Phenolic Compounds from Haskap Berries Have Structure, Combination, and Cell Line-Dependent Impacts on the Longevity-Associated Deacetylase Sirtuin 1.

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It is well established that phenolic compounds from plant sources impact readouts of cell health such as reduced radical and reactive oxygen species. However, it is unclear if specific phenolic structures impact other cellular processes or proteins, such as the evolutionary conserved deacetylase Sirtuin 1 (SIRT1), and if phenolic combinations interact synergistically to do so. We observed that structurally diverse haskap berry phenolics (caffeic acid, cyanidin, kaempferol-3-O-glucoside, and gentisic acid) differentially impacted normal primary human fibroblast growth, which has been linked to SIRT1. These results were consistent with previous work from our lab indicating that haskap phenolic extracts/fractions impact human cell growth via SIRT1-dependent mechanisms. Therefore, we furthered the investigation into SIRT1 and phenolic structure and observed that the individual phenolics or their combinations had no observable impact on SIRT1 transcript abundance or cellular localization. We also observed that select phenolics decreased SIRT1 protein abundance and increased SIRT1 activity. The catechol-containing phenolics outperformed those that lack a catechol group, indicating potential structure-dependent impact(s). Potential synergy between the specific phenolics analyzed was observed in Western blot, and potential antagonism was identified in the SIRT1 activity assay. Results were concomitant with the presence of different phenolic structures, phenolic combinations, and cell type (sex and/or individual differences). These results highlight the possible significance of the catechol structure and indicate that phenolics have the potential to impact cell processes, which the authors hypothesize to be due to mechanisms that are independent of antioxidant activity.