Wanheng Li,1– 4 Qing Liu,5 Siyu Chen,1– 4 Mengfan Zhi,2– 4,6 Peng Yang,1– 4 Yuxing Zhang,1– 4 Zhaoyan Wu,1– 4 Jun Zhang,1– 4 Qiang Feng2– 4,6 

1Department of Orthodontics, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University, Jinan, People’s Republic of China; 2Shandong Key Laboratory of Oral Tissue Regeneration, Jinan, People’s Republic of China; 3Shandong Engineering Research Center of Dental Materials and Oral Tissue Regeneration, Jinan, People’s Republic of China; 4Shandong Provincial Clinical Research Center for Oral Diseases, Jinan, People’s Republic of China; 5Department of Stomatology, Taian Maternity and Child Care Hospital, Taian, People’s Republic of China; 6Department of Human Microbiome, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University, Jinan, People’s Republic of China

Correspondence: Jun Zhang, Department of Orthodontics, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Research Center of Dental Materials and Oral Tissue Regeneration & Shandong Provincial Clinical Research Center for Oral Diseases, No. 44-1 Wenhua Road West, Jinan, Shandong, 250012, People’s Republic of China, Tel +86 13953109816, Fax +86 53188382923, Email zhangj@sdu.edu.cn Qiang Feng, Department of Human Microbiome, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Research Center of Dental Materials and Oral Tissue Regeneration & Shandong Provincial Clinical Research Center for Oral Diseases, No. 44-1 Wenhua Road West, Jinan, Shandong, 250012, People’s Republic of China, Tel +86 135 8913 8598, Fax +86 53188382923, Email fengqiangsdu@163.com

Purpose: 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.
Methods: 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.
Results: 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).
Conclusion: Sal promoted the osteogenic differentiation by inhibiting the activation of the NF-κB pathway and increasing the expression of LEF1.

Keywords: periodontitis, salidroside, osteogenesis, the human periodontal ligament stem cells