoptosis, reducing TNF-a, IL-6, elevating or improving liver cell antioxidant capacity, reducing malondialdehyde.

[0007] In some embodiments, the amount administered is 1 mg-2000 mg or 0.1 μΜ to 1 M or 0.001 to 50.0% (w / w). In some embodiments, the amount administered ranges from 1 mg to 2000 mg, 2 mg to 2000 mg, 5 mg to 1500 mg, 10 mg to 1200 mg, 20 mg to 1000 mg, 30 mg to 800 mg, 30 mg to 500 mg, 40 mg to 300 mg. In some embodiments, the amount administered ranges from 0.005% to 45%, 0.005% to 40%, 0.005% to 30%, 0.005% to 25%, 0.01% to 40%, 0.01% to 30%, 0.01% to 25%, 0.01% to 15%, 0.05% to 30%, 0.05% to 20%, 0.05% to 10%, 0.1% to 35%, 0.1% to 25%, 0.1% to 10%, 0.2% to 25%, 0.2% to 10%, 0.5% to 9%, 1% to 7%, 2% to 7%, 0.005% to 7%, 0.005% to 9% (w / w). In some embodiments, the amount administered ranges from 0.1 μΜ to 1 M (e.g., 0.1 μΜ to 500 μΜ, 1 μΜ to 500 μΜ, 1 μΜ to 5 mM, 1 μΜ to 500 mM, 5 μΜ to 500 μΜ, 5 μΜ to 5 mM, 5 μΜ to 100 mM, 5 μΜ to 500 mM, 50 μΜ to 500 μΜ, 50 μΜ to 5 mM).

[0008] In some embodiments, the effective amount of tetrahydrocurcumin is administered in an amount ranging from 1 mg to 3000 mg. In some embodiments, the amount ranges from 1 mg to 3000 mg, 2 mg to 2500 mg, 2 mg to 2000 mg, 5 mg to 1500 mg, 10 mg to 1200 mg, 20 mg to 1000 mg, 30 mg to 800 mg, 30 mg to 500 mg, 40 mg to 300 mg.

[0009] In some embodiments, the ratio of dihydroberberine or its physiologically acceptable salts, acids, esters and the tetrahydrocurcumin is 10:1 to 1:10. In some embodiments, the ratio of dihydroberberine or its physiologically acceptable salts, acids, esters and the tetrahydrocurcumin can be 10:1 to 1:10, 8:1 to 1:10, 5:1 to 1:10, 2:1 to 1:10, 1:1 to 1:10, 1:1 to 1:5.

[0010] In some embodiments, dihydroberberine or its physiologically acceptable salts, acids, esters are prepared into solid formulations or liquid formulations.

[0011] In some embodiments, dihydroberberine or its physiologically acceptable salts, acids, esters are in the form of suppositories, tablets, pills, granules, powders, films, capsules, beverages, aerosols, spirits, tinctures, tonics, liquid suspensions, syrups.

[0012] In some embodiments, the subject is a mammal. In some embodiments, the subject is a human.

[0013] In some embodiments, the subject group administered dihydroberberine or its physiologically acceptable salts, acids, esters has an improved or modulated level of hepatic metabolism, enhanced or maintained liver function, improved or maintained liver health, greater than a group not administered dihydroberberine or its physiologically acceptable salts, acids, esters.

[0014] In some embodiments, the subject group administered dihydroberberine or its physiologically acceptable salts, acids, esters has a reduced level of aspartate aminotransferase and alanine aminotransferase, greater than a group not administered dihydroberberine or its physiologically acceptable salts, acids, esters.

[0015] In one aspect, the present application provides a composition comprising dihydroberberine or its physiologically acceptable salts, acids, esters, and tetrahydrocurcumin.

[0016] In some embodiments, the composition is administered in an amount ranging from 1 mg to 3000 mg or 0.1 μΜ to 1 M or 0.001 to 50.0% (w / w).

[0017] In some embodiments, the composition is administered at least once a day for 1 week to 7 weeks, 2 weeks to 7 weeks, 3 weeks to 7 weeks, 4 weeks to 7 weeks.

[0018] In some embodiments, the present composition can be administered by oral, intravenous, intramuscular, intraperitoneal, topical instillation, sublingual administration, or the like. For example, the composition is administered by a single dose or multiple divided doses, the daily dose of the composition ranges from 1 mg to 3000 mg, 2 mg to 2500 mg, 2 mg to 2000 mg, 5 mg to 1500 mg, 10 mg to 1200 mg, 20 mg to 1000 mg, 30 mg to 800 mg, 30 mg to 500 mg, 40 mg to 300 mg. In some embodiments, the daily dose ranges from 0.005% to 45%, 0.005% to 40%, 0.005% to 30%, 0.005% to 25%, 0.01% to 40%, 0.01% to 30%, 0.01% to 25%, 0.01% to 15%, 0.05% to 30%, 0.05% to 20%, 0.05% to 10%, 0.1% to 35%, 0.1% to 25%, 0.1% to 10%, 0.2% to 25%, 0.2% to 10%, 0.5% to 9%, 1% to 7%, 2% to 7%, 0.005% to 7%, 0.005% to 9% (w / w). In some embodiments, the daily dose ranges from 0.1 μM to 1 M (e.g., 0.1 μM to 500 μM, 1 μM to 500 μM, 1 μM to 5 mM, 1 μM to 500 mM, 5 μM to 500 μM, 5 μM to 5 mM, 5 μM to 100 mM, 5 μM to 500 mM, 50 μM to 500 μM, 50 μM to 5 mM).

[0019] In some embodiments, the composition is used to improve or modulate liver metabolic level, enhance or maintain liver function, improve or maintain liver health in a subject.

[0020] In some embodiments, the improvement or modulation of liver metabolic level, enhancement or maintenance of liver function, improvement or maintenance of liver health in a subject comprises reducing serum and liver aspartate aminotransferase, alanine aminotransferase, alleviating liver cell inflammation and apoptosis, reducing TNF-a, IL-6, elevating or improving liver cell antioxidant capacity, reducing malondialdehyde.

[0021] In some embodiments, the improvement or modulation of liver metabolic level, enhancement or maintenance of liver function, improvement or maintenance of liver health in a subject group administered with the composition is greater than a group not administered with the composition.

[0022] In some embodiments, the group of subjects administered the composition has a greater reduction in levels of aspartate aminotransferase and alanine aminotransferase than a group not administered the composition.

[0023] In some embodiments, the ratio of dihydroberberine or its physiologically acceptable salts, acids, esters and tetrahydrocurcumin is 1:1 to 1:10. In some embodiments, the ratio of dihydroberberine or its physiologically acceptable salts, acids, esters and tetrahydrocurcumin can be 10:1 to 1:10, 8:1 to 1:10, 5:1 to 1:10, 2:1 to 1:10, 1:1 to 1:10, 1:1 to 1:5.

[0024] In some embodiments, the composition is prepared as a solid formulation or a liquid formulation.

[0025] In some embodiments, the composition is formulated as a nutraceutical, a dietary supplement, a food, a beverage, or an animal feed.

[0026] In some embodiments, the composition is in the form of a suppository, a tablet, a pill, a granule, a powder, a film, a capsule, a beverage, an aerosol, a spirit, a tincture, a tonic, a liquid suspension, a syrup.

[0027] In another aspect, the present application provides a use of dihydroberberine or its physiologically acceptable salts, acids, esters in the preparation of a composition for improving or modulating liver metabolic level, enhancing or maintaining liver function, improving or maintaining liver health in a subject.

[0028] In some embodiments, the composition is used in the preparation of, or is, a nutraceutical, a dietary supplement, a health product, a food, a beverage, an animal feed, wherein the weight ratio of the composition of the present application is 0.1-95%.

[0029] In some embodiments, the weight ratio of the composition of the present application in the nutraceutical, the dietary supplement, the food, the beverage, the animal feed is 1-50%.

[0030] In some embodiments, improving or modulating liver metabolic level, enhancing or maintaining liver function, improving or maintaining liver health in a subject includes reducing serum and liver aspartate aminotransferase, alanine aminotransferase, alleviating hepatocyte inflammation and apoptosis, reducing TNF-α, IL-6, improving or enhancing hepatocyte antioxidant capacity, reducing malondialdehyde.

[0031] In some embodiments, the composition prepared further comprises tetrahydrocurcumin.

[0032] In some embodiments, the ratio of dihydroberberine or its physiologically acceptable salts, acids, esters and tetrahydrocurcumin is 1:1 to 1:10. In some embodiments, the ratio of dihydroberberine or its physiologically acceptable salts, acids, esters and tetrahydrocurcumin can be 10:1 to 1:10, 8:1 to 1:10, 5:1 to 1:10, 2:1 to 1:10, 1:1 to 1:10, 1:1 to 1:5.

[0033] In some embodiments, the amount of the composition used is 1 mg-3000 mg or 0.1 μM to 1 M or 0.001 to 50.0% (w / w). Specifically, the daily amount of the composition ranges from 1 mg to 3000 mg, 2 mg to 2000 mg, 2 mg to 2000 mg, 5 mg to 1500 mg, 10 mg to 1200 mg, 20 mg to 1000 mg, 30 mg to 800 mg, 30 mg to 500 mg, 40 mg to 300 mg. In some embodiments, the daily amount ranges from 0.005% to 45%, 0.005% to 40%, 0.005% to 30%, 0.005% to 25%, 0.01% to 40%, 0.01% to 30%, 0.01% to 25%, 0.01% to 15%, 0.05% to 30%, 0.05% to 20%, 0.05% to 10%, 0.1% to 35%, 0.1% to 25%, 0.1% to 10%, 0.2% to 25%, 0.2% to 10%, 0.5% to 9%, 1% to 7%, 2% to 7%, 0.005% to 7%, 0.005% to 9% (w / w). In some embodiments, the daily amount ranges from 0.1 μM to 1 M (e.g., 0.1 μM to 500 μM, 1 μM to 500 μM, 1 μM to 5 mM, 1 μM to 500 mM, 5 μM to 500 μM, 5 μM to 5 mM, 5 μM to 100 mM, 5 μM to 500 mM, 50 μM to 500 μM, 50 μM to 5 mM). BRIEF DESCRIPTION OF DRAWINGS

[0034] Figure 1 is the result of plasma glutamic transaminase activity of experimental animals in each group in a mouse liver injury model.

[0035] Figure 2 is the result of plasma glutathione transaminase activity of experimental animals in each group in a mouse liver injury model.

[0036] Figure 3 is the result of total cholesterol content in the plasma of experimental animals in each group in a mouse liver injury model.

[0037] Figure 4 is the result of triglyceride content in the plasma of experimental animals in each group in a mouse liver injury model.

[0038] Figure 5 is the result of triglyceride content in the liver of experimental animals in each group in a mouse liver injury model.

[0039] Figure 6 is the result of malondialdehyde content in the liver of experimental animals in each group in a mouse liver injury model.

[0040] Figure 7 is the result of superoxide dismutase activity in the liver of experimental animals in each group in a mouse liver injury model.

[0041] Figure 8 is the result of TNF-α content in the liver of experimental animals in each group in a mouse liver injury model. DETAILED DESCRIPTION

[0042] Reference will now be made in detail to the preferred embodiments of the application, examples of which are illustrated in the accompanying drawings. While the application will be described in conjunction with the preferred embodiments, it will be understood that they are not intended to limit the application to these embodiments. On the contrary, the application is intended to cover alternatives, modifications, and equivalents, which can be included within the spirit and scope of the application as defined by the claims. Furthermore, in the following detailed description of the application, numerous specific details are set forth in order to provide a thorough understanding of the application. However, it will be apparent to one of ordinary skill in the art that the application can be practiced without these specific details. In other instances, well-known methods, procedures, components, and other features are not described in detail in order to avoid unnecessarily obscuring aspects of the application.

[0043] As used herein, the term "or" is intended to mean "and / or" unless otherwise indicated by context. In other words, the term "or" as used herein is the inclusive, not the exclusive, sense.

[0044] As used herein, the singular forms "a", "an" and "the" are intended to include the plural forms as well, unless the context clearly indicates otherwise.

[0045] As used herein, the terms "comprises", "comprising", "includes", "including" or "has", "having" or their variants thereof are intended to cover a non-exclusive inclusion, such that a process, method, article, or apparatus that comprises, has, includes or consists of any combination of the specified steps or elements is not excluded from the scope of the application.

[0046] As used herein, the terms "subject" or "individual" are used interchangeably to refer to any subject to which the methods and compositions of the present disclosure can be applied or administered. The subject can have the potential to have a disease or condition, but the subject need not be ill in order to benefit from the methods and compositions of the present disclosure. Any subject can take the disclosed compositions or be the recipient of the disclosed methods. Herein, the term "subject" refers to an animal (e.g., avian, reptilian, and mammalian). In certain embodiments, the subject can be a mammal including non-primate (e.g., camel, donkey, zebra, cow, horse, cat, dog, rat, and mouse) and primate (e.g., monkey, chimpanzee, human). In certain embodiments, the subject can be a non-human mammal. In other embodiments, the subject can be a human.

[0047] As used herein, the term "administering" means directly administering a compound or a pharmaceutically acceptable salt of a compound or a composition to a subject, or administering to a subject a prodrug derivative or analog of a compound or a pharmaceutically acceptable salt of a compound or a composition, which can form an equivalent amount of the active compound in the subject.

[0048] The contemplated methods include administering an appropriate amount of the substance and composition daily, depending on the formulation and form of the particular substance and composition. This amount daily can be administered in one or more administrations. Typically, the effective amount administered one or more times daily is 1 mg to 2000 mg. The one or more doses can be administered once daily over any time period. For example, the effective dose can be administered daily for one day, for several days, for many days, or indefinitely, the composition can be administered for 7 days and above in a cycle, depending on the desired effect. More typically, the amount administered daily is 1 mg to 3000 mg, 1 mg to 2500 mg, 1 mg to 2000 mg, 2 mg to 2000 mg, 5 mg to 1500 mg, 10 mg to 1200 mg, 20 mg to 1000 mg, 30 mg to 800 mg, 30 mg to 500 mg, 40 mg to 300 mg. More typically, the amount administered daily is 5 mg to 1500 mg.

[0049] The technical features, implementation methods and beneficial effects of the present application are further described in detail below in combination with specific implementation cases. The following examples are only a part of the embodiments of the present application, rather than all the embodiments. The materials and reagents described in the following examples are ordinary commercially available products and can be purchased in the market if not specifically stated. Examples

[0050] Forty C57BL / 6 mice were divided into 5 groups, 8 mice in each group, and fed with high-fat feed for 8 weeks to establish a model. After the modeling was completed, intragastric administration was performed, and the groups and doses are shown in the following table:

[0051]

[0052] The above groups of animals were respectively administered by gavage according to the above-mentioned doses, once a day. The control group and the model group mice were given the same volume of distilled water. After 6 weeks of continuous administration, the animals were sacrificed by intraperitoneal injection of 1 mL of 20% chloral hydrate anesthesia, and blood was collected by enucleation of the eyeball. The liver was taken out and homogenized for detection. The total cholesterol, triglyceride, aspartate aminotransferase (AST), alanine aminotransferase (ALT), superoxide dismutase activity, and low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, malondialdehyde, TNF-α, IL-6 and Caspase-3 content in the plasma and liver were determined by using biochemical kits.

[0053] Long-term high-fat and high-carbohydrate diet can induce metabolic disorders, leading to non-alcoholic fatty liver injury, and ROS also increases. Excessive ROS can cause lipid peroxidation, protein denaturation and DNA damage, directly damaging the structure and function of liver cells, and activating a series of downstream signaling pathways, promoting inflammatory response and apoptosis.

[0054] Figures 1 and 2 are results of plasma glutamic-pyruvic transaminase activity and glutamic-oxalacetic transaminase activity of each group of experimental animals in a mouse liver injury model. As shown in the figures, compared with the damage degree of the model group, the dihydroberberine group can reduce serum glutamic-pyruvic transaminase (ALT) and glutamic-oxalacetic transaminase (AST) by more than 30%. The combination of dihydroberberine and tetrahydrocurcumin can further reduce by more than 40% compared with the dihydroberberine group. Figures 3-5 are results of total cholesterol content in the plasma of each group of experimental animals in a mouse liver injury model, and results of triglyceride content in the plasma and liver. Compared with the damage degree of the model group, the dihydroberberine group can significantly reduce the levels of triglyceride in the liver and plasma, total cholesterol in the plasma, and low-density lipoprotein cholesterol (all reduced by more than 20%), while increasing the level of high-density lipoprotein cholesterol (increased by more than 10%). The combination of dihydroberberine and tetrahydrocurcumin can further reduce the levels of triglyceride in the liver and plasma, total cholesterol in the plasma, and low-density lipoprotein cholesterol by more than 20% compared with the dihydroberberine group, and can further increase the level of high-density lipoprotein cholesterol. Figures 6 and 7 are results of malondialdehyde content, superoxide dismutase activity, and TNF-α content in the liver of each group of experimental animals in a mouse liver injury model. Compared with the damage degree of the model group, the dihydroberberine group can significantly reduce the malondialdehyde (MDA) content in the liver (decreased by more than 30%), increase the superoxide dismutase (SOD) activity level (increased by more than 20%), and effectively down-regulate the expression of inflammatory factors TNF-α, IL-6, and apoptosis-related protein Caspase-3 (all decreased by more than 10%). The combination of dihydroberberine and tetrahydrocurcumin can further reduce the malondialdehyde (MDA) content in the liver, down-regulate the inflammatory factor TNF-α, and further increase the superoxide dismutase (SOD) activity level compared with the dihydroberberine group.

[0055] Dihydroberberine or its physiologically acceptable salt, acid, or ester exhibits excellent performance in improving lipid metabolism, reducing oxidative stress, and inhibiting inflammatory response. Compared with the use of dihydroberberine or tetrahydrocurcumin alone, the combination of dihydroberberine and tetrahydrocurcumin exhibits more significant synergistic effect in improving lipid metabolism, reducing oxidative stress, and inhibiting inflammatory response, with a comprehensive improvement of more than 10%, and is more advantageous in relieving liver injury. In summary, the combination of dihydroberberine and tetrahydrocurcumin can effectively improve liver metabolic disorder, reduce oxidative stress and inflammatory response, and inhibit hepatocyte apoptosis through multi-target and multi-pathway synergistic effect, thereby significantly relieving liver injury, and has good liver protection potential and broad application prospect.

[0056] The above only describes the preferred embodiments of the present application and is not intended to limit the present application. Any person skilled in the art can make various changes, modifications, replacements, and variations to these embodiments without departing from the principles and purposes of the present application, and the scope of the present application is defined by the claims and their equivalents.

Claims

1. A method for improving or modulating liver metabolic level, enhancing or maintaining liver function, improving or maintaining liver health in a subject, characterized in that, The method comprises administering to the subject an effective amount of dihydroberberine or a physiologically acceptable salt, acid, ester thereof.

2. The method of claim 1, wherein, The improvement or regulation of the liver metabolic level, the enhancement or maintenance of liver function, the improvement or maintenance of liver health of the subject comprises lowering serum and liver aspartate aminotransferase, alanine aminotransferase, relieving hepatocyte inflammation and apoptosis, reducing TNF-α, IL-6, improving or improving the antioxidant capacity of hepatocytes, reducing malondialdehyde.

3. The method of claim 1 or 2, the administration amount is 1 mg-2000 mg or 0.1 μM to 1 M or 0.001 to 50.0% (w / w).

4. The method according to any one of claims 1 to 3, characterized in that, The composition further comprises administering an effective amount of tetrahydrocurcumin, the administration amount is 1 mg-3000 mg.

5. The method as claimed in claim 4, characterized in that The ratio of the dihydroberberine or a physiologically acceptable salt, acid, ester thereof and the tetrahydrocurcumin is 10:1 to 1:

10.

6. The method according to any one of claims 1 to 5, characterized in that, The dihydroberberine or a physiologically acceptable salt, acid, ester thereof is prepared into a solid preparation or a liquid preparation.

7. The method according to any one of claims 1 to 6, characterized in that, The dihydroberberine or a physiologically acceptable salt, acid, ester thereof is in the form of a suppository, a tablet, a pill, a granule, a powder, a film, a capsule, a beverage, an aerosol, a spirit, a tincture, a tonic, a liquid suspension, a syrup.

8. The method according to any one of claims 1 to 7, characterized in that, The subject is a mammal.

9. The method according to any one of claims 1-8, characterized in that, The group of subjects administered with dihydroberberine has greater benefits in the improvement or regulation of liver metabolic level, the enhancement or maintenance of liver function, the improvement or maintenance of liver health than the group not administered with the dihydroberberine.

10. A composition characterized in that, The composition comprises dihydroberberine or a physiologically acceptable salt, acid, ester thereof, and tetrahydrocurcumin.

11. The composition according to claim 10, characterized in that, The composition is used in an amount of 1 mg-3000 mg or 0.1 μM to 1 M or 0.001 to 50.0% (w / w).

12. The composition according to claim 10 or 11, characterized in that, The composition is used for improving or regulating the liver metabolic level of the subject, enhancing or maintaining liver function, improving or maintaining liver health.

13. The composition of claim 12, wherein, The improvement or regulation of the liver metabolic level, the enhancement or maintenance of liver function, the improvement or maintenance of liver health of the subject comprises lowering serum and liver aspartate aminotransferase, alanine aminotransferase, relieving hepatocyte inflammation and apoptosis, reducing TNF-α, IL-6, improving or improving the antioxidant capacity of hepatocytes, reducing malondialdehyde.

14. The composition according to any one of claims 10-13, characterized in that, The ratio of the dihydroberberine or a physiologically acceptable salt, acid, ester thereof and the tetrahydrocurcumin is 10:1 to 1:

10.

15. The composition according to any one of claims 10-14, characterized in that, The composition is prepared into a solid preparation or a liquid preparation.

16. The composition according to any one of claims 10-15, characterized in that, The composition is formulated into a nutraceutical, a dietary supplement, a food, a beverage, or an animal feed.

17. The composition according to any one of claims 10-16, characterized in that, The composition is in the form of a suppository, a tablet, a pill, a granule, a powder, a film, a capsule, a beverage, an aerosol, a spirit, a tincture, a tonic, a liquid suspension, a syrup.

18. The composition according to any one of claims 12-17, characterized in that, The group of subjects administered with the composition has greater benefits in the improvement or regulation of liver metabolic level, the enhancement or maintenance of liver function, the improvement or maintenance of liver health than the group not administered with the composition.

19. Use of dihydroberberine or a physiologically acceptable salt, acid, ester thereof in the preparation of a composition for improving or regulating the liver metabolic level of a subject, enhancing or maintaining liver function, improving or maintaining liver health.

20. Use according to claim 19, characterized in that, The improvement or regulation of the liver metabolism level of the subject, the enhancement or maintenance of liver function, the improvement or maintenance of liver health include the reduction of serum and liver aspartate aminotransferase, alanine aminotransferase, the relief of hepatocyte inflammation and apoptosis, the reduction of TNF-α, IL-6, the promotion or improvement of hepatocyte antioxidant capacity, the reduction of malondialdehyde.

21. Use according to claim 19 or 20, characterized in that, The prepared composition also includes tetrahydrocurcumin.

22. Use according to claim 21, characterized in that, The ratio of the dihydroberberine or its physiologically acceptable salt, acid, ester and the tetrahydrocurcumin is 10:1 to 1:

10.

23. The use according to any one of claims 19-22, characterized in that, The amount of the prepared composition is 1 mg-3000 mg or 0.1 μM to 1 M or 0.001 to 50.0% (w / w).

24. The use according to any one of claims 19 to 23, characterized in that, The composition is used for the preparation of a nutritional product, a dietary supplement, a health product, a food, a beverage, an animal feed.

25. Use according to claim 24, characterized in that, The weight ratio of the composition is 0.1-95%.

26. Use according to claim 24 or 25, characterized in that, The weight ratio of the composition is 1-50%.

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