<p>In Ovo and In Silico Evaluation of the Anti-Angiogenic Potential of Syringin</p>

Abstract

Introduction: Cancer is considered as one of the deadliest human diseases today. Angiogenesis, the propagation of new blood vessels from pre-existing vasculature, is a critical step in the progression of cancer as it is essential in the growth and metastasis of tumors. Hence, suppression of angiogenesis is a promising approach in cancer therapy. Syringin, a phenylpropanoid glycoside with a molecular formula of C 17 H 24 O 9 , has been found to exhibit chemopreventive effects. However, its anti-angiogenic activity and the underlying mechanism of action are still unknown. Methods: In this work, in ovo chorioallantoic membrane (CAM) assay has been conducted to evaluate the effect of syringin on neovascularization. Additionally, reverse molecular docking studies have been performed in order to identify the probable enzyme targets in the angiogenesis pathway. Results: Treatment with syringin showed significant dose-dependent inhibition of blood vessel length and junctions in the CAM of duck eggs; the anti-angiogenic activity of syringin at 100 µM and 200 µM is comparable with 200 µM of the positive control celecoxib. The results of reverse docking studies indicate that syringin binds the strongest to dihydrofolate reductase (DHFR) and, to some extent, with transforming growth factorbeta receptor type 1 (TGF-βR1), vascular endothelial growth factor receptor 2 (VEGFR2), and matrix metalloproteinase-2 (MMP-2). Furthermore, ADMET models revealed that syringin potentially possesses excellent pharmacokinetic and toxicity profiles. Conclusion: This study demonstrates the potential of syringin as an anti-angiogenic agent and elicits further investigations to establish its application in cancer suppression.

Editorial: Investigating the impact of bioactive metabolites and extracts in human health and disease

“…Natural products (NPs) have a rich history of utilization in traditional medicine and have been derived from various sources such as plants, marine organisms, fungi, and other biological entities. The cutting-edge application of NPs, their unique molecular structures and modes of action represents a groundbreaking approach to enhancing human health and combating a wide range of diseases ( Aventurado et al, 2020 ). By harnessing the power of NPs, researchers are exploring novel avenues for medical advancements and therapeutic interventions.…”

Bridging the In Vitro to In Vivo gap: Using the Chick Embryo Model to Accelerate Nanoparticle Validation and Qualification for In Vivo studies

“…The CAM vasculature undergoes rapid angiogenesis during development, making it a common model for vascular irritation and angiogenesis. , The vascular development of the CAM takes place during the first 11 days, facilitating experimentation on both rapidly developing vessels during the first 11 days and on mature vessels day 12 and beyond. Due to this versatility, the CAM allows a rapid review of potential antiangiogenic molecules and drug combinations through visualization of their effect on the CAM. − Recently, direct imaging has been combined with quantification of vessel length and number of junctions as a metric of vascular damage caused by pharmacological intervention . While most studies observe effects on CAM vessels after a period of time, the superficial location of the CAM with respect to the embryo and its thinness allow monitoring of therapeutic effects in real time by intravital imaging .…”

“…Due to this versatility, the CAM allows a rapid review of potential antiangiogenic molecules and drug combinations through visualization of their effect on the CAM. 47 − 50 Recently, direct imaging has been combined with quantification of vessel length and number of junctions as a metric of vascular damage caused by pharmacological intervention. 47 While most studies observe effects on CAM vessels after a period of time, the superficial location of the CAM with respect to the embryo and its thinness allow monitoring of therapeutic effects in real time by intravital imaging.…”

“… 47 − 50 Recently, direct imaging has been combined with quantification of vessel length and number of junctions as a metric of vascular damage caused by pharmacological intervention. 47 While most studies observe effects on CAM vessels after a period of time, the superficial location of the CAM with respect to the embryo and its thinness allow monitoring of therapeutic effects in real time by intravital imaging. 51 Due to the importance of angiogenesis in wound healing and the accessibility of the model, the CAM has been extensively used to assess the potential of therapeutics and treatments for wound healing.…”

In Silico Study of the Potential of Garlic Allicin Compound as Anti-Angiogenesis in Breast Cancer

“…In angiogenesis, new blood vessels make it possible for cancer cells to obtain an adequate supply of nutrients and proliferate. 2 Angiogenesis inhibition for breast cancer as a therapeutic approach has shown promising results. 3 This is achieved through inhibition of the vascular endothelial growth factor receptor 2 (VEGFR-2).…”