title: [Synthesis of 4-palmitoyl-sinomenine and its anti-inflammation activity].
abstract: OBJECTIVE
  To synthesize the derivatives of sinomenine, 4-palmitoyl-sinomenine, and explore its therapeutic effect on lipopolysaccharide (LPS)-induced endotoxemia.
  
  
  METHODS
  A highly efficient synthesis of sinomenine derivatives called 4-palmitoyl-sinomenine was made with a molecule of palmitic acid substitutions at C-16 position of ring A. One hour before endotoxemia induction by i.p. injection of 10 mg/kg LPS, high-dose treatment mice (n=5/group) received an i.p. injection of 5 mg/kg sinomenine or 4-palmitoyl-sinomenine while the low-dose treatment mice (n=5/group) received 2.5 mg/kg sinomenine or 4-palmitoyl-sinomenine. Untreated group and normal control group received normal saline. And their survival was monitored hourly for 24 hours. Examination of cytotoxicity of 4-palmitoyl-sinomenine on RAW264.7 cells was conducted at a concentration range of 1 to 125 μmol/L using MTT assay. RAW264.7 cells were exposed to 4-palmitoyl-sinomenine (0, 1, 2, 5, 10 μmol/L) for 24 hours, and then treated with LPS (1 μg/mL) for 6 hours. Then RAW264.7 cells were collected and the mRNA level of IL-6 was detected by real-time quantitative PCR(qRT-PCR).
  
  
  RESULTS
  Sinomenine derivatives were successfully synthesized to get 4-palmitoyl-sinomenine. The survival percentage of 4-palmitoyl-sinomenine treatment groups was higher than that of sinomenine treatment groups at the same treatment concentration. The 4-palmitoyl-sinomenine inhibited RAW264.7 cell proliferation and IL-6 gene transcription.
  
  
  CONCLUSIONS
  The 4-palmitoyl-sinomenine has an anti-inflammation probably through inhibiting the proliferation of RAW264.7 cells and decreasing the inflammatory gene expression and inflammatory cytokine release.
authors.affiliation: Institute of Immunology, Jiangsu University, Zhenjiang 212013, China.
authors.forename: Shasha
authors.initials: S
authors.lastname: Tian
authors.affiliation: Department of Pharmacy, Jiangsu University, Zhenjiang 212013, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Zhang
authors.affiliation: Entry-exit Inspection and Quarantine Bureau of Taicang, Taicang 215400, China.
authors.forename: Fengying
authors.initials: F
authors.lastname: Yang
authors.affiliation: Institute of Immunology, Jiangsu University, Zhenjiang 212013, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Wang
authors.affiliation: Institute of Immunology, Jiangsu University, Zhenjiang 212013, China.
authors.forename: Pei
authors.initials: P
authors.lastname: Shen
authors.affiliation: Department of Pharmacy, Jiangsu University, Zhenjiang 212013, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Tang
authors.affiliation: Institute of Immunology, Jiangsu University, Zhenjiang 212013, China.
authors.forename: Xinxin
authors.initials: X
authors.lastname: Xu
authors.affiliation: Institute of Immunology, Jiangsu University, Zhenjiang 212013, China.
authors.forename: Lidan
authors.initials: L
authors.lastname: Xing
authors.affiliation: Institute of Immunology, Jiangsu University, Zhenjiang 212013, China.
authors.forename: Huaxi
authors.initials: H
authors.lastname: Xu
authors.affiliation: Institute of Immunology, Jiangsu University, Zhenjiang 212013, China.
authors.forename: Zhaoliang
authors.initials: Z
authors.lastname: Su
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D015850:Interleukin-6 / Q000235:genetics; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009019:Morphinans / Q000138:chemical synthesis* / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis
chemical_list: C000591720:4-palmitoyl-sinomenine; D000893:Anti-Inflammatory Agents; D015850:Interleukin-6; D008070:Lipopolysaccharides; D009019:Morphinans; D012333:RNA, Messenger; C009271:sinomenine