Future Perspectives on Targeting the Activated TLR4/NFκB Pathway in Cystic Fibrosis: A Possible Interplay Between Ethnopharmacology and microRNA Therapeutics

Cystic fibrosis (CF) is an inherited genetic disease caused by dysregulation of the cystic fibrosis transmembrane regulator (CFTR) gene, a chronic hyperinflammatory state and frequently occurring severe bacterial infections of the lungs. Novel protocols for treating CF inflammation are highly needed. Among the most interesting fields of pre-clinical investigation, the use of natural products, including those used in ethnopharmacology, appears to be promising. Examples of natural ethnopharmacological products that should be further investigated as potential anti-inflammatory agents for CF include inhibitors of the Toll-like receptor 4 (TLR4)/Nuclear Factor κB (TLR4/NFκB) pathway, such as parthenolide, curcumin and garlic-related constituents. In addition, “miRNA therapeutics” protocols have been reported as able to dampen the expression of pro-inflammatory genes. These two fields of investigation deserve, in the near future, further experimental efforts. Notably, these two approaches can be combined in order to develop novel strategies to improve the inhibitory activity on the expression of key pro-inflammatory genes activated in cystic fibrosis, including those induced by Pseudomonas aeruginosa infection.