title: Inhibition of cholesterol transport in an intestine cell model by pine-derived phytosterols.
abstract: We have quantified the inhibition of intestinal cholesterol transport by pine-derived phytosterols using an HT29-MTX intestine cell model that forms a mucus layer similar to that in the intestine. An artificial intestinal fluid consisting of digested fat, bile salt, cholesterol, and phytosterols was formulated in order to mimic the conditions in the intestine. The apparent permeability coefficient (Papp) of the positive control, i.e., 0.1mM of cholesterol solubilized in the artificial intestine fluid, was found to be 0.33 (±0.17)×10-6cm/s. When 0.1mM β-sitosterol was solubilized alongside, Pappwas effectively zero, corresponding to a total inhibition of cholesterol transport. A similar strong inhibition was found when commercial pine-derived phytosterols, PinVita™ FSP DuPont, were co-solubilized with cholesterol in the dietary model micelles, leading to Papp=0.06 (±0.06)×10-6cm/s, i.e., 5.5 times lower than the cholesterol positive control. Additionally, the effect of potential oral administration formulations generated by the pine-derived phytosterols was also characterized. The formulations were produced as a liquid formulation of the cholesterol-containing artificial intestine fluid. Six liquid formulations were tested of which four displayed a Pappin the range of 0-0.09×10-6cm/s. The remaining two formulations did not show any inhibition effect on cholesterol transport and even enhanced cholesterol transport. It was furthermore observed that the phytosterols were found in the collected intestine cells but not transported to the basolateral region in the intestinal cell model system.
authors.affiliation: MEMPHYS/SPSE, Department of Physics, Chemistry, and Pharmacy, University of Southern Denmark, DK-5230 Odense M, Denmark.
authors.forename: Jinsoo
authors.initials: J
authors.lastname: Yi
authors.affiliation: DuPont Nutritional Biosciences ApS, Edwin Rahrs Vej 38, DK-8220 Brabrand, Denmark.
authors.forename: Tine A
authors.initials: TA
authors.lastname: Knudsen
authors.affiliation: Danish Technological Institute, Kongsvang Allé 29, DK-8000 Aarhus, Denmark.
authors.forename: Anne-Louise
authors.initials: AL
authors.lastname: Nielsen
authors.affiliation: MEMPHYS/SPSE, Department of Physics, Chemistry, and Pharmacy, University of Southern Denmark, DK-5230 Odense M, Denmark.
authors.forename: Lars
authors.initials: L
authors.lastname: Duelund
authors.affiliation: MEMPHYS/SPSE, Department of Physics, Chemistry, and Pharmacy, University of Southern Denmark, DK-5230 Odense M, Denmark.
authors.forename: Morten
authors.initials: M
authors.lastname: Christensen
authors.affiliation: MEMPHYS/SPSE, Department of Physics, Chemistry, and Pharmacy, University of Southern Denmark, DK-5230 Odense M, Denmark.
authors.forename: Pablo
authors.initials: P
authors.lastname: Hervella
authors.affiliation: MEMPHYS/SPSE, Department of Physics, Chemistry, and Pharmacy, University of Southern Denmark, DK-5230 Odense M, Denmark.
authors.forename: David
authors.initials: D
authors.lastname: Needham
authors.affiliation: MEMPHYS/SPSE, Department of Physics, Chemistry, and Pharmacy, University of Southern Denmark, DK-5230 Odense M, Denmark. Electronic address: ogm@memphys.sdu.dk.
authors.forename: Ole G
authors.initials: OG
authors.lastname: Mouritsen
mesh_terms: D065567:Absorption, Physiological; D001692:Biological Transport / Q000187:drug effects; D002478:Cells, Cultured; D002784:Cholesterol / Q000032:analysis / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D004305:Dose-Response Relationship, Drug; D019073:HT29 Cells; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000166:cytology* / Q000187:drug effects*; D008954:Models, Biological; D010316:Particle Size; D010840:Phytosterols / Q000737:chemistry / Q000494:pharmacology*; D028223:Pinus / Q000737:chemistry*; D013329:Structure-Activity Relationship; D013499:Surface Properties
chemical_list: D010840:Phytosterols; D002784:Cholesterol
keywords: Apparent permeability coefficient; Cholesterol; HT29-MTX intestinal cell model; PinVita™ FSP DuPont; Pine-derived phytosterols; Sterol transport; β-Sitosterol