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.

Highlights

  • Herbal medicine consists of natural plant substances that have been used to prevent and treat ailments since ancient times

  • Following traditional claims regarding the use of N. nucifera leaves to cure numerous diseases, in the present study, we investigated the ability of water and methanol extracts of N. nucifera leaves to inhibit vascular endothelial growth factor (VEGF)-induced angiogenesis in vitro and in vivo, along with their

  • Since reactive oxygen species (ROS) derived from growth factor-stimulated receptors are critically important in many aspects of vascular cell behavior including VEGF-induced angiogenesis [10], we examined whether N. nucifera leaf extracts inhibit VEGF-induced ROS production in human umbilical vein endothelial cells (HUVECs) or not

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Summary

Introduction

Herbal medicine consists of natural plant substances that have been used to prevent and treat ailments since ancient times. In Ayurveda, this plant is used as a diuretic and anthelmintic, as well as in the treatment of strangury, vomiting, leprosy, skin diseases, and nervous exhaustion [2]. All parts of N. nucifera, including the leaves, flowers, embryos, and rhizomes, are prescribed as demulcents for hemorrhoids and are beneficial for the treatment of various human diseases [2]. N. nucifera leaves have recently gained popularity in Taiwan as an ingredient in health-related beverages for weight loss [1]. Several studies have shown that N. nucifera possesses pharmacologic and physiologic activities, including antioxidant [3], antiviral and immunomodulatory effects [4]. Another report indicated that N. nucifera leaves possess inhibitory activity towards atopic dermatitis [6]

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