Protective efficacy and related mechanism of deinoxanthin in experimental animal and cell models of periodontitis

As periodontitis is a chronic inflammatory disease resulting in periodontal tissue destruction and tooth loss, studies have tried to development the biomaterials that effectively prevent inflammatory response and oxidative stress without side effects. In this work, we explored whether Deinococcus radiodurans-derived deinoxanthin (DEIX) protects against alveolar bone loss and connective tissue degradation in an experimental rat model of periodontitis investigated the related mechanisms. Oral supplementation with DEIX (25 mg/kg body weight, once per day for 14 consecutive days) protected rats against ligature-mediated loss of alveolar bone and connective tissues. That protection involved the DEIX-induced restoration of the ligature-stimulated disorders, including overproduction of inflammatory mediators, accumulation of reactive oxygen species, and imbalance between osteoclast and osteoblast activity in the inflamed periodontium. In vitro experiments using human periodontal ligament cells (hPDLCs) and THP-1 cells supported the mechanisms by which the direct addition of DEIX (20 µM) recovers lipopolysaccharide (LPS, 2 µg/mL)-stimulated inflammatory responses in the cells. RNA-sequence profiling from the hPDLCs further supported the potency and the related mechanisms of DEIX to protect cells from LPS-mediated inflammatory damages. Collectively, this study introduces the protective role of DEIX in inflammatory periodontal tissue destruction and supports its clinical usefulness for patients who suffering from chronic periodontitis. Overall design: Total RNAs were isolated from human-derived periodontal ligament cells (hPDLCs) for RNA-sequence profiling. In this study, the hPDLCs were exposed to 2 µg/mL lipopolysaccharide (LPS) for seven days followed by the additional-14 days incubation in combination with 20 µM DEIX or not before the RNA extraction. There are four groups: 1) non-treated control hPDLCs (Control-C1-I, C1-II, C1-III), 2) LPS treatment alone (LPS-C2-I, C2-II, C2-III ), 3) LPS and DEIX treatment (LPS+DEIX-C3-I, C3-II, C3-III), and 4) DEIX treatment alone (Only DEIX-C4-I, C4-II, C4-III).