Pharmacokinetic properties of lutein emulsion after oral administration to rats and effect of food intake on plasma concentration of lutein

Sato, Yuki; Kobayashi, Masaki; Itagaki, Shirou; Hirano, Takeshi; Noda, Toshihiro; Mizuno, Satoshi; Sugawara, Mitsuru; Iseki, Ken

doi:10.1002/bdd.746

Cited by 32 publications

(23 citation statements)

References 29 publications

(37 reference statements)

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“…We have demonstrated improvement of the intestinal absorption of poorly water-insoluble functional food components. 25) It remains obscure whether these components are the substrates of NPC1L1 like cholesterol. Further investigations to obtain evidence of pharmaceutical design for theoretical improvement of intestinal absorption of these components are in progress.…”

Section: Effect Of Cholesterol In Lipid Emulsion Particles On the Uptmentioning

confidence: 99%

An Approach to Improve Intestinal Absorption of Poorly Absorbed Water-Insoluble Components <i>via</i> Niemann–Pick C1-Like 1

Takekawa

Sato

Yamaki

et al. 2016

Biological & Pharmaceutical Bulletin

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Dietary and biliary cholesterol absorption contributes to the maintenance of tight control of cholesterol homeostasis. Cholesterol is present as mixed micelles formed by bile salts and phospholipids in the intestinal lumen. Recently, Niemann-Pick C1-Like 1 (NPC1L1) transporter was identified as being critical for cholesterol absorption. However, the uptake mechanism of an enveloped substrate of NPC1L1 in whole lipid emulsion particles remains unclear. In this study, we investigated the uptake mechanism of a substrate of NPC1L1 in lipid emulsion particles. We also investigated whether these particles containing cholesterol can improve the intestinal absorption of other lipophilic components via NPC1L1. The uptake of lysophosphatidylcholine (LPC)-4,4-difluoro-5-(4-phenyl-1,3-butadienyl)-4-bora-3a,4a-diaza-s-indacene-3-propionic acid saccinimidyl ester (BODIPY), a fluorescently labeled phospholipid, in lipid emulsion particles containing cholesterol (1 µM) was significantly increased compared to that without cholesterol in Caco-2 cells. On the other hand, its increased uptake was significantly inhibited by ezetimibe, a selective inhibitor of NPC1L1. These results suggested that not only cholesterol but also some components in lipid emulsion particles are taken up into enterocytes via NPC1L1. We also examined an approach to improve intestinal absorption of a poorly absorbed water-insoluble component, coenzyme Q10 (CoQ10), by this mechanism. The uptake of CoQ10 in lipid emulsion particles containing cholesterol was significantly increased compared to that without cholesterol. Its increased uptake was significantly inhibited by ezetimibe. Though it is still not clear whether CoQ10 is a substrate of NPC1L1, there is a potential for improvement of the absorption of poorly absorbed components by lipid emulsion particles containing cholesterol.Key words Niemann-Pick C1-Like 1; absorption; cholesterol; emulsion; coenzyme Q10Intestinal absorption is an important process in the maintenance of homeostasis in the body. Cholesterol homeostasis is a highly regulated balance of de novo synthesis, dietary cholesterol absorption, and biliary clearance and excretion. Although the cholesterol uptake mechanism in the intestinal lumen is not fully understood, the identification of ezetimibe as a selective inhibitor of intestinal cholesterol absorption suggested that these processes are mediated by a specific transport system rather than by passive diffusion.1) In 2004, Altmann et al. identified Niemann-Pick C1-Like 1 (NPC1L1) as an apically localized sterol transporter in the small intestine.2) NPC1L1 is highly expressed in the small intestine, particularly in the upper intestine.2,3) NPC1L1 protein has 13 predicted transmembrane domains and extensive N-linked glycosylation sites located within the extracellular loops and it contains a sterol sensing domain (SSD).4) It has predicted that the substrates of NPC1L1 have sterol domains and have been mainly thought to transport the substance involving the sterol structure.Cholesterol is pre...

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Section: Effect Of Cholesterol In Lipid Emulsion Particles On the Uptmentioning

confidence: 99%

An Approach to Improve Intestinal Absorption of Poorly Absorbed Water-Insoluble Components <i>via</i> Niemann–Pick C1-Like 1

Takekawa

Sato

Yamaki

et al. 2016

Biological & Pharmaceutical Bulletin

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“…Plasma samples were obtained at a designated time as described previously. 13,15) The samples were kept at −20°C until assay.…”

Section: Methodsmentioning

confidence: 99%

“…13) The equation was the same as that reported previously. 15) The area under the curve (AUC) was calculated by the trapezoidal rule.…”

Section: )mentioning

confidence: 99%

Emulsification Using Highly Hydrophilic Surfactants Improves the Absorption of Orally Administered Coenzyme Q10

Sato

Mutoh

Suzuki

et al. 2013

Biological & Pharmaceutical Bulletin

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Coenzyme Q10 (CoQ10) is an essential component in the electron-transport systems of mitochondria and bacteria and is often used as a supplementary treatment for some diseases. We previously reported that the bioavailability of CoQ10 powder was less than 10%. In this study, we investigated various preparations to improve the intestinal absorption of CoQ10 with focus on the effect of emulsification. We prepared a suspension and some emulsions with four types of surfactants and investigated the plasma concentration profile after oral administration to rats. The absorption of CoQ10 was improved by an emulsion formulation although there was little absorption of CoQ10 when a suspension was administered. However, little CoQ10 was absorbed in the bile duct-ligated group even when the emulsion formulation was administered (about 50% of the control group). Bile and emulsion formulation are essential for absorption of CoQ10. When the preparations containing Tween20 (polysorbate (20) sorbitan monolaurate) and Tween80 (polyoxyethylene (20) sorbitan monooleate) were administered, plasma concentrations of CoQ10 were higher than those obtained with preparations containing Tween65 (polyoxyethylene (20) sorbitan tristearate) and Span20 (sorbitan monolaurate). Tween20 and Tween80 have higher hydrophile-lipophile balance (HLB) values than those Tween65 and Span20. Our study suggests that highly lipophilic compounds like CoQ10 would diffuse the unstirred water layer and would easily access the intestinal apical membrane by an emulsion containing a surfactant with a high HLB value. Attention must be given to CoQ10 supplementation for patients whose bile is not excreted to the intestine such as patients with cholestasis.Key words coenzyme Q10; absorption; bile; emulsion; intestine; lutein Preventive medicine and anti-aging medicine have received much attention recently due to increases in the proportion of elderly people in the population and patients with lifestyle diseases such as hypertension, dislipidemia and diabetes. Oxidative stress is involved in the onset of lifestyle diseases, 1,2) and various antioxidant supplements and antioxidant-fortified functional foods have recently become available. Many epidemiological studies have shown relationships between consumption of polyphenol or carotenoid-rich foods and prevention of these lifestyle diseases. 3,4) Coenzyme Q (CoQ) has a benzoquinone ring linked to a polyisoprenyl chain of 9 or 10 units in mammalian species. CoQ10, also known as ubiquinone, is a ubiquitous component vital to a number of activities related to energy metabolism. CoQ10 also functions in its reduced form as an antioxidant, protecting biological membranes and serum low density lipoprotein (LDL) from lipid peroxidation. 5,6) The use of CoQ10 as a therapeutic cardiovascular agent was based on its fundamental role in mitochondrial function and cellular bioenergetics. 7,8) Many studies have also indicated a beneficial antioxidant effect of CoQ10 as supplementation, and CoQ10 has received much attention due to its an...

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“…The samples were kept at -80°C until assay. The concentration of lutein was determined using an HPLC system as described previously (21).…”

Section: Chemicalsmentioning

confidence: 99%

Intracellular Uptake Mechanism of Lutein in Retinal Pigment Epithelial Cells

et al. 2013

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-Purpose. Lutein is a carotenoid mainly found in green leafy vegetables and is located in the macula lutea in the human eye. It has received much attention recently due to its preventive effect on age-related macular degeneration, and it has been consumed as a supplement. However, little information about the pharmacokinetic properties of lutein is available. Detailed knowledge of pharmacokinetic properties of lutein is needed for the development of pharmaceutics. In this study, we focused on the macular accumulation of lutein and investigated the uptake mechanism into human retinal pigment epithelial cells. Methods. ARPE-19 cells were used for the study on the accumulation mechanism of lutein. The concentration of lutein was determined using an HPLC system. Involvement of scavenger class B type 1 (SR-B1) in the accumulation of lutein in ARPE-19 cells was suggested from the results of an inhibition study using block lipid transport 1 (BLT-1), a selective inhibitor of SR-B1. To investigate the involvement of SR-B1 in more detail, small interfering RNA (siRNA) was transfected and the mRNA and protein expression levels of SR-B1 were assessed by quantitative real-time reverse transcription polymerase chain reaction and Western blotting, respectively. Results. We confirmed a sufficient siRNA knockdown effect in both mRNA and protein expression levels of SR-B1. We then found that lutein uptake was significantly decreased by siRNA knockdown of SR-B1. Conclusion. The uptake of lutein was significantly decreased by 40% compared with the control uptake level. This suggested that active transport of lutein into ARPE-19 cells is mainly via SR-B1, given the result that lutein uptake at 4ºC was about 40% less that that at 37ºC.

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Pharmacokinetic properties of lutein emulsion after oral administration to rats and effect of food intake on plasma concentration of lutein

Cited by 32 publications

References 29 publications

An Approach to Improve Intestinal Absorption of Poorly Absorbed Water-Insoluble Components <i>via</i> Niemann–Pick C1-Like 1

An Approach to Improve Intestinal Absorption of Poorly Absorbed Water-Insoluble Components <i>via</i> Niemann–Pick C1-Like 1

Emulsification Using Highly Hydrophilic Surfactants Improves the Absorption of Orally Administered Coenzyme Q10

Intracellular Uptake Mechanism of Lutein in Retinal Pigment Epithelial Cells

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