枳实化学成分与治疗功能性消化不良关联性分析及实验验证

目的 研究枳实治疗功能性消化不良（functional dyspepsia，FD）的药效物质基础。方法 运用超高效液相色谱-四极杆飞行时间质谱联用（UPLC-Q-TOF-MS/MS）技术对10批枳实水煎液进行分析，确定共有成分；采用不规则喂养和夹尾刺激建立FD大鼠模型，以小肠碳末推进率、胃排空率及血清中胃动素、胃泌素水平为药效指标，采用灰色关联度分析法和Pearson双变量相关性分析建立色谱图中共有峰峰面积与药效指标的相关性，筛选出枳实治疗FD的药效物质，并通过斑马鱼肠蠕动模型进行药效验证。结果 10批枳实水煎液中共指认35个共有成分，通过灰色关联度和Pearson双变量相关性分析，筛选出辛弗林、马尔敏、黄柏酮、N-甲基酪胺、圣草次苷、柚皮苷、橙皮苷和新橙皮苷共8个成分为枳实治疗FD的潜在药效物质。选择药效相关性较强、易得、可测的圣草次苷、柚皮苷、橙皮苷、新橙皮苷和辛弗林进行实验验证，发现这5个成分均显著促进斑马鱼肠道蠕动（P＜0.01）。结论 圣草次苷、柚皮苷、橙皮苷、新橙皮苷和辛弗林为枳实治疗FD的药效物质。

Correlation analysis and experimental verification between chemical components of Aurantii Fructus Immaturus and treatment of functional dyspepsia

ObjectiveTo study the pharmacodynamic basis of Zhishi (Aurantii Fructus Immaturus) in the treatment of functional dyspepsia (FD). Methods UPLC-Q-TOF-MS/MS technology was used to analyze the common components of 10 batches of Aurantii Fructus Immaturus. FD model of rats was established by irregular feeding and tail pinching stimulation, small intestine carbon end advance rate, gastric emptying rate and levels of motilin and gastrin in serum were used as pharmacodynamic indexes, grey correlation analysis method and Pearson bivariate correlation analysis were used to establish the correlation between the peak area of common peak in chromatogram and pharmacodynamic index. Pharmacodynamic substances of Aurantii Fructus Immaturus in the treatment of FD were screened out, and efficacy was verified by zebrafish intestinal motility model. Results A total of 35 common components were identified in 10 batches of Aurantii Fructus Immaturus decoction. Synephrine, malmin, obacunone, N-methyltyramine, eriocitrin, naringin, hesperidin and neohesperidin eight components were screened out as potential pharmacodynamic substances of Aurantii Fructus Immaturus in the treatment of FD through grey correlation and Pearson bivariate correlation analysis. Eriocitrin, naringin, hesperidin, neohesperidin and synephrine with strong efficacy correlation, easy to obtain and measurable were selected for experimental verification, above five components significantly promoted zebrafish intestines peristalsis (P < 0.01). Conclusion Eriocitrin, naringin, hesperidin, neohesperidin and synephrine are the pharmacodynamic substances of Aurantii Fructus Immaturus in the treatment of FD.