Quercetin phospholipid complex significantly protects against oxidative injury in ARPE-19 cells associated with activation of Nrf2 pathway.

Age-related macular degeneration (AMD) is a major cause of blindness worldwide. Oxidative stress plays a crucial role in the pathogenesis of dry AMD. Quercetin has potent anti-oxidative activities, but poor bioavailability limits its therapeutic application. Herein, we prepared the phospholipid complex of quercetin (quercetin-PC), characterized its structure by differential scanning calorimetry, infrared spectrum and x-ray diffraction. Quercetin-PC had equilibrium solubility of 38.36 and 1351.27µg/ml in water and chloroform, respectively, which was remarkably higher than those of quercetin alone. Then we established hydrogen peroxide (H2O2)-induced oxidative injury model in human ARPE-19 cells to examine the effects of quercetin-PC. Quercetin-PC, stronger than quercetin, promoted cell proliferation, and the proliferation rate was increased to be 78.89% when treated with Quercetin-PC at 400µM. Moreover, quercetin-PC effectively prevented ARPE-19 cells from apoptosis, and the apoptotic rate was reduced to be 3.1% when treated with Quercetin-PC at 200µM. In addition, quercetin-PC at 200µM significantly increased the activities of SOD, CAT and GSH-PX, and reduced the levels of reactive oxygen species and MDA in H2O2-treated ARPE-19 cells, but quercetin at 200µM failed to do so. Molecular examinations revealed that quercetin-PC at 200µM significantly activated Nrf2 nuclear translocation and significantly enhanced the expression of target genes HO-1, NQO-1 and GCL by different folds at both mRNA and protein levels. Our current data collectively indicated that quercetin-PC had stronger protective effects against oxidative-induced damages in ARPE-19 cells, which was associated with activation of Nrf2 pathway and its target genes implicated in antioxidant defense.

Preparation of naringenin/ ß-cyclodextrin complex and its more potent alleviative effect on choroidal neovascularization in rats.

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 ß-cyclodextrin (ß-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/ß-CD complex more significantly reduced CNV area than naringenin alone in rats. Furthermore, naringenin and its ß-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/ß-CD complex showed more significant inhibitory effect on VEGF and COX-2 expression than naringenin. These results collectively indicated that naringenin/ß-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.

[Prevention and treatment of age-related macular degeneration by extract of Fructus lycii and its constituents lutein/zeaxanthin: an in vive and in vitro experimental research].

OBJECTIVE: To investigate the in vivo inhibition of extract of Fructus lycii (FL) on the expressions of cathepsin B (Cat B) and cystatin C (Cys C) in high-fat diet and hydroquinone (HQ) induced model mice with age-related macular degeneration (AMD), and to explore the in vitro effects of lutein and zeaxanthin on hydrogen peroxide (H2O2,) induced expressions of matrix metalloproteinase 2 (MMP-2) and tissue inhibitor of metalloproteinase 2 (TIMP-2) on ARPE-19 cells. METHODS: Fifty female 8-month-old C57BL/6 mice were recruited in this research. Ten mice fed with regular diet was taken as the age control group. The rest 40 mice were fed with high fat diet for 6 months, followed by adding HQ (0. 8%) in the drinking water for 3 consecutive months. Then the modeled mice were randomly divided into the model control group (n =10), the high (at the daily dose of 3.75 g/kg), middle (at the daily dose of 2.50 g/kg), and low dose (at the daily dose of 1.25 g/kg) FL groups, 10 in each group. The extract of FL at each dose was respectively administered to mice by gastrogavage for 3 successive months. By the end of the experiment, the mice were killed and their eyeballs were removed. The protein expressions of Cat B and Cys C were observed by immunohistochemical assay. The mRNA and protein expressions of Cat B and Cys C were detected by real-time PCR and Western blot respectively. The drug concentrations of H2O2, lutein, and zeaxanthin were screened and detected using the activity of cell proliferation. The protein expressions of MMP-2 and TIMP-2 were detected using Western blot. RESULTS: Compared with the age control group, the mRNA and protein expressions of Cat B and Cys C were significantly higher in the in vivo model control group (P <0.05, P <0.01). The mRNA expressions of Cat B and Cys C were weaker in the middle and high dose FL groups than in the model control group (P <0. 05, P <0. 01). In in vitro cells, lutein and zeaxanthin could down-regulate the protein expressions of MMP-2 and TIMP-2 in H202 induced ARPE-19 cells (P <0. 05, P <0. 01). CONCLUSIONS: Extract of FL could down-regulate the high protein expressions of Cat B and Cys C in high-fat diet and HQ induced model mice. Lutein and zeaxanthin could down-regulate the protein expressions of MMP-2 and TIMP-2 in H202 induced ARPE-19 cells.

A generic eye model by reverse building based on Chinese population.

The human eye has ethnic difference, the existing typical eye models are based on western eyes. A generic eye model based on Chinese population is presented for the first time. The statistical analyzed ocular parameters based on measured data are used for the initial generic eye model, and the wavefront aberration data obtained at two different pupil diameters are used for reproduction by optimizing the initial generic eye model. The differences and similarities between Chinese generic eye model and western eye models are given. The Chinese generic eye model provides a suitable model for the related further researches and applications on Chinese eye.

[Acupuncture for treatment of 40 cases of convergence insufficient asthenopia with exotropia].

OBJECTIVE: To explore the therapeutic effect of acupuncture on convergence insufficient asthenopia with exotropia. METHODS: Eighty cases of convergence insufficient asthenopia with exotropia were randomly divided into an acupuncture group and an eye drug treatment group, 40 cases in each group. The acupuncture group were treated with acupuncture at Jingming (BL 1), Taiyang (EX-HN 5), Chengqi (ST 1), Hegu (LI4); the eye drug treatment group were treated with local dropping of Aiweiduo. The therapeutic effects and changes of exotropia degree, collecting near point, cumulative score of eye symptoms were observed after 2 and 4 weeks of treatment. RESULTS: after treatment for 2 and 4 weeks, the total effective rates were 87.5% and 92.5% in the acupuncture group which were significantly better than 65.0% and 70.0% in the eye drug treatment group (P<0.01); after treatment of 2 and 4 weeks, the collecting near point and the cumulative score of eye symptoms were significantly better than those before treatment (P<0.01); the acupuncture group in improvement of eye symptoms after treatment of 2 weeks and in collecting near point after treatment of 4 weeks was significantly better than the eye drug treatment group. CONCLUSION: The therapeutic effect of acupuncture on convergence insufficient asthenopia with exotropia is better than that of simple Aiweiduo treatment.