Abstract

Alzheimer’s disease (AD) is an age-related neurodegenerative disease that is mediated by multiple signaling pathways. In recent years, the components of Psoralea Fructus (PF) have demonstrated some anti-Alzheimer effects both in vitro and in vivo. To further reveal the active compounds of PF and their mechanisms regulating key targets of AD, in this study, we identified four prenylated compounds from the 70% ethanolic aqueous extract of PF, namely bavachin, bavachinin, bavachalcone, and isobavachalcone. Multi-target bioactivity analysis showed that these compounds could differentially inhibit neuroinflammation, oxidative damage, and key AD-related protein targets, such as amyloid β-peptide 42, β-secretase, glycogen synthase kinase 3β, and acetylcholinesterase. These compounds may generate beneficial effects in AD prevention and treatment.

Highlights

  • The Leguminosae plant, Cullen corylifolium (L.) Medik

  • We further examined their in vitro anti-Alzheimer’s disease (AD) activities involving multiple drug targets containing and isobavachalcone (4)

  • We further examined the effect of Psoralea Fructus (PF) compounds on LPS-induced production of inflammatory release of these proinflammatory cytokines could be valuable for the treatment of cytokines tumor necrosis factor (TNF)-α and IL-6

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Summary

Introduction

The Leguminosae plant, Cullen corylifolium (L.) Medik. (syn. Psoralea corylifolia L.), is a medicinal plant widely distributed in China, India and Southeastern Asian countries. As we have addressed in our previous reports, long-term dietary intake of the total prenylflavonoids (TPFB) of PF at 50 mg/kg·day significantly improved cognitive performance and AD-like neurobiochemical changes in an age-related AD mouse model SAMP8 [9], and some PF compounds could modulate amyloid β-peptide 42 (Aβ42) aggregation process in vitro [11]. We have demonstrated that major compounds of PF could be absorbed and distributed to the cerebral nuclei of we have demonstrated that major compounds of PF could be absorbed and distributed to Sprague-Dawley rats after oral administration of a single dose of PFE at 1.2 g/kg [12] These data the cerebral nuclei of Sprague-Dawley rats after oral administration of a single dose of PFE at suggested the potential value of PF compounds in AD prevention and treatment, motivated us.

Discussion
Anti-neuroinflammatory effects ofofPsoralea
Anti-Oxidative Effects in PC-12 Cells
Inhibitory
General Information
Plant Material
Chemicals and Reagents
Compound Characterization
Inhibition Assay on NO Release
Inhibition Assay on Cytokine Release
Anti-Oxidative Effect in H2 O2 -Induced PC-12 Cells
Anti-Aggregation Assay of Aβ42
3.10. Docking Studies of Aβ42 Monomer
Conclusions

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