Application of glucosamine to treatment of liver diseases and liver aging

Abstract

The invention provides application of glucosamine to treatment of liver diseases and liver aging. Specifically, the invention provides application of glucosamine (Glucosamine) or a pharmaceutically acceptable salt thereof, and the glucosamine or the pharmaceutically acceptable salt thereof is used for preparing medicines for preventing or treating chemical liver injury, alcoholic liver diseases, non-alcoholic fatty liver diseases and / or liver aging. The invention also discloses application of the compound in preparation of functional foods and / or health foods with auxiliary protection effects on liver diseases and liver aging. The invention further discloses a pharmaceutical composition of the glucosamine or the pharmaceutically acceptable salt thereof and application of the pharmaceutical composition.

Description

Technical Field

[0001] The present invention relates to the field of medicine, and in particular, to the use of glucosamine in treating liver diseases and liver aging, and discloses a new use of glucosamine or a pharmaceutically acceptable salt thereof as an active ingredient in the preparation of a drug for treating and / or preventing liver diseases and / or liver aging. Background Art

[0002] Liver disease refers to a pathological state that affects the normal function or structure of the liver. It may be caused by a variety of factors, including viral infection, alcohol abuse, drug side effects, genetic metabolic abnormalities, autoimmune reactions, etc. The progression of liver disease usually follows a staged development from fatty liver, steatohepatitis, liver fibrosis to cirrhosis. In the fatty liver stage, there is too much fat accumulation in the liver, but the liver cells have not yet suffered serious damage. If not intervened in time, fatty liver may progress to steatohepatitis, at which time the liver cells will have an inflammatory response and liver function will begin to be damaged. If the inflammation persists, the liver cells will be repeatedly damaged, and the fibrous tissue in the liver will proliferate, which will lead to liver fibrosis. Liver fibrosis is a process of liver structural changes that leads to further decline in liver function. If liver fibrosis continues to develop, it will seriously damage the liver structure and form cirrhosis. In the cirrhosis stage, liver function is significantly reduced, and serious complications such as ascites, jaundice, and esophageal varicose bleeding are prone to occur, which seriously affects the patient's quality of life and life expectancy.

[0003] The liver is the largest detoxification organ in the human body, and undertakes important functions such as metabolism, detoxification, energy storage, and synthesis of coagulation factors. In recent years, the morbidity and mortality of liver diseases have continued to rise, and it has become a global public health problem. Chemical liver damage is one of the common types of liver damage, and long-term heavy drinking is its main cause. Excessive alcohol intake not only leads to acute or chronic alcohol poisoning, but may also gradually develop into alcoholic liver disease (ALD). The development of alcoholic liver disease is accompanied by a persistent inflammatory response. This process is not only directly affected by alcohol, but also related to the release of proinflammatory factors by aging hepatocytes, which aggravates the degree of inflammation and liver tissue damage.

[0004] There is a close connection between liver aging and liver disease. As we age, the aging of liver cells will lead to a decline in their metabolic and detoxification functions, making the liver less resistant to various injuries and more susceptible to liver disease. At the same time, long-term liver disease will accelerate the aging process of liver cells, forming a vicious cycle, further exacerbating the decline of liver function and increasing the risk of serious complications such as cirrhosis and liver cancer.

[0005] Non-alcoholic fatty liver disease (NAFLD) is another common liver disease, which is often closely related to insulin resistance and genetic background. Epidemiological data show that the incidence of NAFLD in the adult population in my country has exceeded 25%, and the age of onset is trending earlier, especially in patients with obesity, metabolic syndrome and diabetes.

[0006] There are still many challenges in the treatment of liver diseases and liver aging in the clinic. Although traditional treatments such as liver protection drugs can relieve symptoms, it is difficult to fundamentally reverse liver damage and aging. At present, there is still a lack of effective methods for treating liver diseases and improving liver aging in this field.

[0007] Therefore, there is an urgent need in the art to develop drugs for treating and / or preventing liver diseases and liver aging. Summary of the invention

[0008] The main purpose of the present invention is to provide a new use of glucosamine or a pharmaceutically acceptable salt thereof, in particular, the use of glucosamine or a salt thereof as an active ingredient in the preparation of a medicine or composition for treating and / or preventing liver disease and liver aging, or a food, functional food, special medical food, health product, nutrient supplement, dietary supplement or pharmaceutical composition having an auxiliary protective effect on liver disease and liver aging.

[0009] The first aspect of the present invention provides the use of glucosamine or a pharmaceutically acceptable salt thereof for preparing functional foods, health products or medicines for treating and / or preventing liver diseases and / or liver aging.

[0010]

[0011] In another preferred embodiment, the liver disease is selected from the group consisting of chemical liver injury, alcoholic liver disease, non-alcoholic fatty liver disease, metabolism-related fatty liver disease, or a combination thereof.

[0012] In another preferred embodiment, the liver disease is alcoholic liver disease.

[0013] In another preferred embodiment, the liver disease is selected from the group consisting of fatty liver, hepatitis, liver damage, liver fibrosis, cirrhosis, or a combination thereof.

[0014] In another preferred embodiment, the liver aging is selected from the group consisting of liver aging caused by chemical-induced liver damage and liver aging caused by drinking alcohol.

[0015] In another preferred embodiment, the liver aging is liver aging caused by drinking alcohol.

[0016] In another preferred embodiment, the pharmaceutically acceptable salt is selected from the following group: hydrochloride, sulfate, fumarate, phosphate, citrate, citrate, nitrate, malate, methanesulfonate, oxalate, or a combination thereof; preferably hydrochloride, sulfate, or a combination thereof.

[0017] In another preferred embodiment, glucosamine or a pharmaceutically acceptable salt thereof is used for one or more purposes selected from the following group:

[0018] (a) Improve acute or chronic hepatocellular and liver damage;

[0019] (b) Alleviate fatty degeneration or fat accumulation in hepatocytes or liver tissue;

[0020] (c) reduce oxidative stress damage;

[0021] (d) Eliminate liver senescent cells;

[0022] (e) inhibiting the expression of liver aging markers;

[0023] (f) inhibiting the expression of the senescence-associated secretory phenotype (SASP);

[0024] (g) Improved athletic ability.

[0025] In another preferred embodiment, the invention is used for one or more purposes selected from the following group:

[0026] (a) Alleviate acute or chronic liver cell and liver damage and protect the liver, such as reducing the increase of transaminase, triglyceride, cholesterol, etc. and restoring albumin level.

[0027] (b) Alleviate fatty degeneration or fat accumulation in hepatocytes or liver tissue;

[0028] (c) Reduce oxidative stress damage and improve inflammatory damage;

[0029] (d) Eliminate liver senescent cells and delay liver aging, such as reducing SA-β-gal expression and reducing the rate of SA-β-gal positive cells;

[0030] (e) Inhibit the senescence-associated secretory phenotype (SASP) and improve liver aging, such as reducing the expression of aging markers such as γ-H2AX, p53, and p16;

[0031] (f) Improve inflammatory aging, such as reducing the expression of aging-related secretory phenotypes such as CXCL1, CXCL3, MMP-1, and MMP-7;

[0032] (g) Improve motor ability, such as enhancing alcohol-induced reduction in the grip strength of mice.

[0033] In another preferred embodiment, glucosamine can activate AMPK-related signaling pathways and improve liver diseases and / or liver aging.

[0034] In another preferred embodiment, the AMPK-related signaling pathway is selected from the following group: AMPK / SREBP1 / FAS, AMPK / ACC, AMPK / p38.

[0035] In another preferred embodiment, the glucosamine or a pharmaceutically acceptable salt thereof reduces liver lipid accumulation by activating AMPK / SREBP1 / FAS and AMPK / ACC signaling pathways, and improves liver aging by activating AMPK / p38 pathway.

[0036] The second aspect of the present invention provides another use of the glucosamine or a pharmaceutically acceptable salt thereof for preparing foods, functional foods, special medical foods, health products, nutrient supplements, dietary supplements or pharmaceutical compositions that have auxiliary protective effects on liver diseases and liver aging.

[0037] The third aspect of the present invention provides a pharmaceutical composition comprising:

[0038] i) glucosamine or a pharmaceutically acceptable salt thereof as described in the first aspect of the present invention; and

[0039] ii) a pharmaceutically acceptable carrier.

[0040] In another preferred embodiment, the pharmaceutical composition is used to prepare a drug for treating and / or preventing liver disease and / or liver aging.

[0041] In another preferred embodiment, the liver disease is selected from the group consisting of chemical liver injury, alcoholic liver disease, non-alcoholic fatty liver disease, metabolism-related fatty liver disease, or a combination thereof.

[0042] In another preferred embodiment, the liver disease is alcoholic liver disease.

[0043] In another preferred embodiment, the liver disease is selected from the group consisting of fatty liver, hepatitis, liver damage, liver fibrosis, cirrhosis, or a combination thereof.

[0044] In another preferred embodiment, the liver aging is selected from the group consisting of liver aging caused by chemical-induced liver damage and liver aging caused by drinking alcohol.

[0045] In another preferred embodiment, the liver aging is liver aging caused by drinking alcohol.

[0046] In another preferred embodiment, the pharmaceutical composition is used for one or more uses selected from the following group:

[0047] (a) Improve acute or chronic hepatocellular and liver damage;

[0048] (b) Alleviate fatty degeneration or fat accumulation in hepatocytes or liver tissue;

[0049] (c) reduce oxidative stress damage;

[0050] (d) Eliminate liver senescent cells;

[0051] (e) inhibiting the expression of liver aging markers;

[0052] (f) inhibiting the expression of the senescence-associated secretory phenotype (SASP);

[0053] (g) Improved athletic ability.

[0054] In another preferred embodiment, the pharmaceutical composition is used to prepare food, functional food, special medical food, health care product, nutrient supplement, or dietary supplement that has auxiliary protective effect on liver disease and liver aging.

[0055] The fourth aspect of the present invention provides a method for treating and / or preventing liver disease and / or liver aging, comprising the steps of administering glucosamine, or a pharmaceutically acceptable salt thereof, or the pharmaceutical composition as described in the third aspect of the present invention to a subject.

[0056] In another preferred embodiment, the subject is a mammal, preferably a rodent or a primate, more preferably a mouse, a rat or a human.

[0057] It should be understood that within the scope of the present invention, the above-mentioned technical features of the present invention and the technical features specifically described below (such as embodiments) can be combined with each other to form a new or preferred technical solution. Due to space limitations, they will not be described one by one here. BRIEF DESCRIPTION OF THE DRAWINGS

[0058] Figure 1 The test results showed that glucosamine improved cell survival rate and liver function indicators (AST, ALT) in the alcohol-induced hepatocellular injury model.

[0059] Figure 2 The results of the test showed that glucosamine improved the lipid droplet content in the alcohol-induced hepatocyte steatosis model.

[0060] Figure 3 The results of the test on the lipid droplet content in the free fatty acid-induced hepatocyte steatosis model were shown.

[0061] Figure 4 It was shown that glucosamine improved the superoxide dismutase (SOD) test results in the alcohol-induced hepatocyte oxidative stress model.

[0062] Figure 5 The results showed that glucosamine improved the liver function and inflammatory indexes in mice with acute alcoholic liver injury.

[0063] Figure 6 The results of H&E section staining show that glucosamine improves the liver tissue morphology of mice with acute alcoholic liver injury.

[0064] Figure 7 The results showed that glucosamine improved the liver function test results of mice with chronic alcoholic liver disease.

[0065] Figure 8 The test results showed that glucosamine improved liver inflammation indicators in mice with chronic alcoholic liver disease.

[0066] Fig. 9 The results of the test show that glucosamine reduces the lipid content and lipid droplet levels in the liver of mice with chronic alcoholic liver disease.

[0067] Fig.10 The results show that glucosamine reduces the expression of p16, a liver aging marker, in mice with acute alcoholic liver injury.

[0068] Fig.11 The results of section staining show that glucosamine reduces the positive rate of SA-β-gal, a liver aging marker, in mice with acute alcoholic liver injury.

[0069] Fig.12 The test results showed that glucosamine improved the liver aging-related secretory phenotype CXCL1, CXCL3, MMP-1, and MMP-7 in mice with acute alcoholic liver injury.

[0070] Fig.13 The test results show that glucosamine reduces the expression of liver aging markers γ-H2AX and p53 in mice with chronic alcoholic liver disease.

[0071] Fig.14 The results of the test showing that glucosamine reduces the expression of p16, a liver aging marker, in mice with chronic alcoholic liver disease.

[0072] Fig.15 The results of section staining show that glucosamine reduces the positive rate of SA-β-gal, a liver aging marker, in mice with chronic alcoholic liver disease.

[0073] Fig.16 The test results showed that glucosamine improved the liver aging-related secretory phenotype CXCL1, CXCL3, MMP-1, and MMP-7 in mice with chronic alcoholic liver disease.

[0074] Fig.17Shows the test results of glucosamine improving forelimb grip strength in mice with chronic alcoholic liver disease.

[0075] Fig.18 The results of glucosamine testing on AMPK / p38 pathway proteins in liver tissue of mice with chronic alcoholic liver disease are shown.

[0076] Fig.19 The results of glucosamine testing on AMPK / SREBP1 / FAS and AMPK / ACC pathway proteins in liver tissue of mice with chronic alcoholic liver disease are shown. DETAILED DESCRIPTION

[0077] After extensive and in-depth research, the inventor unexpectedly discovered for the first time that glucosamine or a pharmaceutically acceptable salt thereof can improve liver diseases and / or liver aging, and that glucosamine can activate AMPK-related signaling pathways. On this basis, the inventor completed the present invention.

[0078] the term

[0079] Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs.

[0080] As used herein, when used in reference to a specific recited numerical value, the term "about" means that the value may vary by no more than 1% from the recited value. For example, as used herein, the expression "about 100" includes all values ​​between 99 and 101 (e.g., 99.1, 99.2, 99.3, 99.4, etc.).

[0081] As used herein, the term "comprising" or "including (comprising)" may be open, semi-closed and closed. In other words, the term also includes "consisting essentially of" or "consisting of".

[0082] The words "prevention", "treatment", "improvement", "enhancement", "reduction", "reduction", "mitigation" and the like described in the present invention include delaying and stopping the progression of the disease or symptoms, or eliminating the disease, and do not require 100% inhibition, elimination and reversal. In some embodiments, the composition of the present invention can alleviate or reverse one or more symptoms or indicators of liver disease and liver aging, for example, alleviate and / or reverse by at least about 10%, at least about 30%, at least about 50%, or at least about 80%, compared to the levels observed in the absence of the active ingredient or composition of the present invention.

[0083] Some representative indicators for the treatment of liver diseases and liver aging include (but are not limited to): ALT and AST levels; SOD activity; IL-1β, IL-6, and TNF-α levels; γ-H2AX, p53, p16, CXCL1, CXCL3, MMP-1, and MMP-7 expression levels.

[0084] Active ingredients

[0085] The active ingredient of the present invention is glucosamine.

[0086] The structural formula of glucosamine is shown below, and its CAS number is 3416-24-8.

[0087]

[0088] As used herein, the term "pharmaceutically acceptable salt" refers to a salt formed by a positively charged group on the compound of formula (I) and an anion, or a salt formed by a negatively charged group on the compound of formula (I) and a cation. Suitable anions include, but are not limited to, chloride, bromide, iodide, sulfate, nitrate, phosphate, citrate, methanesulfonate, trifluoroacetate, acetate, malate, toluenesulfonate, tartrate, fumarate, glutamate, glucuronide, lactate, glutarate or maleate, etc. Suitable cations include, but are not limited to, sodium, potassium, magnesium, calcium, ammonium, etc.

[0089] In another preferred embodiment, the pharmaceutically acceptable salt of the present invention refers to the salts formed by the compound represented by the general formula (I) and the following acid, such as but not limited to: hydrofluoric acid, hydrochloric acid, hydrobromic acid, phosphoric acid, acetic acid, oxalic acid, sulfuric acid, nitric acid, methanesulfonic acid, aminosulfonic acid, salicylic acid, trifluoromethanesulfonic acid, naphthalenesulfonic acid, maleic acid, citric acid, acetic acid, lactic acid, tartaric acid, succinic acid, oxalic acid, pyruvic acid, malic acid, glutamic acid, p-toluenesulfonic acid, naphthalenesulfonic acid, ethanesulfonic acid, naphthalene disulfonic acid, malonic acid, fumaric acid , propionic acid, oxalic acid, trifluoroacetic acid, stearic acid, pamoic acid, hydroxymaleic acid, phenylacetic acid, benzoic acid, glutamic acid, ascorbic acid, p-aminobenzenesulfonic acid, 2-acetoxybenzoic acid and isethionic acid, etc.; or a salt formed by the compound represented by the general formula (I) and an inorganic base, such as but not limited to sodium salt, potassium salt, calcium salt, aluminum salt or ammonium salt; or a salt formed by the compound represented by the general formula (I) and an organic base, such as but not limited to methylamine salt, ethylamine salt, ethanolamine salt, hydroxymethylaminomethane (TRIS) ammonium salt, etc.

[0090] The compound of the general formula (I) of the present invention or its pharmaceutically acceptable salt is separated out by distillation, crystallization or recrystallization from water or an organic solvent, and the compound may contain the solvent molecules used. In addition, different crystallization conditions may lead to different crystal forms of the compound. Therefore, the compound shown in the general formula (I) or its pharmaceutically acceptable salt containing different chemical doses of crystallization solvents and all crystal forms is within the scope of the present invention.

[0091] Liver disease

[0092] Liver disease refers to a pathological condition that affects the normal function or structure of the liver, which may be caused by a variety of factors, including viral infection, alcohol abuse, drug side effects, genetic metabolic abnormalities, autoimmune reactions, etc. Liver diseases range from mild liver dysfunction to severe cirrhosis, liver failure and liver cancer. Experiments have shown that the active ingredients or compositions of the present invention can protect liver cells, improve liver function decline, reduce liver cell fat accumulation, improve liver cell antioxidant and anti-inflammatory functions, and / or delay the progression of liver disease.

[0093] Liver aging

[0094] As used herein, liver aging refers to liver aging caused by long-term and heavy drinking. On the one hand, the higher the level of alcohol in the body and the longer the drinking time, the more severe the liver damage tends to be, the higher the expression level of liver aging markers, and the faster the aging of the liver. On the other hand, aging hepatocytes aggravate the damage of alcohol to liver cells through changes in their metabolic and secretory functions, resulting in faster disease progression. Experiments have shown that the active ingredients or compositions of the present invention can inhibit the upregulation of liver aging-related markers, reduce the expression of aging-related secretory phenotypes, improve inflammatory aging, restore liver health, and thus delay liver aging.

[0095] Chemical liver damage

[0096] Chemical liver damage refers to liver damage caused by chemical substances, which may include drugs, industrial toxins, environmental pollutants, etc. As the main detoxification organ, the liver is often exposed to various chemical substances, which may cause direct damage to liver cells or cause liver damage through indirect mechanisms such as inducing oxidative stress and inflammatory response. Experiments have shown that the active ingredients or compositions of the present invention can reduce liver cell damage caused by the chemical substance ethanol, reduce oxidative stress levels, inhibit inflammatory responses, and / or promote the repair and regeneration of damaged liver cells. This effectively prevents and treats liver damage caused by chemical substances, improves the liver's detoxification ability, and protects the liver from chemical damage.

[0097] Alcoholic liver disease

[0098] As used herein, alcoholic liver disease is a liver disease caused by long-term and heavy drinking. The liver is the main organ for the decomposition of alcohol. Drinking alcohol may lead to liver damage, and even alcoholic fatty liver, alcoholic hepatitis, alcoholic liver fibrosis, alcoholic cirrhosis and alcoholic liver failure and other alcoholic liver diseases. Experiments have shown that the active ingredients or compositions of the present invention can improve transaminase indicators, reduce fat accumulation in liver tissue, reduce the expression of inflammatory factors, reduce liver histological damage, and restore liver health in mice with alcoholic liver caused by short-term and long-term drinking, thereby providing therapeutic benefits for alcoholic liver disease.

[0099] Nonalcoholic fatty liver disease

[0100] Non-alcoholic fatty liver disease is a chronic progressive liver disease caused by overnutrition and insulin resistance. The range of this disease includes non-alcoholic fatty liver (NAFL) and non-alcoholic steatohepatitis (NASH). Experiments have shown that the active ingredient of the present invention can reduce the accumulation of hepatocyte lipid droplets caused by free fatty acids, thereby improving liver function and providing therapeutic benefits to NAFLD patients.

[0101] Pharmaceutical compositions and methods of administration

[0102] The present invention also provides a pharmaceutical composition containing the active ingredient of the present invention, which is used to prepare a drug for treating and / or preventing liver diseases and / or liver aging. It can also be used to prepare foods, functional foods, special medical foods, health products, nutrient supplements, and dietary supplements that have auxiliary protective effects on liver diseases and liver aging.

[0103] The present invention also provides a health food, which may include one or more active ingredients of the present invention; and a pharmaceutically or health food acceptable carrier. In particular, the function of the health food is to have an auxiliary protective effect on liver diseases and liver aging.

[0104] The pharmaceutical composition of the present invention comprises:

[0105] i) glucosamine or a pharmaceutically acceptable salt thereof as an active ingredient; and ii) a pharmaceutically acceptable carrier.

[0106] As used herein, the term "effective amount" or "effective dose" refers to an amount that can produce function or activity (ie, treat liver disease and / or liver aging) in humans and / or animals and is acceptable to humans and / or animals.

[0107] As used herein, the term "pharmaceutically acceptable" ingredients are suitable for use in humans and / or mammals without excessive adverse side effects (such as toxicity, irritation and allergic reactions), i.e., substances with a reasonable benefit / risk ratio. The term "pharmaceutically acceptable carrier" refers to a carrier for administration of a therapeutic agent, including various excipients and diluents.

[0108] The pharmaceutical composition of the present invention contains a safe and effective amount of the active ingredient of the present invention and a pharmaceutically acceptable carrier. Such carriers include (but are not limited to): saline, buffer, glucose, water, glycerol, ethanol, and combinations thereof. Usually, the pharmaceutical preparation should match the mode of administration. The dosage form of the pharmaceutical composition of the present invention is injection, oral preparation (tablet, capsule, oral liquid), transdermal agent, sustained release agent. For example, it is prepared by conventional methods using physiological saline or an aqueous solution containing glucose and other adjuvants. The pharmaceutical composition is preferably manufactured under sterile conditions.

[0109] In another preferred embodiment, the composition or preparation is in the form of a solid preparation, a liquid preparation or a semisolid preparation.

[0110] In another preferred embodiment, the composition or preparation is in the form of an oral preparation, an external preparation or an injection preparation.

[0111] In another preferred embodiment, the composition or preparation is in the form of an oral preparation.

[0112] Typically, the composition or preparation is in the form of a tablet, injection, infusion, ointment, gel, solution, microsphere or film.

[0113] Liquid dosage forms for oral administration include pharmaceutically acceptable emulsions, solutions, suspensions, syrups or tinctures. In addition to the active ingredient, the liquid dosage form may contain an inert diluent conventionally used in the art, such as water or other solvents, solubilizers and emulsifiers, for example, ethanol, isopropanol, ethyl carbonate, ethyl acetate, propylene glycol, 1,3-butylene glycol, dimethylformamide and oils, particularly cottonseed oil, peanut oil, corn germ oil, olive oil, castor oil and sesame oil or mixtures of these substances, etc.

[0114] Besides such inert diluents, the composition may also include adjuvants such as wetting agents, emulsifying and suspending agents, sweetening, flavoring, and perfuming agents.

[0115] In addition to the active ingredients, suspensions may contain suspending agents such as, for example, ethoxylated isostearyl alcohols, polyoxyethylene sorbitol and sorbitan esters, microcrystalline cellulose, aluminum methanol and agar, or mixtures of these substances.

[0116] The treatment method of the present invention can be used alone or in combination with other treatment methods or therapeutic drugs (such as drugs for alleviating liver damage).

[0117] The effective amount of the active ingredient of the present invention may vary with the mode of administration and the severity of the disease to be treated. The selection of the preferred effective amount can be determined by a person of ordinary skill in the art based on various factors (e.g., through clinical trials). The factors include, but are not limited to: pharmacokinetic parameters of the active ingredient such as bioavailability, metabolism, half-life, etc.; the severity of the disease to be treated by the patient, the patient's body weight, the patient's immune status, the route of administration, etc. Generally, when the active ingredient of the present invention is administered at a dose of about 0.00001g-6g / kg animal body weight (preferably 0.0001g-2.4g / kg animal body weight) per day, satisfactory results can be obtained. For example, depending on the urgency of the treatment situation, several divided doses may be administered per day, or the dose may be reduced proportionally.

[0118] Typically, when the pharmaceutical composition of the present invention is administered orally, the average daily dose for a 60 kg body weight subject (human) is usually 1-30 g, preferably 2-20 g, more preferably 5-12 g. The daily dose can be taken once, twice or multiple times.

[0119] The effective amount of the active ingredients described in the present invention may vary depending on the mode of administration and the severity of the subject's liver disease and liver aging.

[0120] The pharmaceutically acceptable carriers of the present invention include (but are not limited to): water, saline, liposomes, lipids, peptides, cellulose, nanogels, or combinations thereof. The choice of carrier should match the mode of administration, which are well known to those of ordinary skill in the art.

[0121] When used as a pharmaceutical preparation, the compound or pharmaceutical composition of the present invention can be used once a day or in divided doses. Regardless of the method of use, the optimal dose for an individual should be determined based on the specific treatment. Usually, it is started with a small dose and gradually increased until the most suitable dose is found.

[0122] The main advantages of the present invention include:

[0123] (A) The present invention first discovered that glucosamine has the effect of treating and / or preventing liver diseases and liver aging.

[0124] (B) The glucosamine described in the present invention has a significant liver protective effect.

[0125] (C) The glucosamine of the present invention can reduce lipid accumulation in hepatocytes.

[0126] (D) The glucosamine of the present invention can improve hepatocyte damage and / or liver damage.

[0127] (E) The glucosamine of the present invention has a significant effect of delaying liver aging, thereby promoting the restoration of liver health.

[0128] (F) The glucosamine described in the present invention can improve the motor function of mice with chronic alcoholic liver disease.

[0129] (G) The active ingredient glucosamine of the present invention is a marketed drug with a large amount of clinical application experience, is safe and reliable, and is more conducive to the development of new products of the present invention.

[0130] The present invention will be further described below in conjunction with specific examples. It should be understood that these examples are intended to illustrate the present invention only and are not intended to limit the scope of the present invention. The experimental methods in the following examples where specific conditions are not specified are usually performed under conventional conditions, such as those described in Sambrook et al., Molecular Cloning: A Laboratory Manual (New York: Cold Spring Harbor Laboratory Press, 1989), or under conditions recommended by the manufacturer. Unless otherwise indicated, percentages and parts are weight percentages and weight parts.

[0131] Unless otherwise specified, the glucosamine described in the following examples is glucosamine hydrochloride.

[0132] Example 1 Verification of the protective effect of glucosamine on liver cells

[0133] To investigate the effect of glucosamine on ethanol-induced hepatocyte injury.

[0134] The experimental scheme is as follows: HepG2 cells (human liver cancer cell line) are commonly used cell lines in liver disease research. They can express a variety of liver-specific genes and functional proteins and can be used as an in vitro human liver cell model for related research. In addition, its culture conditions are relatively simple and have good reproducibility in vitro. The experimental groups are divided into blank group, model group, metformin group (50μM, positive drug) and glucosamine group (100μM). HepG2 cells are cultured normally for 12h, and the positive drug and glucosamine mother solution are diluted with culture medium to the concentration to be tested, and the corresponding test solution is added to each well. After incubation with cells for 6h, alcohol modeling is performed. Except for the cells in the normal control group, the culture medium contains 350mM ethanol solution and incubated for 24 hours. After modeling, the cell viability was detected using the CellCounting Kit-8 (CCK-8) method, and the alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels in the cell supernatant were detected using the Nanjing Jiancheng Bioengineering Institute (C009-2-1, C010-2-1) kit. The data were summarized, a bar graph was drawn using Graph Pad, and significant differences were calculated (t-test).

[0135] Experimental results: Figure 1 As shown, compared with the model group, glucosamine significantly increased cell survival rate ( Figure 1 A), reduce ALT ( Figure 1 B) AST( Figure 1 C). This indicates that glucosamine exhibits significant hepatocellular protective effects in the ethanol-induced liver injury model. * indicates P<0.05, ** indicates P<0.01, and *** indicates P<0.001.

[0136] Example 2 Glucosamine reduces alcohol-induced lipid accumulation in hepatocytes

[0137] To investigate the effect of glucosamine on alcohol-induced lipid accumulation in hepatocytes.

[0138] The experimental scheme is as follows: the experimental groups are divided into a blank group, a model group, a simvastatin group (1.56 μg / mL, positive drug) and a glucosamine group (100 μM). HepG2 cells were cultured normally for 12 hours, and the positive drug and glucosamine stock solution were diluted with culture medium to the concentration to be tested. After incubation with cells for 6 hours, alcohol modeling was performed. Except for the cells in the normal control group, the culture medium contained 200 mM ethanol solution and was incubated for 16 hours. After the modeling was completed, the lipid droplet expression content was detected using Nile red dye. The data were summarized, and the fluorescence was quantified using Image J. The bar graph was drawn using Graph Pad, and the significant difference (t-test) was calculated.

[0139] Experimental results: Figure 2 As shown in the figure, compared with the model group, the fluorescence intensity of Nile red in the glucosamine group was significantly weakened, indicating that the level of cellular lipid droplets in the glucosamine group was significantly reduced, which indicates that glucosamine reduces the lipid accumulation in hepatocytes caused by alcohol. * indicates P<0.05, ** indicates P<0.01, and *** indicates P<0.001.

[0140] Example 3 Glucosamine reduces free fatty acid-induced lipid accumulation in hepatocytes

[0141] To investigate the effect of glucosamine on free fatty acid-induced lipid accumulation in hepatocytes.

[0142] The experimental scheme is as follows: the experimental groups are divided into a blank group, a model group, a simvastatin group (1.56 μg / mL, positive drug) and a glucosamine group (100 μM). HepG2 cells were cultured normally for 12 h, and the positive drug and glucosamine stock solution were diluted with culture medium to the concentration to be tested. The cells were exposed to a mixture of free fatty acids for 24 h. The degree of cell lipid accumulation was detected by Nile red staining, and the cell nucleus was marked by DAPI staining. Nile red is a light-resistant, lipophilic fluorescent stain that emits strong fluorescence in a hydrophobic (lipid-rich) environment; DAPI, or 4',6-diamidino-2-phenylindole, is a fluorescent dye that can strongly bind to DNA and is often used to mark the cell nucleus. The data were summarized, and the fluorescence was quantified using Image J. The bar graph was drawn using Graph Pad, and the significant difference (t-test) was calculated.

[0143] Experimental results: Figure 3 As shown, compared with the model group, the cell Nile red fluorescence intensity in the glucosamine group was significantly weakened, indicating that glucosamine reduced the lipid accumulation of hepatocytes induced by free fatty acids. * indicates P<0.05, ** indicates P<0.01, and *** indicates P<0.001.

[0144] Example 4 Glucosamine improves oxidative stress damage in hepatocytes

[0145] To investigate the effect of glucosamine on alcohol-induced oxidative stress injury in hepatocytes.

[0146] The experimental scheme is as follows: the experimental groups are divided into a blank group, a model group, a metformin group (50 μM, positive drug) and a glucosamine group (100 μM). HepG2 cells were cultured normally for 12 hours, and the positive drug and glucosamine mother solution were diluted with culture medium to the concentration to be tested, and the corresponding test solution was added to each well. After incubation with the cells for 6 hours, alcohol modeling was performed. Except for the cells in the normal control group, the culture medium contained 350 mM ethanol solution and was incubated for 24 hours. After the modeling was completed, the SOD content was detected using the Biyuntian Total SOD Activity Detection Kit. The data were summarized, a bar graph was drawn using Graph Pad, and the significant difference (t-test) was calculated.

[0147] Experimental results: Figure 4 As shown in the figure, compared with the model group, the SOD enzyme activity in the glucosamine group was significantly increased, which indicates that glucosamine can improve alcohol-induced hepatocyte oxidative stress injury. * indicates P<0.05, ** indicates P<0.01, and *** indicates P<0.001.

[0148] Example 5 Glucosamine improves liver damage in mice with acute alcoholic liver damage model

[0149] To investigate the effect of glucosamine on improving liver damage in an acute alcoholic liver injury model at the animal level.

[0150] The experimental scheme is as follows: 6-week-old male ICR mice were selected and placed under specific pathogen-free feeding conditions. Metformin (Met) and glucosamine (GlcN) hydrochloride were dissolved in deionized water for administration. The experimental groups were divided into five groups, each with 10 mice, namely: blank group, alcohol group (model group), alcohol plus metformin group (100 mg / kg, Met-100), alcohol plus glucosamine group (250 mg / kg, GlcN-250) and alcohol plus glucosamine group (500 mg / kg, GlcN-500). The mice in the blank group received saline injection, while the mice in the other groups received alcohol gavage (5 g / kg), which was performed 0.5 hours after administration and continued for eight days. All mice were killed 9 hours after the last alcohol administration. Subsequently, the liver tissues were fixed and paraffin-embedded and sectioned, and stained using hematoxylin-eosin (H&E) staining. Blood was collected by enucleation to detect changes in serum transaminase (AST, ALT) levels, and liver tissue was taken to determine the levels of inflammatory factors (IL-1β, IL-6, and TNF-α) in serum and tissue. The data were summarized, a bar graph was drawn using Graph Pad, and significant differences were calculated (t-test).

[0151] Experimental results: Figure 5 As shown in Figure 2, compared with the model group, all glucosamine-treated groups significantly reduced the serum ALT ( Figure 5 A) and AST( Figure 5 E) levels. This result clearly indicates that glucosamine has a positive effect on improving ethanol-induced liver dysfunction, thereby exerting a liver protection effect. In addition, compared with the model group, the glucosamine administration group significantly reduced the inflammatory factor IL-1β ( Figure 5 B, Figure 5 F), IL-6 ( Figure 5 C, Figure 5 G) and TNF-α ( Figure 5 D, Figure 5 H). This finding further reveals the role of glucosamine in inhibiting inflammatory responses, suggesting that glucosamine helps alleviate inflammatory damage to the liver and promotes the recovery of liver function. * indicates P<0.05, ** indicates P<0.01, and *** indicates P<0.001.

[0152] like Figure 6As shown, the liver sections of mice in the model group showed fatty degeneration of hepatocytes, accompanied by mild ballooning. H&E staining showed that the size and number of lipid droplet vacuoles in the glucosamine (GlcN) administration group were significantly reduced. This indicates that glucosamine can reduce the fat accumulation in liver tissue caused by alcohol, thereby alleviating liver histological damage.

[0153] Example 6 Glucosamine improves liver damage in chronic alcoholic liver disease model mice

[0154] To investigate the effect of glucosamine on improving liver damage at the animal level in a chronic alcoholic liver disease model caused by long-term drinking.

[0155] The experimental scheme is as follows: 8-week-old male C57BL / 6J mice were housed under specific pathogen-free feeding conditions. Metformin and glucosamine hydrochloride were dissolved in deionized water for administration. Before the formal experiment, the mice were fed with ordinary solid feed for one week to adapt to the environment. The experimental groups were divided into five groups, each with 10 mice, namely: blank group, alcohol group (model group), alcohol plus metformin group (100 mg / kg, Met-100), alcohol plus glucosamine group (125 mg / kg, GlcN-125) and alcohol plus glucosamine group (250 mg / kg, GlcN-250). The blank group was fed with a control liquid feed without alcohol. The mice in the other groups began to be fed with a liquid feed containing 1% to 4% alcohol to adapt to this new diet. Starting from the 12th day, the mice in the drug group were gavaged with the corresponding drugs from 9:00 to 11:00 am every day, and the mice in the blank group and the model group were gavaged with the same volume of solvent. Every day from 3:00 to 5:00 pm, the liquid alcohol feed of the corresponding concentration was replaced. On the 40th day, the last alcohol gavage was performed at 9:00 am, and the mice were eyeballed and blood was collected at 18:00 pm. The mice were killed, and the liver was dissected and removed. The liver was fixed and paraffin-sectioned for H&E staining and Oil Red O staining. Transaminases (ALT, AST), albumin (ALB), triglycerides (TG), cholesterol (TC) and inflammatory factors (IL-1β, IL-6 and TNFα) were tested accordingly. The data were summarized, and a bar graph was drawn using Graph Pad, and the significant difference (t-test) was calculated.

[0156] Experimental results: Figure 7 As shown in the figure, the liver function indicators of the model group mice caused by long-term drinking were significantly abnormal, specifically ALT ( Figure 7 A) AST( Figure 7 B) ALB Figure 7C) significantly increased, while the glucosamine administration group significantly reduced the levels of ALT, AST, and ALB in serum. This shows that glucosamine can improve liver pathological indicators in this model, thereby playing a protective role in the liver. * indicates P<0.05, ** indicates P<0.01, and *** indicates P<0.001.

[0157] like Figure 8 As shown in Figure 2, compared with the alcohol group, glucosamine significantly reduced the levels of inflammatory factor IL-1β in liver tissue and serum ( Figure 8 A, Figure 8 D) IL-6 ( Figure 8 B, Figure 8 E) and TNFα ( Figure 8 C, Figure 8 F). This indicates that glucosamine can resist inflammatory damage in this model mouse and restore liver health. * indicates P<0.05, ** indicates P<0.01, and *** indicates P<0.001.

[0158] like Fig. 9 As shown in Figure 2, compared with the model group, glucosamine can significantly reduce the level of TG in liver tissue ( Fig. 9 A) TC content ( Fig. 9 B), which shows that glucosamine can reduce the lipid content of the liver; H&E staining ( Fig. 9 C) and Oil Red O staining showed ( Fig. 9 D), there was a large area of ​​lipid deposition in the liver tissue of the model group, and pathological phenomena such as intracytoplasmic fatty vesicles appeared in the liver cells. The number of lipid droplets in the glucosamine group was significantly reduced, and the area of ​​fatty vesicles was reduced, which showed that glucosamine could reduce lipid accumulation in the liver, effectively alleviate the damage to the liver in this model, and restore liver health. * indicates P<0.05, ** indicates P<0.01, and *** indicates P<0.001.

[0159] Example 7 Glucosamine improves liver aging in mice with acute alcoholic liver injury model

[0160] To investigate the effect of glucosamine on improving liver aging at the animal level under the acute alcoholic liver injury model.

[0161] The experimental scheme is as follows: 6-week-old male ICR mice were selected and placed under specific pathogen-free feeding conditions. Metformin and glucosamine hydrochloride were dissolved in deionized water for administration. The experimental groups were divided into five groups, each with 10 mice, namely: blank group, alcohol group, alcohol plus metformin group (100 mg / kg, Met-100), alcohol plus glucosamine group (250 mg / kg, GlcN-250) and alcohol plus glucosamine group (500 mg / kg, GlcN-500). The blank group mice received saline injection, while the other groups of mice received alcohol gavage (5 g / kg), which was performed 0.5 hours after administration and continued for eight days. All mice were killed 9 hours after the last alcohol administration. The contents of liver aging markers (p16, SA-β-gal) and aging-related secretory phenotype SASP (CXCL1, CXCL3, MMP-1, MMP-7) were detected. The data were summarized, histograms were drawn using Graph Pad, and significant differences were calculated (t-test).

[0162] Experimental results: Fig.10 As shown, compared with the alcohol group (model group), the glucosamine administration group significantly reduced the expression of p16 in mouse serum and liver tissue. p16 is a cell cycle inhibitor, and its increased expression is usually associated with cell senescence. This result suggests that glucosamine may inhibit the aging process of liver cells by regulating cell cycle-related signaling pathways.

[0163] like Fig.11 As shown by X-gal staining, in the acute alcoholic liver injury model, the positive rate of SA-β-gal in the liver of the model group mice increased significantly, and glucosamine significantly reduced the positive rate of SA-β-gal, indicating that glucosamine treatment can effectively slow down the aging process of liver cells; these data together indicate that glucosamine treatment can offset alcohol-related premature liver aging and delay liver aging. * indicates P<0.05, ** indicates P<0.01, and *** indicates P<0.001.

[0164] like Fig.12 As shown in Figure 2, the components of SASP in the liver and serum of mice under this model, including the pro-inflammatory factor CXCL1 ( Fig.12 A, Fig.12 E), CXCL3 ( Fig.12 B, Fig.12 F) and matrix metalloproteinase MMP-1 ( Fig.12 C, Fig.12 G) and MMP-7 ( Fig.12 D, Fig.12H) expression levels were significantly increased in the glucosamine group. In the glucosamine group, the expression of these pro-inflammatory factors was significantly reduced. This indicates that glucosamine can effectively inhibit the liver aging-related phenotype SASP, reduce the secretion of pro-inflammatory factors, thereby improving inflammatory aging and promoting the recovery of liver health. * indicates P < 0.05, ** indicates P < 0.01, and *** indicates P < 0.001.

[0165] Example 8 Glucosamine improves liver aging in chronic alcoholic liver disease model mice

[0166] To investigate the effect of glucosamine on improving liver aging at the animal level in a chronic alcoholic liver disease model caused by long-term drinking.

[0167] The experimental scheme was as follows: 8-week-old male C57BL / 6J mice were housed under specific pathogen-free housing conditions. Metformin (Met) and glucosamine (GlcN) hydrochloride were dissolved in deionized water for administration. Before the formal experiment, the mice were fed with ordinary solid feed for one week to adapt to the environment. The experimental groups were divided into five groups, each with 10 mice, namely: blank group, alcohol group, alcohol plus metformin group (100 mg / kg, Met-100), alcohol plus glucosamine group (125 mg / kg, GlcN-125) and alcohol plus glucosamine group (250 mg / kg, GlcN-250). The blank group was fed with a control liquid feed without alcohol. The mice in the other groups began to be fed with a liquid feed containing 1% to 4% alcohol to adapt to this new diet. Starting from the 12th day, the mice in the drug group were gavaged with the corresponding drugs from 9:00 to 11:00 am every day, and the mice in the blank group and the model group were gavaged with the same volume of solvent. Every day from 3:00 to 5:00 pm, the liquid alcohol feed of the corresponding concentration was replaced. On the 40th day, the last alcohol gavage was performed at 9:00 am, and the mice were killed after eyeball removal and blood collection at 18:00 pm. The contents of liver aging markers (γ-H2AX, p53, p16, SA-β-gal) and aging-related secretory phenotype SASP (CXCL1, CXCL3, MMP-1, MMP-7) were detected. The data were summarized, a bar graph was drawn using Graph Pad, and significant differences were calculated (t-test).

[0168] Experimental results: Fig.13 As shown in Figure 2, compared with the alcohol group (model group), the glucosamine group significantly reduced the expression of γ-H2AX ( Fig.13 B) p53( Fig.13C). γ-H2AX is a marker of DNA damage, while p53 is a tumor suppressor protein that also plays an important role in cellular stress and aging responses. These data suggest that glucosamine may slow down the aging process of liver cells by reducing DNA damage and regulating cellular stress responses.

[0169] like Fig.14 As shown, the glucosamine administration group significantly reduced the expression of p16 in mouse serum and liver tissue. As a cell cycle inhibitory protein, the upregulation of p16 expression is an important feature of cell senescence. The reduction of p16 expression by glucosamine further confirms its role in delaying liver cell senescence.

[0170] like Fig.15 As shown, glucosamine significantly reduced the positive rate of SA-β-gal, which is a widely recognized biomarker of cell aging. Increased SA-β-gal activity is usually associated with cell aging, and glucosamine can reduce its activity, indicating its potential anti-aging effect; Fig.15 B plots the positive rates of SA-β-gal in different groups. These results indicate that glucosamine can reduce the expression of liver aging markers in the chronic alcoholic liver disease model and play a role in delaying liver aging. * indicates P<0.05, ** indicates P<0.01, and *** indicates P<0.001.

[0171] like Fig.16 As shown, the expression of CXCL1 in the liver and serum of long-term alcoholic mice was Fig.16 A, Fig.16 E), CXCL3 ( Fig.16 B, Fig.16 F), MMP-1 ( Fig.16 C, Fig.16 G), MMP-7 ( Fig.16 D, Fig.16 H) expression levels were significantly increased. These molecules are part of SASP. They are secreted during cell aging and can promote inflammation and tissue destruction. After glucosamine treatment, the expression levels of these SASP-related indicators were observed to be significantly decreased. This shows that glucosamine can effectively inhibit the liver aging-related phenotype SASP, reduce the secretion of pro-inflammatory factors, thereby improving inflammatory aging and restoring liver health. * indicates P<0.05, ** indicates P<0.01, and *** indicates P<0.001.

[0172] Example 9 Glucosamine improves motor function in chronic alcoholic liver disease model mice

[0173] To investigate the effect of glucosamine on improving the motor function of mice at the animal level in a chronic alcoholic liver disease model caused by long-term drinking.

[0174] The experimental scheme was as follows: 8-week-old male C57BL / 6J mice were housed under specific pathogen-free housing conditions. Metformin and glucosamine hydrochloride were dissolved in deionized water for administration. Before the formal experiment, the mice were fed with ordinary solid feed for one week to adapt to the environment. The experimental groups were divided into four groups, each with 10 mice, namely: blank group, alcohol group, alcohol plus metformin group (100 mg / kg, Met-100), and alcohol plus glucosamine group (250 mg / kg, GlcN-250). The blank group was fed with a control liquid feed without alcohol. The mice in the other groups began to be fed with a liquid feed containing 1% to 4% alcohol to adapt to this new diet. Starting from the 12th day, the mice in the drug group were gavaged with the corresponding drugs from 9:00 to 11:00 am every day, and the mice in the blank group and the model group were gavaged with the same volume of solvent. The liquid alcohol feed of the corresponding concentration was replaced from 3:00 to 5:00 pm every day. On day 39, the experimental mice were placed on a grip strength tester and their tails were gently pulled to test the grip strength of their forelimbs. The data were summarized, a bar graph was drawn using Graph Pad, and significant differences were calculated (t-test).

[0175] Experimental results: Fig.17 As shown, mice that have been drinking alcohol for a long time showed a significant weakening in the grasping strength test, which reflects the negative effects of alcohol on the muscle strength and motor function of mice. However, after supplementing with glucosamine, the grasping strength of these mice was significantly enhanced, indicating that glucosamine has a positive effect on improving the motor function of mice. * indicates P<0.05, ** indicates P<0.01, and *** indicates P<0.001.

[0176] Example 10 Glucosamine improves liver disease and liver aging by activating the AMPK signaling pathway

[0177] In the chronic alcoholic liver disease model caused by long-term drinking, the mechanistic pathway of glucosamine in improving liver disease and liver aging was explored.

[0178] The experimental protocol was as follows: 8-week-old male C57BL / 6J mice were housed under specific pathogen-free housing conditions. Metformin and glucosamine hydrochloride were dissolved in deionized water for administration. Before the formal experiment, the mice were fed with ordinary solid feed for one week to adapt to the environment.

[0179] The experimental group was divided into four groups, with 10 mice in each group, namely: blank group, alcohol group (model group), alcohol plus glucosamine group (125 mg / kg, GlcN-125) and alcohol plus glucosamine group (250 mg / kg, GlcN-250). The blank group was fed with a control liquid feed without alcohol. The mice in the other groups began to be fed with a liquid feed containing 1% to 4% alcohol to adapt to this new diet. Starting from the 12th day, the mice in the drug group were gavaged with the corresponding drugs from 9:00 to 11:00 am every day, and the mice in the blank group and the model group were gavaged with the same volume of solvent. The liquid alcohol feed of the corresponding concentration was replaced from 3:00 to 5:00 pm every day. On the 40th day, the last alcohol gavage was performed at 9:00 am, and the mice were eyeballed and blood was collected at 18:00 pm. The mice were killed and the liver was taken. The liver samples were lysed and homogenized using RIPA, and the extracted proteins were quantified using the BCA protein quantification kit and adjusted to the same concentration. Proteins were separated by SDS-PAGE gel electrophoresis and transferred to 0.22 μm NC membranes. The membranes were then blocked with 5% skim milk powder for 2 h and treated with primary antibodies against GAPDH, AMPK, p-AMPK, ACC, p-ACC, p38, p-p38, SREBP1, and FAS at 4 °C overnight. Finally, the corresponding secondary antibodies were incubated to analyze protein expression. The data were summarized, histograms were drawn using Graph Pad, and significant differences (t-test) were calculated.

[0180] Experimental results: Fig.18 As shown, the liver p-AMPK ( Fig.18 B) and p-p38( Fig.18 C) The protein level was significantly lower than that of the control group, and glucosamine treatment significantly increased the expression of p-AMPK and p-p38. This indicates that glucosamine can activate the AMPK / p38 pathway in mice, thereby improving alcoholic liver damage aging.

[0181] like Fig.19 As shown in Figure 2, compared with the control group, the p-ACC level in the model group was significantly decreased, while glucosamine supplementation was able to significantly increase the p-ACC expression ( Fig.19 B). In contrast, SREBP-1c ( Fig.19 C) and FAS( Fig.19D) expression was significantly increased, while SREBP-1c and FAS protein levels were significantly decreased after glucosamine supplementation. This indicates that glucosamine regulates lipid metabolism in mice with chronic alcoholic liver disease by activating the AMPK / SREBP1 / FAS and AMPK / ACC pathways. The above results indicate that glucosamine can improve liver disease and liver aging by activating the AMPK signaling pathway. * indicates P<0.05, ** indicates P<0.01, and *** indicates P<0.001.

[0182] All documents mentioned in the present invention are cited as references in this application, just as each document is cited as reference individually. In addition, it should be understood that after reading the above teachings of the present invention, those skilled in the art can make various changes or modifications to the present invention, and these equivalent forms also fall within the scope defined by the claims attached to this application.

Claims

1. Use of glucosamine or a pharmaceutically acceptable salt thereof, characterized in that: Used for preparing functional foods, health products or medicines for treating and / or preventing liver diseases and / or liver aging.

2. The use according to claim 1, characterized in that The liver disease is selected from the group consisting of chemical liver injury, alcoholic liver disease, non-alcoholic fatty liver disease, metabolism-related fatty liver disease, or a combination thereof.

3. The use according to claim 1, characterized in that The liver disease is selected from the group consisting of fatty liver, hepatitis, liver damage, liver fibrosis, liver cirrhosis, or a combination thereof.

4. The use according to claim 1, characterized in that The liver aging is selected from the group consisting of liver aging caused by chemical-induced liver damage and liver aging caused by drinking alcohol.

5. The use according to claim 1, characterized in that For one or more uses selected from the following group: (a) Improve acute or chronic hepatocellular and liver damage; (b) Alleviate fatty degeneration or fat accumulation in hepatocytes or liver tissue; (c) reduce oxidative stress damage; (d) Eliminate liver senescent cells; (e) inhibiting the expression of liver aging markers; (f) inhibiting the expression of the senescence-associated secretory phenotype (SASP); (g) Improved athletic ability.

6. The use according to claim 1, characterized in that Glucosamine can activate AMPK-related signaling pathways and improve liver disease and / or liver aging.

7. The use according to claim 6, characterized in that The AMPK-related signaling pathway is selected from the following group: AMPK / SREBP1 / FAS, AMPK / ACC, AMPK / p38.

8. The use according to claim 1, characterized in that The glucosamine or a pharmaceutically acceptable salt thereof is used to prepare foods, functional foods, special medical foods, health products, nutrient supplements, dietary supplements or pharmaceutical compositions that have auxiliary protective effects on liver diseases and liver aging.

9. A pharmaceutical composition comprising: i) glucosamine or a pharmaceutically acceptable salt thereof as claimed in claim 1; as well as ii) a pharmaceutically acceptable carrier.

10. A method for treating and / or preventing liver disease and / or liver aging, characterized in that: The method comprises the steps of: administering glucosamine, or a pharmaceutically acceptable salt thereof, or the pharmaceutical composition as claimed in claim 9 to the subject.

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