Facilitated cellular uptake and suppression of inducible nitric oxide synthase by a metabolite of maritime pine bark extract (Pycnogenol)

► Maritime pine bark extract (Pycnogenol) was reported to inhibit NO production and inducible NO synthase. ► We found that the Pycnogenol metabolite M1 mediates these effects. ► Required effective M1 concentrations were higher than detected earlier in vivo. ► We observed a facilitated phloretin-sensitive uptake of M1 into cells. ► Intracellular M1 accumulation would explain in vivo bioactivity at nanomolar plasma levels.