Salidroside Improves Periodontitis by Mitigating Inflammatory Reactions and Enhancing Osteogenic Differentiation of Human Periodontal Ligament Stem Cells

Salidroside (Sal), a significant bioactive compound found in Rhodiola rosea, is documented to possess various pharmacological properties. This study investigated the effects of Sal in alleviating periodontitis. The rat periodontitis model was utilized to assess the therapeutic impact of Sal on periodontitis. Human periodontal ligament stem cells (hPDLSCs) were used to investigate the effect of Sal on lipopolysaccharide (LPS)-inhibited osteogenic differentiation. RNA sequencing (RNA-seq), and Western blot were employed to analyze the genes and proteins impacted by Sal treatment. Sal significantly alleviated the alveolar bone loss and gingival inflammation in rats periodontitis model. Sal demonstrated a dose-dependent pattern of promoting osteogenesis on hPDLSCs. A concentration of 0.5 μM Sal could effectively counteract the impact of LPS on osteogenic differentiation. Mechanically, Sal inhibited the ratios of phospho-IκBα(p-IκBα)/IκBα and phospho-p65(p-p65)/p65 in Nuclear Factor kappa-B (NF-κB) pathway and reduced the expressions of interleukin-6 (IL-6) and interleukin-8 (IL-8). Sal increased the expression of lymphoid enhancer-binding factor 1 (LEF1). Sal promoted the osteogenic differentiation by inhibiting the activation of the NF-κB pathway and increasing the expression of LEF1.