Consumption of an anthocyanin-rich extract increases circulating BDNF and BDNF gene expression in healthy subjects consuming a high fat meal

Abstract

Brain-derived neurotrophic factor (BDNF) is a growth factor that has a central role in sustaining brain function. Besides the brain, BDNF is also expressed in immune cells. In preclinical models, anthocyanin (AC) consumption has been associated with benefits in BDNF homeostasis. This study investigated in healthy adults if the simultaneous consumption of a high fat meal (HFM) with a cyanidin/delphinidin-rich extract (CDRE) could affect circulating BDNF, and BDNF expression in peripheral blood mononuclear cells (PBMCs). Underlying mechanisms were investigated in Jurkat T cells. While the HFM did not affect serum BDNF in the placebo group, simultaneous CDRE consumption caused a significant cumulative (1-3 h) BDNF increase, peaking at 2 h post-meal. The area under the curve (AUC) for the most abundant phenolic acids measured in serum, i.e. 4-hydroxyhippuric acid (HA) and 4-hydroxy-3-methoxybenzoic acid (vanillic acid, VA)-3-O-glucuronide correlated with the AUC for serum BDNF. As evaluated in Jurkat-T cells, this could be due to HA and VA capacity to increase cytosolic calcium. The CDRE also increased BDNF expression in PBMCs 3 h post-consumption. In vitro and molecular modeling evidence point to two mechanisms of action: i) indirect protection of BDNF expression through CDRE anti-inflammatory actions, and ii) a direct capacity of HA and VA to activate the β2-adrenergic receptor and downstream cAMP/PKA/CREB-mediated BDNF gene expression. While the short-term effects of CDRE consumption can be due to their presence in the extract, AC and phenolic acid metabolism by the microbiota would later generate HA and VA and consequently benefit BDNF homeostasis.