Pharmaceutical implications of curcumin in the development of drugs for cf pharmacotherapy: Combined effects with genistein

The Cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel plays an essential role in salt and water transport across epithelia and mutations of CFTR causing its dysfunction result in the genetic disease cystic fibrosis (CF). Various mutations induce CFTR channel dysfunction and various pharmacological approaches are currently being explored. The G551D mutation in CFTR is a common cause of CF, characterized by an extremely low open probability despite its normal trafficking to the plasma membrane. Recently we investigated the potentiation effect of curcumin, especially its combined effect with a flavonoid genistein, on G551D-CFTR activity using the patch-clamp technique. Curcumin potentiated G551D-CFTR less than genistein at their maximally effective concentrations. However, curcumin showed an additive effect with genistein and, more importantly, a significant synergistic effect with genistein in a low concentration range. This does not only suggest that multiple mechanisms are involved in action of the CFTR potentiators, but also pose pharmaceutical implications of curcumin in the development of drugs for CF pharmacotherpy.