Dietary Total Prenylflavonoids from the Fruits of Psoralea corylifolia L. Prevents Age-Related Cognitive Deficits and Down-Regulates Alzheimer’s Markers in SAMP8 Mice

Abstract

Alzheimer’s disease (AD) is a serious threat for the aging society. In this study, we examined the preventive effect of the total prenylflavonoids (TPFB) prepared from the dried fruits of Psoralea corylifolia L., using an age-related AD mouse model SAMP8. We found that long-term dietary TPFB at 50 mg/kg·day significantly improved cognitive performance of the SAMP8 mice in Morris water maze tests, similar to 150 mg/kg·day of resveratrol, a popular neuro-protective compound. Furthermore, TPFB treatment showed significant improvements in various AD markers in SAMP8 brains, which were restored to near control levels of the normal mice, SAMR1. TPFB significantly reduced the level of amyloid β-peptide 42 (Aβ42), inhibited hyperphosphorylation of the microtubule-associated protein Tau, induced phosphorylation of Ser9 of the glycogen synthase kinase 3β (GSK-3β), and decreased the expression of the proinflammatory cytokines TNFα, IL-6, and IL-1β. Finally, TPFB also markedly reduced the level of serum derivatives of reactive oxygen metabolites (d-ROMs), a biomarker of oxidative stress in vivo. These results showed that dietary TPFB could effectively prevent age-related cognitive deficits and AD-like neurobiochemical changes, and may have a potential role in the prevention of Alzheimer’s disease.

6-Bromoindirubin-3′-Oxime (6BIO) Suppresses the mTOR Pathway, Promotes Autophagy, and Exerts Anti-aging Effects in Rodent Liver

“…The level of Akt phosphorylation was observed because Akt is upstream of both the mTOR pathway and GSK-3β pathway. Previous studies have reported that inhibition of the mTOR pathway and GSK-3β pathway ameliorated age-related pathologic changes (Chen et al., 2018; Yuan et al., 2018). The results showed that 6BIO not only inhibits GSK-3β signaling, in concordance with the findings of previous studies (Ko et al., 2018), but also inhibits mTOR signaling, whereas rapamycin inhibits the mTOR pathway but activates GSK-3β signaling via feedback activation of Akt originating from S6K (Wu et al., 2018).…”

Inhibitory Effects of Isobavachalcone on Tau Protein Aggregation, Tau Phosphorylation, and Oligomeric Tau-Induced Apoptosis

“…48 It could also effectively prevent age-related cognitive deficit in mice. 49 Moreover, an imbalance between the pro-oxidant and antioxidant produces oxidative stress in the early stage of AD. 50 The generation of ROS and free radicals would cause toxicities to neural cells such as lipid peroxides accumulation, carbonyl proteins disorder, and oxidative DNA damage in the brain.…”

“…It has been reported that isobavachalcone significantly inhibits both oligomerization and fibrillization of Aβ 42 . It could also effectively prevent age-related cognitive deficit in mice . Moreover, an imbalance between the pro-oxidant and anti-oxidant produces oxidative stress in the early stage of AD .…”

Combined Modeling Study of the Binding Characteristics of Natural Compounds, Derived from Psoralea Fruits, to β-Amyloid Peptide Monomer

“…PF has been utilized as a conventional Chinese pharmaceutical for well-being supplement fixing [ 24 ]. PF has been reported to contain compounds with molecular diversity, with a few of these displaying estrogen-like, anti-oxidant, osteoblastic, anticancer, antidepressant, anti-inflammatory, hepatoprotective [ 25 ], and antimicrobial activities [ 26 ]. Furthermore, in an AD mouse model, long-term dietary intakes of PF’s total prenylflavonoids (TPFB) at 50 mg/kg day significantly enhanced cognitive function and AD-like neurobiochemical alterations [ 27 ], and could modulate amyloid β-peptide 42 (Aβ42) aggregations in vitro [ 28 ].…”