Phloridzin derivatives inhibiting proinflammatory cytokine expression in human cystic fibrosis IB3-1 cells

Cystic Fibrosis (CF) is the most diffuse autosomal recessive genetic disease present in caucasian people. A persistent recruitment of neutrophils in the bronchi of CF patients contributes to exacerbate the airway tissue damage, suggesting the importance of modulating the expression of chemokines during the patient management. The identification of innovative anti-inflammatory drugs is considered a therapeutic target to prevent the progressive tissue deterioration1. Phloridzin, isolated from Malus domestica by a selective Molecular Imprinting extraction, and its structural analogues, Phloridzin eptaproprionate (F1) and Phloridzin tetraproprionate (F2)2, have been firstly investigated to discover their ability in reducing mainly IL-6 and IL-8 expression, released from CF cells under the control of the NF-kB Transcription Factor (TF), in human CF bronchial epithelial cells (IB3-1) stimulated with TNF-α. Among all the derivatives tested, F2 was the most interesting, demonstrating inhibitory effects also on the expression and production of different cytokines involved in CF inflammation processes, including RANTES, VEGF, GM-CSF, IL-12, G-CSF, MIP-1b, IL-17, IL-10 and IP-10, without any correlated anti- proliferative and pro-apoptotic effects.