Silibinin Attenuates Experimental Periodontitis by Downregulation of Inflammation and Oxidative Stress

Abstract

Periodontitis is an oral microbiota-induced inflammatory disease, in which inflammation and oxidative stress play a critical role. Silibinin (SB), a Silybum marianum-derived compound, exhibits strong anti-inflammatory and antioxidative properties. We adopted a rat ligature-induced periodontitis model and a lipopolysaccharide- (LPS-) stimulated human periodontal ligament cells (hPDLCs) model to evaluate the protective effects of SB. In the <i>in vivo</i> model, SB reduced alveolar bone loss and apoptosis of PDLCs in the periodontal tissue. SB also maintained the expression of nuclear factor-E2-related factor 2 (Nrf2), a key regulator of cellular resistance to oxidative stress, and attenuated lipid, protein, and DNA oxidative damages in the periodontal lesion area. Meanwhile, in the <i>in vitro</i> model, SB administration reduced the production of intracellular reactive oxidative species (ROS). Furthermore, SB exerted a strong anti-inflammatory property in both <i>in vivo</i> and <i>in vitro</i> models by inhibiting the expression of inflammatory mediators including nuclear factor-<i>κ</i>B (NF-<i>κ</i>B) as well as nucleotide binding oligomerization domain- (NOD-) like receptor family pyrin domain-containing 3 (NLRP3) and downregulating the levels of proinflammatory cytokines. This study, for the first time, demonstrates that SB exhibits the anti-inflammatory and antioxidative properties against periodontitis by downregulating the expression of NF-<i>κ</i>B and NLRP3 and upregulating Nrf2 expression, suggesting a promising potential clinical application of SB in periodontitis.