基于组效关系的石上柏挥发油抗肿瘤有效成分的辨识

目的:基于GC-MS分析,建立了石上柏挥发油的化学成分与其抑制人肺癌A459细胞株和肝癌7721细胞株的谱效关系模型,寻找与药效显著相关的活性成分。方法:采用噻唑蓝法(MTT)测定石上柏挥发油抑制人肺癌A459细胞和肝癌7721细胞活性,以半数抑制浓度(IC50)为评价指标;采用GC-MS分析,确定了11个特征峰;利用Simca-p11.5软件的正交投影偏最小二乘法(Orthogonal Partial least squares,OPLS)和SPSS 18.0软件的双变量相关分析(Bivariate),研究特征峰与药效的相关性,根据S-载荷图、变异权重参数值(variable importance in projection,VIP)和皮尔逊相关系数(Pearson)来辨识显著活性成分。结果:GC-MS分析石上柏共得到71个化合物,鉴定出其中64个化合物,其相对峰面积分别占总峰面积的98.19%。主要包括萜类,脂肪酸及其烃类化合物。不同产地石上柏挥发油对A549和7721细胞株具有一定的抑制作用,其中抑制A549细胞最高的IC50为46.81 mg·L-1(S6);抑制7721细胞最高的IC50为34.02 mg·L-1(S5)。通过OPLS和Bivariate数据分析,发现5个挥发油成分,即芳樟醇、橙花叔醇、新植二烯、亚油酸甲酯、植酮,与石上柏挥发油抑制肺癌A549细胞和肝癌7721细胞活性显著相关。结论:该方法能快速、有效地建立石上柏挥发油谱效相关关系,可为石上柏挥发油化学成分药理性质的研究提供参考依据。

Composition Activity Relationship of Selaginella doederleinii Volatile Oil Based on Anticancer Activity

Objective:The composition-activity relationship (CAR) model of volatile oil from Selaginella doederleinii was established to recognize the active compounds based on GC-MS analysis. Method:MTT method was adopted to mensurate the inhibition effects of the volatile oil from various habit at sagainst human lung cancer A459 cell and hepatocellular carcinoma 7721 cell line. Half maximal inhibitory concentration (IC₅₀) was used as the evaluation index and 11 characteristic peaks of the volatile oil were identified by GC-MS. The orthogonal partial least squares(OPLS) and bivariate correlation analysis was respectively performed on SIMCA-P 11.5 and SPSS 18.0 software to construct the CAR model of S. doederleinii volatile oil. Result:The results showed that five peaks,including peak 1,8,10,3 and 9,were significantly related to anti-tumor activity according to scores plot from 11 peaks screened,variable importance in projection (VIP) values in OPLS and Pearson correlation coefficient in bivariate correlation analysis. Peak 1,8,10,3 and 9 were identified as linalool, nerolidol, methyl linolenate, methyl linoleate and phytone, respectively. Conclusion:This method can quickly and effectively establish the spectrum-effect relationship for volatile oil from S. doederleinii,providing experimental basis for studying their pharmacological properties.