ReferenceID 2297
Matrine suppresses NLRP3 inflammasome activation via regulating PTPN2/JNK/SREBP2 pathway in sepsis
Phytomedicine
Background: Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. Abnormal activation of NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflam
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- Reference Id
- 2297
- Evidence Id
- 18887
- Core Evidence Id
- 18887
- Source Reference Id
- 4622
- Herb2 Reference Id
- HBREF005419
- Subject Paper Key
- HBIN034558_36610161
- Pubmed Id
- 36610161
- Doi
- 10.1016/j.phymed.2022.154574
- Paper Title
- Matrine suppresses NLRP3 inflammasome activation via regulating PTPN2/JNK/SREBP2 pathway in sepsis
- Paper Abstract
- Background: Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. Abnormal activation of NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome plays a vital role in the pathogenesis of sepsis. Matrine is proved to show good anti-inflammatory properties, whereas its effect and the underlying molecular machinery on sepsis remains unclear. Purpose: The aim of this study is to evaluate the effect and mechanism of Matrine on sepsis. Study design: THP-1 cells and J774A.1 cells were stimulated by lipopolysaccharide (LPS) with nigericin or adenosine triphosphate (ATP) to establish an in vitro model. Cecal ligation and puncture (CLP)-induced sepsis mouse model was used. Matrine was given by gavage. Methods: To investigate the NLRP3 inflammasome activation, phorbol myristate acetate (PMA)-induced THP-1 cells were first primed with LPS and then stimulated by matrine, followed by treatment with nigericin or ATP. The concentration of interleukin 1β (IL-1β) and interleukin 18 (IL-18) in the cell culture supernatant was detected. The mechanism was explored by cell death assay, immunoblots and immunofluorescence in vitro. C57BL/6 mice were intragastrically administered with matrine for 5 days before CLP. The therapeutic effect of matrine was evaluated by symptoms, pathological analysis, ELISA and RT-qPCR. Results: Our results revealed that matrine inhibited IL-1β and IL-18 secretion, suppressed caspase-1 activation, reduced cell death, and blocked ASC speck formation upon NLRP3 inflammasome activation. Furthermore, matrine restrains NLRP3 inflammasome activation as well as pyroptosis through regulating the protein tyrosine phosphatase non-receptor type 2 (PTPN2)/JNK/SREBP2 signaling. Matrine also prominently improved the symptoms and pathological changes with reduced levels of TNF-α, IL-1β, and IL-6 in the lung tissues and serum in a dose-dependent manner. Conclusion: Matrine effectively alleviates the symptoms of CLP-induced sepsis in mice, restrains NLRP3 inflammasome activation by regulating PTPN2/JNK/SREBP2 signaling pathway, and may become a promising therapeutic agent for sepsis treatment.
- Journal
- Phytomedicine
- Publish Year
- 2023
- Experiment Subject
- mouse; j774a.1 cells; thp-1 cells
- Experiment Type
- Animal & Cell Experiment
- Phenotype Related
- Sepsis; Organ Dysfunction; Cecal Ligation And Puncture
- Paper Title Cn
- Paper Title En
- Matrine suppresses NLRP3 inflammasome activation via regulating PTPN2/JNK/SREBP2 pathway in sepsis
- Bilingual Status
- semi_complete