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Application of SGLT2 inhibitor in regulation of inflammation

A technology for inhibiting inflammation and inhibitors, applied in the application field of sodium-glucose cotransporter 2 inhibitors in regulating inflammation, can solve the problems of poor patient compliance, lack of anti-inflammatory drugs, etc., and achieve the effect of improving inflammatory symptoms

Active Publication Date: 2019-08-20
SHENZHEN GRADUATE SCHOOL TSINGHUA UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, these NSAIDs such as aspirin usually have some gastrointestinal reactions, such as gastric ulcer, gastric bleeding, etc., and the patient compliance is relatively poor [Shin, S.J., Noh, C.K., Lim, S.G., Lee, K.M. & Lee, K.J.Non-steroidal anti- inflammatory drug-induced enteropathy. Intestinal research 15, 446-455, doi:10.5217 / ir.2017.15.4.446(2017).]
Therefore, there is still a lack of ideal anti-inflammatory drugs in clinic

Method used

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  • Application of SGLT2 inhibitor in regulation of inflammation
  • Application of SGLT2 inhibitor in regulation of inflammation
  • Application of SGLT2 inhibitor in regulation of inflammation

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0046] Example 1. In vitro lipopolysaccharide-induced inflammatory cell model and activity evaluation

[0047] 1. Experimental materials

[0048] 1. Compound

[0049] SGLT2 inhibitors (CAN, Empagliflozin, Dapagliflozin, Bexagliflozin, Ipragliflozin and Tofogliflozin hydrate), Metformin hydrochloride, Rosaglitazone, Glibenclamide, Salsalate, Liraglutide, Sitagliptin and Insulin were purchased from MedChemExpress (MCE) Hongyan Chemical Reagent Factory. Dimethyl sulfoxide (DMSO), absolute ethanol and isopropanol were purchased from Shenggong Bioengineering (Shanghai) Co., Ltd.; lipopolysaccharide (LPS) was purchased from Sigma-Aldrich (Lot. No. L4391), dissolved in ultra-pure water and frozen at -20°C.

[0050] 2. Cell source

[0051] Mouse monocytes / macrophages (RAW264.7) and human peripheral blood monocytes (THP-1) were purchased from the Cell Resource Center of Shanghai Academy of Biological Sciences, Chinese Academy of Sciences.

[0052] 3. Cell biology reagents

[0053] DMEM high-suga...

Embodiment 2

[0103] Example 2. Research on anti-inflammatory mechanism of SGLT2 inhibitor represented by CAN

[0104] 1. Experimental materials

[0105] 1. Biochemical reagents

[0106] p62 (PM045) was from Medical & Biological Laboratories; LC3 (L7543) was from Sigma-Aldrich; β-actin antibody (A1978) was from Sigma-Aldrich; glucose kit was purchased from Zhongsheng Beikong Biotechnology Co., Ltd.; Intracellular glucose metabolism test kit (Agilent Seahorse XFpGlycolysis Stress Test Kit, XFp FluxPak, 103022-100, Agilent Technologies, Inc., USA); ECL reagent (Pierce TM ECL Western blotting substrate) was purchased from ThermoFisher Scientific, USA).

[0107] 2. Primer sequence

[0108] p62 (Forward: 5’-GAACTCGCTATAAGTGCAGTGT-3’; Reverse: 5’-AGAGAAGCTATCAGAGAGGTGG-3’), produced by ThermoFisher Scientific (Invitrogen TM )synthesis. The Actin primers in Table 1 of Example 1 were used for control.

[0109] 3. Instrument

[0110] Confocal fluorescence microscope (FV1000, Olympus, Japan); Seahorse XFp c...

Embodiment 3

[0157] Example 3. Modeling and activity evaluation of lipopolysaccharide-induced lung inflammation in mice

[0158] 1. Experimental materials

[0159] 1. Laboratory animals and food

[0160] NIH male mice (about 20g) were purchased from Guangdong Medical Laboratory Animal Center (SPF grade, license number: Guangdong Jianzheng, SCXK (Guangdong) 2013-0002). SPF-grade food was purchased from Guangdong Medical Laboratory Animal Center.

[0161] 2. Chemical reagents

[0162] 4% paraformaldehyde: 4g paraformaldehyde, prepared with 100ml physiological saline. Anesthetic: 10% uratan injection: 10g uratan, prepared with 100ml normal saline.

[0163] 2. Experimental method

[0164] After the experimental group and the control group animals were grouped according to their weight balance, the experiment was started. First, dissolve the appropriate amount of LPS and CAN in PBS, and prepare the relevant solutions. The experimental group was intragastrically administered with CAN at a dose of 50 mg / ...

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PUM

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Abstract

The invention discloses application of an SGLT2 inhibitor in regulation of inflammation. The invention provides the application of the SGLT2 inhibitor in any one of the following: (a1) preparation ofa product for preventing and / or treating an inflammatory disease; and (a2) prevention and / or treatment of an inflammatory disease. The anti-inflammatory action mechanism of the SGLT2 inhibitor mainlyimproves the inflammatory symptoms by inhibiting carbohydrate metabolism in immune cells, activating autophagy, up-regulating the expression of p62 protein, and inhibiting the production of inflammatory factors. Most SGLT2 inhibitors are tested for clinical safety and are therefore relatively safe.

Description

Technical field [0001] The present invention relates to the field of biomedicine, in particular to the application of sodium-glucose co-transporter 2 (hereinafter referred to as SGLT2) inhibitors in regulating inflammation. Background technique [0002] Inflammation is a complex biological defensive response of body tissues to external stimuli such as pathogens, cell damage, or other irritating substances [Ferrero-Miliani,L.,Nielsen,OH,Andersen,PS&Girardin,SEChronic inflammation:importance of NOD2and NALP3in interleukin-1betageneration. Clinical and experimental immunology 147,227-235, doi:10.1111 / j.1365-2249.2006.03261.x(2007).]. However, excessive inflammation can cause damage to body tissues and organs. In the case of inflammatory stress, immune cells will release a large number of inflammatory factors. The release of too much inflammatory factors will promote the occurrence of tissue inflammation and damage, thereby inducing various diseases, such as peritonitis, rheumatoid ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/381A61P29/00
CPCA61K31/381
Inventor 谢伟东徐晨珂钟今王威许乃寒张雅鸥
Owner SHENZHEN GRADUATE SCHOOL TSINGHUA UNIV
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