ReferenceID 1477
Cardamonin protects against lipopolysaccharide-induced myocardial contractile dysfunction in mice through Nrf2-regulated mechanism
Acta Pharmacol Sin
In patients with sepsis, lipopolysaccharide (LPS) from the outer membrane of gram-negative bacteria triggers cardiac dysfunction and heart failure, but target therapy for septic cardiomyopathy remains unavailable. In thi
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- Reference Id
- 1477
- Evidence Id
- 18067
- Core Evidence Id
- 18067
- Source Reference Id
- 2957
- Herb2 Reference Id
- HBREF003754
- Subject Paper Key
- HBIN019722_32317756
- Pubmed Id
- 32317756
- Doi
- 10.1038/s41401-020-0397-3
- Paper Title
- Cardamonin protects against lipopolysaccharide-induced myocardial contractile dysfunction in mice through Nrf2-regulated mechanism
- Paper Abstract
- In patients with sepsis, lipopolysaccharide (LPS) from the outer membrane of gram-negative bacteria triggers cardiac dysfunction and heart failure, but target therapy for septic cardiomyopathy remains unavailable. In this study we evaluated the beneficial effects of cardamonin (CAR), a flavone existing in Alpinia plant, on endotoxemia-induced cardiac dysfunction and the underlying mechanisms with focus on oxidative stress and apoptosis. Adult mice were exposed to LPS (4 mg/kg, i.p. for 6 h) prior to functional or biochemical assessments. CAR (20 mg/kg, p.o.) was administered to mice immediately prior to LPS challenge. We found that LPS challenge compromised cardiac contractile function, evidenced by compromised fractional shortening, peak shortening, maximal velocity of shortening/relengthening, enlarged LV end systolic diameter and prolonged relengthening in echocardiography, and induced apoptosis, overt oxidative stress (O2- production and reduced antioxidant defense) associated with inflammation, phosphorylation of NF-kappaB and cytosolic translocation of transcriptional factor Nrf2. These deteriorative effects were greatly attenuated or mitigated by CAR administration. However, H&E and Masson's trichrome staining analysis revealed that neither LPS challenge nor CAR administration significantly affected cardiomyocyte cross-sectional area and interstitial fibrosis. Mouse cardiomyocytes were treated with LPS (4 microg/mL) for 6 h in the absence or presence of CAR (10 muM) in vitro. We found that addition of CAR suppressed LPS-induced defect in cardiomyocyte shortening, which was nullified by the Nrf2 inhibitor ML-385 or the NF-kappaB activator prostratin. Taken together, our results suggest that CAR administration protects against LPS-induced cardiac contractile abnormality, oxidative stress, apoptosis, and inflammation through Nrf2- and NF-kappaB-dependent mechanism.
- Journal
- Acta Pharmacol Sin
- Publish Year
- 2021
- Experiment Subject
- mouse; patient
- Experiment Type
- Animal Experiment
- Phenotype Related
- Sepsis; Heart Failure; Interstitial Fibrosis; Cardiac Dysfunction; Septic Cardiomyopathy; Cardiac Contractile Abnormality
- Paper Title Cn
- Paper Title En
- Cardamonin protects against lipopolysaccharide-induced myocardial contractile dysfunction in mice through Nrf2-regulated mechanism
- Bilingual Status
- semi_complete