CN-121978340-A - Use of SMOX in preparing medicine for treating hepatocyte inflammation

Abstract

The invention belongs to the technical field of biological medicines, and discloses an application of SMOX in preparing a medicine for treating hepatocyte inflammation. Expression of SMOX in AML12 cells was stimulated by LPS. SMOX inhibition inhibits LPS-induced inflammatory responses in AML12 cells. LPS induces the transfer of β -catenin from the cytosol to the nucleus, whereas SMOX down-regulation or inhibition may partially reverse this process. The in vivo use of SMOX inhibitor MDL72527 or SMOX knockout mice for intervention can significantly improve liver function injury, reduce intrahepatic inflammation, reduce nuclear translocation of beta-catenin in liver tissue, and alleviate carbon tetrachloride-induced liver fibrosis of mice. The invention provides a new treatment strategy for hepatitis and liver fibrosis and a new idea for inhibiting early liver cancer.

Inventors

• HU TINGTING
• YAN YE
• PAN SHUANG
• DONG XIULI
• Lin Tiesu

Assignees

• 温州医科大学附属第一医院

Dates

Publication Date

20260505

Application Date

20231222

Claims (8)

1. Use of smox in the manufacture of a medicament for the treatment of hepatocyte inflammation.
2. Use of smox inhibitors in the manufacture of a medicament for the treatment of hepatocyte inflammation.
3. 3. The use of SMOX in the manufacture of a medicament for the treatment of hepatocyte inflammation as claimed in claim 1 wherein SMOX inhibition or knockout is effective in reducing LPS-induced AML12 hepatocyte inflammatory response.
4. 4. The use of SMOX according to claim 1 for the preparation of a medicament for the treatment of hepatocyte inflammation, wherein down-regulation or inhibition of SMOX partially reverses the transfer of β -catenin from the cytosol to the nucleus.
5. 5. The use of SMOX in the manufacture of a medicament for the treatment of hepatocyte inflammation as claimed in claim 1, wherein the in vivo intervention in a SMOX inhibitor MDL72527 or SMOX knockout mouse reduces intrahepatic inflammation, reduces nuclear translocation of β -catenin in liver tissue, and reduces carbon tetrachloride-induced liver fibrosis in the mouse.
6. 6. The method for determining the application of SMOX in preparing a medicament for treating hepatocyte inflammation according to any one of claims 1-5, specifically comprising: (1) The effect of SMOX inhibition on LPS-induced inflammatory responses in the mouse hepatocyte line AML12 was validated using small interfering RNAs or SMOX inhibitor MDL 72527; (2) Determining whether LPS is able to induce β -catenin into the nucleus by Western blotting and immunofluorescence, and whether it is able to reverse this process by interfering SMOX with expression or using SMOX inhibitors; (3) SMOX inhibitor MDL72527 and SMOX knockout mice were used to verify the above hypothesis.
7. 7. Use of SMOX according to claim 1 for the preparation of a medicament for the treatment of hepatocyte inflammation, wherein the medicament is formulated as a liquid or solid formulation.
8. 8. The use of SMOX in the manufacture of a medicament for the treatment of hepatocyte inflammation as claimed in claim 1, wherein the medicament is in the form of an injection, an oral liquid, a granule, a powder, a tablet, a capsule or a patch for external use.

Description

Use of SMOX in preparing medicine for treating hepatocyte inflammation Technical Field The invention belongs to the technical field of biological medicines, and particularly relates to an application of SMOX in preparation of a medicine for treating hepatocyte inflammation. Background The liver plays an important role in the life activities of organisms, and plays roles in metabolism of substances such as proteins, lipids, saccharides and the like, and in vivo metabolism of drugs, alcohol, poisons and the like through biosynthesis, biotransformation, detoxification and the like. Meanwhile, liver is also an organ frequently affected by various pathogenic factors or diseases, such as abnormal metabolism, medicines, microorganisms and the like, which can cause liver injury. Most liver injuries often accompanied by inflammatory reactions, liver fibrosis, cirrhosis, liver failure and cancer have been shown to be the most common forms of liver disease progression and outcome. Therefore, the liver diseases with different causes need to be fully known about the association with inflammation and targeted treatment is performed to delay the disease progression and improve the quality of life. Liver fibrosis is a common pathological basis for the development of various chronic liver diseases to cirrhosis, the essence of which is the imbalance of synthesis and degradation of extracellular matrix in the liver, leading to the massive deposition of extracellular matrix, especially collagen, in the liver. The continuous development of liver fibrosis leads to dysfunction and failure of corresponding organs, which seriously endangers life health. Slowing down, preventing and even reversing hepatic fibrosis, and has great significance for reducing the occurrence of serious complications, improving the life quality of patients and improving the survival rate. Therefore, the development of the anti-hepatic fibrosis medicine has obvious application value. Spermine oxidase (spermine oxidase, SMOX) is a FAD-dependent enzyme that specifically oxidizes Spermine (SPM), producing Spermidine (SPD), hydrogen peroxide (H 2O2) and aldehyde 3-aminopropionaldehyde (3-AP), which play a dominant role in mammalian polyamine catabolism. SMOX as a metabolic enzyme, besides performing the conventional metabolic functions, it also enables the regulation of cell proliferation, survival, apoptosis, stress response, tumor microenvironment reconstruction, etc. through post-translational self-acetylation modification, etc. Prior art treatment of hepatocyte inflammation with non-steroidal anti-inflammatory drugs (NSAIDs) Nonsteroidal anti-inflammatory drugs (NSAIDs) are currently commonly used in the treatment of hepatocyte inflammation. Such agents reduce the production of prostaglandins by inhibiting Cyclooxygenase (COX), thereby reducing the inflammatory response. Problems of the prior art 1. Side effects while NSAIDs are effective in reducing inflammation and pain in the short term, long term use can cause a range of side effects such as gastrointestinal damage, impairment of renal function, and cardiovascular events. 2. The therapeutic effect is limited in that NSAIDs reduce inflammation mainly by inhibiting prostaglandin production, but this does not address the root cause of hepatocyte inflammation. For some severe or chronic hepatitis, the therapeutic effects of NSAIDs may be limited. 3. The nuclear translocation of beta-catenin cannot be reversed, namely the action mechanism of NSAIDs is irrelevant to the regulation and control of beta-catenin, so that the NSAIDs cannot reverse the nuclear translocation of beta-catenin, which can limit the application of the NSAIDs in treating some diseases related to the nuclear translocation of beta-catenin (such as liver cancer). Disclosure of Invention Aiming at the problems existing in the prior art, the invention provides an application of SMOX in preparing a medicament for treating hepatocyte inflammation. The invention is realized in this way, SMOX is applied in preparing the medicine for treating the hepatic cell inflammation. Use of SMOX inhibitor in preparing medicine for treating hepatocyte inflammation is provided. Further, SMOX inhibition or knockout can be effective in reducing LPS-induced AML12 hepatocyte inflammatory response. Further, down-regulation or inhibition of SMOX partially reverses the transfer of β -catenin from the cytosol to the nucleus. Further, in vivo intervention with SMOX inhibitor MDL72527 or SMOX knockout mice can reduce intrahepatic inflammation, reduce nuclear translocation of β -catenin in liver tissue, and reduce carbon tetrachloride-induced liver fibrosis in mice. Another object of the present invention is to provide a method for determining the application of SMOX in the preparation of a medicament for treating hepatocyte inflammation, specifically comprising: (1) The effect of SMOX inhibition on LPS-induced inflammatory responses in the mouse hepatocyte line AML12 was