Citral reduces alveolar bone loss and inflammatory mediators in ligature-induced periodontitis: implications for novel therapeutic strategies

This study investigated the effects of systemic citral administration on healthy and inflamed gingiva, alveolar bone loss, and inflammatory mediators in a rat model of ligature-induced periodontitis, given the limitations and adverse effects of current periodontal therapies. In this model, a ligature was placed around the first lower right molars of adult male rats for either 7 or 15 days to induce periodontitis. Animals received a daily gavage of citral [a mixture of monoterpenoids found in Cymbopogon citratus (lemongrass) essential oil] or vehicle. Alveolar bone loss was quantified by measuring the distance between the cementoenamel junction (CEJ) and the alveolar bone crest (BC) using image analysis software. Gingival levels of TNF-α, IL-1β, IL-6, and IL-10, as well as plasma TNF-α, were determined by ELISA. Nitric oxide (NO) in gingival tissue was measured via chemiluminescence, and MMP-2 activity was analyzed by gelatin zymography. In situ detection of reactive oxygen species (ROS) was used to assess local oxidative stress in the gingival tissue. The results showed that citral had no significant effect on healthy gingiva. However, in animals with periodontitis, 14-day citral treatment significantly reduced alveolar bone loss, decreased pro-inflammatory cytokines (TNF-α, IL-1β, IL-6), increased IL-10, lowered plasma TNF-α, and inhibited both NO production and MMP-2 activity. Additionally, citral attenuated the marked increase in ROS levels observed in the gingival tissue from periodontitis-induced animals. These findings suggest that citral exerts potent anti-inflammatory and antioxidant effects and may represent a promising therapeutic strategy for managing periodontal inflammation and associated bone loss.