title: 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.affiliation: State Key Laboratory of Natural Medicines, Department of Natural Medicinal Chemistry, China Pharmaceutical University, Nanjing 210009, People's Republic of China.
authors.forename: Chao
authors.initials: C
authors.lastname: Guo
authors.affiliation: State Key Laboratory of Natural Medicines, Department of Natural Medicinal Chemistry, China Pharmaceutical University, Nanjing 210009, People's Republic of China.
authors.forename: Lei
authors.initials: L
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Natural Medicines, Department of Natural Medicinal Chemistry, China Pharmaceutical University, Nanjing 210009, People's Republic of China.
authors.forename: Jun
authors.initials: J
authors.lastname: Luo
authors.affiliation: State Key Laboratory of Natural Medicines, Department of Natural Medicinal Chemistry, China Pharmaceutical University, Nanjing 210009, People's Republic of China.
authors.forename: Chao
authors.initials: C
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Natural Medicines, Department of Natural Medicinal Chemistry, China Pharmaceutical University, Nanjing 210009, People's Republic of China.
authors.forename: Yuanzheng
authors.initials: Y
authors.lastname: Xia
authors.affiliation: State Key Laboratory of Natural Medicines, Department of Natural Medicinal Chemistry, China Pharmaceutical University, Nanjing 210009, People's Republic of China.
authors.forename: Ting
authors.initials: T
authors.lastname: Ma
authors.affiliation: State Key Laboratory of Natural Medicines, Department of Natural Medicinal Chemistry, China Pharmaceutical University, Nanjing 210009, People's Republic of China. Electronic address: cpu_lykong@126.com.
authors.forename: Lingyi
authors.initials: L
authors.lastname: Kong
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D044950:Flavanones / Q000494:pharmacology*; D051547:Heme Oxygenase-1 / Q000378:metabolism; D007249:Inflammation / Q000188:drug therapy*; D053612:Janus Kinases / Q000378:metabolism; D008070:Lipopolysaccharides / Q000276:immunology; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D000067996:RAW 264.7 Cells; D050791:STAT Transcription Factors / Q000378:metabolism; D029909:Sophora / Q000276:immunology*
chemical_list: D000893:Anti-Inflammatory Agents; D044950:Flavanones; D008070:Lipopolysaccharides; D008565:Membrane Proteins; D051267:NF-E2-Related Factor 2; C495636:Nfe2l2 protein, mouse; D050791:STAT Transcription Factors; C064849:vexibinol; D051547:Heme Oxygenase-1; C496542:Hmox1 protein, mouse; D019869:Phosphatidylinositol 3-Kinases; D053612:Janus Kinases; D051057:Proto-Oncogene Proteins c-akt
keywords: Inflammation; LPS; RAW264.7; Sophoraflavanone G