Suppressive Effects of Okinawan Food Items on Free Radical Generation from Stimulated Leukocytes and Identification of Some Active Constituents: Implications for the Prevention of Inflammation-associated Carcinogenesis

Okinawa prefecture in Japan is a distinct area characterized by unique traditional food habits and longevity. ‍Prolonged exposure to activated leukocytes, playing pivotal roles in chronic inflammation-associated carcinogenesis, ‍is known to lead to oxidative and nitrosative damage to macromolecules in the body since they are primary sources ‍of free radicals, such as superoxide anion (O2 ‍-) and nitric oxide (NO). In this study, we estimated anti-oxidative and ‍anti-nitrosative activities of Okinawan food items by employing two cellular experimental systems: (1) phorbol ‍ester-induced O2 ‍- generation from differentiated HL-60 human promyelocytic leukemia cells; and (2) ‍lipopolysaccharide (LPS)-induced NO generation in RAW264.7 murine macrophages. A total of 138 food items, ‍consisting of 42 samples unique to Okinawa and 96 common in the Japanese main island, were purchased at local ‍markets in Okinawa and extracted with chloroform. When tested at a concentration of 100 ìg/ml, 38% (16/42) of ‍the former showed 70% or more inhibition of O2 ‍- generation while 21% (20/96) of the latter did so. In parallel, 64% ‍(27/42) of the former showed significant NO generation suppression in contrast to 48% (46/96) of the latter . Twentyone ‍active species were further tested at a concentration of 20 ìg/ml, and eleven species, including sugar cane, wild ‍turmeric, and zedoary, were indicated to be most promising items with anti-oxidative and anti-nitrosative properties. ‍In addition, some of the active constituents (chebulagic acid, a resveratrol derivative, and sesquiterpenoids) were ‍identified. Our results suggest that food items typical in the Okinawa area have higher cancer preventive potential ‍than those common in Japan.