Inhibition of Hypoxia-Inducible Factor-1α and Vascular Endothelial Growth Factor by Chrysin in a Rat Model of Choroidal Neovascularization

Abstract

Age-related macular degeneration (AMD) is a leading cause of irreversible vision loss among the elderly population. Vascular endothelial growth factor (VEGF) is essential for choroidal neovascularization (CNV) development in advanced, wet AMD. Chrysin (5,7-dihydroxyflavone) is a natural flavonoid with anti-inflammatory, anti-oxidative, and anti-angiogenic effects. We hypothesized that intravitreally injected chrysin may inhibit CNV due to its inhibitory effect on angiogenesis. To determine the effects of chrysin on an experimental CNV model, we induced CNV in Brown Norway rats with a diode laser. One week later, rats were injected intravitreally with chrysin in the right eye and vehicle in the left eye. The following week, we evaluated chrysin’s effects via the CNV grade assessed with fluorescein angiography and histologic analyses. Hypoxia-inducible factor-1 alpha (HIF-1α) and VEGF expression in the retina/choroid complex were also measured in both eyes. The mean CNV grade was significantly lower in chrysin-treated vs. control eyes (2.34 ± 1.14 vs. 2.97 ± 1.05, p < 0.001), as was the mean CNV thickness (33.90 ± 4.89 vs. 38.50 ± 5.43 μm, p < 0.001) and mean HIF-1α and VEGF levels (both p < 0.001). Compared to chrysin-treated eyes, the relative risk of control eyes developing high-leakage lesions was 2.03 (95% confidence interval: 1.46–2.83). Since chrysin inhibited laser-induced CNV and downregulated HIF-1α and VEGF expression, it is a candidate for treating wet AMD and other CNV-associated conditions.

The Antiangiogenic Effect of Sanguinarine Chloride on Experimental Choroidal Neovacularization in Mice via Inhibiting Vascular Endothelial Growth Factor

“…Though it is highly beneficial, the frequent intravitreal administration is associated with severe side-effects such as infection, bleeding, endophthalmitis, inflammation, and retinal detachment. Besides, the huge economic burden for both patients and society should not be ignored ( Ferrara et al, 2006 ; Song et al, 2020 ). Our current study offered an optional, effective, and inexpensive alternative treatment for the treatment of wet AMD.…”

“…Though it is effective in preventing and reducing neovascularization in some patients, it also has limitations including the need for frequent intravitreal injection and inducement of macular disorders. What’s more, the current therapy is expensive and a huge burden for both patients and society ( Song et al, 2020 ). Therefore, the replacement of the current therapy is in urgent need.…”

Chrysin Inhibits High Glucose-Induced Migration on Chorioretinal Endothelial Cells via VEGF and VEGFR Down-Regulation

“…Its biological characteristics have been approved by previous studies. Our previous work, as well as other scholarly works, found that chrysin can provide antioxidant, anti-inflammatory, and anti-angiogenic effects [ 13 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 ]. The results of this study allow us to have better understanding of the possible pharmacological mechanism and biological activity of chrysin in DR.…”

“…This, in turn, reduces the expression of VEGF and inhibits angiogenesis. Recently, chrysin was also found to inhibit laser-induced choroidal neovascularization (CNV) and down-regulate HIF-1α and VEGF expression [ 34 ]. Integrating these results, we speculate that the inhibitory effect of chrysin on the expression of HIF-1α and VEGF in a high glucose environment may contribute to the prevention or treatment of DR.…”

Chrysin: Perspectives on Contemporary Status and Future Possibilities as Pro-Health Agent

“…The most recent research suggests that chrysin may be used to treat eye diseases leading to blindness, such as macular degeneration or choroidal neovascularization [86], and also autoimmune diseases [87].…”