In Ovo and In Silico Evaluation of the Anti-Angiogenic Potential of Syringin

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 C₁₇H₂₄O₉, 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 factor-beta 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.

Keywords:

• syringin
• angiogenesis
• cancer
• molecular docking
• reverse docking
• dihydrofolate reductase
• DHFR
• TGF-ßR1
• VEGFR2
• MMP-2

Acknowledgments

This study was funded by the Institutional Grant for Invigorating Basic Research on Health Sciences Phase II research program of the Department of Science and Technology-National Research Council of the Philippines (Project No. Q-006). The authors are also thankful to The Graduate School and the Research Center for the Natural and Applied Sciences, University of Santo Tomas, Manila, Philippines, as well as to the staff of the Emerging Interdisciplinary Research (EIDR) laboratory (OVPAA-EIDR 12-001-121102) of the University of the Philippines Manila for the training, assistance, and for allowing them to use the facilities.

Disclosure

The authors report grants from the National Research Council of the Philippines during the conduct of the study. The authors report no other potential conflicts of interest in this work.