Ixeris dentata and Lactobacillus gasseri media protect against periodontitis through Nrf2-HO-1 signalling pathway

Periodontitis is an infectious inflammation in the gums characterized by loss of periodontal ligaments and alveolar bone. Its persistent inflammation could result in tooth loss and other health issues. Ixeris dentata (IXD) and Lactobacillus gasseri media (LGM) demonstrated strong antioxidant activity, which may prevent oxidative and inflammatory periodontitis. Here, IXD and LGM extracts were investigated for antioxidative activity against oral discomfort and evaluated for their synergistic effect against oxidative and inflammatory periodontitis in a mouse model. IXD/LGM suppressed pro-inflammatory cytokines like interleukin (IL)-1β, IL-6, and TNF-α. Additionally, it reduced pro-inflammatory mediators, nitric oxide, iNOS (inducible nitric oxide synthase), and COX-2 (cyclooxygenase-2) and enhanced AKT, Nrf2, and HO-1 activation. Similarly, IXD/LGM treatment elevated osteogenic proteins and mRNAs; alkaline phosphatase, collagen type 1 (COL1), osteopontin (OPN), and runt-related transcription factor 2 (RUNX2). Hematoxylin and Eosin (H&E) staining and micro-CT analysis confirm the positive impact of IXD/LGM on the periodontal structure and its associated inflammation. These findings demonstrate that IXD/LGM inhibits oxidative stress, periodontal inflammation, and its resultant alveolar bone loss in which Akt (also known as protein kinase B)-nuclear factor-erythroid 2-related factor 2 (Nrf2)-hemoxygenase-1 (HO-1) signaling is involved. Thus, IXD/LGM is a potential candidate against oxidative/inflammatory stress-associated periodontitis.