Dual Role of Phenyl Amides from Hempseed on BACE 1, PPARγ, and PGC-1α in N2a-APP Cells

Abstract

In Alzheimer’s disease (AD) the accumulation of amyloid β (Aβ) plaques in the brain leads to neuroinflammation, neuronal cell dysfunction, and progressive memory loss. Therefore, blocking the formation of Aβ plaques has emerged as one of the most promising strategies to develop AD treatments. Hempseed is widely used as a food, and recently its compounds have shown beneficial effects on neuroinflammation. The objective of this study was to investigate whether a fraction rich in phenyl amide compounds, N - trans -caffeoyltyramine (CAFT) and N - trans -coumaroyltyramine (CUMT), can affect gene expression: β-site amyloid-precursor-protein-cleaving enzyme 1 (BACE 1), peroxisome proliferator-activated receptor gamma (PPAR γ), and PPARγ-coactivator-1α (PGC-1α) in N2a-APP cells. The mRNA levels were measured using RT-qPCR. The ethyl acetate fraction and CAFT were found to reduce BACE1 gene expression and are promissory PPARγ and PGC-1α natural agonists. The results show that hempseed compounds can inhibit the expression of BACE 1, which is involved in the accumulation of Aβ plaques and positively affect transcription factors involved in complex and diverse biological functions.

Possible neuroprotective effects of amide alkaloids from Bassia indica and Agathophora alopecuroides: in vitro and in silico investigations

“…Taking into account previous reports that have discussed the possible neuroprotective activity of N-trans-feruloyltyramine through the stimulation of neurogenesis and neurotrophins, 34 in addition to the role of N-trans-caffeoyltyramine and N-transcoumaroyltyramine in the reduction of BACE1 gene expression, 6 our study results suggested the contribution of amide alkaloids as effective lead compounds for the development of AD therapies. Furthermore, the study reveals the benecial effects of B. indica and A. alopecuroides in the prevention as well as the potential treatment of neurodegenerative diseases owing to their phenyl amide contents.…”

“…Recently, bioactive compounds derived from plants have shown promising therapeutic activity in neurodegenerative diseases, making their evaluation as a source of alternative medicine for AD an effective approach. 6 Halophytes are plants with substantial economic potential and are potential sources of medication. 7 Several species of halophytes have been utilized in folk medicine for their ability to produce various bioactive compounds, such as terpenes, saponins, and alkaloids.…”

“…Recently, bioactive compounds derived from plants have shown promising therapeutic activity in neurodegenerative diseases, making their evaluation as a source of alternative medicine for AD an effective approach. 6…”

Synthesis and properties of the kojic acid dimer and its potential for the treatment of Alzheimer's disease

“…Although the pathogenesis of AD is not completely clear, several hallmarks are associated with the pathological development of AD, including the abnormal accumulation of amyloid-β (Aβ) and tau protein, reactive oxygen species (ROS), and metal ions along with neuroinflammation. [8][9][10][11] Aβ is generated by the proteolysis of amyloid precursor protein (APP). The protein is first cleaved at its N-terminus by β-secretase (also called β-site APP cleavage enzyme1 (BACE1)), 12 and then the carboxy-terminal fragment (CTFβ) is cleaved by γ-secretase to form Aβ-peptide.…”

“…Although the pathogenesis of AD is not completely clear, several hallmarks are associated with the pathological development of AD, including the abnormal accumulation of amyloid-β (Aβ) and tau protein, reactive oxygen species (ROS), and metal ions along with neuroinflammation. 8–11…”