Application of alnulone and analogue thereof in prevention and treatment of fatty liver disease

Abstract

The invention belongs to the technical field of biological medicines, and provides application of alnulone and analogues thereof in prevention and treatment of fatty liver diseases and auxiliary blood fat reduction. The invention also provides a composition for treating fatty liver diseases or assisting in reducing blood fat. The composition comprises an effective dose of alnulone and analogues thereof. The alnnulone and the analogue thereof provided by the invention have the effects of reducing blood triglyceride and liver triglyceride and reversing liver fatty degeneration in vivo, can improve liver fibrosis and inflammation symptoms of a mouse with steatohepatitis, and are good in safety, free of toxic and side effects and free of toxic and side effects. The compound can be used for preparing medicines for preventing and treating fatty liver diseases, steatohepatitis and related diseases.

Description

Technical Field

[0001] The invention belongs to the technical field of biomedicine, and specifically relates to an application of alnus ketone in the prevention and treatment of fatty liver disease. Background Art

[0002] The disclosure of this background information is intended to enhance understanding of the general background of the invention and should not necessarily be taken as an acknowledgment or any form of suggestion that this information constitutes the prior art already known to a person skilled in the art.

[0003] With the dramatic changes in modern people's eating habits and lifestyles, metabolic dysfunction-associated fatty liver disease (MASLD), also known as non-alcoholic fatty liver disease (NAFLD) or metabolic-associated fatty liver disease (MAFLD), has become the most common chronic liver disease and a global health problem. Its prevalence and incidence are increasing, especially in my country. This type of fatty liver disease includes a series of liver diseases including simple steatosis, steatohepatitis and its related liver fibrosis and cirrhosis. Metabolic dysfunction-associated fatty liver disease (MASH), also known as non-alcoholic steatohepatitis (NASH) or metabolic-associated fatty liver disease, is a severe form of fatty liver disease, which can further develop into advanced fibrosis, cirrhosis, hepatocellular carcinoma, and ultimately lead to liver-related death. In fact, MASLD is becoming the leading cause of liver failure and liver transplantation in the coming decades, resulting in huge medical costs each year. With its increasing incidence and severe impact, fatty liver disease will continue to cause a heavy health and socioeconomic burden worldwide.

[0004] Despite this, there are very few therapeutic drugs for the above-mentioned fatty liver disease, especially effective drugs for reversing liver fibrosis. In existing clinical studies, ursodeoxycholic acid can only improve biochemical indicators of liver function, but cannot relieve fatty liver hepatitis. Although obeticholic acid, another commonly used drug, farnesoid X receptor agonist, has the effect of alleviating liver fibrosis, adverse reactions such as itching and dyslipidemia have hindered its clinical approval. So far, only one drug, liver-selective thyroxine receptor β agonist, has been approved for the clinical treatment of MASH with fibrosis. Therefore, there is an urgent need to discover more effective and safe drugs to cope with the increasing burden of fatty liver disease.

[0005] Natural products have many advantages in the prevention and treatment of various diseases due to their wide sources, broad therapeutic spectrum, and high safety. Alnus ketone is a non-phenolic diarylheptane and a natural active product derived from the Chinese medicinal herb cardamom. Previous studies have found that alnus ketone has anti-tumor and antibacterial activities. In the prior art, related medical uses of alnus ketone are also disclosed: CN116019792A The use of alnus ketone in inhibiting and treating gastric cancer discloses that alnus ketone inhibits the proliferation of undifferentiated gastric cancer cells HGC-27. CN115364080A The use of alnus ketone in the preparation of drugs for the prevention and treatment of glucose metabolism disorders discloses the use of alnus ketone in the preparation of drugs for glucose metabolism disorders. CN117159514A Application of alnus ketone in the preparation of drugs for preventing or treating atopic dermatitis, discloses the application of alnus ketone in the preparation of drugs for atopic dermatitis, and the combined application of alnus ketone and other drugs for atopic dermatitis. CN118217267A Application of alnus ketone or its derivatives in the preparation of drugs for treating thrombocytopenia, discloses the application of alnus ketone or its derivatives in the preparation of drugs for treating thrombocytopenia. Alnus ketone has no effect on the cell viability of megakaryocytes in vitro, and is safer to use. It has a certain activity in promoting differentiation, maturation and proplatelet production of megakaryocytes in vitro. However, whether this compound has a preventive and therapeutic effect in fatty liver disease, fatty hepatitis and related liver diseases has not been reported before. Summary of the invention

[0006] In order to find drugs or drug lead compounds that can be used for metabolic liver diseases such as fatty liver disease and fatty liver hepatitis, the present invention provides a new medical application of alder ketone, which can improve liver fatty degeneration, fibrosis and inflammation, and is used for the prevention and treatment of fatty liver disease.

[0007] To achieve the above purpose, the present invention adopts the following technical solution.

[0008] A use of a linear diarylheptane compound and its derivatives in preparing a drug for treating and preventing fatty liver disease.

[0009] A use of a linear diarylheptane compound and a derivative thereof in the preparation of a health product for assisting in lowering blood lipids.

[0010] The structural formula of the linear diarylheptane compound is: , Wherein, R1, R2, R3, and R4 are independently selected from -H, -OH, and -OCH3.

[0011] Preferably, the compound is selected from: Compound 1: (Alderone); Compound 2: ; Compound 3: ;or, Compound 4: (Tsaokoarylone).

[0012] The derivatives of the linear diarylheptane compounds are physiologically acceptable salts formed by the linear diarylheptane compounds and inorganic bases or organic bases, including but not limited to alkali metal salts, alkaline earth metal salts, ammonium salts, and salts formed with nitrogen-containing organic bases, such as sodium salts, potassium salts, calcium salts, and magnesium salts. The nitrogen-containing organic bases are not limited to procaine, trimethylamine, triethylamine, tributylamine, pyridine, N,N-dimethylaniline, N-methylpiperidine, N-methylmorpholine, diethylamine, dicyclohexylamine, dibenzylamine, N-benzyl-β-phenethylamine, and N,N'-dibenzylethylenediamine.

[0013] The derivative is a physiologically acceptable ester formed by the linear diarylheptane compound and an inorganic acid or an organic acid; the inorganic acid is selected from sulfuric acid, phosphoric acid, carbonic acid, and hydrochloric acid; the organic acid is selected from formic acid, acetic acid, propionic acid, butyric acid, maleic acid, oxalic acid, methanesulfonic acid, succinic acid or fatty acid.

[0014] The linear diarylheptane compound can be obtained by chemical synthesis or biological extraction. Preferably, the biological extraction source is selected from cardamom, alnus sibiricum, turmeric, tsaoko and the like.

[0015] The diseases include, but are not limited to, metabolic dysfunction-associated fatty liver disease, metabolic-related fatty liver disease, non-alcoholic fatty liver disease, alcoholic fatty liver disease, metabolic dysfunction-associated fatty liver disease, metabolic-related fatty liver disease, non-alcoholic fatty liver disease, alcoholic fatty liver disease, liver fibrosis and the resulting cirrhosis.

[0016] A composition for treating fatty liver disease or assisting in lowering blood lipids, comprising an effective dose of linear diarylheptane compounds and their derivatives, plants containing linear diarylheptane compounds and their derivatives, or plant extracts containing linear diarylheptane compounds and their derivatives.

[0017] Preferably, the plant containing linear diarylheptane compounds is selected from the group consisting of Alnus fragrans, Alnus truncatus, Curcuma longa and Amomum villosum.

[0018] The above composition can be prepared according to methods well known in the art or disclosed in the prior art.

[0019] The above composition also includes pharmaceutically or food acceptable excipients for preparing the active ingredients into any dosage form suitable for human or animal use. Preferably, the composition can be taken in the form of an oral preparation or an injection preparation. In order to facilitate medication, the composition can also be prepared into a sustained release preparation or a controlled release preparation. The above oral preparations include tablets, capsules, granules, oral liquids or syrups.

[0020] The present invention has the following advantages: The present invention has experimentally confirmed that alnus ketone has the effects of reducing blood triglycerides and liver triglycerides, reversing liver fatty degeneration in vivo, and improving liver fibrosis and inflammatory symptoms in mice with fatty liver hepatitis, and has good safety and no toxic side effects, and can be used to prepare preventive and therapeutic drugs for fatty liver disease, fatty liver hepatitis and related diseases. BRIEF DESCRIPTION OF THE DRAWINGS

[0021] Figure 1 Serum triglyceride levels in mice with fatty liver disease after treatment with control solvent and alderone; Figure 2 Hepatic triglyceride levels in mice with fatty liver disease treated with control solvent and alderone; Figure 3 The liver histological morphology of fatty liver disease mice treated with control solvent and alderone was HE staining, Oil Red O staining and Masson staining; Figure 4 The quantitative levels of lipid droplets and vacuoles in liver histology, the quantitative levels of lipids by Oil Red O staining, and the quantitative levels of fibrosis by Masson staining in mice with fatty liver disease treated with control solvent and alderone; Figure 5 Serum triglyceride levels in mice with steatohepatitis treated with control solvent and alderone; Figure 6 Hepatic triglyceride levels in mice with steatohepatitis treated with control solvent and alderone; Figure 7 The liver histological morphology of mice with fatty liver hepatitis treated with control solvent and alderone was HE staining, Oil Red O staining and Masson staining. Figure 8 The quantitative levels of lipid droplet vacuoles, lipid quantification by Oil Red O staining, and fibrosis quantification by Masson staining in liver histology of mice with steatohepatitis treated with control solvent and alderone; Fig. 9 The expression levels of inflammatory factors in the liver of mice with steatohepatitis treated with control solvent and alderone; Fig.10 The body weights of mice after treatment with control solvent and alderone. DETAILED DESCRIPTION

[0022] The present invention is further described below in conjunction with the examples and drawings, but the present invention is not limited by the following examples. It can be confirmed through experiments that compounds 1-4 can improve the blood lipid and liver fat levels of mice with fatty liver disease, reverse liver fatty degeneration and alleviate liver fibrosis in mice with fatty liver disease. Taking compound 1 (alderone) as an example, the research process is specifically described. Compound 1 (alderone) used in the example is purchased from commercial channels, and the HPLC purity is not less than 98%.

[0023] Example 1 Alnus ketone improves blood lipid and liver lipid levels and reverses liver fatty degeneration in mice with fatty liver disease 1. Construction of animal model of fatty liver disease Wild-type C57BL / 6J mice (purchased from Beijing Weitong Lihua Company) were fed a high-fat diet (60% fat, Research Diet) from 8 weeks of age and continued for 12 weeks. Mice fed with this high-fat diet can develop metabolic damage phenotypes such as obesity, increased blood lipid levels, liver lipid accumulation and fatty degeneration, and are a commonly used mouse model of fatty liver disease.

[0024] 2. Alnus ketone dosing regimen Mice with fatty liver disease were randomly divided into two groups: the alderone group: alderone powder (purchased from Shanghai Taoshu Biotechnology Co., Ltd.) was dissolved in corn oil containing 5% DMSO, and C57 mice were intraperitoneally injected at a dose of 10 mg / kg every day; the control group: the same model mice were intraperitoneally injected with the same dose of corn oil solvent containing 5% DMSO every day. After two weeks of administration, samples were collected to observe the treatment results of alderone on mice with fatty liver disease.

[0025] 3. Triglyceride content detection (1) Serum: After continuous intraperitoneal injection of alderone for 14 days, mice with fatty liver disease were fasted for 6 hours and blood was collected. Serum was collected by centrifugation at 3000 rpm for 15 minutes at 4°C, and the triglyceride content in serum was detected according to the liquid sample triglyceride (TG) content enzymatic assay kit (purchased from Beijing Pulilai Gene Technology Co., Ltd.). The absorbance was measured by the colorimetric method using an enzyme marker.

[0026] (2) Liver: When sampling, cut an equal amount of liver samples and freeze them in liquid nitrogen. Before testing, add lysis buffer to the samples for fragmentation, then centrifuge at 4°C 12000g for 10 minutes to obtain the supernatant. The triglyceride content in the supernatant was detected using the tissue cell triglyceride (TG) content enzymatic assay kit (purchased from Beijing Pulilai Gene Technology Co., Ltd.), and the protein content in the supernatant was detected using the BCA protein quantification kit (purchased from Thermo Fisher Scientific). The absorbance was measured by colorimetry using an enzyme-labeled instrument. The triglyceride content of each sample was corrected using the protein content.

[0027] 4. Liver histology HE staining, Oil Red O staining, Masson staining and quantification (1) HE staining: Fresh liver tissue was fixed in 4% paraformaldehyde fixative for at least 24 hours, dehydrated and embedded, and 5 μm tissue sections were cut. The sections were routinely dewaxed into distilled water. Hematoxylin staining was performed for 2 minutes, and the tissues were washed with tap water to turn blue. After washing with distilled water, the tissues were stained with eosin for 1 minute, dehydrated with gradient alcohol, and sealed with neutral gum. Images were collected under a microscope, and the vacuolar area was quantitatively analyzed using Image J software.

[0028] (2) Oil Red O staining: Mouse liver frozen sections were rewarmed and fixed in 4% paraformaldehyde fixative for 20 minutes. After washing with distilled water, they were stained with 60% isopropanol for 2 minutes, then directly stained in Oil Red O staining solution in the dark for 20 minutes, washed with distilled water, stained with hematoxylin for 2 minutes, and then washed with distilled water and sealed with glycerol gelatin. Images were collected under a microscope, and the positive area of ​​Oil Red staining was quantitatively analyzed using Image J software.

[0029] (3) Masson staining: The sections were routinely dewaxed to distilled water. The sections were stained with mordant solution in a 60°C incubator for 1 hour, and then rinsed with distilled water 3 times, 3 minutes each time. The sections were dripped with lapis lazuli blue stain for 2 minutes, and washed with distilled water 2 times, 10 seconds each time. The sections were dripped with Mayer's hematoxylin stain for 2 minutes, and washed with distilled water 2 times, 10 seconds each time. The sections were differentiated with acidic differentiation solution and washed with water. The sections were rinsed with tap water for 10 minutes to return to blue. The sections were dripped with Ponceau fuchsin stain for 5 minutes, and washed with distilled water 2 times, 10 seconds each time. The sections were differentiated with phosphomolybdic acid solution for 5 minutes. The upper solution was discarded and aniline blue stain was directly added for 3 minutes. The sections were washed with weak acid solution for 2 minutes. The sections were rapidly dehydrated with 95% ethanol for 3 seconds. The sections were dehydrated with anhydrous ethanol 2 times, 5 seconds each time. The sections were transparentized with xylene 2 times, 2 minutes each time. The sections were sealed with neutral gum. Images were collected under a microscope, and the positive area of ​​Masson staining was quantitatively analyzed using Image J software.

[0030] The data analysis results after the above experiments showed that in the diet-induced fatty liver disease mouse model, the serum triglyceride level of mice was significantly reduced after treatment with alder ketone ( Figure 1 ), triglyceride levels in the liver decreased significantly ( Figure 2 More importantly, the results of liver histological HE staining showed that the lipid droplet vacuoles in hepatocytes were significantly reduced after treatment with alder ketone, while there were no other adverse effects on the morphology of hepatocytes ( Figure 3 In addition, liver oil red O staining showed that the lipid level in hepatocytes was significantly reduced after treatment with alnus ketone; liver Masson staining showed that alnus ketone could significantly alleviate the already formed liver fibrosis ( Figure 3 and Figure 4 ).

[0031] The experimental data of the above examples show that alnus ketone can effectively improve the blood lipid and liver lipid levels of fatty liver disease animal models, reverse and treat liver fatty degeneration, and has a significant improvement effect on liver fibrosis, providing sufficient in vivo biological evidence for the application of alnus ketone in fatty liver disease.

[0032] Example 2 Alnus ketone alleviates liver fibrosis and inflammation levels in mice with steatohepatitis 1. Construction of animal model of fatty liver disease Wild-type C57BL / 6J mice (purchased from Beijing Weitong Lihua Company) were fed a methionine choline-deficient diet (A02082002B, Research Diet) starting at 8 weeks of age and continued for 4 weeks. Mice fed a methionine choline-deficient diet developed significant fatty liver within 2 weeks, and then rapidly evolved into hepatitis and fibrosis, which can simulate the pathophysiological process of fatty liver hepatitis and is a commonly used preclinical fatty liver hepatitis mouse model.

[0033] 2. Alnus ketone dosing regimen The mice with fatty liver disease were randomly divided into two groups: the alderone group: the alderone powder (purchased from Shanghai Taoshu Biotechnology Co., Ltd.) was dissolved in corn oil containing 5% DMSO, and C57 mice were intraperitoneally injected at a dose of 10 mg / kg every day; the control group: the same model mice were intraperitoneally injected with the same dose of 5% DMSO in corn oil every day. After two weeks of administration, the samples were collected to observe the treatment results of alderone on mice with fatty liver disease.

[0034] 3. Serum and liver triglyceride detection, liver histological staining (1) Triglyceride: After 14 days of continuous intraperitoneal injection of alnus ketone into mice with fatty liver disease, serum was collected according to the method described in Example 1 and the triglyceride content in serum was detected according to the instructions of the assay kit. The triglyceride content in the supernatant of the lysate of the liver sample was detected according to the method described in Example 1 and the instructions of the assay kit, and the content was corrected by protein content.

[0035] (2) HE staining: Fresh liver tissue was fixed in 4% paraformaldehyde fixative for at least 24 hours, dehydrated and embedded, and 5 μm tissue sections were cut. The sections were routinely dewaxed into distilled water. Hematoxylin staining was performed for 2 minutes, and the tissues were washed with tap water to turn blue. After washing with distilled water, the tissues were stained with eosin for 1 minute, dehydrated with gradient alcohol, and sealed with neutral gum. Images were collected under a microscope, and the vacuolar area was quantitatively analyzed using Image J software.

[0036] (3) Oil Red O staining: Mouse liver frozen sections were rewarmed and fixed in 4% paraformaldehyde fixative for 20 minutes. After washing with distilled water, they were stained with 60% isopropanol for 2 minutes, then directly stained in Oil Red O staining solution in the dark for 20 minutes, washed with distilled water, stained with hematoxylin for 2 minutes, and then washed with distilled water and sealed with glycerol gelatin. Images were collected under a microscope, and the positive area of ​​Oil Red staining was quantitatively analyzed using Image J software.

[0037] (3) Masson staining: The sections were routinely dewaxed to distilled water. The sections were stained with mordant solution in a 60°C incubator for 1 hour, and then rinsed with distilled water 3 times, 3 minutes each time. The sections were dripped with lapis lazuli blue stain for 2 minutes, and washed with distilled water 2 times, 10 seconds each time. The sections were dripped with Mayer's hematoxylin stain for 2 minutes, and washed with distilled water 2 times, 10 seconds each time. The sections were differentiated with acidic differentiation solution and washed with water. The sections were rinsed with tap water for 10 minutes to return to blue. The sections were dripped with Ponceau fuchsin stain for 5 minutes, and washed with distilled water 2 times, 10 seconds each time. The sections were differentiated with phosphomolybdic acid solution for 5 minutes. The upper solution was discarded and aniline blue stain was directly added for 3 minutes. The sections were washed with weak acid solution for 2 minutes. The sections were rapidly dehydrated with 95% ethanol for 3 seconds. The sections were dehydrated with anhydrous ethanol 2 times, 5 seconds each time. The sections were transparentized with xylene 2 times, 2 minutes each time. The sections were sealed with neutral gum. Images were collected under a microscope, and the positive area of ​​Masson staining was quantitatively analyzed using Image J software.

[0038] 4. Detection of liver inflammatory factor expression levels The liver samples frozen in liquid nitrogen after sampling were used to extract total RNA from liver tissue using the TRIZOL method, reverse transcribed into cDNA, and then real-time quantitative fluorescence PCR was used to detect inflammatory factors in liver tissue ( Tnfα, Adgre1, Ccl2 ) mRNA expression changes.

[0039] The above experimental results show that after the induction of methionine choline deficiency diet, the liver lipid accumulation of mice increased significantly, and Masson staining showed obvious liver fibrosis, indicating that the mouse model of fatty hepatitis and liver fibrosis was successfully established. After the fatty hepatitis mice were treated with alder ketone, the serum triglyceride level of the mice was significantly reduced ( Figure 5 ), triglyceride levels in the liver decreased significantly ( Figure 6 ). The results of liver histological staining showed that the lipid droplet vacuoles and neutral lipid content in hepatocytes were significantly reduced after treatment with alder ketone, while there were no other adverse effects on hepatocyte morphology ( Figure 7 More importantly, Masson staining of the liver showed a significant reduction in liver fibrosis after treatment with alder ketone ( Figure 8 ), and in the liver Tnfα, Ccl2 The expression levels of multiple inflammatory factors such as Fig. 9 ).

[0040] In addition, there was no significant decrease in body weight in mice with fatty liver disease after treatment with alderone ( Fig.10 ), indicating that alnus ketone treatment has good safety and no obvious toxic side effects on mice.

[0041] The above experimental data all confirm that alnus ketone can effectively alleviate the symptoms of fatty liver disease, fatty liver hepatitis, and liver fibrosis animal models, especially reduce blood lipids and liver lipid levels, reverse and treat liver fatty degeneration, and effectively reduce the already formed liver fibrosis and reduce the level of liver inflammation. These results provide sufficient in vivo biological evidence for the application of alnus ketone in fatty liver disease.

[0042] The above studies, by constructing an animal model of fatty liver disease to simulate the pathological process of human fatty liver disease, revealed the new function of alnus ketones in significantly improving the body's lipid metabolism, treating fatty liver disease, fatty liver hepatitis and liver fibrosis, without obvious toxic side effects. This indicates that alnus ketones can be used as a new and effective drug for the clinical prevention and treatment of fatty liver disease.

[0043] The above is only an embodiment of the present application and is not intended to limit the present application. For those skilled in the art, the present application may have various changes and variations. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present application should be included in the scope of the claims of the present application.

Claims

1. Use of a linear diarylheptane compound and its derivatives in the preparation of a drug for treating and preventing fatty liver disease, characterized in that: The structural formula of the linear diarylheptane compound is: Wherein, R1, R2, R3, and R4 are independently selected from -H, -OH, and -OCH3; The derivative of the linear diarylheptane compound is a physiologically acceptable salt formed by the linear diarylheptane compound and an inorganic base or an organic base; or a physiologically acceptable ester formed by the linear diarylheptane compound and an inorganic acid or an organic acid.

2. Use of a linear diarylheptane compound and its derivatives in the preparation of a health product for assisting in lowering blood lipids, characterized in that: The structural formula of the linear diarylheptane compound is: Wherein, R1, R2, R3, and R4 are independently selected from -H, -OH, and -OCH3; The derivative of the linear diarylheptane compound is a physiologically acceptable salt formed by the linear diarylheptane compound and an inorganic base or an organic base; or a physiologically acceptable ester formed by the linear diarylheptane compound and an inorganic acid or an organic acid.

3. The use according to claim 1 or 2, characterized in that: The linear diarylheptane compound is selected from: Compound 1: ; Compound 2: ; Compound 3: ; or, Compound 4: .

4. The use according to claim 1 or 2, characterized in that: The salt is selected from alkali metal salts, such as sodium salts and potassium salts; alkaline earth metal salts, such as calcium salts and magnesium salts; ammonium salts; salts formed with nitrogen-containing organic bases; The inorganic acid is selected from sulfuric acid, phosphoric acid, carbonic acid or hydrochloric acid; the organic acid is selected from formic acid, acetic acid, propionic acid, butyric acid, maleic acid, oxalic acid, methanesulfonic acid, succinic acid or fatty acid.

5. The use according to claim 4, characterized in that: The nitrogen-containing organic base is selected from procaine, trimethylamine, triethylamine, tributylamine, pyridine, N,N-dimethylaniline, N-methylpiperidine, N-methylmorpholine, diethylamine, dicyclohexylamine, dibenzylamine, N-benzyl-β-phenethylamine or N,N'-dibenzylethylenediamine.

6. The use according to claim 1 or 2, characterized in that: The linear diarylheptane compounds are obtained by chemical synthesis or biological extraction; preferably, the source of biological extraction is selected from cardamom, alnus truncatula, turmeric or amomum villosum.

7. The use according to claim 1, characterized in that: The disease is selected from metabolic dysfunction-associated fatty liver disease, metabolism-related fatty liver disease, non-alcoholic fatty liver disease, alcoholic fatty liver disease, metabolic dysfunction-associated fatty liver disease, metabolism-related fatty liver disease, non-alcoholic fatty liver disease, alcoholic fatty liver disease, liver fibrosis and cirrhosis caused by it.

8. A composition for treating fatty liver disease or assisting in lowering blood lipids, characterized in that: Comprising an effective dose of linear diarylheptane compounds and their derivatives, plants containing linear diarylheptane compounds and their derivatives, or plant extracts containing linear diarylheptane compounds and their derivatives; The structural formula of the linear diarylheptane compound is: Wherein, R1, R2, R3, and R4 are independently selected from -H, -OH, and -OCH3; The derivative of the linear diarylheptane compound is a physiologically acceptable salt formed by the linear diarylheptane compound and an inorganic base or an organic base; or a physiologically acceptable ester formed by the linear diarylheptane compound and an inorganic acid or an organic acid.

9. The composition according to claim 8, characterized in that The linear diarylheptane compound is selected from: Compound 1: ; Compound 2: ; Compound 3: ; or, Compound 4: ; The salt is selected from alkali metal salts, such as sodium salts and potassium salts; alkaline earth metal salts, such as calcium salts and magnesium salts; ammonium salts; salts formed with nitrogen-containing organic bases; The nitrogen-containing organic base is selected from procaine, trimethylamine, triethylamine, tributylamine, pyridine, N,N-dimethylaniline, N-methylpiperidine, N-methylmorpholine, diethylamine, dicyclohexylamine, dibenzylamine, N-benzyl-β-phenethylamine or N,N'-dibenzylethylenediamine; The inorganic acid is selected from sulfuric acid, phosphoric acid, carbonic acid or hydrochloric acid; the organic acid is selected from formic acid, acetic acid, propionic acid, butyric acid, maleic acid, oxalic acid, methanesulfonic acid, succinic acid or fatty acid; Preferably, the plant containing linear diarylheptane compounds is selected from Alnus fragrans, Alnus truncatus, Curcuma longa or Amomum villosum.

10. The composition according to claim 8, characterized in that The composition also includes pharmaceutically or food acceptable excipients; the composition is taken orally or by injection; the composition is a sustained-release preparation or a controlled-release preparation; the oral preparation is selected from tablets, capsules, granules, oral liquids or syrups.

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