Article ; Online: 1-Deoxynojirimycin attenuates septic cardiomyopathy by regulating oxidative stress, apoptosis, and inflammation via the JAK2/STAT6 signaling pathway.
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie
2022 Volume 155, Page(s) 113648
Abstract: Cardiac dysfunction caused by sepsis is the predominant reason for death in patients with sepsis. However, the effective drugs for its prevention and the molecular mechanisms remain elusive. 1-Deoxynojirimycin (DNJ), a natural iminopyranose, exhibits ... ...
| Abstract | Cardiac dysfunction caused by sepsis is the predominant reason for death in patients with sepsis. However, the effective drugs for its prevention and the molecular mechanisms remain elusive. 1-Deoxynojirimycin (DNJ), a natural iminopyranose, exhibits various biological properties, such as hypoglycemic, antitumor, antiviral, and anti-inflammatory activities. However, whether DNJ can mediate biological activity resistance in sepsis-induced myocardial injury and the underlying mechanisms are unclear. Janus kinase and signal transducer and activator of transcription (JAK/STAT) signaling is an important pathway for the signal transduction of several key cytokines in the pathogenesis of sepsis, which can transcribe and modulate the host immune response. This study was conducted to confirm whether DNJ mediates oxidative stress, apoptosis, and inflammation in cardiomyocytes, thereby alleviating myocardial injury in sepsis via the JAK2/STAT6 signaling pathway. Septic cardiomyopathy was induced in mice using lipopolysaccharide (LPS), and they were then treated with DNJ. The results showed that DNJ markedly improved sepsis-induced cardiac dysfunction, attenuated reactive oxygen species generation, reduced cardiomyocyte apoptosis, and mitigated inflammation. Mechanistically, increased JAK2/STAT6 phosphorylation was observed in the mouse sepsis models, which decreased significantly after DNJ oral treatment. To further confirm whether DNJ mediates the JAK2/STAT6 pathway, the selective inhibitor fedratinib was used to block the JAK2 signaling pathway in vitro, which enhanced the protective effects of DNJ against the sepsis-induced cardiac damage. Collectively, these findings suggest that DNJ attenuates sepsis-induced myocardial injury by decreasing myocardial oxidative damage, apoptosis, and inflammation via the regulation of the JAK2/STAT6 signaling pathway. |
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| MeSH term(s) | Mice ; Animals ; 1-Deoxynojirimycin/pharmacology ; Lipopolysaccharides/pharmacology ; Reactive Oxygen Species ; Janus Kinase 2/metabolism ; Signal Transduction ; Apoptosis ; Inflammation/drug therapy ; Oxidative Stress ; Janus Kinases/metabolism ; Sepsis/complications ; Sepsis/drug therapy ; Cytokines/metabolism ; Hypoglycemic Agents/pharmacology ; Cardiomyopathies/drug therapy ; Cardiomyopathies/etiology ; Heart Diseases/drug therapy ; Antiviral Agents/pharmacology |
| Chemical Substances | 1-Deoxynojirimycin (19130-96-2) ; Lipopolysaccharides ; Reactive Oxygen Species ; Janus Kinase 2 (EC 2.7.10.2) ; Janus Kinases (EC 2.7.10.2) ; Cytokines ; Hypoglycemic Agents ; Antiviral Agents ; Stat6 protein, mouse |
| Language | English |
| Publishing date | 2022-09-13 |
| Publishing country | France |
| Document type | Journal Article |
| ZDB-ID | 392415-4 |
| ISSN | 1950-6007 ; 0753-3322 ; 0300-0893 |
| ISSN (online) | 1950-6007 |
| ISSN | 0753-3322 ; 0300-0893 |
| DOI | 10.1016/j.biopha.2022.113648 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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