title: Intestinal transport of HDND-7, a novel hesperetin derivative, in in vitro MDCK cell and in situ single-pass intestinal perfusion models.
abstract: 1. Hesperetin (HDND) possesses extensive bioactivities, however, its poor solubility and low bioavailability limit its application. HDND-7, a derivative of HDND, has better solubility and high bioavailability. In this study, we investigated the intestinal absorption mechanisms of HDND-7. 2. MDCK cells were used to examine the transport mechanisms of HDND-7 in vitro, and a rat in situ intestinal perfusion model was used to characterize the absorption of HDND-7. The concentration of HDND-7 was determined by HPLC. 3. In MDCK cells, HDND-7 was effectively absorbed in a concentration-dependent manner in both directions. Moreover, HDND-7 showed pH-dependent and TEER-independent transport in both directions. The transport of HDND-7 was significantly reduced at 4 °C or in the presence of NaN3. Furthermore, the efflux of HDND-7 was apparently reduced in the presence of MRP2 inhibitors MK-571 or probenecid. However, P-gp inhibitor verapamil had no effect on the transport of HDND-7. The in situ intestinal perfusion study indicated HDND-7 was well-absorbed in four intestinal segments. Furthermore, MRP2 inhibitors may slightly increase the absorption of HDND-7 in jejunum. 4. In summary, all results indicated that HDND-7 might be absorbed mainly by passive diffusion via transcellular pathway, MRP2 but P-gp may participate in the efflux of HDND-7.
authors.affiliation: a School of Pharmacy, Anhui Medical University , Hefei , China.
authors.forename: Ruonan
authors.initials: R
authors.lastname: Chen
authors.affiliation: a School of Pharmacy, Anhui Medical University , Hefei , China.
authors.forename: Lan
authors.initials: L
authors.lastname: Li
authors.affiliation: a School of Pharmacy, Anhui Medical University , Hefei , China.
authors.forename: Chenlin
authors.initials: C
authors.lastname: Shen
authors.affiliation: a School of Pharmacy, Anhui Medical University , Hefei , China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Huang
authors.affiliation: a School of Pharmacy, Anhui Medical University , Hefei , China.
authors.forename: Taotao
authors.initials: T
authors.lastname: Ma
authors.affiliation: a School of Pharmacy, Anhui Medical University , Hefei , China.
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Meng
authors.affiliation: a School of Pharmacy, Anhui Medical University , Hefei , China.
authors.forename: Zhengyue
authors.initials: Z
authors.lastname: Qian
authors.affiliation: a School of Pharmacy, Anhui Medical University , Hefei , China.
authors.forename: Yangyang
authors.initials: Y
authors.lastname: Li
authors.affiliation: a School of Pharmacy, Anhui Medical University , Hefei , China.
authors.forename: Jun
authors.initials: J
authors.lastname: Li
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D001692:Biological Transport; D004285:Dogs; D006569:Hesperidin / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D007413:Intestinal Mucosa / Q000378:metabolism*; D061985:Madin Darby Canine Kidney Cells; D051381:Rats
chemical_list: C000623093:8-(N,N-diethyl)-methyl-amino-3',5,7-trihydroxy-4'-methoxyflavanone; D006569:Hesperidin; C013015:hesperetin
keywords: HDND-7; MDCK cell; MRP2; absorption; in situ single-pass intestinal perfusion