Reduction of oxidative stress blunts the NLRP3 inflammatory cascade in LPS stimulated human gingival fibroblasts and oral mucosal epithelial cells

Abstract

The therapeutic armamentarium for the treatment of oral mucositis is very poor. Catechin and baicalin are two natural flavonoids that have been individually reported to have a curative potential. Flavocoxid is a mixed extract containing baicalin and catechin showing antioxidant effects and anti-inflammatory activity mainly due to a dual inhibition of inducible cyclooxygenase (COX-2), 5-lipoxygenase (5-LOX) and NLRP3 pathway. The aim of this study was to evaluate the anti-inflammatory and anti-oxidant effects of flavocoxid in an "in vitro" model of oral mucositis induced by triggering an inflammatory phenotype in human gingival fibroblasts (GF) and human oral mucosal epithelial cells (EC). GF and EC were challenged with lipopolysaccharide (LPS 2 μg/ml) alone or in combination with flavocoxid (32 μg/ml). Flavocoxid increased Nrf2, prompted a marked reduction in malondialdehyde levels and reduced the expression of COX-2 and 5-LOX together with PGE₂, and LTB₄ levels. Flavocoxid caused also a great decrease in the expression of NF-κB and turned off NLRP3 inflammasome and its downstream effectors signal, as caspase-1, IL-1β and IL-18 in both GF and EC cells stimulated with LPS. These results suggest a correlation between oxidative stress and NLRP3 activation and indicate that flavocoxid suppresses the inflammatory storm that accompanies oral mucositis. This preclinical evidence deserves to be confirmed in a clinical setting.

Keywords: 5-LOX; COX-2; Flavocoxid; NLRP3; Oral mucositis; ROS.