title: Anti-angiogenic effect of Nelumbo nucifera leaf extracts in human umbilical vein endothelial cells with antioxidant potential.
abstract: Nelumbo nucifera Gaertn (Nymphaeaceae) has long been used as a traditional herb in Chinese, Japanese, Indian, and Korean medicinal practices since prehistoric times and flourishes today as the primary form of medicine. This study reports for the first time the potent ability of N. nucifera leaf extracts to inhibit vascular endothelial growth factor (VEGF)-induced angiogenesis in vitro and in vivo, as well as their antioxidant efficacy in various scavenging models and an analysis of their chemical composition. In vivo anti-angiogenic activity was evaluated in a chick chorioallantoic membrane (CAM) model using fertilized chicken eggs, in human umbilical vein endothelial cells (HUVECs) by using cell viability, cell proliferation and tube formation assays, and by determining intracellular reactive oxygen species (ROS) in vitro. The antioxidant efficacy of N. nucifera leaf extracts was determined in various scavenging models, including total phenolic and flavonoid content. The chemical composition of N. nucifera leaf extracts was determined by GC-MS analysis, which revealed the presence of different phytochemicals. The IC50 values for the DPPH radical scavenging activities of water and methanol extracts were found to be 1699.47 and 514.36 μg ml(-1), and their total phenolic and flavonoid contents were 85.01 ± 2.32 and 147.63 ± 2.23 mg GAE g dry mass(-1) and 35.38 ± 1.32 and 41.86 ± 1.07 mg QA g dry mass(-1), respectively. N. nucifera leaf extracts (10-100 μg ml(-1)) exhibited significant dose-dependent inhibition of VEGF-induced angiogenesis, as well as VEGF-induced proliferation and tube formation in HUVECs. In this study, N. nucifera leaf extracts displayed potent antioxidant and inhibitory effects on VEGF-induced angiogenesis. N. nucifera exerted an inhibitory effect on VEGF-induced proliferation and tube formation, as well as CAM angiogenesis in vivo. Moreover, N. nucifera leaf extracts significantly blocked VEGF-induced ROS production in HUVECs, confirming their possible anti-angiogenic mechanism.
authors.affiliation: Department of Food Science and Technology, Yeungnam University, Gyeongsan, Gyeongbuk, 712-749, Republic of Korea.
authors.forename: Jong Suk
authors.initials: JS
authors.lastname: Lee
authors.affiliation: Department of Food Science and Technology, Yeungnam University, Gyeongsan, Gyeongbuk, 712-749, Republic of Korea.
authors.forename: Shruti
authors.initials: S
authors.lastname: Shukla
authors.affiliation: College of Pharmacy, Yeungnam University, Gyeongsan, Gyeongbuk, 712-749, Republic of Korea.
authors.forename: Jung-Ae
authors.initials: JA
authors.lastname: Kim
authors.affiliation: Department of Food Science and Technology, Yeungnam University, Gyeongsan, Gyeongbuk, 712-749, Republic of Korea.
authors.forename: Myunghee
authors.initials: M
authors.lastname: Kim
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D000975:Antioxidants / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D002642:Chick Embryo; D005419:Flavonoids / Q000737:chemistry / Q000494:pharmacology; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects* / Q000378:metabolism*; D006801:Humans; D031653:Nelumbo / Q000737:chemistry*; D018919:Neovascularization, Physiologic / Q000187:drug effects; D010636:Phenols / Q000737:chemistry / Q000494:pharmacology; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D018515:Plant Leaves / Q000737:chemistry*; D017382:Reactive Oxygen Species / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism / Q000494:pharmacology
chemical_list: D020533:Angiogenesis Inhibitors; D000975:Antioxidants; D005419:Flavonoids; D010636:Phenols; D010936:Plant Extracts; D017382:Reactive Oxygen Species; D042461:Vascular Endothelial Growth Factor A