Glycyrrhiza uralensis and Semilicoisoflavone B Reduce Aβ Secretion by Increasing PPARγ Expression and Inhibiting STAT3 Phosphorylation to Inhibit BACE1 Expression
التفاصيل البيبلوغرافية
العنوان:
Glycyrrhiza uralensis and Semilicoisoflavone B Reduce Aβ Secretion by Increasing PPARγ Expression and Inhibiting STAT3 Phosphorylation to Inhibit BACE1 Expression
cope : Glycyrrhiza uralensis extract (GUE) has been reported to improve amyloid beta (Aβ) induced cognitive deficits in mice. However, the mechanisms underlying this effect and the components involved have not been previously explored. Extracellular Aβ plaques are one of the major pathological hallmarks of Alzheimer's disease (AD). Therefore, decreasing Aβ levels is one strategy for preventing the etiology of AD. This study aimed to test the effect of GUE and semilicoisoflavone B (SB) on Aβ secretion and investigate the mechanism underlying this effect. Methods and results : GUE and its bio-activated compound SB reduced Aβ secretion. We found that this effect contributed to the down-regulation of the β-secretase-1 (BACE1) protein and mRNA. In a subsequent mechanism study, we found that GUE and SB regulated BACE1 transcription factors by inducing the expression of peroxisome proliferator activated receptor-γ (PPARγ) and inhibiting the phosphorylation of signal transducer and activator of transcription 3 (STAT3). In addition, the effect of GUE and SB on BACE1 expression and Aβ secretion were attenuated by treatment with PPARγ-siRNA or its antagonist, GW9662. Conclusion : These findings indicate that GUE and SB may function as PPARγ agonists, thereby inhibiting BACE1 expression and ultimately reducing the secretion of Aβ. This article is protected by copyright. All rights reserved