Overview of Angiogenesis Inhibitors from Natural Sources

Angiogenesis, the biological process of formation of new blood vessels from pre-existing ones, is essential for many diseases and its modulation is considered to be an important therapeutic strategy. It is controlled by various pro and anti-­angiogenic fa

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Overview of Angiogenesis Inhibitors from Natural Sources Dipti Gatne and Veeranjaneyulu Addepalli

Abstract Angiogenesis, the biological process of formation of new blood vessels from pre-existing ones, is essential for many diseases and its modulation is considered to be an important therapeutic strategy. It is controlled by various pro and antiangiogenic factors. Plants, animals, microbes, and marine are the natural sources of various chemical constituents possessing anti-angiogenic activity which may act as leads in future angiogenesis inhibitors therapy. This review highlights the antiangiogenic activity of many constituents from natural sources along with their biochemical mechanisms. Keywords Angiogenesis • Natural molecules • Phytoconstituents • Terpenes • Polyphenolics

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Introduction

The formation of new blood vessels from pre-existing ones, known as angiogenesis, is a biological process essential for wound healing, organ growth and repair, embryonic development, and reproduction. The process of angiogenesis is tightly regulated by a balance between pro-angiogenic and anti-angiogenic factors [1]. Uncontrolled angiogenesis, by virtue of its ability to supply oxygen and nutrients to ischemic

D. Gatne Department of Pharmaceutical Chemistry, SPP School of Pharmacy & Technology Management, SVKM’s NMIMS, V. L. Mehta Road, Mumbai, Maharashtra, India V. Addepalli () Department of Pharmacology, SPP School of Pharmacy & Technology Management, SVKM’s NMIMS, V. L. Mehta Road, Mumbai 400056, Maharashtra, India e-mail: [email protected] J.L. Mehta and N.S. Dhalla (eds.), Biochemical Basis and Therapeutic Implications of Angiogenesis, Advances in Biochemistry in Health and Disease 6, DOI 10.1007/978-1-4614-5857-9_26, © Springer Science+Business Media New York 2013

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areas, is a major contributor towards a number of major pathological diseases such as tumor progression, inflammatory disorders, obesity, asthma, diabetes, and proliferative retinopathies [2]. Therefore, modulation of angiogenesis is considered to be a therapeutic strategy of great importance. Numerous inducers of angiogenesis have been reported in literature including vascular endothelial growth factor (VEGF) family, angiopoietins, transforming growth factors (TGF), platelet-derived growth factor (PDGF), tumor necrosis factor-α (TNF-α), interleukins, and the members of the fibroblast growth factor (FGF) family [3–5]. Angiogenesis inhibitors are able to inhibit the key events of the angiogenic processes such as proliferation, migration, and tube formation of endothelial cells; expression of the growth factors such as VEGF, FGF, EGF, PDGF; activation of matrix metalloproteinases (MMPs), PI3K/Akt signaling pathway, farnesyltransferase, etc. [6–9]. Extensive research in the field of angiogenesis has led to discovery of several mechanisms which confer resistance to the anti-angiogenic agents. These mechanisms, both intrinsic and acquired include intratumor hypoxia, upregulation of antiapoptotic as well as compensato