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An Approach to Improve Intestinal Absorption of Poorly Absorbed Water-Insoluble Components via Niemann Pick C1-Like 1
| Title: | An Approach to Improve Intestinal Absorption of Poorly Absorbed Water-Insoluble Components via Niemann Pick C1-Like 1 |
| Authors: | Takekawa, Yuto Browse this author | | Sato, Yuki Browse this author →KAKEN DB | | Yamaki, Yoshiaki Browse this author | | Imai, Mei Browse this author | | Noto, Kazuma Browse this author | | Sumi, Masato Browse this author →KAKEN DB | | Takekuma, Yoh Browse this author →KAKEN DB | | Iseki, Ken Browse this author →KAKEN DB | | Sugawara, Mitsuru Browse this author →KAKEN DB |
| Keywords: | Niemann Pick C1-Like 1 | | absorption | | cholesterol | | emulsion | | coenzyme Q10 |
| Issue Date: | Mar-2016 |
| Publisher: | The Pharmaceutical Society of Japan |
| Journal Title: | Biological & pharmaceutical bulletin |
| Volume: | 39 |
| Issue: | 3 |
| Start Page: | 301 |
| End Page: | 307 |
| Publisher DOI: | 10.1248/bpb.b15-00359 |
| PMID: | 26934923 |
| Abstract: | 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 Cl-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 mu m) 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. |
| Type: | article |
| URI: | http://hdl.handle.net/2115/61283 |
| Appears in Collections: | 薬学研究院 (Faculty of Pharmaceutical Sciences) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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Submitter: 菅原 満
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