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CN-122005606-A - Application of auricularia auricula monomer polysaccharide ME-2 in preparation of drugs for preventing and treating fatty liver diseases related to metabolic dysfunction

CN122005606ACN 122005606 ACN122005606 ACN 122005606ACN-122005606-A

Abstract

The invention discloses application of black fungus monomeric polysaccharide ME-2 in preparing a medicament for preventing and treating fatty liver diseases related to metabolic dysfunction. The first system of the study of the invention proves that ME-2 has obvious intervention effect on MASLD full course of disease. The invention discloses the breakthrough function of ME-2 as a liver metabolism regulator for the first time, and can reduce liver steatosis, serum transaminase level and dyslipidemia in MASLD full course in a dose-dependent manner by directly correcting liver lipid metabolism disorder (such as regulating Srebp-1c, ACC1, FASN and other core genes). Importantly, its therapeutic effect results from intervention on metabolic sources, as opposed to known anti-inflammatory mechanisms of use. Meanwhile, ME-2 has the remarkable advantages of clear structure, taking metabolic regulation as a core, safety and innocuity, and provides a brand new drug candidate for MASLD prevention and treatment.

Inventors

  • LIANG JUN
  • XIA YONGGANG

Assignees

  • 黑龙江中医药大学

Dates

Publication Date
20260512
Application Date
20260413

Claims (10)

  1. 1. The application of the black fungus monomeric polysaccharide ME-2 in preparing the medicine for preventing and/or treating the fatty liver disease related to metabolic dysfunction is characterized in that the preparation method of the black fungus monomeric polysaccharide ME-2 comprises the following steps: S1, extracting black fungus by using water as an extraction solvent to obtain a black fungus water extract; S2, adsorbing the black fungus water extract by using macroporous resin to remove pigments and proteins, and eluting to obtain a black fungus macroporous resin water eluent; S3, intercepting a part with the molecular weight of more than or equal to 3000 Da in the macroporous resin water eluent of the black fungus to obtain refined total polysaccharide of the black fungus; S4, deeply removing impurities from the black fungus refined total polysaccharide by anion exchange resin, and separating and purifying by DEAE ion exchange according to charge to obtain monomer polysaccharide ME-2.
  2. 2. The use according to claim 1, wherein the metabolic dysfunction-related fatty liver disease comprises metabolic dysfunction-related steatohepatitis of hepatocyte simple steatosis at an early stage of the metabolic dysfunction-related fatty liver disease and at a stage of inflammation progression.
  3. 3. The use according to claim 1 or 2, wherein the medicament acts by reducing liver weight and liver organ index in the subject.
  4. 4. The use according to claim 1 or 2, wherein the medicament acts by reducing hepatic steatosis in a subject.
  5. 5. The use according to claim 1 or 2, wherein the medicament acts by inhibiting or alleviating liver fibrosis associated with steatohepatitis associated with metabolic dysfunction in a subject.
  6. 6. The use according to claim 1 or 2, wherein the medicament acts by alleviating early liver collagen deposition associated with simple steatosis in hepatocytes of the subject.
  7. 7. The use according to claim 1 or 2, wherein the medicament acts by lowering serum glutamic pyruvic transaminase, glutamic oxaloacetic transaminase and/or triglyceride levels in a subject.
  8. 8. The use according to claim 1 or 2, wherein the medicament acts by down-regulating mRNA expression of lipid synthesis associated cholesterol regulatory element binding protein-1 c, acetyl-coa carboxylase 1 and fatty acid synthase in liver tissue of a subject.
  9. 9. The use according to claim 1 or 2, further comprising pharmaceutically acceptable excipients.
  10. 10. The use according to claim 9, wherein the adjuvant is selected from any one or a combination of at least two of fillers, binders, wetting agents, disintegrants, emulsifiers, co-solvents, solubilisers, osmotic pressure regulators, colorants, pH regulators, antioxidants, bacteriostats or buffers.

Description

Application of auricularia auricula monomer polysaccharide ME-2 in preparation of drugs for preventing and treating fatty liver diseases related to metabolic dysfunction Technical Field The invention relates to the technical field of biological medicines, in particular to application of black fungus monomeric polysaccharide ME-2 in preparing medicines for preventing and treating fatty liver diseases related to metabolic dysfunction. Background Metabolic dysfunction-related fatty liver disease (MASLD) is the most common chronic liver disease worldwide, with a global prevalence of about 38.8%. The disease spectrum of the liver steatosis can progress from simple liver steatosis to metabolic dysfunction-related steatohepatitis (MASH) accompanied by inflammation and injury, to liver fibrosis, liver cirrhosis and liver cancer. The current clinical treatment has the defects of lack of medicines for effectively blocking disease progression in early stage, and few medicines (such as Rametirome) obtained in MASH stage, and the limitations of high price and narrow applicable population. Other therapeutic approaches such as insulin sensitizers are accompanied by side effects such as weight gain, cardiovascular risk, etc. Therefore, there is an urgent clinical need to develop a novel drug that can safely, effectively and economically intervene in the full course of MASLD. The black fungus (Auricularia auricula) is edible and medicinal fungi of the Auricularia, is rich in a plurality of active ingredients such as polysaccharide and the like, and the polysaccharide component of the black fungus has wide pharmacological activity in the aspects of regulating glycolipid metabolism, protecting liver and the like. Chinese patent application CN118599020a discloses that a black fungus heteropolysaccharide (AAPs) can alleviate non-alcoholic steatohepatitis induced by chemical poisons in combination with high fat diets by modulating intestinal flora. The application provides a preliminary clue for the application of the black fungus polysaccharide in the liver disease field, but the adopted polysaccharide is a heteropolysaccharide with an undefined structure, is not an active molecule with a single structure, and the structure-activity relationship between the structure and the drug effect cannot be clarified. Meanwhile, the chemical poison induction model cannot simulate the pathological process of human MASLD with metabolic disorder as a core, and the whole-course treatment value of MASLD is difficult to confirm. Therefore, it is urgent to identify polysaccharide monomers with definite structures and clear activities from black fungus, and directly verify the intervention capability of the polysaccharide monomers on liver lipid metabolism. Chinese patent application CN114957508A discloses a novel high acetyl black fungus monomer polysaccharide ME-2 with a definite structure and application thereof in preventing and treating silicosis, and subsequently, chinese patent application CN117752702A, CN118453641A sequentially discloses that the black fungus monomer polysaccharide ME-2 can be used for tumor immunotherapy and pulmonary nodule therapy. However, no report is available at present on the role of the black fungus monomeric polysaccharide ME-2 in fatty liver diseases related to metabolic dysfunction. Disclosure of Invention For the purposes of facilitating the description and understanding of the invention, the terms used hereinafter have the following specific meanings unless otherwise indicated: MASLD A complete disease spectrum of fatty liver disease associated with metabolic dysfunction. MASL in the present invention, the early stage of MASLD is specified, and its core pathological feature is simple steatosis of liver cells. This definition is intended to clearly distinguish between the different stages of the disease. MASH refers to the stage of inflammation progression of MASLD, i.e., steatohepatitis associated with metabolic dysfunction. The invention aims to provide a novel medical application of black fungus monomeric polysaccharide ME-2, in particular to an application of high-acetyl novel black fungus monomeric polysaccharide ME-2 in prevention and/or treatment MASLD or preparation of a medicament for preventing and/or treating MASLD, so as to solve the problems that a novel natural active ingredient medicament which has a clear structure and high safety and can simultaneously interfere with MASL and MASH and MASLD in the whole course of disease is lacking in the prior art. The black fungus monomer polysaccharide ME-2 is prepared according to the method of the Chinese patent application CN114957508A, and the preparation method of the black fungus monomer polysaccharide ME-2 comprises the following steps: S1, extracting black fungus by using water as an extraction solvent to obtain a black fungus water extract; S2, adsorbing the black fungus water extract by using macroporous resin to remove pigments and proteins, and