'Antioxidant' berries, anthocyanins, resveratrol and rosmarinic acid oxidize hydrogen sulfide to polysulfides and thiosulfate: A novel mechanism underlying their biological actions.

Nutraceutical polyphenol catechins in green tea oxidize HS to polysulfides (PS) in buffer and in cells thereby conveying their cytoprotective effects. Here we measure HS oxidation in buffer and HEK293 cells by over-the-counter nutraceuticals, blueberry, bilberry and cranberry, and by polyphenols, cyanadin (Cya), quercetin (Que), rosmarinic acid (RA) and resveratrol (Res). HS and PS were measured with specific fluorophores, AzMc and SSP4 respectively, and thiosulfate (TS) production was measured in buffer using silver nanoparticles (AgNPs). All compounds increased polysulfide production from HS in buffer and increased polysufides in cells. Decreasing oxygen from 100% to 21% and 0% progressively decreased PS production by Que and RA in buffer and Que decreased PS production in cells incubated in 5% O compared to 21% O. Que, RA and Res, but not Cya, increased TS production from HS in 21% O but not in 0% O. Superoxide dismutase did not affect PS production from HS by Que or TS production from HS by Que, RA or Res, whereas catalase inhibited TS production by all three polyphenols. Conversely, these polyphenols only slightly reduce a mixed polysulfide (KS) or thiosulfate to HS in 0% O. Collectively, our results suggest that polyphenols are autoxidized to a semiquinone radical and that this, in turn, oxidizes HS to a thiyl radical from which polysulfides and thiosulfate derived. They also suggest that this is catalyzed by a semiquinone radical and it is independent of either superoxide or hydrogen peroxide concomitantly produced during polyphenol autoxidation. The polysulfides produced in these reactions are potent antioxidants and also initiate a variety of downstream cytoprotective effector mechanisms. It is also possible that HS can be regenerated from the thiosulfate produced in these reactions by other cellular reductants and reused in subsequent reactions.