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Application of PGC-1 alpha activating agent in preparation of drug for treating sepsis

A PGC-1, 1.PGC-1 technology, applied in the field of medicine, can solve the problem of lack of effective methods and drugs for sepsis, achieve the effects of increasing the number, enhancing ATP synthesis, and inhibiting excessive inflammatory reactions

Pending Publication Date: 2020-04-28
YUNNAN UNIV OF TRADITIONAL CHINESE MEDICINE
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] One of the purposes of the present invention is to propose the application of a PGC-1α activator in the preparation of drugs for the treatment of sepsis, which solves the technical problem of lack of effective methods and drugs for sepsis in the prior art

Method used

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  • Application of PGC-1 alpha activating agent in preparation of drug for treating sepsis
  • Application of PGC-1 alpha activating agent in preparation of drug for treating sepsis
  • Application of PGC-1 alpha activating agent in preparation of drug for treating sepsis

Examples

Experimental program
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Effect test

Embodiment 1

[0035] This embodiment provides a direct activator of PGC-1α. Preferably, the PGC-1α direct activator is a SIRT1 activator. More preferably, the SIRT1 activator is one or more of SRT3025 HCl, CAY10602, SRT1720HCl, SRT2104 (GSK2245840), SRT2183 and structural analogs and derivatives thereof.

[0036] As mentioned earlier, SIRT1 can catalyze the deacetylation of PGC-1α, thereby activating PGC-1α. Among them, SRT1720 HCl is a specific activator of SIRT1.

[0037] Next, the protective effect of SRT1720 HCl activator on septic CLP mice was tested through the following experimental procedures.

[0038] Before the experimental operation, the KM mice were adaptively raised for 3 days in an environment with a temperature of about 22°C and a humidity of 40%, with a 12h day / night cycle every day and no special pathogenic bacteria. During the feeding process, the mice were fed with standard pellet feed. Drinking water and food ad libitum. They were randomly divided into control group ...

Embodiment 2

[0046] This embodiment provides a direct activator of PGC-1α. Preferably, the PGC-1α direct activator is an ARβ2-PKA-PGC-1α activator. More preferably, the ARβ2-PKA-PGC-1α activator is one or more of aconitine and its structural analogues and derivatives.

[0047] Aconitine is a natural ARβ2 receptor activator extracted from the traditional Chinese medicine Fuzi, which can promote the expression of PGC-1α through the aforementioned ARβ2-PKA-PGC-1α pathway.

[0048] Next, the protective effect of aconitine activator on septic CLP mice was tested through the following experimental procedures.

[0049]Before the experimental operation, the KM mice were adaptively raised for 3 days in an environment with a temperature of about 22°C and a humidity of 40%, with a 12h day / night cycle every day and no special pathogenic bacteria. During the feeding process, the mice were fed with standard pellet feed. Drinking water and food ad libitum. Randomly divided into control group and aconi...

Embodiment 3

[0056] This embodiment provides an indirect activator of PGC-1α. Preferably, the indirect PGC-1α activator is an Nrf-2 activator. More preferably, the Nrf-2 activator is one or more of Oltipaz, resveratrol, Curcumin, 4-Octyl Itaconate, Diethylmaleate, TBHQ and structural analogs and derivatives thereof.

[0057] Oltipaz can activate Nrf-2. As mentioned above, Nrf-2 activation can promote the expression of PGC-1α, thereby activating mitochondrial production.

[0058] Next, the protective effect of Oltipaz activator on septic CLP mice was tested through the following experimental procedures.

[0059] Before the experimental operation, the KM mice were adaptively raised for 3 days in an environment with a temperature of about 22°C and a humidity of 40%, with a 12h day / night cycle every day and no special pathogenic bacteria. During the feeding process, the mice were fed with standard pellet feed. Drinking water and food ad libitum. They were randomly divided into control group...

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Abstract

The invention discloses an application of a PGC-1 alpha activating agent in preparation of a drug for treating sepsis, relates to the technical field of drugs and solves the technical problem of lackof effective methods and drugs for the sepsis in the prior art. According to the application of the PGC-1 alpha activating agent in preparation of the drug for treating sepsis, the activity of PGC-1 alpha can be enhanced through the PGC-1 alpha activating agent, production of mitochondria can be directly started through activity enhancement of PGC-1 alpha, so that the number of mitochondria is increased, besides, oxygen utilization is increased, the ATP synthesis is enhanced, energy metabolism is enhanced, excessive inflammatory reaction is inhibited, and the effect on treating sepsis is realized.

Description

technical field [0001] The invention relates to the technical field of medicine, in particular to the application of a PGC-1α activator in the preparation of medicines for treating sepsis. Background technique [0002] On February 23, 2016, the Society of Critical Care Medicine (SCCM) and the European Society of Intensive Care Medicine (ESICM) updated the second version of the definition of sepsis (Sepsis 2.0). The "Global Consensus on the Definition of Sepsis and Septic Shock (Sepsis 3.0)" was released in "JAMA", which states that sepsis is a life-threatening multiple organ dysfunction syndrome caused by severe infection that causes the body to overreact (Multiple Organ Dysfunction Syndrome, MODS). This definition highlights that MODS is the most important pathological feature of sepsis and a determinant of death from sepsis. [0003] With the aging population and the increase of invasive medical methods, the incidence of sepsis is increasing worldwide. Due to the lack o...

Claims

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Application Information

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IPC IPC(8): A61K45/00A61P29/00A61P39/06A61K31/05A61K31/12A61K31/225A61K31/498A61K31/7056A61K31/155A61K31/7076A61K31/20A61K31/4985
CPCA61K45/00A61P29/00A61P39/06A61K31/05A61K31/12A61K31/225A61K31/498A61K31/7056A61K31/155A61K31/7076A61K31/20A61K31/4985
Inventor 李奇峰林青李明泓李秀芳代蓉杨云欧阳竞锋
Owner YUNNAN UNIV OF TRADITIONAL CHINESE MEDICINE
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