Siweixizangmaoru Decoction Ameliorated Type II Collagen-Induced Arthritis in Rats via Regulating JAK2-STAT3 and NF-κB Signaling Pathway

Biol Pharm Bull. 2024;47(9):1511-1524. doi: 10.1248/bpb.b24-00362.

Abstract

Siweixizangmaoru decoction (SXD) is widely used as an anti-rheumatoid arthritis (RA) in Tibet, however, the specific anti-inflammatory mechanism of SXD is still unclear. This research attempts to examine the efficacy and possible mechanisms of SXD in treating RA. The primary chemical components of SXD were identified using UHPLC-Q-Exactive Orbitrap MS. We established a lipopolysaccharide (LPS)-induced RAW264.7 macrophage inflammatory injury model to explore the anti-inflammatory mechanism of SXD and validated it through in vivo experiments. According to our research in vitro as well as in vivo, SXD exhibits anti-inflammatory qualities. SXD can suppress nitric oxide (NO) and pro-inflammatory factor production in RAW264.7 cells activated by LPS. The mechanism underlying this effect might be connected to the janus tyrosine kinase 2-signal transducer and activator of transcription 3 (JAK2/STAT3) and nuclear factor-κB (NF-κB) signaling pathways. In vivo, SXD alleviates joint swelling, decreases the generation of inflammatory factors in the serum, lowers oxidative stress, and improves joint damage. In short, SXD improves joint degeneration and lowers symptoms associated with RA by regulating inflammation via the suppression of NF-κB and JAK2/STAT3 signaling pathway activation.

Keywords: Siweixizangmaoru decoction; janus tyrosine kinase 2–signal transducer and activator of transcription 3 (JAK2/STAT3); mechanism; nuclear factor-κB (NF-κB); rheumatoid arthritis.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents* / pharmacology
  • Anti-Inflammatory Agents* / therapeutic use
  • Arthritis, Experimental* / drug therapy
  • Arthritis, Experimental* / metabolism
  • Arthritis, Experimental* / pathology
  • Arthritis, Rheumatoid / drug therapy
  • Arthritis, Rheumatoid / metabolism
  • Collagen Type II / metabolism
  • Drugs, Chinese Herbal* / pharmacology
  • Drugs, Chinese Herbal* / therapeutic use
  • Janus Kinase 2* / metabolism
  • Lipopolysaccharides
  • Male
  • Medicine, Tibetan Traditional / methods
  • Mice
  • NF-kappa B* / metabolism
  • Nitric Oxide / metabolism
  • Oxidative Stress / drug effects
  • RAW 264.7 Cells
  • Rats
  • Rats, Sprague-Dawley
  • STAT3 Transcription Factor* / metabolism
  • Signal Transduction* / drug effects

Substances

  • Janus Kinase 2
  • NF-kappa B
  • STAT3 Transcription Factor
  • Drugs, Chinese Herbal
  • Anti-Inflammatory Agents
  • Jak2 protein, rat
  • Collagen Type II
  • Lipopolysaccharides
  • Nitric Oxide
  • Stat3 protein, rat