目的 探讨生白术发挥健脾作用的有效部位及化学成分。方法 采用“ig番泻叶＋疲劳游泳＋饥饱失常”的方法复制脾虚大鼠模型，给予生白术水提物、多糖及除糖部位治疗，通过一般行为学特征、小肠推进率及胃内残留率、消化吸收功能、水液代谢功能、组织病理结构和神经递质等指标，评价生白术治疗脾虚的有效部位；进一步采用HP-20型大孔树脂柱色谱制备除糖部位不同体积分数乙醇洗脱组分，通过α-二氟甲基鸟氨酸（difluoromethylornithine，DFMO）诱导的大鼠小肠上皮细胞（intestinal epithelial cell-6，IEC-6）生长抑制模型，评价不同浓度乙醇洗脱组分对细胞活力的影响；最后采用超高效液相色谱-串联四极杆飞行时间质谱（UPLC-Q-TOF/MS）技术对有效组分进行化学成分表征，并定向分离主要化学成分，评估其对DFMO诱导的IEC-6细胞活力的影响。结果 生白术水提物及其除糖部位主要通过调节神经递质水平、促进胃肠动力、修复组织损伤和提高消化吸收能力、炎症因子水平显著改善脾虚大鼠的症状；除糖部位中90%乙醇洗脱组分（CT-90E）在0.1～0.15 mg/L可逆转DFMO所致的IEC-6细胞生长抑制；CT-90E组分中的8-表白术内酯（12.5～100 μmol/L）、白术内酯Ⅱ（50～100 μmol/L）、白术内酯Ⅰ（25～50 μmol/L）及邻苯二甲酸（12.5～50 μmol/L）可逆转DFMO诱导的IEC-6细胞生长抑制。结论 生白术水提物治疗脾虚药效显著，除糖部位是其治疗脾虚的活性部位，其中CT-90E组分可促进肠黏膜的修复，而8-表白术内酯、白术内酯Ⅱ、白术内酯Ⅰ及邻苯二甲酸为CT-90E组分中修复肠黏膜的主要活性成分。

Objective To explore the active fractions and chemical components with spleen-invigorating effect from raw rhizomes of Atractylodes macrocephala. Methods The rat model of spleen-deficiency was replicated by the method of “ig senna leaves + fatigued swimming + abnormal hunger and satiety”, Which was treated with water extract from raw rhizomes of A. macrocephala, polysaccharides and non-polysaccharide parts. The effective fractions of raw rhizomes of A. macrocephala in treating spleen deficiency were evaluated using various indicators, including general behavioral characteristics, gastrointestinal (GI) transit rate, gastric residual rate, digestive and absorption functions, water and fluid metabolism, tissue pathological structure, and neurotransmitters of rats with spleen-deficiency. The non-polysaccharide part was subjected to chromatography on a HP-20 macroporous resin column eluted with different concentrations of aqueous ethanol. The intestine epithelial cell (IEC-6) growth inhibition model induced by α-difluoromethylornithine (DFMO) was applied to assay the cell viability of the obtained fractions. The chemical constituents in the active fraction were analyzed by ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS). The main constituents were isolated and evaluated for their impact on IEC-6 cell viability induced by DFMO. Results The water extract and non-polysaccharide part from raw rhizomes of A. macrocephala significantly improved the symptoms of spleen-deficiency rats, mainly by regulating neurotransmitter levels, promoting gastrointestinal motility, repairing tissue damage, enhancing digestive and absorption capabilities, and modulating inflammatory factors. The 90% ethanol-elution fraction from non-polysaccharide part (CT-90E) at concentrations of 0.1—0.15 mg/L could reverse the growth inhibition of IEC-6 cells induced by DFMO. The main components in CT-90E, including 8-epiatylenolide (12.5—100 μmol/L), atractylenolide II (50—100 μmol/L), atractylenolide I (25—50 μmol/L), and phthalic acid (12.5—50 μmol/L) could reverse the growth inhibition of IEC-6 cells induced by DFMO. Conclusion The water extract of raw rhizomes of A. macrocephala exhibits significant effect in treating spleen deficiency, with the non-polysaccharide part identified as the active part responsible for treating spleen deficiency. Among the fractions of non-polysaccharide part, CT-90E promotes the repair of intestinal mucosa, with 8-epiatylenolide, atractylenolide II, atractylenolide I, and phthalic acid identified as the main active components responsible for mucosal repair.

R284.1;R285

国家自然科学基金资助项目（82073992）；中国医学科学院医学与健康科技创新工程项目（2023-I2M-2-006）