Sophoraflavanone G from Sophora alopecuroides inhibits lipopolysaccharide-induced inflammation in RAW264.7 cells by targeting PI3K/Akt, JAK/STAT and Nrf2/HO-1 pathways.

Abstract

Sophoraflavanone G (SG), a prenylated flavonoid from Sophora alopecuroides, has been reported to have many pharmacological activities including anti-inflammation. However, the molecular mechanisms of its anti-inflammatory activity remain largely unclear. In this study we investigated the effects and the underlying molecular mechanisms of SG on lipopolysaccharide (LPS)-induced inflammation in RAW264.7 cells. Pretreatment with SG inhibited LPS-induced production of nitric oxide (NO) and prostaglandin E2 (PGE2) through reducing the expressions of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). SG also decreased the expressions of pro-inflammatory cytokines, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1β (IL-1β), both in the protein and gene levels. Further experiments demonstrated that SG downregulated the LPS-induced upregulation of phosphorylated phosphoinositide-3-kinase and Akt (PI3K/Akt). SG also attenuated the expression of phosphorylated Janus kinase signal transducer and activator of transcription (JAK/STAT). In addition, SG upregulated heme oxygenase-1 (HO-1) expression via nuclear translocation of nuclear factor E2-related factor 2 (Nrf2). Taken together, SG may act as a natural agent to treat some inflammatory diseases by targeting PI3K/Akt, JAK/STAT and Nrf2/HO-1 pathways.

• Authors: Chao Guo, Lei Yang, Jun Luo, Chao Zhang, Yuanzheng Xia, Ting Ma, Lingyi Kong
• Journal: International immunopharmacology (Int Immunopharmacol) Vol. 38 Pg. 349-56 (Sep 2016) ISSN: 1878-1705 [Electronic] Netherlands
• PMID: 27351825 (Publication Type: Journal Article)
• Copyright: Copyright © 2016 Elsevier B.V. All rights reserved.

Chemical References

• Anti-Inflammatory Agents
• Flavanones
• Lipopolysaccharides
• Membrane Proteins
• NF-E2-Related Factor 2
• Nfe2l2 protein, mouse
• STAT Transcription Factors
• vexibinol
• Heme Oxygenase-1
• Hmox1 protein, mouse
• Phosphatidylinositol 3-Kinases
• Janus Kinases
• Proto-Oncogene Proteins c-akt

Topics

• Animals
• Anti-Inflammatory Agents (pharmacology)
• Flavanones (pharmacology)
• Heme Oxygenase-1 (metabolism)
• Inflammation (drug therapy)
• Janus Kinases (metabolism)
• Lipopolysaccharides (immunology)
• Macrophages (drug effects, immunology)
• Membrane Proteins (metabolism)
• Mice
• NF-E2-Related Factor 2 (metabolism)
• Phosphatidylinositol 3-Kinases (metabolism)
• Proto-Oncogene Proteins c-akt (metabolism)
• RAW 264.7 Cells
• STAT Transcription Factors (metabolism)
• Sophora (immunology)