Application of biochanin A in preparation of medicine for preventing or treating non-alcoholic fatty liver disease

Abstract

The invention relates to application of biochanin A in preparation of medicines for preventing or treating liver diseases or liver injury. The biochanin A has the characteristics of remarkable curative effect, safety, reliability, small toxic and side effects and the like when being used for treating the non-alcoholic fatty liver disease; the biochanin A reduces the accumulation of lipid peroxidation products and reduces the neutral lipid level by inhibiting the iron accumulation of liver tissues, so that the fatty degeneration of the liver and the liver injury are relieved. Starting from a monomeric compound, the compound intervenes in the non-alcoholic fatty liver disease, the levels of ALT, AST and TC in serum of a model mouse and TG in liver tissue are remarkably reduced, liver adiposis and inflammatory injury are relieved, and the compound has a good clinical application prospect.

Description

Technical Field

[0001] The present invention belongs to the field of biomedical technologies, and particularly relates to the use of biochanin A in the preparation of a drug for preventing or treating non-alcoholic fatty liver disease. Background Art

[0002] Non-alcoholic fatty liver disease (NAFLD) is a clinicopathological syndrome characterized by excessive intrahepatic fat deposition excluding alcohol and other definite liver-damaging factors, and is an acquired metabolic stress-induced liver injury closely related to insulin resistance and genetic susceptibility. It is not an independent disease and is often accompanied by metabolic disorders, and is one of the main causes leading to cirrhosis, liver failure, hepatocellular carcinoma and liver disease-related deaths. Since the pathogenesis of NAFLD has not been fully elucidated, Western medicine treatment mainly starts from increasing exercise, reducing energy intake, and reducing body weight, combined with drugs that have potential efficacy for NAFLD, so as to achieve the effects of insulin sensitization, lipid regulation and anti-inflammation, antioxidant, and regulation of intestinal flora. However, the clinical efficacy of oral drugs is poor, long-term medication is accompanied by serious adverse reactions, the benefit of single drug application is limited, and combined medication may reduce the adverse reactions of drugs. At present, there is no drug with definite efficacy on the market, and the development of new drugs is imminent.

[0003] Traditional Chinese medicine believes that the main pathological factors of NAFLD are phlegm, dampness, turbidity, stasis, and heat, and the main inducing factors are improper diet, excessive work and rest, emotional disorder, prolonged illness and weakness, and congenital deficiency. The disease location is in the liver, involving the spleen and kidney. Some experts also believe that the disease location is in the middle jiao, involving the liver, spleen, kidney, and gastrointestinal tract. The liver stores blood and governs dispersion and discharge with its yin-natured body and yang-natured function; the spleen is the foundation of acquired constitution, controlling blood and governing transportation and transformation. Abnormal distribution of qi, blood, and body fluids produces phlegm, turbid fat, and after a long illness, it enters the blood and collaterals, and phlegm and stasis are mutually knotted, forming phlegm, dampness, turbidity, stasis, and heat. In the early stage, the disease is mostly in the liver and spleen, and in the long term, it involves the kidney. Therefore, the syndrome of liver depression and spleen deficiency is commonly seen in the early stage.

[0004] Biochanin A (BCA) is an O-methylated isoflavone compound, which is widely present in some edible plants, such as soybeans, red clover, alfalfa, peanuts, and chickpeas. BCA has a variety of pharmacological activities, has good antioxidant, anti-inflammatory, and anti-tumor effects, and has been widely used in the fields of medicine and health products. However, in the prior art, there is no report on the use of biochanin A for the prevention or treatment of liver diseases. Summary of the Invention

[0005] The first aspect of the present invention is to provide the use of biochanin A in the preparation of a drug for preventing or treating liver diseases or liver injuries.

[0006] Further, the liver disease is non-alcoholic fatty liver disease, and the liver injury is liver injury caused by non-alcoholic fatty liver disease.

[0007] Glutathione peroxidase 4 (GPX4) is a selenium-containing protein mainly present in the cytoplasm and mitochondria, which can scavenge lipid hydroperoxides, convert toxic lipid hydroperoxides into non-toxic lipid alcohols, play a protective role in lipid peroxidation reactions, and is regarded as a key protein regulating ferroptosis.

[0008] The second aspect of the present invention lies in providing the use of biochanin A in the preparation of a drug for inhibiting the ferroptosis pathway and alleviating hepatic steatosis.

[0009] The third aspect of the present invention lies in providing the use of biochanin A in the preparation of a drug for reducing the accumulation of iron and lipid peroxidation products in liver tissue.

[0010] The fourth aspect of the present invention lies in providing a drug for treating liver diseases or liver injuries, which contains the active ingredient biochanin A and other pharmaceutically acceptable excipients.

[0011] Furthermore, the liver disease is non-alcoholic fatty liver disease, and the liver injury is the liver injury caused by non-alcoholic fatty liver disease.

[0012] The present invention treats non-alcoholic fatty liver disease by using the monomeric compound biochanin A in leguminous plants, which has the characteristics of significant curative effect. Moreover, this monomeric compound belongs to the drugs of homologous medicine and food, is safe and reliable, and has small toxic and side effects. Starting from the monomeric compound component, it intervenes in non-alcoholic fatty liver disease, significantly reduces the levels of plasma alanine aminotransferase, aspartate aminotransferase, and liver tissue triglyceride, has significant anti-inflammatory and lipid accumulation inhibitory effects, and has good clinical application prospects, providing a new way for the treatment of non-alcoholic fatty liver disease. Description of the Drawings

[0013] Figure 1 Shows the effects of biochanin A on the liver-to-body ratio and liver weight levels of non-alcoholic fatty liver disease mice; Figure 2 Shows the effects of biochanin A on the levels of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), cholesterol (TC), and liver tissue triglyceride (TG) in non-alcoholic fatty liver disease mice; Figure 3 Is the result diagram of H&E staining; Figure 4 Is the result diagram of immunohistochemical staining; Figure 5 Shows the effects of biochanin A on the iron content and malondialdehyde in the liver tissue of non-alcoholic fatty liver disease mice. Detailed Embodiments

[0014] The following further describes the present invention with specific embodiments for better understanding the technical solution.

[0015] Example

[0016] Reagent materials: Biochanin A was purchased from Chengdu Mansite Biotechnology Co., Ltd.; ALT, AST, TC, TG and tissue iron Fe detection kits were purchased from Nanjing Jiancheng.

[0017] Experimental materials: Biochanin A; non-alcoholic fatty liver disease model diet high-fat diet (ResearchDiets, D12492); SPF-grade C57BL / 6 mice Methods: Thirty-two mice were divided into a normal group, a model group, a low-dose biochanin A group (25 mg / kg), and a high-dose biochanin A group (50 mg / kg) according to the random number table method, with 8 mice in each group. The mice were adaptively fed for 7 days. The model group, the low-dose biochanin A group, and the high-dose biochanin A group were respectively modeled by high-fat diet feeding for 12 weeks. From the 9th week of modeling, the low-dose biochanin A group and the high-dose biochanin A group were respectively given biochanin A. After the modeling was completed, H&E staining was used to detect the lipid accumulation level in the liver tissues of mice; biochemical detection was used to detect plasma ALT and AST in mice, as well as cholesterol and triglyceride levels in liver tissues; statistical analysis was performed on the results.

[0018] Results: 1. Effects of biochanin A on liver / body ratio and liver weight levels in non-alcoholic fatty liver disease mice Mice were fed a high-fat diet for 12 weeks to establish a NAFLD model. Biochanin A was intragastrically administered from the 9th week of modeling for 4 consecutive weeks. Biochanin A improved the liver weight and liver / body ratio in non-alcoholic fatty liver disease mice, and the results are as Figure 1 shown.

[0019] 2. Effects of biochanin A on serum ALT, AST, TC, and liver tissue TG in non-alcoholic fatty liver disease mice The results of the biochemical detection experiment are as Figure 2 shown. Compared with the normal group, the levels of serum ALT, AST, TC and liver tissue TG in the model group mice were significantly increased (P<0.01). After treatment with biochanin A, the levels of serum ALT, AST, TC and liver tissue TG in non-alcoholic fatty liver disease mice were reduced (P<0.01).

[0020] 3. Effects of biochanin A on lipid accumulation levels in non-alcoholic fatty liver disease mice The results of H&E staining are as Figure 3As shown, compared with the normal group, the liver tissue of mice in the model group showed mixed macrovesicular and microvesicular steatosis, and the lipid accumulation in the liver tissue increased. However, each dose of biochanin A could significantly reduce the lipid accumulation and the level of hepatic steatosis in mice with non-alcoholic fatty liver disease.

[0021] 4. Effect of Biochanin A on the Key Ferroptosis Protein GPX4 in the Liver Tissue of Mice with Non-Alcoholic Fatty Liver Disease The results of immunohistochemical staining were as Figure 4 shown. Compared with the normal group, the expression of glutathione peroxidase 4 (GPX4) in the liver of mice in the model group decreased, the lipid accumulation in the liver tissue increased, and the tissue damage was obvious. However, each dose of biochanin A could improve the expression level of GPX4, and significantly reduce the lipid accumulation in the liver tissue and the liver damage.

[0022] 5. Effect of Biochanin A on the Iron Content and Malondialdehyde in the Liver Tissue of Mice with Non-Alcoholic Fatty Liver Disease The results were as Figure 5 shown. Compared with the normal group, the iron content and the level of malondialdehyde (MDA) in the liver tissue of mice in the model group were significantly increased (P<0.05). Biochanin A could significantly reduce the iron content and the MDA level in the liver tissue of NAFLD mice (P<0.05).

[0023] The above results showed that biochanin A had a significant improvement effect on the mouse model of non-alcoholic fatty liver disease induced by high-fat diet, and at the same time reduced the level of liver lipid accumulation in mice, suggesting that this monomer compound has good application prospects for non-alcoholic fatty liver disease.

Claims

1. Application of biochanin A in the preparation of drugs for preventing or treating liver disease or liver damage.

2. The use according to claim 1, characterized in that The liver disease is non-alcoholic fatty liver disease, and the liver damage is liver damage caused by non-alcoholic fatty liver disease.

3. Application of biochanin A in the preparation of drugs that inhibit ferroptosis pathway and alleviate hepatic steatosis.

4. Application of biochanin A in the preparation of drugs for reducing the accumulation of iron and lipid peroxidation products in liver tissue.

5. A drug for treating liver disease or liver damage, characterized in that: The medicine contains the active ingredient biochanin A and other pharmaceutically acceptable excipients.

6. A drug for treating liver disease or liver damage according to claim 5, characterized in that: The liver disease is non-alcoholic fatty liver disease, and the liver damage is liver damage caused by non-alcoholic fatty liver disease.

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