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  3. Paeoniflorin alleviated experimental Sjögren's syndrome by inhibiting NLRP3 inflammasome activation of submandibular gland cells via activating Nrf2/HO-1 pathway

Paeoniflorin alleviated experimental Sjögren's syndrome by inhibiting NLRP3 inflammasome activation of submandibular gland cells via activating Nrf2/HO-1 pathway

  • Free Radic Biol Med. 2025 Jun:233:355-364. doi: 10.1016/j.freeradbiomed.2025.03.043.
Tingting Jiang 1,  Xuanqi Liu 2,  Shumin Wang 2,  Yu Chen 2,  Yong Wang 3,  Xiaojing Li 4,  Genhong Yao 5
Affiliations

Affiliations

  • 1 Department of Rheumatology and Immunology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, 210008, China.
  • 2 Department of Rheumatology and Immunology, Nanjing Drum Tower Hospital, Clinical College of Nanjing Drum Tower Hospital, Nanjing University of Chinese Medicine, Nanjing, 210008, China.
  • 3 State Key Laboratory of Analytical Chemistry for Life Science & Jiangsu Key Laboratory of Molecular Medicine, Medical School, Nanjing University, Nanjing, 210093, China. Electronic address: yongwang@nju.edu.cn.
  • 4 Department of Rheumatology and Immunology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, 210008, China. Electronic address: lxjnju@163.com.
  • 5 Department of Rheumatology and Immunology, Nanjing Drum Tower Hospital, Clinical College of Nanjing Drum Tower Hospital, Nanjing University of Chinese Medicine, Nanjing, 210008, China; State Key Laboratory of Analytical Chemistry for Life Science & Jiangsu Key Laboratory of Molecular Medicine, Medical School, Nanjing University, Nanjing, 210093, China. Electronic address: yaogenhong@nju.edu.cn.
PMID: 40158745 DOI: 10.1016/j.freeradbiomed.2025.03.043
Abstract

Background: Total glucosides of white paeony (TGP) has been used for treatment of Sjögren's syndrome (SS) patients. Paeoniflorin (PF) is the main active ingredient of TGP and has antioxidant and anti-inflammatory effects, but its underlying mechanism on SS remains to be explored. Aberrant activation of NLRP3 inflammasome can cause injury of submandibular gland (SG) in SS. However, whether PF regulates NLRP3 inflammasome activation in SS is unknown.

Objective: This study aims to investigate whether PF alleviated SS through suppressing NLRP3 inflammation activation and to explore the mechanism of PF in improving Sjögren-like symptoms in non-obese diabetic (NOD) mice.

Methods: The gene expression profiles of the labial gland (LG) between SS patients and non-SS patients were analyzed by bioinformatics. Non-obese diabetic (NOD) mice were selected as SS model. Mice were divided into normal saline group and two different doses of PF-treatment groups (50 and 100 mg/kg). The SS-like symptoms and pathological changes of submandibular gland (SG) were analyzed after 4 weeks of administration. SG cells were treated with or without PF and with or without ML385 (a specific inhibitor of Nrf2) in vitro, and then lipopolysaccharide(LPS) and adenosine triphosphate (ATP) were used to induce NLRP3 inflammasome activation in SG cells. Results NLRP3 was up-regulated in LG of SS patients and SG of SS mice. PF alleviated SS-like symptoms in SS mice. Compared with control group, NLRP3 and Caspase-1 in the SG, and serum IL-1β and IL-18 of NOD mice were decreased in PF group. Furthermore, we found that PF inhibited NLRP3 activation via activating the Nrf2/HO-1 pathway in SG cells. In addition, we observed the activation of Nrf2/HO-1 in the SG of mice after PF administration.

Conclusions: Our findings suggested that PF inhibited NLRP3 inflammasome activation through regulating the Nrf2/HO-1 axis in SG of SS mice, which might be the underlying mechanism for the therapeutic effects of PF on SS.

Keywords

NLRP3 inflammasome; Nrf2/HO-1; Paeoniflorin; Sjögren's syndrome; submandibular gland.

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