The prepared and characterized polysaccharide polymer in Saposhnikovia divaricata(Trucz.) Schischk effectively controls the course of rheumatoid arthritis via TLR4/TRAF6–NF-κB/IκB-α signaling pathway

• Published in: Biomedicine & pharmacotherapy 2023-04, Vol.160, p.114416, Article 114416
• Main Authors: Sun, Xialin, Zhang, Tingwen, Liu, Shuangli, Zhao, Yan, Sun, Xin
• Format: Article
• Language: English
• Subjects: Invasion; Rheumatoid arthritis; Saposhnikovia divaricata polysaccharide; Structural characterization; TLR4–NF-κB pathway
• ISSN: 0753-3322; 1950-6007
• DOI: 10.1016/j.biopha.2023.114416

Saposhnikovia divaricata (Trucz.) Schischk is a traditional Chinese herbal medicine that is widely used to regulate rheumatoid arthritis (RA). We extracted SD-a, a polysaccharide from S. divaricata, and analyzed its structure by chemical and spectral analysis. We further studied the anti-rheumatoid effect of SD-a in collagen-induced arthritis (CIA) rats and the molecular mechanism in RA fibroblast-like synoviocytes (RA-FLS). The results show that SD-a (MW 192.20 kDa) is composed of Man, GluA, GalA, Glu, Gal, and Ara, at a molar ratio of 4.16:1.97:37.46:2.12:16.42:37.87. Its main chain is →{[4)-α-D-GalAp-(1→5)-α-L-Araf-(1→4)-α-D-GalAp-(1→5)-α-L-Araf-(1→6)-β-D-Galp-(1]8→3,6)-α-D-Manp-(1→3)-β-D-Manp-(1→4,6)-β-D-Glcp-(1}23→. SD-a can significantly increase Bax and reduce Bcl-2 protein expression in RA-FLS, thus inducing apoptosis. It can also significantly inhibit the protein expression of matrix metalloproteinases 2/9 (MMP2/9) in RA-FLS, thereby inhibiting cell migration and invasion. Moreover, SD-a inhibited the course of RA in CIA rats by regulating the TLR4/TRAF6–NF-κB/IκB-α pathway. The present study indicates that SD-a might be used for RA treatment. [Display omitted] •Isolate the polysaccharide SD-a from Saposhnikovia divaricata (Trucz.) Schischk.•SD-a is mainly composed of Galactose, Mannose, Arabinose and Glucose.•SD-a has a significant inhibitory effect on CIA induced rheumatoid arthritis in rats.•SD-a reduces the invasion and migration of RA-FLS and reduces the protein expression of MMP2/9.•SD-a inhibits the release of inflammatory factors through the TLR4/NF-κB pathway.