CN116159048A - Application of fucoxanthin in preparation of medicine for treating NLRP3 induced liver cell apoptosis related diseases - Google Patents

Abstract

The invention relates to an application of fucoxanthin in preparing a medicament for treating NLRP3 induced liver cell apoptosis related diseases. Experimental research shows that fucoxanthin can directly target and inhibit NLRP3 inflammation corpuscle and reduce hepatocyte apoptosis and collagen deposition induced by NLRP3 inflammation corpuscle, thereby having protective effect on liver injury induced by NLRP3 inflammation corpuscle. The invention provides a new drug design scheme for treating liver cell apoptosis related diseases such as alcoholic liver disease, non-alcoholic liver disease, acute and chronic liver failure, viral hepatitis, liver cirrhosis, autoimmune liver disease, liver cancer and the like.

Description

Application of fucoxanthin in preparation of medicine for treating NLRP3 induced liver cell apoptosis related diseases

Technical Field

The invention relates to the technical field of natural medicines, in particular to application of fucoxanthin in preparing a medicine for treating NLRP3 induced liver cell apoptosis related diseases.

Background

Fucoxanthin is considered to be the most abundant natural carotenoid, accounting for about 10% of the total amount of carotenoids in nature. It is mainly present in large algae (such as brown algae, etc.) and microalgae (such as diatom, golden algae, etc.), and plays a key role in algae photosynthesis. The ingested fucoxanthin is hydrolyzed into fucoxanthin under the action of digestive enzymes (such as lipase and cholesterol esterase) in gastrointestinal tract, and then enters the systemic circulation through lymph, and part of fucoxanthin is degraded into Amarouciaxanthin A in liver. The fucose Huang Suchun and Amarouciaxanthin A are then further metabolized by enzymatic reactions such as isomerization, dehydrogenation, deacetylation, oxidation and demethylation. Studies have shown that fucoxanthin has a variety of biological properties and exhibits superior antioxidant effects over vitamin E and vitamin C. It can prevent the cytotoxic effect of the oxidizing agent and has the function of resisting UV-B radiation and DNA damaging factors. In addition, the research also proves that the fucoxanthin has the biological activities of anti-inflammatory, weight losing, anti-cancer and the like, and has potential therapeutic effects on various diseases.

Pyrodeath, also known as cell inflammatory necrosis, is a newly discovered apoptosis. The classical pathway of pyro-death has the molecular mechanism as follows: when the body is stimulated externally, the nucleotide binding oligomerization domain-like receptor protein 3 (nucleotide oligomerization domain-like receptor protein-3, NLRP 3) on the surface of the innate immune cells recognizes pathogen-related molecular patterns, causes NLRP3 oligomerization and binds to the caspase-associated speck-like protein containing a caspase-recruitment domain (ASC) containing focal apoptosis-related spot-like protein (caspase-associated speck-like protein containing a caspase-recruitment domain) to recruit caspasesThe precursor-1 (pre-caspase-1) assembles into NLRP3 inflammatory minibodies, which in turn activate caspase-1. Activated caspase-1 cleaves the substrate gasdermin D (GSDMD) into pore-forming active amino-terminal (GSDMD-N) that binds to the plasma membrane and forms large pores, which break cell permeation barrier, na ⁺ And water molecules enter the cell in large quantities, causing the cell to expand so that the cell membrane breaks; on the other hand, the cell content and inflammatory factors IL-1 beta and IL-18 are released, and the inflammatory reaction is promoted. Thus, NLRP3 inflammatory bodies are also known as focal apoptotic bodies. Studies have reported that activation of NLRP3 pyroptosomes can promote pyroapoptosis of hepatic parenchymal cells, and activation of hepatic stellate cells, thereby mediating liver injury and hepatic collagen fiber deposition, playing an important role in various liver diseases such as alcoholic liver disease, non-alcoholic fatty liver, viral hepatitis, liver cirrhosis, liver cancer, etc.

The liver serves as a metabolic hub in the human body and plays an important role in the metabolism of sugar, fat and proteins, and disorders of these metabolic functions can induce a range of liver diseases. Among them, lipid metabolism abnormality is one of the most common, and is commonly found in various chronic liver injury diseases, and is a key driving factor. The liver can transport excess triglycerides out of the liver via Very Low Density Lipoprotein (VLDL) form and store it as white fat. When the triglyceride content in the body is too high, the excessive triglyceride can enter a non-oxidative way to generate toxic lipid, and induce cell death. Metabolic abnormalities can also lead to increased synthesis and accumulation of cholesterol in the liver to form cholesterol crystals, inducing hepatocyte damage. In the above pathological process, focal death corpuscle NLRP3 is a key intermediate link. Both triglycerides and cholesterol activate the focal apoptotic body NLRP3 and induce the production of cytokines IL-1 beta and IL-18 leading to hepatocyte focal death. Studies have reported that in the liver of NLRP3 knock-in mice, significant scorching of hepatocytes occurs and the degree of inflammation and fibrosis is also greatly increased. Researchers have significantly reduced the extent of hepatocyte apoptosis following treatment with the IL-1 β inhibitor anakinra, but collagen deposition has not been significantly improved. Subsequently, a study found spontaneous hepatocyte coke death and collagen fiber precipitation in the liver of NLRP3 knock-in mice, and the use of Cycychalasin B significantly improved hepatic stellate cell activation and reduced IL-1 beta and alpha-SMA protein expression levels. In contrast, in NLRP3 knockout mice, the deletion of NLRP3 may protect the mouse liver from diet-induced steatohepatitis. In addition, the NLRP3 specific inhibitor MCC950 can reduce the expression level of IL-1 beta in liver and circulation of mice with metabolic syndrome and block the conversion of the mice to nonalcoholic hepatitis. It can be seen that the liver cell apoptosis induced by NLRP3 pyroptosis is an important driving factor in the occurrence and development of various chronic liver diseases. With the changes of the living environment and the dietary structure of human beings, the prevalence of liver diseases is increasing as a metabolic center in the human body. According to the statistics of 2021 world health statistics report, about 3.5 hundred million people suffer from liver diseases worldwide, and about 100 ten thousand people die from liver diseases every year. The sanitary expenditure associated with liver diseases brings great burden to the economic development, so the prevention and treatment of liver diseases are serious and far away. As described above, there is increasing evidence that NLRP 3-induced hepatocyte coke apoptosis plays an important driving role in various liver diseases, including alcoholic fatty liver, non-alcoholic fatty liver, acute and chronic liver failure, viral hepatitis, autoimmune liver disease, and hepatocellular carcinoma, etc.

Targeted inhibition of focal death is a promising therapeutic approach for liver disease, and has received extensive attention from researchers and clinicians worldwide. However, currently, clinically, there is no positively therapeutic drug for most liver diseases such as non-alcoholic fatty liver, liver fibrosis, etc. Fucoxanthin is taken as a natural component, has few side effects, and some researches at present disclose that the fucoxanthin has biological activities of resisting oxidation, preventing cytotoxicity of an oxidant, resisting UV-B radiation, resisting inflammation, losing weight, resisting cancer and the like, but the biological activity of Guan Yanzao flavins for reducing the apoptosis of hepatic cells by inhibiting NLRP3 pyrosis corpuscles is not yet reported.

Disclosure of Invention

First, the technical problem to be solved

In view of the above-mentioned shortcomings and drawbacks of the prior art, the present invention proposes the use of fucoxanthin in the preparation of a medicament for treating liver diseases associated with NLRP3 induced hepatocyte coke death. Experiments prove that the fucoxanthin has the activity of regulating and controlling the upstream signal channel of the pyrosis to reduce the pyrosis of liver cells, especially reduces the pyrosis of liver cells by inhibiting NLRP3 pyrosis corpuscles, can play a good therapeutic role in liver diseases related to the pyrosis of liver cells induced by NLRP3, and provides a new drug design scheme with positive therapeutic effect for the treatment of liver diseases.

(II) technical scheme

In order to achieve the above purpose, the main technical scheme adopted by the invention comprises the following steps:

use of fucoxanthin in the preparation of a medicament for treating NLRP3 induced liver cell apoptosis related diseases.

Preferably, the NLRP3 induced liver cell apoptosis-related diseases include, but are not limited to: alcoholic liver disease, non-alcoholic liver disease, acute and chronic liver failure, viral hepatitis, cirrhosis, autoimmune liver disease, and hepatocellular carcinoma.

Preferably, the NLRP 3-induced hepatocyte coke death-related disease comprises a hepatocoke death-related disease induced by lipotoxicity.

Preferably, the liver cells are treated in 0.25-2.5. Mu. Mol/L fucoxanthin.

(III) beneficial effects

According to the experiment provided by the invention, fucoxanthin can directly inhibit NLRP3 inflammation corpuscle in a targeted manner and reduce hepatocyte apoptosis and collagen deposition induced by the NLRP3 inflammation corpuscle, so that the fucoxanthin has a protective effect on liver injury induced by the NLRP3 inflammation corpuscle. The invention provides a new drug design scheme for treating liver cell apoptosis related diseases such as alcoholic liver disease, non-alcoholic liver disease, acute and chronic liver failure, viral hepatitis, liver cirrhosis, autoimmune liver disease, liver cancer and the like. Fucoxanthin is used as a natural compound, has no immunogenicity, has no anaphylactic reaction and no off-target effect, can replace or partially replace hepatopathy treatment medicines, and reduces the use amount of antibody hepatopathy medicines and side effects thereof. Therefore, the fucoxanthin has good application prospect in the future treatment of the liver diseases related to the scorch.

Drawings

FIG. 1 is a graph showing the experimental results of fucoxanthin decreasing activation of focal apoptotic bodies NLRP3 in the liver; wherein A: the result of western blot detection of the expression level of the focal death small NLRP3 related protein in liver tissue; B-E: quantitative analysis of expression levels of NLRP3, caspase-1, IL-1 beta, IL-18 proteins in liver tissues of each treatment group (< 0.05 p, n=4).

FIG. 2 is an experimental result of fucoxanthin to reduce lipid toxicity induced apoptosis of hepatocytes; wherein, A is the TUNEL staining result of the liver tissue section; quantitative analysis of TUNEL staining of liver tissue sections of each treatment group (×p <0.05, n=4).

FIG. 3 is an experimental result of fucoxanthin in reducing liver collagen deposition by inhibiting NLRP3, wherein A is a masson stain of liver tissue sections of each treatment group; quantitative analysis of the volume fraction of masson stained Collagen (CVF) of liver tissue for each treatment group (# p <0.05, n=4).

FIG. 4 is an experimental result of oleic acid treated hepatocyte oil red O staining; wherein A: oil red staining pictures of liver cells of each treatment group; b: oil red staining positive area statistics (x # # p <0.05, n=4) in hepatocytes of each treatment group.

FIG. 5 is a graph showing experimental results of fucoxanthin effective to inhibit liver enzyme elevation; wherein A: statistical plots of changes in glutamate pyruvate transaminase (ALT) levels in liver tissues of each treatment group; b: statistical plots of changes in glutamate oxaloacetate transaminase (AST) levels in liver tissue of each treatment group (t# # p <0.05, n=4).

FIG. 6 shows the results of an experiment in which fucoxanthin increases the protein and glycogen content in the liver; a, double staining of liver tissue slices PAS-naphtholsulfonic acid S, and staining glycogen and protein in the liver slices of each treatment group to detect the relative content; b, relatively quantifying the content of the dyed protein in the liver tissue slice; liver tissue section staining glycogen is relatively quantified; BCA assay detects protein concentration in liver tissue (< p 0.05, n=4).

Detailed Description

The invention will be better explained by the following detailed description of the embodiments with reference to the drawings.

1. Preparation work and experimental method

1. Fucoxanthin source

Fucoxanthin (HPLC > 90% purity) was extracted from large scale cultured marine diatom phaeodactylum tricornutum, offered by the company de merter biotechnology (zhuhai) limited.

2. Cell and animal experimental grouping:

(1) Cell experiment grouping: the primary mouse liver cells are adopted, oleic acid is used for intervention, and the specific grouping is as follows:

CTL group: blank control group: culturing liver cells normally for 72 hours without any treatment;

OA group: oleic acid stimulation group: culturing for 24 hours without any treatment, and further stimulating for 48 hours with 200 mu mol/l oleic acid;

oa+0.01FU group: firstly, 0.01 mu mol/L of fucose Huang Suyu is treated for 24 hours, and then 200 mu mol/L of oleic acid is stimulated for 48 hours;

oa+0.05FU group: firstly, 0.05 mu mol/L of fucose Huang Suyu is treated for 24 hours, and then 200 mu mol/L of oleic acid is stimulated for 48 hours;

oa+0.25FU group: treatment with 0.25. Mu. Mol/L fucose Huang Suyu was performed for 24h, followed by stimulation with 200. Mu. Mol/L oleic acid for 48h;

oa+1.25FU group: first, 1.25 mu mol/L of fucose Huang Suyu is treated for 24 hours, and then 200 mu mol/L of oleic acid is stimulated for 48 hours;

oa+2.5fu group: treatment with 2.5. Mu. Mol/L fucose Huang Suyu was performed for 24h, followed by stimulation with 200. Mu. Mol/L oleic acid for 48h;

oa+5fu group: treatment was performed for 24h with 5. Mu. Mol/L fucose Huang Suyu followed by stimulation with 200. Mu. Mol/L oleic acid for 48h.

(2) Animal experiment group:

according to the effective concentration of fucoxanthin under action, which is explored by cell experiments, 18C 57BL/6 normal mice and 54 ApoE-/-gene mice (purchased from Vermilion laboratory animal technologies Co., ltd. (Beijing)) are grouped as follows (18 mice per group);

group A: c57BL/6 normal mice+normal diet;

group B: apoE-/-mice+high fat diet;

group C: apoE-/- + high fat diet + DMSO (equivalent DMSO solvent to fucose Huang Suzu) gavage control;

group D: apoE-/- + high fat diet + fucoxanthin (0.0018 mg/d) intragastric group (calculated as 20g per mouse body weight and scaled up with increasing body weight);

group E: apoE-/- + high fat diet + fucoxanthin (0.018 mg/d) gavage group (calculated as 20g per mouse body weight and scaled up with increasing body weight).

3. Animal model construction

The experimental protocol was approved by the university of martial arts animal experiment center (martial arts) ethics committee. The specific experimental scheme is as follows: all mice were fed adaptively for one week after entering a protective environment without specific pathogens and normal feed was fed for one week. Group a continued whole course normal feed feeding (abbreviated as blank control); after the group B common feed feeding is finished, high-fat feed feeding is carried out until the experiment is finished (short for high-fat control); after the group C adaptive feeding is finished, the high-fat feed is fed and simultaneously the gastric lavage treatment with the same dose of DMSO (within a safe dosage range) as that of the fucose Huang Suzu is carried out until the experiment is finished (for short, saline control); after the group D adaptive feeding is finished, high-fat feed feeding is carried out, and 0.0018mg/D fucoxanthin (dissolved in physiological saline containing DMSO at the same dosage as the group C) is subjected to gastric lavage treatment until the experiment is finished (abbreviated as low-dosage FU); after the end of the group E adaptive feeding, the high-fat feed was fed, and the gastric lavage treatment was performed with 0.018mg/d fucoxanthin (dissolved in DMSO-containing physiological saline at the same dose as the group C) until the end of the experiment (abbreviated as high dose FU).

4. Experimental material selection and detection:

a. after the cell experiment modeling is completed, fixing cells by paraformaldehyde, and dyeing by oil red;

b. every 4 weeks, 6 mice in each group are randomly taken, euthanized and sampled, and liver functions are checked by blood sampling;

c. collecting liver specimen, preparing pathological section, and performing Pinus massoniana staining and TUNEL staining detection

Measuring liver collagen deposition and liver cell coke death degree;

d. liver specimens are collected, relevant protein detection is carried out, and a specific molecular mechanism of fucoxanthin playing a role is explored.

2. Experimental results

1. Fucoxanthin reduces hepatocyte pyroapoptosis by targeted inhibition of NLRP3 pyroptosis corpuscles

Protein expression levels were assessed by detecting focal apoptotic body NLPR3 and its downstream signaling proteins in liver tissue of each treatment group. The experimental results are shown in FIG. 1.

FIG. 1A shows the result of western blot detection of the expression level of a focal death receptor NLRP3 related protein in liver tissue; B-E: quantitative analysis of expression levels of NLRP3, caspase-1, IL-1 beta, IL-18 proteins in liver tissues of each treatment group (< 0.05 p, n=4). As shown by the experimental results, compared with the blank control group, the expression or activation level of the focal death small NLRP3 and the downstream signal proteins (Caspase-1, IL-1 beta, IL-18 and other proteins) thereof in the liver tissues of the mice with simple high-fat diet (high-fat control and saline control) is obviously increased; and the expression or activation level of the focal death corpuscle NLRP3 and the downstream signal proteins (Caspase-1, IL-1 beta, IL-18 and other proteins) in the low dose FU and the high dose FU groups is obviously reduced.

As a result of the above experiment, when the experimental mice were fed with a high-fat feed while being subjected to gastric treatment with fucose Huang Suguan, the expression of focal death corpuscles NLRP3 and its downstream signaling proteins (Caspase-1, IL-1 β, IL-18, etc.) was significantly inhibited in liver cells of the mice, thereby confirming that fucoxanthin could target-inhibit the focal death corpuscles of NLRP3 and further alleviate the focal death level of liver cells induced by NLRP 3. NLRP 3-induced hepatocyte coke apoptosis is known to play an important driving role in various liver diseases, thus demonstrating that fucoxanthin can be used to treat NLRP 3-induced hepatocyte coke apoptosis-related diseases. In the above experiments, no significant difference was seen between the low dose group and the high dose group.

2. Fucoxanthin targeted inhibition of NLRP3 to mitigate lipotoxicity-induced hepatocyte coke death

The experiments further performed TUNEL staining and quantitative analysis of liver tissue from each treatment group. The experimental results are shown in FIG. 2.

FIG. 2A is a fluorescence photograph of TUNEL staining results of liver tissue sections; fig. 2B is a quantitative analysis of TUNEL staining of liver tissue sections of each treatment group (×p <0.05, n=4).

The results showed that the high-fat control group had the highest number of TUNEL-stained positive cells, followed by the saline control group, which also had a higher number of TUNEL-stained positive cells. The number of TUNEL-stained positive cells in the low-dose FU and high-dose FU groups was significantly lower than that in the high-fat control and saline control groups, and especially the low-dose FU groups had the lowest number of TUNEL-stained positive cells. Thus, the high-fat diet obviously increases the number of the mouse liver cells TUNEL staining positive cells, and the number of the TUNEL positive cells is obviously reduced after the fucoxanthin is treated, thus proving that the fucoxanthin can reduce the level of hepatocoke death induced by lipotoxicity. And as can be seen from fig. 2B, low dose FU reduced lipid toxicity induced levels of hepatocyte coke death better than high dose FU.

3. Fucoxanthin reduces liver collagen deposition by inhibiting NLRP3

In a variety of chronic liver diseases, NLRP3 focal apoptotic body activation stimulates hepatic stellate cell synthesis and secretion of collagen fibers. In the experiments, the protective effect of fucoxanthin on liver fibrosis was evaluated by masson staining liver tissue and calculating the collagen volume fraction. The experimental results are shown in FIG. 3.

FIG. 3A is a schematic representation of the masson staining of liver tissue sections from each treatment group; fig. 3B shows the results of quantitative analysis of the masson stained Collagen Volume Fraction (CVF) of liver tissue for each treatment group (# p <0.05, n=4). The gray (left) bars in fig. 3B are 8 weeks of feeding and gavage treatment of mice, and the black (right) bars are statistics of 12 weeks of feeding and gavage treatment of mice. Wherein, the volume fraction of collagen CVF% in liver tissue of the high-fat control group mice is highest, and the control group is followed by saline. The collagen volume fraction CVF% was significantly lower in liver tissue of low-dose FU and high-dose FU groups of mice. From this, it is demonstrated that high-fat diet causes collagen fibrous hyperplasia of liver tissue, the volume fraction of collagen CVF% increases, and the degree of fibrosis increases; the liver fibrosis of the mice treated with fucoxanthin was significantly improved, and the therapeutic effect of the low dose group (low dose FU group) was better than that of the high dose group (high dose FU group), indicating that fucoxanthin was not in a positive linear relationship with the dose.

4. Determination of optimal fucoxanthin intervention concentration

In the experiment, the primary liver cells are treated for 24 hours by using the fucose Huang Suyu with different concentrations, then oleic acid with the final concentration of 200 mu mol/L is added into a culture system to stimulate the liver cells for 48 hours, and the accumulation degree of fatty acid is estimated by oil red staining, so that the proper concentration of fucoxanthin for playing a role is explored. The experimental results are shown in FIG. 4.

FIG. 4A is a photograph of oil red staining of hepatocytes of different concentration treatment groups; b: statistical plot of oil red staining positive area in hepatocytes for different concentration treatment groups (= # # p <0.05, n=4)

As can be seen from the figure, the blank (CTL group: normal cultured hepatocytes for 72 hours, without any treatment) had the lowest area of red staining positive with oil, followed by sequentially increasing the area of red staining positive with oil by OA+1.25FU (1.25. Mu. Mol/L for Huang Suyu hours, 200. Mu. Mol/L for 48 hours), OA+0.25FU (0.25. Mu. Mol/L for Huang Suyu hours, 200. Mu. Mol/L for 48 hours), OA+2.5FU (2.5. Mu. Mol/L for Huang Suyu hours, 200. Mu. Mol/L for 48 hours), OA+0.05FU (0.05. Mu. Mol/L for Huang Suyu hours, 200. Mu. Mol/L for 48 hours), OA+0.01FU (0.01. Mu. Mol/L for Huang Suyu hours, 200. Mu. Mol/L for 48 hours), and so on, respectively, with oil by increasing the area of red staining positive with oil by OA+5.5FU (2.5. Mu. Mol/L for Huang Suyu hours, 200. Mu. Mol/L for 24 hours).

Thus, it is demonstrated that fucoxanthin can improve oleic acid-induced liver steatosis at lower dosage ranges. Moreover, the improvement effect of fucoxanthin FU on oleic acid-induced hepatic steatosis and the fucoxanthin treatment dose are not in a forward linear relationship or a reverse linear relationship, but have remarkable effect in the concentration range of 0.25 to 2.5 mu mol/L, and are especially optimal in the concentration range of 1.25 mu mol/L. The method provides technical support for the design of the liver disease treatment medicine taking fucoxanthin as the medicine active ingredient.

5. Fucoxanthin can effectively inhibit liver enzyme elevation

During the experimental process, the influence of fucoxanthin on the liver is detected by detecting the levels of glutamic pyruvic transaminase ALT and glutamic oxaloacetic transaminase AST in serum. The experimental results are shown in FIG. 5.

FIG. 5A is a statistical plot of changes in glutamate pyruvate transaminase (ALT) levels in liver tissue of various treatment groups (blank, high fat control, saline control, low dose FU and high dose FU); fig. 5B is a statistical plot of changes in glutamate oxaloacetate transaminase (AST) levels in liver tissue of each treatment group (t# ×p <0.05, n=4). Wherein the left to right bar graphs in each group correspond to statistics of feeding and intragastric treatments for 1 month, 2 months and 3 months in sequence. The results in FIGS. 5A and 5B show that both ALT and AST (U/L) were higher in the serum of mice from the high fat control and saline control groups, and lower in the other groups. This demonstrates that high fat diets lead to elevated levels of ALT and AST in the serum of mice and that the levels gradually increase with time of molding, but that ALT and AST in the serum of low-and high-dose FU groups of mice treated with fucoxanthin FU by gavage were significantly reduced with high fat diets. These experimental results demonstrate that fucoxanthin can effectively inhibit liver enzyme elevation, i.e., fucoxanthin can significantly improve and alleviate liver injury problems. Wherein, the improvement effect of the low-dose FU is better than that of the high-dose FU group, which indicates that the protective effect of the fucoxanthin on the liver is not in positive linear relation with the dosage of the fucoxanthin. This is consistent with previous experimental findings.

6. Fucoxanthin can increase protein and glycogen content in liver

During the experiment, PAS-naphtholsulfons double staining was performed on liver sections of each treatment group (blank control, high fat control, saline control, low dose FU and high dose FU), relative quantitative analysis was performed on proteins and glycogen in liver tissue, and further absolute quantitative analysis was performed using BCA (bicinchoninic acid) method. The experimental results are shown in FIG. 6.

FIG. 6A is a graph showing PAS-naphtholsulfonic acid S double staining of liver tissue sections, relative amounts of glycogen and protein in each treatment group liver section were measured by staining; FIG. 6B is a relative quantification of stained protein content of liver tissue sections; FIG. 6C is a relative quantification of glycogen stained liver tissue sections; panel D shows protein concentration in liver tissue detected by BCA method (p <0.05, n=4).

As can be seen from the illustration, the relative liver tissue protein content, glycogen content and BCA method protein concentration of the high-fat control group and the saline control group are low, while the relative liver tissue protein content, glycogen content and BCA method protein concentration of the low-dose FU group and the high-dose FU group are high, and especially the low-dose FU group is low. Thus, it is demonstrated that the protein and glycogen content of the diet fed with a simple high fat diet is reduced relative to the normal diet, and that the protein and glycogen content of the intervention group given with low concentrations of fucoxanthin is significantly increased, whereas the effect of the high dose group is rather lower than that of the group with low dose FU.

In conclusion, the low-dose FU not only reduces the death of liver cell coke by targeted inhibition of NLRP3 coke death corpuscle and reduces liver injury and liver diseases caused by cell coke death, but also can increase the protein and glycogen content in the liver by intervention of the low-dose FU, thereby effectively protecting the liver.

Finally, it should be noted that: the above embodiments are only for illustrating the technical solution of the present invention, and not for limiting the same; although the invention has been described in detail with reference to the foregoing embodiments, it will be understood by those of ordinary skill in the art that: the technical scheme described in the foregoing embodiments can be modified or some or all of the technical features thereof can be replaced by equivalents; such modifications and substitutions do not depart from the spirit of the invention.

Claims (3)

1. Use of fucoxanthin in the preparation of a medicament for treating NLRP3 induced liver cell apoptosis related diseases.

2. The use according to claim 1, wherein the NLRP3 induced hepatocyte focal death-related disease comprises, but is not limited to: alcoholic liver disease, non-alcoholic liver disease, acute and chronic liver failure, viral hepatitis, cirrhosis, autoimmune liver disease, and hepatocellular carcinoma.

3. The use according to claim 1, wherein the NLRP3 induced hepatocyte coke death-related disease comprises a hepatocoke death-related disease induced by lipotoxicity.

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