Suppression of Macrophage Activation by Sodium Danshensu via HIF-1α/STAT3/NLRP3 Pathway Ameliorated Collagen-Induced Arthritis in Mice

• Published in: Molecules (Basel, Switzerland) Vol. 28; no. 4; p. 1551
• Main Authors: Wu, Danbin, Xu, Jia, Jiao, Wei, Liu, Lijuan, Yu, Jiahui, Zhang, Mingying, Chen, Guangxing
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 01.02.2023; MDPI
• Subjects: Antiarthritic agents; Arthritis; Cell activation; Collagen; Cytokines; Cytotoxicity; Edema; Experiments; Hyperplasia; Hypoxia; Hypoxia-inducible factor 1a; hypoxia-inducible factor-1α; IL-1β; Inflammation; Interleukin 6; Macrophages; Metabolism; Methotrexate; NOD-like receptor protein 3 inflammasome; Phosphorylation; Protein expression; Proteins; Remission; Rheumatoid arthritis; Rheumatoid factor; Serum levels; signal transducer and activator of transcription 3; Sodium; sodium Danshensu; Stat3 protein; Synovium; Tumor necrosis factor-TNF; China; NOD-like receptor protein 3 inflammasome; signal transducer and activator of transcription 3; hypoxia-inducible factor-1α; rheumatoid arthritis; sodium Danshensu
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules28041551

It is still a clinical challenge to sustain the remission of rheumatoid arthritis (RA); thus, identifying more effective and safer agents for RA treatment remains an urgent demand. We investigated the anti-arthritic activity and potential mechanism of action of sodium Danshensu (SDSS), a structurally representative water-soluble derivative of Danshen, on collagen-induced arthritis (CIA) mice. Our results showed that paw edema, synovium hyperplasia, bone destruction, and the serum levels of both IL-1β and IL-6 were ameliorated by SDSS (40 mg/kg·d) in CIA mice. In addition, there was no difference between SDSS and methotrexate (MTX, 2 mg/kg·3d) treatment in the above indicators. Further mechanism studies illustrated that SDSS inhibited IL-1β secretion by downregulating the HIF-1α/STAT3/NLRP3 pathway in macrophages. On the other hand, HIF-1α accumulation and HIF-1α/STAT3/NLRP3 pathway activation by IOX4 stimulation reduced the therapeutic effect of SDSS. These findings demonstrate that SDSS displays anti-arthritic activity in CIA mice and prevents proinflammatory cytokines secretion in macrophages by suppressing the HIF-1α/STAT3/NLRP3 pathway.