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

• Published in: International immunopharmacology Vol. 38; pp. 349 - 356
• Main Authors: Guo, Chao, Yang, Lei, Luo, Jun, Zhang, Chao, Xia, Yuanzheng, Ma, Ting, Kong, Lingyi
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.09.2016
• Subjects: Animals; Anti-Inflammatory Agents - pharmacology; Flavanones - pharmacology; Heme Oxygenase-1 - metabolism; Inflammation; Inflammation - drug therapy; Janus Kinases - metabolism; Lipopolysaccharides - immunology; LPS; Macrophages - drug effects; Macrophages - 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; RAW264.7; Sophora - immunology; Sophoraflavanone G; STAT Transcription Factors - metabolism; NO; PGE2; COX-2; HO-1; Inflammation; IL-1β; LPS; IL-6; PIAS; NF-κB; STAT; SG; TNF-α; PI3K; Sophoraflavanone G; JAK; Nrf2; RAW264.7; Keap1; iNOS
• DOI: 10.1016/j.intimp.2016.06.021
• ISSN: 1567-5769

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. [Display omitted] •SG attenuated LPS-induced production of NO, PGE2, TNF-α, IL-1β and IL-6.•SG reduced the pro-inflammatory gene expression in protein and mRNA levels.•SG inhibited the LPS-induced PI3K/Akt activation.•SG inhibited the LPS-induced JAK/STAT activation.•SG activated the Nrf2/HO-1 signaling pathway.