[Synthesis of 4-palmitoyl-sinomenine and its anti-inflammation activity].

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. CONCLUSION: 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.