AB0082 ANTI-INFLAMMATORY EFFECTS OF TOTAL SAPONINS OF PANAX JAPONICUS ON RHEUMATOID ARTHRITIS

Background Rheumatoid arthritis (RA) is a common autoimmune disease with inflammation [1] . Total saponins of Panax japonicus (TSPJs) are effective components extracted from Panax japonicus [2] . They are known to exhibit anti-inflammatory and immunosuppressoive properties, but their effect of anti-inflammation in collagen-induced arthritis (CIA) remains unclear. Objectives To investigate the anti-inflammatory targets of TSPJ predicted by bioinformatics and the verification in CIA mice. Methods The targets of RA are obtained in the GeneCards database. we used Cytoscape 3.7.2 software to construct a protein-protein interactions (PPI) network and obtain the hub genes. There are four effective components of TSPJ: Araloside A, chikusetsusaponin IVa, ginsenoside Rg2, and ginsenoside Ro. Through molecular docking between the screened hub genes and the four effective components of TSPJ, the possibility of TSPJ treating CIA mice can be predicted. The collagen II (CII) and complete Freund’s adjuvant (CFA) were used to induce the CIA model. After establishing the model, 32 DBA1/J mice were divided into C group (n=8), M group (n=8), L group(n=8), and H group(n=8). The L and H groups were gavaged with TSPJ at 30 mg/kg or 150 mg/kg, and the C and M groups were gavaged with normal saline. The thickness of the hind paw, number of swollen joints, and arthritis index were evaluated. After 11 days of treatment, all the mice were sacrificed after anesthesia. Sera were collected to centrifuge tubes and the levels of inflammatory factor were determined by the ELISA kit following the instruction. Results A gene list that enriches 263 genes was obtained by searching RA from the GeneCards database. The hub genes of the top 3 obtained from Cytoscape 3.7.2 software were tumor necrosis factor (TNF), interleukin-1β (IL-1β), and interleukin-6 (IL-6). In addition, interleukin-17A (IL-17A), a classical inflammatory index in the top 10, was selected and included in the predicted target. The results of molecular docking between the predicted target and the components of TSPJ showed that the combined pose has good stability. The numerical value of hind paw thickness, swollen joint counts, and arthritis index in the intervention groups were lower than those in the M group, suggesting TSPJ played a critical role in improving pathological changes. Compared to those of the C group, the serum levels of TNF-α, IL-1β, IL-6, and IL-17A were increased in the M group. Compared to those of the M group, the levels of TNF-α, IL-1β, IL-6, and IL-17A in the L and H groups were decreased. Compared to those of the L group, the levels of TNF-α, IL-1β, IL-6, and IL-17A in the H group were decreased. The results suggested that TSPJ may decrease the levels of TNF-α, IL-1β, IL-6, and IL-17A in CIA mice. These results suggest that TSPJ may inhibit the inflammatory effects of CIA mice. Conclusion Current study demonstrated a novel inhibitory effect of TSPJ on inflammation in CIA mice, and TSPJ can act on the targets predicted by bioinformatics of CIA mice, suggesting the potential of TSPJ as a therapeutic agent for RA and providing new ideas for the clinical treatment of RA. References [1]Scherer HU, Haupl T, Burmester GR. The etiology of rheumatoid arthritis. J Autoimmun[J]. 2020;110:102400 [2]Guo X, Ji J, Jose Kumar Sreena GS, et al. Computational Prediction of Antiangiogenesis Synergistic Mechanisms of Total Saponins of Panax japonicus Against Rheumatoid Arthritis. Front Pharmacol[J]. 2020;11:566129 Acknowledgements Jingkai Zhang: Preparation, data presentation, and specifically writing the initial draft. Xiang Guo: Application of statistical, Verification. Qinpeng Bu and Xiaolan Shen: Conducting a research and investigation process, Provision of study materials. Zhitao Feng: Ideas, Design of methodology, and including mentorship external to the core team. Disclosure of Interests None declared