title: Preparation of naringenin/ β-cyclodextrin complex and its more potent alleviative effect on choroidal neovascularization in rats.
abstract: Choroidal neovascularization (CNV) is characterized by abnormal blood vessels growing from the choroid. Current remedies for CNV have not shown favorable therapeutic efficacy. It is urgent to identify and develop more safe and potent anti-CNV agents via multiple technologies. We previously showed that the natural product naringenin attenuated CNV. However, naringenin has poor water solubility and low bioavailability. Here, we prepared the β-cyclodextrin (β-CD) complex of naringenin and characterized it using infrared spectra and X-ray diffraction analyses. Determination of content and solubility in the complex showed that naringenin accounted for 20.53% in the complex and its solubility was increased by more than 10-fold. Using a laser-induced CNV model in rats we demonstrated that naringenin/β-CD complex more significantly reduced CNV area than naringenin alone in rats. Furthermore, naringenin and its β-CD complex significantly inhibited the mRNA and protein expression of VEGF, COX-2, PI3K, p38MAPK, MMP-2, and MMP-9 in retina and choroid tissues. Naringenin/β-CD complex showed more significant inhibitory effect on VEGF and COX-2 expression than naringenin. These results collectively indicated that naringenin/β-CD complex could be a promising therapeutic option for CNV and that the beneficial effects could be linked to the anti-inflammatory properties of naringenin.
authors.affiliation: Department of Ophthalmology, Affiliated Hospital of Nanjing University of Traditional Chinese Medicine, 155 Hanzhong Road, Nanjing 210029, China.
authors.forename: Xin-rong
authors.initials: XR
authors.lastname: Xu
authors.affiliation: College of Pharmacy, Nanjing University of Traditional Chinese Medicine, Nanjing 210023, China.
authors.forename: Hai-tao
authors.initials: HT
authors.lastname: Yu
authors.affiliation: Department of Ophthalmology, Affiliated Hospital of Nanjing University of Traditional Chinese Medicine, 155 Hanzhong Road, Nanjing 210029, China.
authors.forename: Li
authors.initials: L
authors.lastname: Hang
authors.affiliation: Department of Ophthalmology, Affiliated Hospital of Nanjing University of Traditional Chinese Medicine, 155 Hanzhong Road, Nanjing 210029, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Shao
authors.affiliation: Department of Ophthalmology, Affiliated Hospital of Nanjing University of Traditional Chinese Medicine, 155 Hanzhong Road, Nanjing 210029, China.
authors.forename: Shu-hua
authors.initials: SH
authors.lastname: Ding
authors.affiliation: Department of Clinical Laboratory, Affiliated Hospital of Nanjing University of Traditional Chinese Medicine, Nanjing 210029, China.
authors.forename: Xue-wen
authors.initials: XW
authors.lastname: Yang
mesh_terms: D020533:Angiogenesis Inhibitors / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D002829:Choroid / Q000098:blood supply / Q000187:drug effects; D020256:Choroidal Neovascularization; D044950:Flavanones / Q000737:chemistry / Q000494:pharmacology; D008297:Male; D020782:Matrix Metalloproteinases / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects; D013055:Spectrophotometry, Infrared; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D014961:X-Ray Diffraction; D047392:beta-Cyclodextrins / Q000737:chemistry / Q000494:pharmacology
chemical_list: D020533:Angiogenesis Inhibitors; D044950:Flavanones; D042461:Vascular Endothelial Growth Factor A; D047392:beta-Cyclodextrins; C467498:vascular endothelial growth factor A, rat; D020782:Matrix Metalloproteinases; C005273:naringenin