Zedoary Turmeric, which is the rhizomes of three species of Curcuma including Curcuma phaeocaulis, Curcuma kwangsiensis and Curcuma wenyujin, has been used over a long periods as a traditional Chinese medicine for removing blood stasis and alleviating pain. The essential oil extracted from the herb medicine which consisted most of the bioactive components in Zedoary Turmeric is also named Zedoary Turmeric Oil (Ezhu oil). It has many biological activities, such as anti-tumor, anti-inflammatory and anti-virus activities. Up to now, the researches concerning oral absorption and metabolism mechanism of Zedoary Turmeric Oil are less, the problems of which components could be well absorbed and could use as the marker compound for analysis purpose need to be solved. The Caco-2 cell line is derived from a human colorectal carcinoma. The utility of this cell line stems from the fact that the Caco-2 cells differentiate spontaneously to enterocytes under conventional cell culture conditions upon reaching confluence on porous polycarbonate membranes, and thus resemble small intestinal epithelium. Several active transport systems that are located in the intestinal epithelium (such as sugars, amino acids, dipeptides, bile acids and cobalamin intrinsic factor) are also expressed in Caco-2 cells. This model has well in vitro-in vivo correlations for drug absorption. The research about oral absorption mechanism of Zedoary Turmeric Oil using Caco-2 cell model has not been seen in publications. The current study will use Caco-2 cell model to investigate the absorption mechanism of Zedoary Turmeric Oil and the influence of transport directions, drug concentrations and other compositions to the permeability of active compounds in the essential oil. Caco-2 cell model was applied to investigate the transport mechanism of Zedoary Turmeric Oil and some of its active components, including curdione, germacrone, furanodiene and curcumol. Apparent permeability coefficients of above active compounds and Zedoary Turmeric Oil across Caco-2 cell monolayers were measured as a function of direction of transport and concentration of each component. In addition, the effects of other components on the permeability of curdione and germacrone were also investigated.The apparent permeability coefficients (Papp) of curdione, germacrone and curcumol are all at 10S cm/s level, which is comparable to transcellular marker of propranolol and did not significantly change with transport directions and drug concentrations (P>0.05). Furanodiene and other high lipophilic components in Zedoary Turmeric Oil (e.g. furanodiene, curzerene and B elemene) could not transport across Caco-2 cell monolayer. Components other than selected compounds in Zedoary Turmeric Oil did not interfere with the permeability coefficient of curdione and germacrone (P>0.05). No metabolites could be detected in receiver side during the transport study with Zedoary Turmeric Oil and selected active compounds. The above results indicated that the transcellular transports are predominantly by passive diffusion for Zedoary Turmeric Oil and its selected active components. The high lipophilic components in Zedoary Turmeric Oil, e.g. furanodiene, could not transport across the Caco-2 monolayer and most of them were uptake into cell monolayer and could not reach to receiver side. Other components in Zedoary Turmeric Oil did not influence the transport of the active components in the essential oil.

莪術油(Zedoary Turmeric Oil)爲营科植物蓬莪術Curcuma phaeocaulis Val.. 廣西我術 Curcuma twangsiensis S. G. Lee et C. F. Liang或溫郁金CurcumaWenyujin. Y.H. chen et C. Ling的乾燥根莖提取所得的揮發油，在转術中含量爲1%-2.5%。已從揮發油中分離出;莪術醇(CurcuToD、我術二酮(Curdione)、呋喃三烯(Guranodiene)、吉馬間(Germacrone)等20多種成分，主要鵀萜類及倍牛萜類術生物。據報導其藥理作用主要有抗炎、鎭痛、抗腫瘤等，臨床上主要用於治療腫瘤及病毒性感染。目前主要以莪術油汪射液使用，但近年來對其注射液的不良反應報導很多，有待開發其口服製劑。到目 前爲止，對莪術油及其單體的口服吸收 機理及代謝的研究較少，哪些單體成分可口服吸收並可用作口服劑型的質控標準有待解決。 Caco-2細胞來源於人結腸癌細胞，在體外培養條件下，能分化成連續的細胞 單分子層，具有細胞極性及微絨毛結構，可表達各種蛋白載體和酶，被認爲是目前較理想的體外吸收模型，與藥物體內吸收有良好的相關性。利用Caco-2吸收模型對莪術油吸收機理的研究在國內外末見文獻報導。本研究將運用Caco-2紐胞模型研究我術油及其部分單體的吸收機理，考察轉運方向，藥物濃度，及總油中其他活性成分對活性單體透過的影響，聞明可吸收的單體成分，爲其口服製劑開發和質控提供理論依據。 本實驗首先研究了我術油及其部分單體在不同條件下的穩定性情況，考察其穩定性影響因素並優化分析條件。應用Caco-2體外細胞吸收模型，分别考察了莪 術油及其部分活性單體，包括莪術二酮、吉馬酮、呋喃二烯、莪術醇在不同轉運 方向，不同濃度下的轉運情況，並比較各單體與揮發油中相應成分在同一濃度下的轉運倩況。探用高效液相色譜法測定藥物濃度，計算其表觀渗透係數。 結果表明，裁術二酮、吉馬酮、莪術醇有較高的表觀渗透係數，且不隨轉運 方向及給藥濃度的影響而改變(P>0.05)；而呋喃二烯及揮發油中其它高脂溶性成分，包括呋喃二烯(Furanodiene)、我術烯(Curzerene)、B-欖香烯(B-elermene)，在 Caco-2細胞模型上不透過;揮發油中其他成分不影響活性成分義術二酮、吉馬酮在細胞模型上的透過(P>0.05)；莪術油及其活性單體透過Caco-2單層細胞膜後並無可被檢測的代謝產物產生。本研究證明莪術油及其部分單體在Caco-2細胞模型中的轉運機制爲被動擴散，莪術油中高脂溶性成分及呋喃二烯單體由於被單層細胞膜攝取而不透過 Caco-2細胞，揮發油中其他成分對單體成分的透過無影響。