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.
Highlights
Choroidal neovascularization (CNV) is a common cause of blindness worldwide
We subsequently examined the expression of vascular endothelial growth factor (VEGF), cyclooxygenase-2 (COX-2), phosphatidylinositol-3-kinase (PI3K), p38 mitogen-activated protein kinase (p38MAPK), matrix metalloproteinase (MMP)-2, and MMP-9 in retina and choroid tissues of rats
Many patients with subfoveal CNV could not be treated because of the risk of central vision loss associated with laser photocoagulation [16]
Summary
Choroidal neovascularization (CNV) is a common cause of blindness worldwide It is characterized by new, abnormal blood vessels growing from the choroid through breaks in Bruch’s membrane or the basement membrane of the retinal pigment epithelium [1]. Pegaptanib sodium, an anti-VEGF aptamer, was approved for neovascular AMD in 2004 [5], and the anti-VEGF antibody bevacizumab has been used intravenously [6] and intravitreally [7] to treat CNV By these treatments, very effective results are obtained and their further improvement is still possible, it is reasonable and necessary to look for more successful and definitive alternatives. Naringenin has poor water solubility and low bioavailability, which greatly limit its potential utility in the treatment of CNV. We prepared naringenin/β-CD complex and characterized its physical and chemical properties, and we further evaluated its efficacy on laser-induced CNV in rats and explored the preliminary mechanisms
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