European journal of pharmacology
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Sulforaphane has received considerable attention in recent years due to its antioxidant and anti-inflammatory properties. Its preventive effect in the inhibition of airway inflammation is known; however, whether it affects mixed granulocyte asthma (corticosteroid resistance phenotype) is largely undiscovered. Therefore, we assessed the effect of pharmacological activation of Nrf2, a redox-sensitive transcription factor, using sulforaphane in a mouse model of mixed granulocyte airway inflammation. ⋯ Collectively, our study presents the evidence that activation of Nrf2 by sulforaphane reduces neutrophilic airway inflammation by upregulation of antioxidants and downregulation of inflammatory cytokines in airways. This is possibly the basis for reversal of corticosteroid resistance in this model. This shows the therapeutic potential of sulforaphane in mixed granulocyte asthma.
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Hemoglobinopathies, such as β-thalassemia, and sickle cell disease (SCD) are caused by abnormal structure or reduced production of β-chains and affect millions of people worldwide. Hereditary persistence of fetal hemoglobin (HPFH) is a condition which is naturally occurring and characterized by a considerable elevation of fetal hemoglobin (HbF) in adult red blood cells. Individuals with compound heterozygous β-thalassemia or SCD and HPFH have milder clinical symptoms. ⋯ In our study, deletion of 200bp of BCL11A erythroid enhancer including GATAA motif leads to strong induction of γ-hemoglobin expression in K562 cells, but not in KU-812 and KG-1 cells. Altogether, our findings highlight the therapeutic potential of CRISPR-Cas9 as a precision genome editing tool for treating β-thalassemia. In addition, our data indicate that KU-812 and KG-1 cell lines are not good models for studying HbF reactivation through inactivation of BCL11A silencing pathway.
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Nobiletin (3',4',5,6,7,8-hexamethoxyflavone), a dietary polymethoxylated flavonoid found in Citrus fruits, was reported to exhibit protective activity against ischemia/reperfusion (I/R). However, the role of nobiletin in myocardial I/R injury remains unclear. This study was designed to examine the cardioprotective effect of nobiletin from myocardial hypoxia/reoxygenation (H/R) injury in vitro, and to explore the potential molecular mechanisms. ⋯ Furthermore, we observed that pretreatment with nobiletin significantly activated the Akt/GSK-3β signaling pathway in H/R-stimulated H9c2 cells. Taken together, these findings demonstrated that nobiletin attenuates myocardial I/R injury via the activation of Akt/GSK-3β pathway in H9c2 cardiomyocytes. Thus, nobiletin may be regarded as a promising drug for the prevention of myocardial I/R injury and ischemic heart disease.