Metabolism and Anti-inflammatory Activity of Anthocyanins in Human Oral Cavity.

摘要

Anthocyanins (ACN), natural pigment flavonoids, exhibit chemopreventive, chemotherapeutic, and anti-inflammatory activities in the oral cavity. ACN have recently been included into products for the promotion of oral health. However, it is unclear which ACN-rich foods could be most efficacious. Since fruits and vegetables contain unique mixtures of ACNs, an understanding of effect of ACN structure on metabolism, bioavailability, and bioactivity is needed for providing sound dietary recommendations and development of products containing ACN for promotion of oral health.;ACN extracts from blueberry, chokeberry, black raspberry, red grape, and strawberry were incubated ex vivo for 60 min in human saliva (Chapter 2). Degradation of chokeberry ACN was primarily enzymatic and mediated by bacteria. Glycosides of delphinidin (Dp) and petunidin (Pt) were more susceptible to chemical degradation than those of cyanidin (Cy), pelargonidin (Pg), peonidin (Pn) and malvidin (Mv) in both intact and artificial saliva. Stability of di- and tri-saccharide conjugates of anthocyanidins was slightly greater than that of mono-saccharide derivatives. The ex vivo degradation was significantly decreased in saliva obtained after volunteers rinsed their mouths with anti-bacterial chlorhexidine.;I next examined whether the ex vivo finds could be recapitulated in vivo by having subject retain for 5 minutes either chokeberry or red grape juice in their mouths (Chapter 3). Retained juice, oral washings and buccal scrapings were collected and analyzed for stability of ACN in the oral cavity, binding to buccal mucus and uptake into buccal cells. Cy-3-glucoside preferentially accumulated with the buccal cells compared to other Cy glycosides. Anti-bacterial treatment resulted in greater stability of ACN in retained juice. Loss of Dp glucosides exceeded that of Pt, Cy, Pn and Mv glucosides during oral retention of red grape juice. Lesser relative amounts of Dp and Pt glucosides were associated with mucus and buccal cells than Cy, Pn and Mv glucosides, suggesting their instability and limited accessibility to the oral epithelium.;I investigated inhibitory activity of ACN mixtures on pro-inflammatory cytokine secretion by oral epithelial cells. ACN extracts from black raspberry, blueberry, chokeberry, red grape, strawberry, and hibiscus were incubated with cells prior to, simultaneously or after addition of IL-1β followed by measurement of IL-8 secretion (Chapter 4). Chokeberry extract reduced IL-1β induced IL-8 secretion by SCC-25 in a dose response manner. The efficacy of inhibitory activity depended on both the ACN composition of the extract (Pg-rich (strawberry) > five anthocyanidins (red grape) > Cy-rich (chokeberry and black raspberry) ≈ Cy-Dp disaccharide (hibiscus) extracts) and the type of cell (effect on SCC-25 cancer cells > OKF-6/TERT-2 non-cancer cells). Pre-conditioning medium, by incubating with extracts for 24 h to allow degradation of approximately 90% of ACN, minimally affected inhibitory activity in SSC-25 cultures, demonstrating that degradation products contributed to the bioactivity.;These data demonstrated that the natural ACN composition determines stability, bioaccessibility to the buccal epithelium, and anti-inflammatory activity with oral epithelium. The effects of ACN structure and their degradation products merit further consideration for the development of sound dietary recommendations and/or formulation of ACN-rich products for the promotion of oral health.