Inhibition of naringenin complex with β-cyclodextrin on experimental choroidal neovascularization in rats
10.3760/cma.j.issn.2095-0160.2015.12.007
- VernacularTitle:柚皮素β-环糊精包合物对大鼠实验性脉络膜新生血管的抑制作用
- Author:
Xinrong, XU
;
Haitao YU
;
Li, HANG
;
Yan, SHAO
;
Shuhua, DING
;
Xuewen, YANG
- Publication Type:Journal Article
- Keywords:
Naringenin;
β-Cyclodextrin;
Choroidal neovascularization
- From:
Chinese Journal of Experimental Ophthalmology
2015;33(12):1083-1088
- CountryChina
- Language:Chinese
-
Abstract:
Background Choroidal neovascularization (CNV) leads to blindness in many fundus diseases.Study showed that naringenin suppresses CNV,but it presents with poor bioavailability because of its poor solubility in water.β-cyclodextrin (β-CD) can increase the water-solubility of drugs, however, whether the inhibitory effect of naringenin on CNV can be improved after clathrated with β-CD remains unclear.Objective This study was to compare the inhibitory effects of naringenin with naringenin/β-CD compounds on CNV in rats.Methods Naringenin/β-CD clathrate compounds were prepared with saturated solution,the solubility of naringenin in water was calculated based on standard curve.Thirty-two male Brown Norway rats were randomized into normal control group, model control group, naringenin group and naringenin/β-CD group.Laser-induced CNV models were created in the right eyes of rats from the model control group, naringenin group and naringenin/β-CD group.Naringenin and naringenin/β-CD clathrate compounds were intraperitoneally injected at a dose of 20 mg/kg in the rats of naringenin group and naringenin/β-CD group since the day after modeling, respectively, once per day for 4 weeks, and equal volume of DMSO was injected in the same way in the model control group.Fluorescein isothiocyanate dextran (FITC-D) was injected via rat hypoglossal vein for the preparation of flatmounts of choroid in the fourth week,and the areas of CNV were measured and compared among the groups.The retinal pigment epithelium (RPE)-choroid-sclera tissues were isolated from the rats, and the relative expression levels of vascular endothelial growth factor (VEGF) , cyclooxygenase-2 (COX-2),phosphatidylinositol-3-kinase (PI3K),p38mitogen-activated protein kinase (p38MAPK), matrix metalloproteinase (MMP)-2, MMP-9 mRNA and their proteins in RPE-choroid-sclera tissue were detected using real-time PCR and Western blot.Results The solubility of naringenin in water increased by 11.8 folds after encapsulated with β-CD.The CNV areas in the model control group, naringenin group and naringenin/β-CD group were (34.56± 1.67), (20.90± 1.47) and (13.20± 1.38) × 103 μm2 , respectively, showing significant reduces in the naringenin group and naringenin/β-CD group compared with the model control group (t =3.973 ,P＜O.05;t =5.532, P＜0.01) ,and the CNV area in the naringenin/β-CD group was significantly smaller than that in the naringenin group (t =3.605,P＜0.05).The relative expression levels of VEGF, COX-2, PI3K, p38MAPK, MMP-2, MMP-9 mRNA and their proteins were significantly declined in the normal control group,naringenin group and naringenin/β-CD group in comparison with the model control group (all at P＜0.05).In addition, the expression levels of VEGF mRNA and COX-2 mRNA and their proteins were significantly lower in the naringenin/β-CD group than those in the naringenin group (all at P＜0.05).Conclusions The naringenin/β-CD clathrate compounds can improve the water solubility of naringenin and enhance their inhibitory effect on rats CNV.The inhibitory effect of naringenin on rats CNV probably is associated with anti-inflammatory pathway.
