Ruscogenin Ameliorated Sjögren’s Syndrome by Inhibiting NLRP3 Inflammasome Activation

• Published in: Evidence-based complementary and alternative medicine 2022-06, Vol.2022, p.1-11
• Main Authors: He, Jing, Wang, Yue, Xu, Lei, Xu, Changsong, Zhu, Yamei, Xu, Meimei, Chen, Yueyue, Guo, Liang, Hu, Wei, Xu, Dake, Jing, Rongyue, Xu, Bo
• Format: Article
• Language: English
• Subjects: Acinar cells; Apoptosis; BAX protein; Bcl-2 protein; Caspase-1; Disease; Ethanol; Flow cytometry; Gene expression; IL-1β; Immune system; Inflammasomes; Inflammation; Interleukin 17; Interleukin 6; Laboratory animals; Polymerase chain reaction; Propidium iodide; Sjogren's syndrome; Submandibular gland; Tumor necrosis factor-α
• ISSN: 1741-427X; 1741-4288
• DOI: 10.1155/2022/6425121

This article investigated the role and the specific mechanism of Ruscogenin in Sjögren's syndrome (SS). NOD/ShiLtJ mice were treated with Ruscogenin, and acinar cells isolated from submandibular glands were treated with TNF-α, Ruscogenin and transfected with NLRP3 overexpression plasmid. Salivary flow rate (SFR) was measured at weeks 11, 13, 15, 17, and 20. Histological analysis of the submandibular glands was conducted by hematoxylin-eosin staining assay. IL-6, IL-17, TNF-α, and IL-1β mRNA expression was detected through qRT-PCR. AQP 5, AQP 4, P2X7R, NLRP3, caspase 1, IL-1β, Bax, and Bcl-2 protein levels were tested by western blot. Cell apoptosis was assessed through acridine orange and propidium iodide (AO/PI) staining assay and flow cytometry assay. Ruscogenin ameliorated the SFR and submandibular gland inflammation of NOD/ShiLtJ mice. Ruscogenin promoted the preservation of acinar cells and suppressed inflammation-related factors (P2X7R, NLRP3, caspase 1, and IL-1β) in submandibular gland tissues of NOD/ShiLtJ mice. Ruscogenin inhibited acinar cell apoptosis in NOD/ShiLtJ mice and reversed TNF-α-induced apoptosis and inflammation of acinar cells. NLRP3 overexpression reversed the repressive effect of Ruscogenin on TNF-α-induced inflammation and apoptosis of acinar cells. Ruscogenin ameliorated SS by inhibiting NLRP3 inflammasome activation.