Enhancement of Naringenin Bioavailability by Complexation with Hydroxypropoyl-β-Cyclodextrin

View/ Open
Author
Shulman, Maria
Cohen, Merav
Soto-Gutierrez, Alejandro
Yagi, Hiroshi
Goldwasser, Jonathan
Lee-Parsons, Carolyn W.
Benny-Ratsaby, Ofra
Published Version
https://doi.org/10.1371/journal.pone.0018033Metadata
Show full item recordCitation
Shulman, Maria, Merav Cohen, Alejandro Soto-Gutierrez, Hiroshi Yagi, Hongyun Wang, Jonathan Goldwasser, Carolyn W. Lee-Parsons, Ofra Benny-Ratsaby, Martin L. Yarmush, and Yaakov Nahmias. 2011. Enhancement of naringenin bioavailability by complexation with Hydroxypropoyl-β-Cyclodextrin. PLoS ONE 6(4): e18033.Abstract
The abundant flavonoid aglycone, naringenin, which is responsible for the bitter taste in grapefruits, has been shown to possess hypolipidemic and anti-inflammatory effects both in vitro and in vivo. Recently, our group demonstrated that naringenin inhibits hepatitis C virus (HCV) production, while others demonstrated its potential in the treatment of hyperlipidemia and diabetes. However, naringenin suffers from low oral bioavailability critically limiting its clinical potential. In this study, we demonstrate that the solubility of naringenin is enhanced by complexation with β-cyclodextrin, an FDA approved excipient. Hydroxypropoyl-β-cyclodextrin (HPβCD), specifically, increased the solubility of naringenin by over 400-fold, and its transport across a Caco-2 model of the gut epithelium by 11-fold. Complexation of naringenin with HPβ2CD increased its plasma concentrations when fed to rats, with AUC values increasing by 7.4-fold and Cmax increasing 14.6-fold. Moreover, when the complex was administered just prior to a meal it decreased VLDL levels by 42% and increased the rate of glucose clearance by 64% compared to naringenin alone. These effects correlated with increased expression of the PPAR co-activator, PGC1α in both liver and skeletal muscle. Histology and blood chemistry analysis indicated this route of administration was not associated with damage to the intestine, kidney, or liver. These results suggest that the complexation of naringenin with HPβCD is a viable option for the oral delivery of naringenin as a therapeutic entity with applications in the treatment of dyslipidemia, diabetes, and HCV infection.Other Sources
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3071816/pdf/Terms of Use
This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAACitable link to this page
http://nrs.harvard.edu/urn-3:HUL.InstRepos:5146964
Collections
- HMS Scholarly Articles [15665]
Contact administrator regarding this item (to report mistakes or request changes)