Abstract
Mitophagy, a process of sequestering and eliminating damaged mitochondria from cells, is a critical process for maintaining proper cellular functions. This process has been investigated as a potential therapeutic target for cancer, aging, and a few neurodegenerative diseases. Quercetin and other polyphenols found in cranberries, teas and other plants have shown anti-aging properties, however, the anti-aging mechanisms are still poorly understood. The abilities of quercetin, a few other polyphenols, a cranberry extract and a tea extract to induce mitophagy were examined in normal human fibroblast WS1 cells under a confocal microscope. Quercetin demonstrated comparable efficacy to urolithin A, a known mitophagy inducer, in inducing mitophagy in WS1 cells, with maximum efficacy at 10 μM, followed by decreasing efficacy with increasing concentration. Polyphenols induced mitophagy with maximum effective concentrations of 5 μg/mL for anthocyanins, 50 μg/mL for proanthocyanidins and 0.4 μg/mL for flavonols. Dilutions of a cranberry extract induced mitophagy and showed the same trend as quercetin. The cranberry dilution with a concentration of 4 μg/mL was the strongest mitophagy inducer. Flavonols appear to be the strongest contributor to cranberry’s ability to induce mitophagy. Anthocyanins also contribute significantly, however, proanthocyanidins have a smaller contribution. The most abundant polyphenols in tea, catechins, were also examined for the ability to induce mitophagy in normal human fibroblast WS1 cells. Catechin and epigallocatechin demonstrated comparable efficacy to quercetin and urolithin A in inducing mitophagy in WS1ivcells, with maximum efficacy at 10 μM, followed by decreasing efficacy with increasing concentration. Epicatechin, epicatechin gallate and epigallocatechin gallate (EGCG) demonstrated comparable efficacy to catechin and epigallocatechin in their ability to induce mitophagy in WS1 cells. The maximum effective concentration for each polyphenol was 5 μM. At concentrations higher than 5 μM efficacy was decreased. Dilutions of a tea extract induced mitophagy and showed the same trend as the catechins with the most effective concentration being 5 μg/mL. EGCG and epigallocatechin were identified as the strongest contributors to tea’s ability to induce mitophagy. The data in this study demonstrate that the polyphenols in cranberries and teas are powerful inducers of mitophagy in human fibroblast cells. Working at micromolar concentration, cranberry flavonols and tea EGCG and epigallocatechin are the most effective inducers. The results shed new light on the mechanism of action of the health benefits of cranberry and teas.