Effect of Glucoraphanin on the Abundance of Nrf2 Regulated Genes Within Circulating Small Extracellular Vesicles: A Pilot Dietary Intervention

Cruciferous vegetables, including broccoli, are associated with a reduced risk of age-related chronic diseases. Broccoli accumulates glucoraphanin, which is hydrolyzed to sulforaphane, an isothiocyanate, that activates antioxidant genes via nuclear factor (erythroid-derived 2)-like 2 (Nrf2) transcription factor, thereby alleviating age-related diseases. However, sulforaphane's rapid metabolism and excretion raise questions about its efficacy on peripheral tissues. We hypothesize that consumption of a glucoraphanin-rich broccoli soup induces small extracellular vesicles (sEVs) in the systemic circulation, containing Nrf2-induced antioxidant genes, mediating the effects of broccoli consumption on peripheral tissues. Nine adults participated in a two-arm, single-blinded, randomized crossover trial and consumed a glucoraphanin-rich broccoli soup (intervention) and a control soup. Plasma samples were analyzed to quantify abundance of Nrf2 regulated genes within circulating sEVs, while urine samples were analyzed to determine sulforaphane pharmacokinetics. While sulforaphane was detected in urine following the intervention (p < 0.001), there were no differences in the abundance of Nrf2 regulated genes quantified within circulating sEVs. Urinary sulforaphane profiling confirmed the intervention's efficacy; however, the genes examined were unaltered within circulatory sEVs. Given that EV mRNA does not always relate to function, future studies exploring EV proteomics may provide further insights into sulforaphane's underlying mechanisms.