title: Transport of curcumin derivatives in Caco-2 cell monolayers.
abstract: Curcumin (Cur) is a strong natural antioxidant, who can prevent multiple diseases such as anti-cancer, anti-inflammatory, have a resistance to alzheimer's disease and various malignant diseases. But it has poor oral bioavailability due to its poor aqueous solubility, as well as instability. While its novel derivatives (CB and FE), showed better anti-tumor activity, better anti-oxidant activity and better stability than the original drug (Cur). The aim of this study was to study the intestinal transport of Cur, CB and FE using an in vitro Caco-2 cell monolayer model. The results showed that Cur had a lower permeability coefficient (1.13×10-6±0.11×10-6cm/s) for apical-to-basolated (AP-BL) transport at 25μM, while the transport rate for AP to BL flux of CB (3.18×10-6±0.31×10-6cm/s) and FE (5.28×10-6±0.83×10-6cm/s) were significantly greater than that of Cur. The efflux ratio (ER) value at the concentration of 25μM was 1.31 for Cur, 1.26 for CB and 1.33 for FE, suggesting there was no active efflux involved in the translocation across the Caco-2 cell monolayers for the three compounds. Furthermore, the transport flux of CB and FE was in a concentration dependent manner, suggesting the intestinal transport mechanism in them was passive transport. In summary, the results demonstrated that both the intestinal permeability of CB and FE across Caco-2 cell monolayers was significantly improved compare to Cur. Thus they might show a higher oral bioavailability in vivo, and show the potential application in clinic or nutraceutical.
authors.affiliation: College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou 310014, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Zeng
authors.affiliation: Collaborative Innovation Center of Yangtze River Region Green Pharmaceuticals, Zhejiang University of Technology, Hangzhou 310014, China.
authors.forename: Zhe L
authors.initials: ZL
authors.lastname: Shen
authors.affiliation: Hangzhou No. 2 High School of Zhejiang Province, Hangzhou 310014, China.
authors.forename: Shuo
authors.initials: S
authors.lastname: Zhai
authors.affiliation: College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou 310014, China.
authors.forename: Jia L
authors.initials: JL
authors.lastname: Xu
authors.affiliation: Collaborative Innovation Center of Yangtze River Region Green Pharmaceuticals, Zhejiang University of Technology, Hangzhou 310014, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Liang
authors.affiliation: College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou 310014, China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Shen
authors.affiliation: College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou 310014, China. Electronic address: li_qingyong@126.com.
authors.forename: Qing Y
authors.initials: QY
authors.lastname: Li
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000378:metabolism; D001692:Biological Transport / Q000502:physiology; D018938:Caco-2 Cells; D002463:Cell Membrane Permeability / Q000502:physiology*; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D003474:Curcumin / Q000737:chemistry* / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007408:Intestinal Absorption / Q000502:physiology*
chemical_list: D000970:Antineoplastic Agents; D003474:Curcumin
keywords: Caco-2 cell monolayers; Curcumin derivatives; Intestinal permeability; Intestinal transport; Passive transport