Ab0803 Total Glucosides of Paeony Inhibiting Nlrp3 Inflammasome Activation of Submandibular Gland Cells in Mice With Sjögren’s Syndrome

Background: Sjögren's syndrome (SS) is a chronic systemic autoimmune disease. So far, there is no specific treatment for this disease. Some therapeutic drugs have shown certain effects. However, they also increase the risk of infection and malignant tumors in patients. Therefore, exploring novel medicine with good therapeutic effects and few side effects is urgently needed. Total glucosides of paeony (TGP) is the main active ingredient of white peony. Clinical studies have shown that TGP had certain curative effects in the treatment of rheumatoid arthritis, systemic lupus erythematosus and SS. However, the mechanisms of the beneficial effects of TGP on SS remain to be elucidated. Objectives: We aim to explore the relationship between the therapeutic effects of TGP in the treatment of SS and NLRP3 inflammasome activation in submandibular gland (SG) cells. Methods: Female non-obese diabetic (NOD) mice were selected as the model of SS. TGP was administered intragastrically every day for 4 weeks in NOD mice. The SS-like symptoms and pathological changes of the SG of mice were analyzed. The activation of NLRP3 inflammasome in SG was detected. The SG cells with activation of NLRP3 inflammasome were treated with or without TGP. Then, NLRP3 inflammasome activation was assessed. Results: Compared with control mice, NOD mice showed SS-like symptoms and lymphocyte infiltration in SG, and the expression of NLRP3 inflammasome in SG was significantly increased. The SS-like symptoms were alleviated, and lymphocyte infiltration in SG was reduced, and the level of NLRP3 inflammasome in SG mice was decreased after TGP treatment (Figure 1). TGP also significantly inhibit the activation of NLRP3 inflammasome of SG cells in vitro (Figure 2). Conclusion: In summary, our findings indicated that SG cells showed excessive NLRP3 inflammasome activation, other than an injured target in SS. We demonstrated that TGP alleviated the symptoms of experimental Sjögren's syndrome. Our data highlight that the beneficial effects of TGP on SS is related to limit overactivation of NLRP3 inflammasome of SG. These findings not only reveal the new mechanism of TGP in the treatment of SS, but also provide new evidence for the further application of TGP in the treatment of SS. REFERENCES: NIL. Acknowledgements: NIL. Disclosure of Interests: None declared.