Sweroside Alleviated LPS-Induced Inflammation via SIRT1 Mediating NF-κB and FOXO1 Signaling Pathways in RAW264.7 Cells

Molecules. 2019 Mar 1;24(5):872. doi: 10.3390/molecules24050872.

Abstract

Pterocephalus hookeri was used as a traditional Chinese medicine for the treatment of rheumatoid arthritis. Sweroside was a main iridoid isolated from P. hookeri. The present study aimed to investigate the anti-inflammatory effect mechanism of sweroside. In RAW264.7 cells induced by lipopolysaccharide (LPS), the abnormal proliferation, the NO content increase, and the downregulated Sirtuin1 (SIRT1) expression were observed. Sweroside could alleviate the inflammation by inhibiting cell proliferation through arresting the cell cycle at the G0/G1 phase, by suppressing pro-inflammatory cytokines and by promoting anti-inflammatory cytokines in LPS-induced RAW264.7 cells. Further mechanism research indicated that sweroside could activate the SIRT1, then suppress the nuclear factor-kappa B (NF-κB) and promote the Forkhead transcription factor O1 (FOXO1) signaling pathways. The present study indicated that sweroside may be the main anti-inflammatory constituent of P. hookeri and a promising candidate for anti-inflammation therapy.

Keywords: FOXO1; NF-κB; Pterocephalus hookeri; SIRT1; inflammation; sweroside.

MeSH terms

  • Animals
  • Arthritis, Rheumatoid / drug therapy*
  • Arthritis, Rheumatoid / genetics
  • Arthritis, Rheumatoid / pathology
  • Disease Models, Animal
  • Forkhead Box Protein O1 / genetics*
  • Gene Expression Regulation / drug effects
  • Humans
  • Inflammation / chemically induced
  • Inflammation / drug therapy*
  • Inflammation / genetics
  • Inflammation / pathology
  • Iridoid Glucosides / administration & dosage*
  • Lipopolysaccharides / toxicity
  • Mice
  • NF-kappa B / genetics
  • Proto-Oncogene Proteins c-akt / genetics
  • RAW 264.7 Cells
  • Signal Transduction / drug effects
  • Sirtuin 1 / genetics*
  • Transcription Factor RelA / genetics

Substances

  • Forkhead Box Protein O1
  • Foxo1 protein, mouse
  • Iridoid Glucosides
  • Lipopolysaccharides
  • NF-kappa B
  • Transcription Factor RelA
  • Proto-Oncogene Proteins c-akt
  • Sirt1 protein, mouse
  • Sirtuin 1
  • sweroside