Protective Effect of a Novel (2S, 3R, 4S)-Chromene-3-Carboxamide Derivative, Z20 Against Sepsis-Induced Organ Injury
Autor: | Peng Chen, Yuhang Wang, Na Li, Mengwei Niu, Yong Wang, Li-Yan Zeng |
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Rok vydání: | 2020 |
Předmět: |
0301 basic medicine
medicine.medical_specialty business.industry Immunology Inflammation Pharmacology medicine.disease Intensive care unit Rheumatology law.invention Proinflammatory cytokine Sepsis 03 medical and health sciences 030104 developmental biology 0302 clinical medicine In vivo law 030220 oncology & carcinogenesis Internal medicine medicine Immunology and Allergy medicine.symptom business Receptor Survival rate |
Zdroj: | Inflammation. 43:1222-1232 |
ISSN: | 1573-2576 0360-3997 |
DOI: | 10.1007/s10753-019-01174-z |
Popis: | Sepsis, a systemic inflammatory response mediated by excessive production of diverse inflammatory cytokines, remains the vital cause of morality in the intensive care unit (ICU). TLR4-MD2 (toll-like receptor 4-myeloid differentiation factor 2) complex activated by LPS serves as an effective target to decrease the inflammation during sepsis. In this study, we evaluated the effects of a new small molecule Z20 structural based on (2S, 3R, 4S)-chromene-3-carboxamide on LPS-induced sepsis in mice. We found Z20 markedly improved the survival rate and attenuated the multiply organs injury after LPS administration in mice. In addition, Z20 significantly alleviated organ inflammation as characterized by diminished inflammatory factors expression in vivo. Furthermore, by employing surface plasmon resonance (SPR) experiment, we identified that TLR4-MD2 complex was the potential target for Z20. Finally, we performed the safety assessment experiment to confirm the safety of Z20 in vivo. In conclusion, Z20, as a potential TLR4-MD2 inhibitor, effectively attenuated LPS-induced organ injury and inflammation. |
Databáze: | OpenAIRE |
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