Changes in the intestinal absorption mechanism of icariin in the nanocavities of cyclodextrins

Ye Zhang,1 Qiang-Song Wang,1 Yuan-Lu Cui,1 Fan-Cui Meng,2 Ke-Ming Lin11Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, People&#39;s Republic of China; 2Tianjin Key Laboratory of Molecular Design and Drug Discovery, Tianjin...

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Autores principales:	Zhang Y, Wang QS, Cui YL, Meng FC, Lin KM
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2012
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/8487d89c45c14e2e8ce8a39631100585
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spelling	oai:doaj.org-article:8487d89c45c14e2e8ce8a396311005852021-12-02T01:30:29ZChanges in the intestinal absorption mechanism of icariin in the nanocavities of cyclodextrins1176-91141178-2013https://doaj.org/article/8487d89c45c14e2e8ce8a396311005852012-08-01T00:00:00Zhttp://www.dovepress.com/changes-in-the-intestinal-absorption-mechanism-of-icariin-in-the-nanoc-a10591https://doaj.org/toc/1176-9114https://doaj.org/toc/1178-2013Ye Zhang,1 Qiang-Song Wang,1 Yuan-Lu Cui,1 Fan-Cui Meng,2 Ke-Ming Lin11Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, People&#39;s Republic of China; 2Tianjin Key Laboratory of Molecular Design and Drug Discovery, Tianjin Institute of Pharmaceutical Research, Tianjin, People&#39;s Republic of ChinaAbstract: Icariin is a bioactive herbal ingredient isolated from Herba epimedii, which has been widely used for the treatment of osteoporosis and male sexual dysfunction in traditional Chinese medicine. The major objective of this work is to investigate the different enhancing effects of &beta;-cyclodextrin (&beta;-CD) and hydroxypropyl-&beta;-cyclodextrin (HP-&beta;-CD) on the intestinal absorption of icariin, and to identify the molecular mechanisms of this action. Host&ndash;guest-type interactions of icariin with cyclodextrins nanocavities were unambiguously demonstrated by the phase-solubility diagram, ultraviolet spectroscopy, Fourier transform infrared spectroscopy, differential scanning calorimetry, X-ray powder diffractometry, and two dimensional proton nuclear magnetic resonance rotating-frame Overhauser effect spectroscopy. These results were further supported using molecular modeling studies. The rat single-pass intestinal perfusion model showed that the absorption of icariin was affected by P-glycoprotein (Pgp). The icariin/HP-&beta;-CD inclusion complex provided greater enhancement in the intestinal absorption than the icariin/&beta;-CD inclusion complex. Therefore, the enhancing effect was involved in a solubilizing effect and/or Pgp inhibitory effect. Finally, fluorescence anisotropy measurements and Pgp adenosine triphosphatase (ATPase) assay demonstrated that &beta;-CD exhibited no effect on Pgp, while HP-&beta;-CD showed inhibition by restraining the Pgp ATPase activity rather than changing the fluidity of cell membrane.Keywords: icariin, cyclodextrin, inclusion complex, molecular modeling, P-glycoprotein (Pgp), intestinal absorptionZhang YWang QSCui YLMeng FCLin KMDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2012, Iss default, Pp 4239-4249 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 Zhang Y Wang QS Cui YL Meng FC Lin KM Changes in the intestinal absorption mechanism of icariin in the nanocavities of cyclodextrins
description	Ye Zhang,1 Qiang-Song Wang,1 Yuan-Lu Cui,1 Fan-Cui Meng,2 Ke-Ming Lin11Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, People&#39;s Republic of China; 2Tianjin Key Laboratory of Molecular Design and Drug Discovery, Tianjin Institute of Pharmaceutical Research, Tianjin, People&#39;s Republic of ChinaAbstract: Icariin is a bioactive herbal ingredient isolated from Herba epimedii, which has been widely used for the treatment of osteoporosis and male sexual dysfunction in traditional Chinese medicine. The major objective of this work is to investigate the different enhancing effects of &beta;-cyclodextrin (&beta;-CD) and hydroxypropyl-&beta;-cyclodextrin (HP-&beta;-CD) on the intestinal absorption of icariin, and to identify the molecular mechanisms of this action. Host&ndash;guest-type interactions of icariin with cyclodextrins nanocavities were unambiguously demonstrated by the phase-solubility diagram, ultraviolet spectroscopy, Fourier transform infrared spectroscopy, differential scanning calorimetry, X-ray powder diffractometry, and two dimensional proton nuclear magnetic resonance rotating-frame Overhauser effect spectroscopy. These results were further supported using molecular modeling studies. The rat single-pass intestinal perfusion model showed that the absorption of icariin was affected by P-glycoprotein (Pgp). The icariin/HP-&beta;-CD inclusion complex provided greater enhancement in the intestinal absorption than the icariin/&beta;-CD inclusion complex. Therefore, the enhancing effect was involved in a solubilizing effect and/or Pgp inhibitory effect. Finally, fluorescence anisotropy measurements and Pgp adenosine triphosphatase (ATPase) assay demonstrated that &beta;-CD exhibited no effect on Pgp, while HP-&beta;-CD showed inhibition by restraining the Pgp ATPase activity rather than changing the fluidity of cell membrane.Keywords: icariin, cyclodextrin, inclusion complex, molecular modeling, P-glycoprotein (Pgp), intestinal absorption
format	article
author	Zhang Y Wang QS Cui YL Meng FC Lin KM
author_facet	Zhang Y Wang QS Cui YL Meng FC Lin KM
author_sort	Zhang Y
title	Changes in the intestinal absorption mechanism of icariin in the nanocavities of cyclodextrins
title_short	Changes in the intestinal absorption mechanism of icariin in the nanocavities of cyclodextrins
title_full	Changes in the intestinal absorption mechanism of icariin in the nanocavities of cyclodextrins
title_fullStr	Changes in the intestinal absorption mechanism of icariin in the nanocavities of cyclodextrins
title_full_unstemmed	Changes in the intestinal absorption mechanism of icariin in the nanocavities of cyclodextrins
title_sort	changes in the intestinal absorption mechanism of icariin in the nanocavities of cyclodextrins
publisher	Dove Medical Press
publishDate	2012
url	https://doaj.org/article/8487d89c45c14e2e8ce8a39631100585
work_keys_str_mv	AT zhangy changesintheintestinalabsorptionmechanismoficariininthenanocavitiesofcyclodextrins AT wangqs changesintheintestinalabsorptionmechanismoficariininthenanocavitiesofcyclodextrins AT cuiyl changesintheintestinalabsorptionmechanismoficariininthenanocavitiesofcyclodextrins AT mengfc changesintheintestinalabsorptionmechanismoficariininthenanocavitiesofcyclodextrins AT linkm changesintheintestinalabsorptionmechanismoficariininthenanocavitiesofcyclodextrins
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Changes in the intestinal absorption mechanism of icariin in the nanocavities of cyclodextrins

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