RESUMEN
In Alzheimer's disease (AD) the accumulation of amyloid ß (Aß) plaques in the brain leads to neuroinflammation, neuronal cell dysfunction, and progressive memory loss. Therefore, blocking the formation of Aß 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: ß-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 Aß plaques and positively affect transcription factors involved in complex and diverse biological functions.
Asunto(s)
Amidas/farmacología , Secretasas de la Proteína Precursora del Amiloide , Ácido Aspártico Endopeptidasas , Cannabis/química , PPAR gamma , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma , Enfermedad de Alzheimer , Péptidos beta-Amiloides , Animales , Línea Celular , Expresión Génica/efectos de los fármacos , Ratones , Estructura Molecular , Fitoquímicos/farmacología , Semillas/química , España , Tiramina/farmacologíaRESUMEN
Hempseed (Cannabis sativa L.) has beneficial impact on human health mainly because of its wide variability of bioactive compounds. However, many of them are not fully characterized yet. In this work, hempseed was defatted and through a bio-guided studied, two fractions (F03 and F05) with the highest content of phenols, flavonoids and antioxidant capacity were selected. Fractions were chemically analyzed by UHPLC HRMS/MS. The anti-inflammatory capacities of these compounds were evaluated on human monocytes using flow cytometry, RT-qPCR and Elisa procedures. A high amount of phenolic compounds were identified, with the major compound being: N-trans-caffeoyltyramine (6.36 mg g-1 in F05 and 1.28 mg g-1 in F03). Both, F03 and F05 significantly reduced the inflammatory competence of LPS-treated human primary monocytes, decreasing TNF-α and IL-6 gene expression and secretion. These findings indicate that in the defatted fraction of the hempseed there are a wide number of compounds with beneficial potential to prevent and treat inflammatory disorders, as well as other processes caused by oxidative stress.