Journal of Shanghai Jiao Tong University (Medical Science) >

2025 , Vol. 45 >Issue 10: 1279 - 1287

DOI: https://doi.org/10.3969/j.issn.1674-8115.2025.10.003

Basic research

Therapeutic effect of artesunate on spontaneous mouse models of Sjögren syndrome (NOD/Ltj mouse)

  • LI Yanxiang ,
  • SHI Huan ,
  • YU Chuangqi
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  • Department of Oral Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine; College of Stomatology, Shanghai Jiao Tong University; National Center for Stomatology; National Clinical Research Center for Oral Diseases; Shanghai Key Laboratory of Stomatology; Shanghai Research Institute of Stomatology, Shanghai 200011, China
YU Chuangqi, E-mail: ycq616@hotmail.com.

Received date: 2024-11-27

  Accepted date: 2025-04-27

  Online published: 2025-10-28

Supported by

National Natural Science Foundation of China(82174041);Natural Science Foundation of Shanghai(22ZR1437400);Shanghai Young Science and Technology Talents Sailing Program(22YF1422300)

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Abstract

Objective ·To elevate the therapeutic effect of artesunate (ART) on NOD/Ltj mice (non-obese diabetic mice, the spontaneous models of Sjögren syndrome), and explore its potential impact on the distribution of B lymphocyte subsets. Methods ·ICR mice were used as the blank control group, and NOD/Ltj mice were randomly divided into disease and ART groups. NOD/Ltj mice and ICR mice were treated with ART (10 mg/ kg) or its vehicle (0.5%CMC) by oral gavage every other day for 4 weeks. Body weight, salivary flow rate, submandibular gland index, and spleen index were measured. Cytokines in plasma, including interleukin-6 (IL-6), interferon-γ (IFN-γ), and B-cell activating factor (BAFF) in serum, were detected by cytometric bead array (CBA). Hematoxylin-Eosin (H-E) staining of submandibular glands was used to observe the infiltration of lymphocyte. Flow cytometry was applied to analyze the distribution of B lymphocyte subsets in the spleen. The mRNA expression of Prdm1, Il-6r, Il-6, and Stat3 in spleen B lymphocytes was detected by RT-qPCR. The effect of ART on B cells was further detected by CCK-8 and Annexin V-FITC/PI staining by flow cytometry. Results ·Compared to the disease group, ART significantly improved the symptoms of Sjögren syndrome in NOD/Ltj mice. ART treatment also resulted in a reduction in the levels of BAFF, IL-6, and IFN-γ in the plasma (all P<0.05). Moreover, lymphocyte infiltration around the glandular ducts in the submandibular glands was greatly improved in the ART group compared with the disease group. Flow cytometry analysis revealed that the proportion of Naïve B cells in the ART group was significantly increased compared with the disease group, along with a significant reduction in the proportions of double-negative B cells, switched memory B cells, and plasmablasts (all P<0.05). The relative mRNA expression levels of Prdm1, Il-6r,and Stat3 in the ART group were significantly lower than those in the disease group (all P<0.05). The CCK8 assay results showed that after 6 h of treatment, with the extension of the culture time, cell proliferation in the ART group was significantly inhibited; after 24 h of treatment, the number of apoptotic cells in the ART group was significantly higher than that in the control group (P<0.001). Conclusion ·ART demonstrates therapeutic effects in NOD/Ltj mice, potentially through modulating the distribution of peripheral B lymphocyte subsets. It can inhibit the expression of Prdm1, thereby regulating the differentiation of B lymphocytes into plasma cells and plasmablasts.

Key words： Sj?gren syndrome (SS); artesunate (ART); NOD/Ltj mouse; B lymphocyte

Cite this article

LI Yanxiang , SHI Huan , YU Chuangqi . Therapeutic effect of artesunate on spontaneous mouse models of Sjögren syndrome (NOD/Ltj mouse)[J]. Journal of Shanghai Jiao Tong University (Medical Science), 2025 , 45(10) : 1279 -1287 . DOI: 10.3969/j.issn.1674-8115.2025.10.003

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