莪术油在Caco-2细胞模型中的吸收机制研究

 目的研究莪术油及其部分活性单体在Caco-2体外细胞吸收模型中的吸收机制,并比较各成分以单体形式及以总油形式在细胞模型上透过的异同。方法应用Caco-2体外细胞吸收模型,分别考察莪术油(Zedoary Turmeric oil,ZTO)及其部分单体,包括莪术二酮(curdione)、吉马酮(germacrone)、呋喃二烯(furanodiene)、莪术醇(curcumol)在不同方向,不同浓度下的转运情况,并比较各单体与挥发油中相应成分在同一浓度下的转运情况。采用高效液相色谱法测定药物浓度,计算其表观渗透系数。结果莪术二酮、吉马酮、莪术醇有很高的表观渗透系数,且不随转运方向及给药浓度影响(P>0.05);而呋喃二烯及挥发油中的其他高脂溶性成分[包括呋喃二烯、莪术烯(curzerene)、β-榄香烯(β-elemene)]在Caco-2细胞模型上不透过;挥发油中其他成分不影响莪术二酮、吉马酮在细胞模型上的透过(P>0.05);莪术油及其活性单体透过Caco-2单层细胞膜后并无代谢产物可被检测。结论莪术油及其部分单体在Caco-2细胞模型中的转运机制为被动扩散,莪术油中高脂溶性成分及呋喃二烯由于被单层细胞膜摄取而不透过Caco-2细胞,挥发油中其他成分对单体成分的透过无影响。

Study on Absorption Mechanisms of Zedoary Turmeric Oil by Caco-2 Cell Model

OBJECTIVE To investigate absorption mechanisms of Zedoary Turmeric oil (ZTO) by Caco-2 monolayers model.METHODS Caco-2 cell model was applied to investigate the transportation of ZTO and its active components,including curdione,germacrone,furanodiene and curcumol. Permeability coefficients of above active compounds and ZTO across Caco-2 cell monolayers were measured as a function of direction transport and concentration of each component. In addition,the effects of other components on the permeability of curdione and germacrone were also investigated. RESULTS The apparent permeability coefficients (P_app) of curdione,germacrone and curcumol were high.Compared with transcellular marker propranolol,the apparent permeability coefficients of curdione, germacrone and curcumol were not significantly changed by transport direction and drug concentrations(P>0.05). Furanodiene and other high lipophilic components in ZTO (e.g. furanodiene,curzerene and β-elemene) did not transport across Caco-2 cell monolayer. Components other than selected compounds in ZTO did not interfere the permeability coefficient of curdione and germacrone (P>0.05). No metabolites were detected in receiver side during the transport study with ZTO and selected active compounds. CONCLUSION The above results indicate that transcellular transport was dominated by passive diffusion for ZTO and its selected active components. The high lipophilic components in ZTO,e.g. furanodiene,could not transport across the Caco-2 monolayer and most of them were uptake into cell monolayers and could not reach to receiver side. Other components in ZTO did not influence the transport of the active essential oil.