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PKM2 regulating agent and preparation method and application thereof

A technology of PKM2 and regulator, which is applied in the field of PKM2 regulator and its preparation, can solve the problems of liver cell necrosis, poor effect, and unsatisfactory curative effect, so as to promote inflammatory response, delay liver damage, and simple preparation method controllable effect

Pending Publication Date: 2019-12-20
XIANGYA HOSPITAL CENT SOUTH UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, after ALF, a large number of liver cells undergo necrosis in a short period of time, resulting in the current treatment methods for preventing and treating liver cell death far behind the speed of ALF liver cell death. The effect is not satisfactory

Method used

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  • PKM2 regulating agent and preparation method and application thereof
  • PKM2 regulating agent and preparation method and application thereof
  • PKM2 regulating agent and preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0043] A PKM2 regulator of the present invention: comprising 2 μg / ml melittin and PBS solution.

[0044] Its control principle is as figure 1 Shown: During liver energy metabolism, glucose is converted into pyruvate; after ALF, hepatic macrophages are activated and proliferate in large numbers, and aerobic glycolysis of macrophages occurs, which is called the Warburg effect (metabolic reprogramming): Increased glucose uptake rate, through the autophosphorylation of pyruvate dehydrogenase kinase, inactivates pyruvate dehydrogenase, blocks the conversion of pyruvate to Acetyl-CoA, and enters the mitochondria for TCA; the increased glucose in the case of enhanced LDHA activity Under this condition, a large amount of lactic acid is generated, thereby activating the PI3K / Akt / mTOR signaling pathway, promoting the high expression of PKM2, thereby activating and promoting the overexpression of the transcription factor HIF-1α, making it enter the nucleus and bind to the inflammatory ge...

Embodiment 2

[0047] Investigate the effect of the PKM2 regulator of Example 1 on the cell viability of the RAW264.7 cell line:

[0048] (1) Preparation of RAW264.7 mouse macrophage cell line inflammation model:

[0049]The RAW264.7 cell line was purchased from the Shanghai Cell Bank of the Chinese Academy of Sciences. After recovery, culture was carried out in DMEM (Dulbecco's modification of Eagle's medium Dulbecco, modified Eagle's medium, containing 10% fetal bovine serum and 1% double antibody). During the experiment, the RAW264.7 cell line was inoculated in a 96-well plate (density: 1×10 5 cells / cm 2 ), add complete medium and shake gently to distribute the cells evenly. Placed at 37°C, 5% CO 2 1. A cell incubator with appropriate saturated humidity, and wait for the cells to reach a confluence of more than 70%. At present, the cell injury and inflammation model caused by LPS is a classic model of liver dysfunction and failure recognized at home and abroad. Therefore, we then add...

Embodiment 3

[0068] Investigate the oxidative stress level of the PKM2 regulator of Example 1 on the RAW264.7 macrophage cell line inflammation model:

[0069] (1) Preparation of RAW264.7 mouse macrophage cell line inflammation model: same as in Example 2.

[0070] (2) Grouping: the RAW264.7 cell line was randomly divided into 3 groups:

[0071] 2.1. Normal control group (Control): without any treatment;

[0072] 2.2. Model group (LPS): give 100ng / ml LPS treatment;

[0073] 2.3. Melittin treatment group (Melittin): 100 ng / ml LPS + 2 μg / ml melittin were given for treatment.

[0074] (3) Chemiluminescence detection experiment: extract cell lysate, detect SOD (superoxide dismutase, superoxide dismutase), MDA (malondialdehyde, malondialdehyde), CAT (catalase, catalase) and GSH by chemiluminescence (glutathione, glutathione). Operate according to the instructions of Nanjing Jiancheng Bioengineering Research LDH, SOD, MDA, CAT and GSH test boxes:

[0075] 3.1. Preparation of standard soluti...

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Abstract

The invention discloses a PKM2 regulating agent and a preparation method and an application thereof. The PKM2 regulating agent comprises melittin. The preparation method of the PKM2 regulating agent comprises the following steps of dissolving the melittin in a PBS solution, and carrying out ultrasonic treatment to obtain the PKM2 regulating agent. According to the PKM2 regulating agent, the melittin is used for performing targeted inhibition on the PKM2-mediated Warburg effect to reduce the inflammatory response, delay the liver injury degree and achieve the pharmacological effect of liver protection; and the PKM2 regulating agent can be used for preparing medicines for treating acute liver injury, delaying the liver injury degree and treating the inflammatory response caused by hepatic macrophage proliferation.

Description

technical field [0001] The invention relates to the technical field of medicines, in particular to a PKM2 regulator and its preparation method and application. Background technique [0002] Acute liver failure (ALF) is a disease that causes massive necrosis of liver cells and severe liver function damage due to various reasons in a short period of time, and causes complications such as hepatic encephalopathy, coagulation dysfunction, jaundice and ascites. group of clinical syndromes. The main causes of ALF are: drugs, hepatitis virus and autoimmunity and other factors. Regrettably, so far there are no drugs that can reverse the natural progression of ALF. If liver transplantation is not carried out in time for ALF, the mortality rate will exceed 70%, and only 14% of ALF patients recover from the existing medical treatment methods. Although liver transplantation is currently the most effective treatment method, the conflicts of scarcity of liver source, high cost and rejec...

Claims

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Application Information

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IPC IPC(8): A61K38/17A61P1/16A61P29/00
CPCA61K38/1767A61P1/16A61P29/00Y02A50/30
Inventor 范学工裴思雅王杨黄泽炳黄燕
Owner XIANGYA HOSPITAL CENT SOUTH UNIV
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