Therapeutic potency and the related mechanism of deinoxanthin in experimental animal and cell models of periodontitis

Periodontitis is a chronic inflammatory disease that leads to the destruction of periodontal tissue, ultimately resulting in tooth loss. Studies have aimed to develop biomaterials that effectively prevent inflammatory responses and oxidative stress in the progression of periodontitis, without adverse side effects. Here, we explored whether Deinococcus radiodurans-derived deinoxanthin (DEIX) protects against alveolar bone loss and connective tissue degradation in an experimental rat model of periodontitis and investigated the related mechanisms using human-derived periodontal ligament cells (hPDLCs) and THP-1 cells. Oral supplementation with DEIX (25 mg/kg body weight, once per day for 14 consecutive days) protected rats against ligature-mediated periodontal destruction. 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 supported the associated mechanisms by which the direct addition of DEIX (20 µM) recovers lipopolysaccharide (LPS, 2 µg/mL)-stimulated inflammatory responses in hPDLCs and THP-1 cells. RNA sequence profiling from the DEIX and/or LPS-exposed hPDLCs further supported the protective mechanisms of DEIX on LPS-stimulated inflammatory and oxidative damage. Collectively, this study highlights the potential of DEIX to protect against inflammatory periodontal tissue destruction and demonstrates its clinical utility for patients with chronic periodontitis.