川芎中抑制脂多糖诱导的RAW264.7和BV2细胞系NO生成的新的丁苯酞衍生物--川芎螺内酯  

Chuanliguspirolide, a new butylphthalide derivative from Chuanxiong Rhizoma and its inhibition on NO production in LPS-activated RAW264.7 and BV2 cell lines

作　　者：郑怡然 韦玮 杨秀伟[1] ZHENG Yi-ran;WEI Wei;YANG Xiu-wei(State Key Laboratory of Natural and Biomimetic Drugs, Department of Natural Medicines, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China)

机构地区：[1]北京大学药学院天然药物学系,天然药物及仿生药物国家重点实验室,北京100191

出　　处：《中草药》2018年第7期1497-1503,共7页Chinese Traditional and Herbal Drugs

基　　金：国家自然科学基金资助项目(81473321); “十二五”国家科技支撑计划(2011BAI07B08)

摘　　要：目的研究川芎95%乙醇提取物的化学成分及其抑制脂多糖(LPS)诱导的小鼠巨噬细胞RAW264.7和小鼠小胶质细胞BV2一氧化氮(NO)生成的生物学活性。方法采用硅胶、高效液相色谱等柱色谱方法进行分离纯化,通过化合物的谱学数据鉴定其结构。采用LPS离体诱导RAW264.7和BV2细胞系NO生成模型,研究化合物对NO生成的抑制活性。结果从川芎95%乙醇提取物中分离出3个丁苯酞衍生物,分别鉴定为Z-3′,8′,3′a,7′a-四氢-6,3′,7,7′a–二聚藁本内酯-8′-酮(1)、Z,Z′-3.3′a,7.7′a-二聚藁本内酯(2)和川芎螺内酯(3)。对LPS诱导的细胞NO生成抑制作用,在RAW264.7细胞模型,化合物1~3和阳性对照药吲哚美辛的半数抑制浓度(IC_(50))分别为(31.60±2.62)、(21.20±0.61)、(30.12±2.90)、(54.62±7.53)μmol/L;在BV2细胞模型,化合物1~3和阳性对照药姜黄素的IC_(50)分别为(21.99±4.40)、(15.43±1.34)、(12.20±3.40)、(10.58±1.41)μmol/L。结论化合物3为新化合物,命名为川芎螺内酯。生物活性实验结果提示化合物1~3可能具有潜在的抗炎作用。Objective To study the chemical constituents of 95% ethanol aqueous extract of Chuanxiong Rhizoma and the bioactivities of inhibition on nitric oxide（NO） production in lipopolysaccharides（LPS）-activated murine macrophage RAW264.7 and mouse microglia BV2 cell lines. Methods The compounds were separated and purified by silica gel column and high performance liquid chromatographies, and their structures were determined by spectroscopic data analysis. Using LPS-activated RAW264.7 and BV2 cell line models in vitro, all of the isolated compounds were evaluated for the inhibition against NO production. Results Three butylphthalide derivatives were obtained and identified as Z-3′,8′,3′a,7′a-tetrahydro-6,3′,7,7′a-diligustilide-8′-one（1）, Z,Z′-3.3′a,7.7′a-diligustilide（2）, and chuanliguspirolide（3）, respectively. For the inhibition of NO production in the LPS-activated two cell lines, the half inhibitory concentration（IC（50）） values of compounds 1—3 and indomethacin as a positive control drug in RAW 264.7 cell line model were（31.60 ± 2.62）,（21.20 ± 0.61）,（30.12 ± 2.90）, and（54.62 ± 7.53） μmol/L, respectively, while IC（50） values of compounds 1—3 and curcumin as a positive control drug in BV2 cell line model were（21.99 ± 4.40）,（15.43 ± 1.34）,（12.20 ± 3.40）, and（10.58 ± 1.41） μmol/L, respectively. Conclusion Compound 3 named as chuanliguspirolide is a new one. The results of bioactivity assays indicated that compounds 1—3 are potential anti-inflammatory agents.

关 键 词：川芎 伞形科 丁苯酞衍生物 川芎螺内酯 RAW264.7细胞系 BV2细胞系 药效物质基础 

分 类 号：R284.1[医药卫生—中药学]