title: Natural product inhibitors of ocular angiogenesis.
abstract: Natural products are characterized by high chemical diversity and biochemical specificity; therefore, they are appealing as lead compounds for drug discovery. Given the importance of angiogenesis to many pathologies, numerous natural products have been explored as potential anti-angiogenic drugs. Ocular angiogenesis underlies blinding eye diseases such as retinopathy of prematurity (ROP) in children, proliferative diabetic retinopathy (DR) in adults of working age, and age-related macular degeneration (AMD) in the elderly. Despite the presence of effective therapy in many cases, these diseases are still a significant health burden. Anti-VEGF biologics are the standard of care, but may cause ocular or systemic side effects after intraocular administration and patients may be refractory. Many anti-angiogenic compounds inhibit tumor growth and metastasis alone or in combination therapy, but a more select subset of them has been tested in the context of ocular neovascular diseases. Here, we review the promise of natural products as anti-angiogenic agents, with a specific focus on retinal and choroidal neovascularization. The multifunctional curcumin and the chalcone isoliquiritigenin have demonstrated promising anti-angiogenic effects in mouse models of DR and choroidal neovascularization (CNV) respectively. The homoisoflavanone cremastranone and the flavonoid deguelin have been shown to inhibit ocular neovascularization in more than one disease model. The isoflavone genistein and the flavone apigenin on the other hand are showing potential in the prevention of retinal and choroidal angiogenesis with long-term administration. Many other products with anti-angiogenic potential in vitro such as the lactone withaferin A, the flavonol quercetin, and the stilbenoid combretastatin A4 are awaiting investigation in different ocular disease-relevant animal models. These natural products may serve as lead compounds for the design of more specific, efficacious, and affordable drugs with minimal side effects.
authors.affiliation: Eugene and Marilyn Glick Eye Institute, Department of Ophthalmology, Indiana University School of Medicine, Indianapolis, IN, United States; Department of Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis, IN, United States; Department of Biochemistry, Faculty of Pharmacy, Cairo University, Cairo, Egypt.
authors.forename: Rania S
authors.initials: RS
authors.lastname: Sulaiman
authors.affiliation: Eugene and Marilyn Glick Eye Institute, Department of Ophthalmology, Indiana University School of Medicine, Indianapolis, IN, United States; Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN, United States.
authors.forename: Halesha D
authors.initials: HD
authors.lastname: Basavarajappa
authors.affiliation: Eugene and Marilyn Glick Eye Institute, Department of Ophthalmology, Indiana University School of Medicine, Indianapolis, IN, United States; Department of Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis, IN, United States; Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN, United States; Melvin and Bren Simon Cancer Center, Indiana University School of Medicine, Indianapolis, IN, United States. Electronic address: tcorson@iupui.edu.
authors.forename: Timothy W
authors.initials: TW
authors.lastname: Corson
mesh_terms: D020533:Angiogenesis Inhibitors / Q000627:therapeutic use; D000818:Animals; D001688:Biological Products; D005128:Eye Diseases / Q000473:pathology / Q000517:prevention & control*; D006801:Humans; D009389:Neovascularization, Pathologic / Q000473:pathology / Q000517:prevention & control*
chemical_list: D020533:Angiogenesis Inhibitors; D001688:Biological Products
keywords: Angiogenesis; Blinding diseases; Choroidal neovascularization; Natural compounds; Polyphenols; Retinal neovascularization; Small molecules