Pharmaceutical Implications of Curcumin in the Development of Drugs for CF Pharmacotherapy: Combined Effects with Genistein (pp. 223-234)
Authors: (Yoshiro Sohma, Ying-chun Yu, Haruna Miki, Yumi Nakamura, Akiko Hanyuda, Hui-Yi Lin, Masato Yasui, Silvia Bompadre, Tzyh-Chang Hwang, Departments of Pharmacology, Keio University School of Medicine, Shinjuku, Tokyo, Japan, and others)
Abstract: 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 pharmocotherapy.