Tian Shasha, Zhang Rong, Yang Fengying, Wang Ting, Shen Pei, Tang Jian, Xu Xinxin, Xing Lidan, Xu Huaxi, Su Zhaoliang
Institute of Immunology, Jiangsu University, Zhenjiang 212013, China.
Department of Pharmacy, Jiangsu University, Zhenjiang 212013, China.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi. 2014 Mar;30(3):262-5.
To synthesize the derivatives of sinomenine, 4-palmitoyl-sinomenine, and explore its therapeutic effect on lipopolysaccharide (LPS)-induced endotoxemia.
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).
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.
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.
合成青藤碱衍生物4-棕榈酰青藤碱，并探讨其对脂多糖（LPS）诱导的内毒素血症的治疗作用。
通过在A环C-16位用一分子棕榈酸取代，高效合成青藤碱衍生物4-棕榈酰青藤碱。在腹腔注射10 mg/kg LPS诱导内毒素血症前1小时，高剂量治疗组小鼠（n = 5/组）腹腔注射5 mg/kg青藤碱或4-棕榈酰青藤碱，而低剂量治疗组小鼠（n = 5/组）腹腔注射2.5 mg/kg青藤碱或4-棕榈酰青藤碱。未治疗组和正常对照组注射生理盐水。每小时监测它们的存活情况，持续24小时。使用MTT法在1至125 μmol/L浓度范围内检测4-棕榈酰青藤碱对RAW264.7细胞的细胞毒性。RAW264.7细胞暴露于4-棕榈酰青藤碱（0、1、2、5、10 μmol/L）24小时，然后用LPS（1 μg/mL）处理6小时。然后收集RAW264.7细胞，通过实时定量PCR（qRT-PCR）检测IL-6的mRNA水平。
成功合成青藤碱衍生物得到4-棕榈酰青藤碱。在相同治疗浓度下，4-棕榈酰青藤碱治疗组的存活百分比高于青藤碱治疗组。4-棕榈酰青藤碱抑制RAW264.7细胞增殖和IL-6基因转录。
4-棕榈酰青藤碱可能通过抑制RAW264.7细胞增殖、降低炎症基因表达和炎症细胞因子释放而具有抗炎作用。
