Application of fusarium in preparation of medicine for preventing or treating metabolic dysfunction or related complications thereof

Abstract

The invention belongs to the technical field of biological medicine, and particularly relates to application of fusarium to preparation of medicine for preventing or treating metabolic dysfunction or related complications thereof. The fusarium is selected from one or more of the following fusarium: Fusarium foetidum, Fusarium pseudocirculanum, Fusarium catenatum, or Fusarium liriodendum, and the fusarium is selected from one or more of the following fusarium: Fusarium foetidum, Fusarium pseudocirculanum, Fusarium catenatum, or Fusarium liriodendum, and the fusarium liriodendum is selected from the following one or more of the following fusarium strains: Fusarium foetidum, Fusarium pseudocirculanum, Fusarium catenatum, and Fusarium liriodendum. The fusarium provided by the invention can remarkably control body weight, improve blood sugar, blood fat and metabolic dysfunction symptoms related to fatty degenerative liver diseases, and can be used for preparing medicines for treating diabetes mellitus, hyperlipidemia, obesity and metabolic dysfunction related to fatty degenerative liver diseases.

Description

Technical Field

[0001] The present invention belongs to the field of biomedicine technology. Specifically, the present invention relates to Fusarium ( Fusarium spp. ) in the treatment and prevention of metabolic diseases, specifically in the treatment of metabolic dysfunction associated with fatty liver disease and its complications. Background Art

[0002] Metabolic diseases refer to diseases caused by disorders in one or more links of the human body's metabolism. They are characterized by obesity, hypertension, hyperglycemia, and dyslipidemia, and are gradually becoming a serious challenge to global public health. With the changes in lifestyle and the westernization of dietary structure, the incidence of these diseases continues to rise, posing a major threat to human health. Fatty liver disease, especially fatty liver disease associated with metabolic dysfunction, is closely related to metabolic diseases such as type 2 diabetes, obesity, and insulin resistance, and is a concomitant disease of multiple metabolic diseases. Finding targets and drugs for metabolic dysfunction associated with fatty liver disease has become one of the important directions in the field of metabolic disease research.

[0003] In recent years, many studies have reported that intestinal microorganisms regulate the occurrence and development of host metabolic diseases through various mechanisms. Regulating the composition of intestinal flora through dietary intervention, probiotic supplementation and fecal microbiota transplantation has become a potential treatment for metabolic diseases. It has been found that the Bacteroidetes, Firmicutes and Proteobacteria in intestinal bacteria regulate phenotypes related to liver lipid metabolism disorders such as hepatocyte injury, inflammation and fibrosis. Intestinal fungi are an important part of the intestinal microecology, and their rich active metabolites have important regulatory functions on the host's metabolic processes and immune system. However, there are few studies on the role of intestinal fungi in metabolic diseases such as obesity, cardiovascular and cerebrovascular diseases, and metabolic dysfunction associated with fatty liver disease, and their mechanism of action is still unclear.

[0004] Fusarium is a common fungus in the environment. Recent studies have found that Fusarium is also a common symbiotic fungus in the intestines of humans and mice. Studies have shown that its content in the intestines of patients with metabolic dysfunction associated with fatty liver disease is reduced. However, no studies have found that Fusarium ( Fusarium spp. ) on metabolic diseases, and whether its bacteria can alleviate or treat metabolic dysfunction and its complications associated with fatty liver disease. The inventors have conducted extensive and in-depth research and experiments and found that Fusarium odoratum ( Fusarium wilt ), Fusarium pseudocircularis ( Fusarium pseudocircinatum )、Fungiella catenella( Fusarium catenatum ) or Fusarium tulipii ( Fusarium liriodendrum) has the effect of preventing and treating metabolic diseases (including metabolic dysfunction related to diabetes, hyperlipidemia, obesity and fatty liver disease, etc.). Fusarium wilt ), Fusarium pseudocircularis ( Fusarium pseudocircinatum )、Fungiella catenella( Fusarium catenatum ) or Fusarium tulipii ( Fusarium liriodendrum ) was fed to experimental subjects, and it was found that the active ingredient can inhibit liver fat accumulation and fibrosis, and effectively alleviate metabolic dysfunction and complications associated with fatty liver disease. The present invention was completed on this basis. Summary of the invention

[0005] In order to overcome the defects of the prior art, the present invention provides the use of Fusarium in the preparation of a medicament for preventing or treating metabolic dysfunction or its related complications.

[0006] Specifically, the present invention is realized through the following technical solutions: In a first aspect, the present invention provides a Fusarium species having the effect of preventing or treating metabolic dysfunction or its related complications, wherein the Fusarium species is selected from the following: Fusarium odoratum Fusarium wilt )LM0001, the deposit number is CGMCC No. 41901, the deposit date is April 2, 2025, the deposit location is the General Microbiology Center of China Microbiological Culture Collection Administration (CGMCC), and the depository address is Institute of Microbiology, Chinese Academy of Sciences, No. 3, No. 1 Beichen West Road, Chaoyang District, Beijing; Fusarium pseudocircularis ( Fusarium pseudocircinatum )LM1063, the deposit number is CGMCC No.41902, the deposit date is April 2, 2025, the deposit location is the General Microbiology Center of China Microbiological Culture Collection Administration (CGMCC), and the deposit address is Institute of Microbiology, Chinese Academy of Sciences, No. 3, No. 1 Beichen West Road, Chaoyang District, Beijing; Fusarium chain Fusarium catenatum )LM0193, the deposit number is CGMCC No. 41903, the deposit date is April 2, 2025, the deposit place is the General Microbiology Center of China Microbiological Culture Collection Administration (CGMCC), and the depository address is Institute of Microbiology, Chinese Academy of Sciences, No. 3, No. 1 Beichen West Road, Chaoyang District, Beijing; or Fusarium tiliaceum Fusarium liriodendrum )LM0200, the deposit number is CGMCC No. 41904, the deposit date is April 2, 2025, the deposit location is the General Microbiology Center of China Microbiological Culture Collection Administration (CGMCC), and the deposit unit address is Institute of Microbiology, Chinese Academy of Sciences, No. 3, No. 1 Beichen West Road, Chaoyang District, Beijing.

[0007] In a second aspect, the present invention provides a use of Fusarium in the preparation of a medicament for preventing or treating metabolic dysfunction or its related complications, wherein the Fusarium is selected from one or more of the following Fusarium: Fusarium stinking ), Fusarium pseudocircularis ( Fusarium pseudocircinatum )、Fungiella catenella( Fusarium chained ) or Fusarium tulipii ( Fusarium liriodendrum ).

[0008] In one embodiment, the present invention provides Fusarium foetidum ( Fusarium wilt ), Fusarium pseudocircularis ( Fusarium pseudocircinatum )、Fungiella catenella( Fusarium catenatum ) and / or Fusarium tuftii ( Fusarium liriodendrum ) for treating metabolic dysfunction and complications associated with fatty liver disease. More specifically, when the test animals ingest a choline-free high-fat model feed, the Fusarium odoratum ( Fusarium stinking ), Fusarium pseudocircularis ( Fusarium pseudocircinatum )、Fungiella catenella( Fusarium chained ) and Fusarium tulipii ( Fusarium liriodendrum ) has the ability to inhibit the increase in liver weight / body weight ratio, aggravation of inflammation and aggravation of fibrosis in the test animals.

[0009] In one embodiment, the associated comorbidity is selected from one or more of the following: overweight, obesity, diabetes, high cholesterol, high triglycerides, or cirrhosis.

[0010] In one embodiment, the Fusarium is selected from one or more of the following Fusarium: Fusarium odoratum Fusarium wilt )LM0001, the deposit number is CGMCC No. 41901, the deposit date is April 2, 2025, the deposit location is the General Microbiology Center of China Microbiological Culture Collection Administration (CGMCC), and the depository address is Institute of Microbiology, Chinese Academy of Sciences, No. 3, No. 1 Beichen West Road, Chaoyang District, Beijing; Fusarium pseudocircularis ( Fusarium pseudocircinatum )LM1063, the deposit number is CGMCC No.41902, the deposit date is April 2, 2025, the deposit location is the General Microbiology Center of China Microbiological Culture Collection Administration (CGMCC), and the deposit address is Institute of Microbiology, Chinese Academy of Sciences, No. 3, No. 1 Beichen West Road, Chaoyang District, Beijing; Fusarium chain Fusarium catenatum)LM0193, the deposit number is CGMCC No. 41903, the deposit date is April 2, 2025, the deposit location is the General Microbiology Center of China Microbiological Culture Collection Administration (CGMCC), and the depository address is Institute of Microbiology, Chinese Academy of Sciences, No. 3, No. 1 Beichen West Road, Chaoyang District, Beijing; or Fusarium tiliaceum Fusarium liriodendrum )LM0200, the deposit number is CGMCC No. 41904, the deposit date is April 2, 2025, the deposit location is the General Microbiology Center of China Microbiological Culture Collection Administration (CGMCC), and the deposit unit address is Institute of Microbiology, Chinese Academy of Sciences, No. 3, No. 1 Beichen West Road, Chaoyang District, Beijing.

[0011] According to a preferred embodiment of the present invention, the above-mentioned Fusarium odoratum ( Fusarium wilt ), Fusarium pseudocircularis ( Fusarium pseudocircinatum )、Fungiella catenella( Fusarium catenatum ) and / or Fusarium tuftii ( Fusarium liriodendrum The obese mouse model induced by a choline-deficient, aminoacid-defined and high-fat diet (CDAA-HFD) treated with the strain can maintain the liver weight / body weight ratio without increase compared with the untreated control group, and contribute to the reduction of AST and ALT and the alleviation of inflammation and fibrosis. Therefore, the strain can be used to treat metabolic dysfunction associated with fatty liver disease and the diseases caused by it, such as high cholesterol, liver cirrhosis, etc.

[0012] In one embodiment, the medicament is for the treatment of diabetes, hyperlipidemia, obesity, steatotic liver disease, or cirrhosis.

[0013] In one embodiment, the drug further comprises a pharmaceutically acceptable excipient, a pharmaceutically acceptable medium and a carrier, which can be selected according to the route of administration. The drug may further comprise auxiliary active ingredients, carriers, excipients, diluents, sweeteners or spices, etc.

[0014] The pharmaceutically acceptable excipient refers to a conventional drug carrier in the field of pharmaceutical preparations, selected from one or more of fillers, binders, disintegrants, lubricants, suspending agents, wetting agents, pigments, flavoring agents, solvents, and surfactants.

[0015] The filler of the present invention includes but is not limited to starch, microcrystalline cellulose, sucrose, dextrin, lactose, powdered sugar, glucose, etc.; the lubricant includes but is not limited to magnesium stearate, stearic acid, sodium chloride, sodium oleate, sodium lauryl sulfate, poloxamer, etc.; the binder includes but is not limited to water, ethanol, starch slurry, syrup, hydroxypropyl methylcellulose, sodium carboxymethyl cellulose, sodium alginate, polyvinyl pyrrolidone, etc.; the disintegrant includes but is not limited to starch effervescent mixture, i.e. sodium bicarbonate and citric acid, tartaric acid, low-substituted hydroxypropyl cellulose, etc.; the suspending agent includes but is not limited to polysaccharides such as acacia gum, agar, alginic acid, cellulose ether and carboxymethyl chitosan, etc.; the solvent includes but is not limited to water, a balanced salt solution, etc.

[0016] The drug can be made into various solid oral preparations, liquid oral preparations, etc. Pharmaceutically acceptable oral solid preparations include: ordinary tablets, dispersible tablets, enteric-coated tablets, granules, capsules, dripping pills, powders, etc., and oral liquid preparations include oral liquids, emulsions, etc. The above-mentioned various dosage forms can be prepared according to conventional processes in the field of pharmaceutical preparations.

[0017] In the medical use described herein, the administration time, number of administrations, and frequency of administration of Fusarium need to be determined according to the specific diagnosis results of the disease, which is within the technical scope mastered by those skilled in the art.

[0018] The treatment plan for test animals is applied to humans, and the effective doses of all drugs for humans can be converted by the effective doses of the drugs for test animals. This is also easy to achieve for ordinary technicians in this field.

[0019] In order to better understand the essence of the present invention, the following specific implementation method uses pharmacodynamic experiments and their results to further illustrate the new use of Fusarium in the pharmaceutical field of the present invention.

[0020] Compared with the prior art, the present invention has the following beneficial effects: The advantage of the present invention is that the Fusarium provided by the present invention can significantly control the liver weight / body weight ratio, improve liver inflammation and fibrosis, and can be used to prepare drugs for treating metabolic dysfunction and complications associated with fatty liver disease. DETAILED DESCRIPTION

[0021] The preferred embodiments of the present invention are described below. It should be understood that the preferred embodiments described herein are only used to illustrate and explain the present invention and are not intended to limit the present invention. If no specific techniques or conditions are specified in the embodiments, the techniques or conditions described in the literature in this field or the product instructions are used. The experimental methods used in the following embodiments are conventional methods unless otherwise specified. If the manufacturer of the reagents or instruments used is not specified, they are all conventional products that can be purchased through regular channels.

[0022] The strain used in the following examples was isolated from healthy human feces and its specific name is Fusarium foetidum ( Fusarium stinking ), Fusarium pseudocircularis ( Fusarium pseudocircinatum )、Fungiella catenella( Fusarium chained ) and Fusarium tulipii ( Fusarium liriodendrum ).

[0023] Fusarium odoratum Fusarium wilt )LM0001, the deposit number is CGMCC No. 41901, the deposit date is April 2, 2025, the deposit location is the General Microbiology Center of China Microbiological Culture Collection Administration (CGMCC), and the depository address is Institute of Microbiology, Chinese Academy of Sciences, No. 3, No. 1 Beichen West Road, Chaoyang District, Beijing; Fusarium pseudocircularis ( Fusarium pseudocircinatum )LM1063, the deposit number is CGMCC No.41902, the deposit date is April 2, 2025, the deposit location is the General Microbiology Center of China Microbiological Culture Collection Administration (CGMCC), and the deposit address is Institute of Microbiology, Chinese Academy of Sciences, No. 3, No. 1 Beichen West Road, Chaoyang District, Beijing; Fusarium chain Fusarium catenatum )LM0193, the deposit number is CGMCC No. 41903, the deposit date is April 2, 2025, the deposit location is the General Microbiology Center of China Microbiological Culture Collection Administration (CGMCC), and the depository address is Institute of Microbiology, Chinese Academy of Sciences, No. 3, No. 1 Beichen West Road, Chaoyang District, Beijing; or Fusarium tiliaceum Fusarium liriodendrum )LM0200, the deposit number is CGMCC No. 41904, the deposit date is April 2, 2025, the deposit location is the General Microbiology Center of China Microbiological Culture Collection Administration (CGMCC), and the deposit unit address is Institute of Microbiology, Chinese Academy of Sciences, No. 3, No. 1 Beichen West Road, Chaoyang District, Beijing.

[0024] Example: Fusarium ( Fusarium spp. Effects of choline-deficient, amino acid-defined and high-fat diet (CDAA-HFD) on liver weight / body weight ratio, liver function, inflammation, liver fibrosis, and total cholesterol and triglycerides in mice with metabolic dysfunction associated with steatotic liver disease 1. Materials and Methods: Fusarium Fusarium spp.) Adjust the concentration to 10 6 spores / mL, the gavage bacteria quantity is 0.1 mL / 10 g body weight, and the frequency is once a week. The bacterial liquid needs to be cultured in advance, activated weekly to ensure freshness, and the concentration is measured separately.

[0025] C57BL / 6J Mice were purchased from Beijing Weitonglihua Experimental Animal Technology Co., Ltd., with a temperature of 20-24°C, a constant humidity of 50-60%, a light period of 12 hours (8:00-20:00), soundproofing, free access to food and water, and experiments were conducted after one week of adaptation. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) detection kits (Zhongsheng Beikong) were purchased from Beijing Boyu Zhongkang Trading Co., Ltd. Total cholesterol (TC) and triglyceride (TG) detection kits (Biosino) were purchased from Beijing Zhongshan Jinqiao Biotechnology Co., Ltd.

[0026] C57BL / 6J Six mice, 16 weeks old, weighing 28-30 g, were used as the normal control group (Group 1). Male hepatitis model mice induced by CDAA-HFD, 8-week-old C57BL / 6J The mice were fed with CDAA-HFD diet for 5 weeks. After successful modeling, they were continued to be fed with CDAA-HFD diet for 3 weeks and were divided into 6 groups: PBS administration group (model group) (group 2), Ff Drug-treated group (administered with Fusarium odoratum, group 3), Fp Drug administration group (administered with Fusarium pseudocircularis, group 4), Fc Drug administration group (administered with Fusarium chain, group 5), Fl There were 6 mice in each group, including the drug-treated group (administered with Fusarium truncatum, group 6) and the negative control strain-administered group (Candida albicans, group 7). The model control group was given an equal amount of PBS, and the mice in the drug-treated group were gavaged with 0.1 mL / 10 g body weight of bacterial solution for 3 consecutive weeks. One week after the last administration, blood was collected and centrifuged at 3000 rpm at 4°C to measure the liver weight, body weight, alanine aminotransferase, and aspartate aminotransferase of mice in each group.

[0027] SPSS 27.0 was used for data analysis, and the measurement data were expressed as mean ± standard deviation (mean ± SD). The sample distribution was determined by the Shapiro-Wilk normality test. The Student's t test (between two groups) or One-way ANOVA (between multiple groups) was used to compare normally distributed variables, the same standard deviation was tested by Tukey's test, and different standard deviations were tested by Dunnett's T3 test; the Mann-Whitney U test (between two groups) or Kruskal-Wallis test (between multiple groups) was used to compare non-normally distributed data;P The difference was statistically significant when the value was <0.05.

[0028] 2. Experimental results: The experimental results are shown in the following Tables 1 to 9. The experimental results show that compared with the control group and the model group, Fusarium can significantly improve the increase in liver weight and liver weight / body weight ratio caused by CDAA-HFD, improve the levels of alanine aminotransferase and aspartate aminotransferase in mice, and improve the levels of total cholesterol and triglycerides in mice.

[0029] Table 1 Effects of Fusarium on body weight in CDAA-HFD-induced hepatitis mouse model

[0030] Table 2 Effects of Fusarium on liver weight in CDAA-HFD-induced hepatitis mouse model

[0031] Table 3 Effect of Fusarium on liver weight / body weight ratio in CDAA-HFD-induced hepatitis mouse model

[0032] Table 4 Effects of Fusarium on ALT in CDAA-HFD-induced hepatitis mouse model

[0033] Table 5 Effects of Fusarium on AST in CDAA-HFD-induced hepatitis mouse model

[0034] Table 6 Effects of Fusarium on plasma TC in CDAA-HFD-induced hepatitis mouse model

[0035] Table 7 Effects of Fusarium on plasma TG in CDAA-HFD-induced hepatitis mouse model

[0036] Table 8 Effects of Fusarium on liver TC in CDAA-HFD-induced hepatitis mouse model

[0037] Table 9 Effects of Fusarium on liver TG in CDAA-HFD-induced hepatitis mouse model

[0038] Note: In Table 1-9, compared with Group 1, P <0.05, P <0.01; compared with group 2, # P <0.05, ## P <0.01.

[0039] 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.

Claims

1. A Fusarium fungus having the effect of preventing or treating metabolic dysfunction or its related complications, characterized in that: The Fusarium is selected from the following: Fusarium odoratum Fusarium foetens )LM0001, the deposit number is CGMCC No. 41901, the deposit date is April 2, 2025, the deposit location is the General Microbiology Center of China Microbiological Culture Collection Administration (CGMCC), and the depository address is Institute of Microbiology, Chinese Academy of Sciences, No. 3, No. 1 Beichen West Road, Chaoyang District, Beijing; Fusarium pseudocircularis ( Fusarium pseudocircinatum )LM1063, the deposit number is CGMCC No. 41902, the deposit date is April 2, 2025, the deposit location is the General Microbiology Center of China Microbiological Culture Collection Administration (CGMCC), and the deposit address is Institute of Microbiology, Chinese Academy of Sciences, No. 3, No. 1 Beichen West Road, Chaoyang District, Beijing; Fusarium chain Fusarium catenatum )LM0193, the deposit number is CGMCC No. 41903, the deposit date is April 2, 2025, the deposit place is the General Microbiology Center of China Microbiological Culture Collection Administration (CGMCC), and the depository address is Institute of Microbiology, Chinese Academy of Sciences, No. 3, No. 1 Beichen West Road, Chaoyang District, Beijing; or Fusarium tiliaceum Fusarium liriodendri )LM0200, the deposit number is CGMCC No. 41904, the deposit date is April 2, 2025, the deposit location is the General Microbiology Center of China Microbiological Culture Collection Administration (CGMCC), and the deposit unit address is Institute of Microbiology, Chinese Academy of Sciences, No. 3, No. 1 Beichen West Road, Chaoyang District, Beijing.

2. Use of Fusarium in the preparation of a medicament for preventing or treating metabolic dysfunction or its related complications, characterized in that: The Fusarium is selected from one or more of the following Fusarium: Fusarium foetens ), Fusarium pseudocircularis ( Fusarium pseudocircinatum )、Fungiella catenella( Fusarium catenatum ) or Fusarium tulipii ( Fusarium liriodendri ).

3. The use according to claim 2, characterized in that: The Fusarium is selected from one or more of the following Fusarium: Fusarium odoratum Fusarium foetens )LM0001, the deposit number is CGMCC No. 41901, the deposit date is April 2, 2025, the deposit location is the General Microbiology Center of China Microbiological Culture Collection Administration (CGMCC), and the depository address is Institute of Microbiology, Chinese Academy of Sciences, No. 3, No. 1 Beichen West Road, Chaoyang District, Beijing; Fusarium pseudocircularis ( Fusarium pseudocircinatum )LM1063, the deposit number is CGMCC No. 41902, the deposit date is April 2, 2025, the deposit location is the General Microbiology Center of China Microbiological Culture Collection Administration (CGMCC), and the deposit address is Institute of Microbiology, Chinese Academy of Sciences, No. 3, No. 1 Beichen West Road, Chaoyang District, Beijing; Fusarium chain Fusarium catenatum )LM0193, the deposit number is CGMCC No. 41903, the deposit date is April 2, 2025, the deposit place is the General Microbiology Center of China Microbiological Culture Collection Administration (CGMCC), and the depository address is Institute of Microbiology, Chinese Academy of Sciences, No. 3, No. 1 Beichen West Road, Chaoyang District, Beijing; or Fusarium tiliaceum Fusarium liriodendri )LM0200, the deposit number is CGMCC No. 41904, the deposit date is April 2, 2025, the deposit location is the General Microbiology Center of China Microbiological Culture Collection Administration (CGMCC), and the deposit unit address is Institute of Microbiology, Chinese Academy of Sciences, No. 3, No. 1 Beichen West Road, Chaoyang District, Beijing.

4. The use according to claim 2 or claim 3, characterized in that: The medicament is used for preventing or treating metabolic dysfunction associated with fatty liver disease.

5. The use according to claim 2 or claim 3, characterized in that: The related complications are selected from one or more of the following: overweight, obesity, diabetes, high cholesterol, high triglycerides or cirrhosis.

6. The use according to claim 2 or claim 3, characterized in that: The medicine is used for treating diabetes, hyperlipidemia, obesity, fatty liver disease or liver cirrhosis.

7. The use according to claim 2 or claim 3, characterized in that: The medicament further comprises a pharmaceutically acceptable excipient.

8. The use according to claim 7, characterized in that: The dosage form of the drug is an oral dosage form.

9. The use according to claim 8, characterized in that: The oral dosage form is selected from freeze-dried powder, capsule, tablet or granule.

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