目的 考察白芷中呋喃香豆素类成分对难吸收药物葛根素、芍药苷、长春新碱吸收的影响, 探讨白芷中呋喃香豆素类成分对不同结构药物吸收的影响规律。方法 采用Caco-2细胞模型, 以各药物透过Caco-2细胞单层的表观渗透系数(P_app)为指标, 分别考察白芷中呋喃香豆素类成分(欧前胡素、异欧前胡素、佛手柑内酯、氧化前胡素)对葛根素、芍药苷、长春新碱透过Caco-2细胞单层的影响。结果 4个呋喃香豆素类成分对3种单体成分转运的影响不同, 欧前胡素、异欧前胡素、氧化前胡素能显著促进葛根素透过Caco-2细胞单层转运(P<0.05、0.01), 佛手柑内酯对葛根素透过Caco-2细胞单层转运无明显影响;欧前胡素、佛手柑内酯对芍药苷透过Caco-2细胞单层转运无明显影响, 但异欧前胡素、氧化前胡素显著抑制芍药苷透过Caco-2细胞单层转运(P<0.05、0.01);欧前胡素、异欧前胡素、氧化前胡素能显著促进长春新碱透过Caco-2细胞单层转运(P<0.05、0.01), 佛手柑内酯能显著抑制长春新碱透过Caco-2细胞单层转运(P<0.05)。结论 不同呋喃香豆素对同一药物的肠道转运的影响不同, 虽然同为呋喃香豆素, 对药物的转运可表现为完全相反的作用。同一呋喃香豆素与不同药物联合使用, 其对联合用药物肠道转运的影响也不相同。

Objective To investigate the influence of furan coumarins from Angelicae Dahuricae Radix on intestinal absorption of puerarin, paeoniflorin, and vincristine, and to explore the influence law of furan coumarins on the intestinal absorption of the drugs with different structures. Methods The apparent permeability coefficient (P_app) of drugs across the Caco-2 cell monolayers as evaluated index and Caco-2 cell model was used to study the absorption effects of furan coumarins (imperatorin, isoimperatorin, bergapten, and oxypeucedanin) on the transport of puerarin, paeoniflorin, and vincristine across Caco-2 cell monolayers. Results There are different effects of the four coumarins on puerarin, paeoniflorin, and vincristine. For imperatorin, isoimperatorin, and oxypeucedanin could improve the transport of puerarin on Caco-2 cell significantly (P < 0.05, 0.01), while bergapten has no effect on the transport of puerarin across Caco-2 cell monolayers. For imperatorin and bergapten have no effect on the transport of paeoniflorin: However isoimperatorin and oxypeucedanin could significantly inhibit the transport of paeoniflorin across Caco-2 cell monolayers (P < 0.05, 0.01). Iperatorin, isoimperatorin, and oxypeucedanin could improve the transport of vincristine across Caco-2 cell monolayers significantly (P < 0.05, 0.01), but bergapten could significantly restrain the transport of vincristine across Caco-2 cell monolayers (P < 0.05). Conclusion Different furan coumarins have different effects on the intestinal transport of the same medicine. Although the structures all are the furan type, the influence shows the opposite effect on drug transport. The same furan coumarin combined with different drugs have the different influences on the intestinal transport of compatibility drugs.

国家青年自然科学基金项目(81303237);江西省卫生厅项目(2012A030);江西省青年科学基金项目(20114BAB215040)