Paeonol attenuates ligation-induced periodontitis in rats by inhibiting osteoclastogenesis via regulating Nrf2/NF-κB/NFATc1 signaling pathway.

Paeonol is a natural phenolic compound in Moutan Cortex with multiple biological functions, such as anti-inflammatory and anti-oxidant activity. Recent evidence has proven that persistent inflammation, oxidative stress, along with nuclear factor E2-related factor 2 (Nrf2) signaling dysfunction in periodontium are the possible causes of alveolar bone resorption, and ultimately lead to periodontitis. The present study was designed to explore the protective effects of paeonol on ligation-induced periodontitis in rats, and investigate the possible mechanism. We found that treatment with paeonol (40, 80 mg/kg, intraperitoneal injection) for 7 days remarkably decreased the expression of receptor activator of nuclear factor kappa-B ligand increased the expression of osteoprotegrin and inhibited the formation of osteoclasts. This function of paeonol might be correlated with its ability to reduce inflammatory factors (IL-1β, IL-6 and TNF-α) and alleviate oxidative stress (SOD, MDA, GSH and ROS) in gingival tissues. Besides, paeonol increased Nrf2 activity. Silence of Nrf2 using specific siRNA diminished the inhibitory effect of paeonol on NF-κB p65 activation and downstream expression, suggesting that Nrf2 was essential for protective effect of paeonol. These results showed that paeonol protected against periodontitis-aggravated osteoclastogenesis and alveolar bone lesion via regulating Nrf2/NF-κB/NFATc1 signaling pathway.