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

Abstract

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 β-cyclodextrin (β-CD) and hydroxypropyl-β-cyclodextrin (HP-β-CD) on the intestinal absorption of icariin, and to identify the molecular mechanisms of this action. Host-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-β-CD inclusion complex provided greater enhancement in the intestinal absorption than the icariin/β-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 β-CD exhibited no effect on Pgp, while HP-β-CD showed inhibition by restraining the Pgp ATPase activity rather than changing the fluidity of cell membrane.

Icariin and Its Metabolites as Potential Protective Phytochemicals Against Alzheimer’s Disease

“…Despite the numerous studies on icariin, the main challenge remains its very low oral bioavailability due to the physicochemical characteristics ( Chen et al, 2008 ), and P-glycoprotein-mediated efflux in intestinal mucosa ( Zhang Y. et al, 2012 ). Different studies indicated the importance of icariin hydrolysis by lactase phlorizin hydrolase in the small intestine and by microbiota β-glucosidase to release metabolites before its absorption ( Zhao et al, 2010 ; Chen et al, 2011 ; Qian et al, 2012 ).…”

“…Fortunately, the modern techniques offer a range of methods to overcome this issue. To increase icariin bioavailability, researchers have developed several drug delivery systems such as combining icariin with snailase (an exogenous hydrolase) to improve intestinal hydrolysis ( Liu et al, 2017 ), encapsulating icariin into liposome ( Yang et al, 2012 ), producing icariin/hydroxylpropyl-beta-cyclodextrin inclusion complex that enhances intestinal absorption probably through a solubilizing effect and/or the inhibition of P-glycoprotein ( Zhang Y. et al, 2012 ).…”

Icariin: A Promising Natural Product in Biomedicine and Tissue Engineering

“…In the FTIR spectrogram, the characteristic peaks at ≈1650, 1600, 1510, 1070, and 1260 cm −1 can be assigned to free icariin. In differential scanning calorimetry, the endothermic peak at ≈250 °C is related to icariin [ 97 ].…”

Phytochemicals Mediate Autophagy Against Osteoarthritis by Maintaining Cartilage Homeostasis

“…Icariin has a low bioavailability due to its poor absorption, which poses additional limitations to its clinical application ( Li et al, 2015 ). However, it has been found that the bioavailability of icariin can be improved by pharmacological methods ( Zhang et al, 2012 ). Therefore, the studies on the activation of autophagy to maintain the homeostasis of chondrocytes by icariin are of guidance for the prevention and treatment of OA.…”