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Application of sglt2 inhibitors in regulating inflammation

An inhibitor and inflammation technology, applied in the application field of sodium-glucose co-transporter 2 inhibitors in the regulation of inflammation, can solve the problems of poor patient compliance and lack of anti-inflammatory drugs, and achieve the effect of improving inflammatory symptoms

Active Publication Date: 2022-04-19
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 inhibitors in regulating inflammation
  • Application of sglt2 inhibitors in regulating inflammation
  • Application of sglt2 inhibitors in regulating inflammation

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

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

[0047] 1. Experimental materials

[0048] 1. Compound

[0049] SGLT2 inhibitors (CAN, Empagliflozin, Dapagliflozin, Bexagliflozin, Ipragliflozin and Tofogliflozin hydrate), Metformin hydrochloride, Rosglitazone, Glibenclamide, Salsalate, Liraglutide, Sitagliptin and Insulin were purchased from MedChemExpress (MCE) in the United States; chloroform was from Tianjin Hongyan Chemical Reagent Factory, dimethyl sulfoxide (DMSO), absolute ethanol and isopropanol were purchased from Sangon Bioengineering (Shanghai) Co., Ltd.; lipopolysaccharide (LPS) was purchased from Sigma-Aldrich (Lot.No. L4391), dissolved in ultrapure water and stored at -20°C.

[0050] 2. Cell source

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

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; the 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, American Agilent Technologies, Inc. company); ECL reagent (Pierce TM ECL Western blotting substrate) was purchased from Thermo Fisher Scientific, USA).

[0107] 2. Primer sequence

[0108] p62 (Forward: 5'-GAACTCGCTATAAGTGCAGTGT-3'; Reverse: 5'-AGAGAAGCTATCAGAGAGGTGG-3') was purchased from ThermoFisher Scientific (Invitrogen TM )synthesis. The Actin primers in Table 1 of Example 1 were used as controls.

[0109] 3. Instrument

[0110] Fluorescence confocal microscope (FV1...

Embodiment 3

[0157] Example 3: Production of LPS-induced pulmonary inflammation model and activity evaluation in mice

[0158] 1. Experimental materials

[0159] 1. Experimental animals and food

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

[0161] 2. Chemical reagents

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

[0163] 2. Experimental method

[0164] After the animals in the experimental group and the control group were divided into balanced groups according to body weight, the experiment was started. Firstly, appropriate amounts of LPS and CAN were dissolved in PBS to prepare relevant solutions. 12 hours in advance and 1 hour in advance, the ...

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Abstract

The invention discloses an application of an SGLT2 inhibitor in regulating inflammation. The present invention provides the application of the SGLT2 inhibitor in any of the following: (a1) preparing products for preventing and / or treating inflammatory diseases; (a2) preventing and / or treating inflammatory diseases. The anti-inflammatory mechanism of SGLT2 inhibitors mainly improves inflammatory symptoms by inhibiting glucose metabolism in immune cells, activating autophagy, up-regulating the expression of p62 protein, and inhibiting the production of inflammatory factors. Most SGLT2 inhibitors have undergone clinical safety testing, so they are relatively safe.

Description

technical field [0001] The invention relates to the field of biomedicine, in particular to the application of sodium-glucose co-transporter 2 (Sodium-glucose co-transporter 2, hereinafter referred to as SGLT2) inhibitor in regulating inflammation. Background technique [0002] Inflammation is a complex biological defense response of body tissues to external stimuli such as pathogens, cell damage, or other irritating substances [Ferrero-Miliani, L., Nielsen, O.H., Andersen, P.S. & Girardin, S.E. Chronic inflammation: importance of NOD2and NALP3in interleukin-1betageneration. Clinical and experimental immunology 147, 227-235, doi:10.1111 / j.1365-2249.2006.03261.x(2007).]. But 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, excessive and prolonged release of inflammatory factors will promote the occurrence of tissue inflammatory damage, thereby inducing a va...

Claims

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Application Information

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Patent Type & Authority Patents(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