The natural flavonoid myricetin inhibits gastric H⁺, K⁺-ATPase

Myricetin (3,3’,4’,5,5’,7-hexahydroxyflavone), a major flavonoid in berries and red wine, has been recently used as a health food supplement based on its antioxidant and antitumor properties. We report here that myricetin preferentially exerts inhibitory effects on gastric H⁺, K⁺-ATPase. Myricetin inhibited H⁺, K⁺-ATPase with a sub-micromolar IC₅₀ value in an enzyme assay using freeze-dried tubulovesicles prepared from hog stomach. Na⁺, K⁺-ATPase and Ca²⁺-ATPase were also inhibited by myricetin in a dose-dependent manner, but the IC₅₀ values for these enzymes were approximately an order of magnitude higher compared to the H⁺, K⁺-ATPase. In structure-inhibitory functional analysis of sixteen myricetin derivatives, several phenolic hydroxy groups attached to the flavonoid backbone were highlighted as essential modifications for the inhibition of P₂-type ATPases. Furthermore, oral administration of myricetin significantly attenuated histamine-induced gastric acid secretion in an in vivo mouse assessment. Therefore, myricetin derivatives seem to be useful seed compounds for developing new drugs and supplements to alleviate gastric acid secretion.