Abstract
Natural stilbenes are an important group of nonflavonoid phytochemicals of polyphenolic structure characterized by the presence of a 1,2-diphenylethylene nucleus. Stilbenes have an extraordinary potential for the prevention and treatment of different diseases, including cancer, due to their antioxidant, cell death activation, and anti-inflammatory properties which associate with low toxicity under in vivo conditions. This review aims to discuss various approaches related to their mechanisms of action, pharmacological activities in animal models and humans, and potential chemoprevention in clinical studies. The biological activity of natural stilbenes is still incompletely understood. Furthermore, after administration to animals or humans, these molecules are rapidly metabolized. Thus pharmacokinetics and/or activities of the natural structures and their metabolites may be very different. Novel drug formulations have been postulated in order to improve stability and bioavailability, to minimize side effects, and to facilitate interaction with their domains in target proteins. These pharmacological improvements should lead stilbenes to become effective candidates as anticancer drugs.
Highlights
Despite the fact that the total European population comprises just one-ninth of the world’s population, the percentage of the global burden of cancer in Europe is of approximately 25% [1]
At the beginning of 21st century cancer was the second cause of death only preceded by cardiovascular diseases and followed by diseases derived from complications associated with diabetes and chronic respiratory diseases [4]
Multiple evidences suggest that oxidative stress induced by reactive oxygen species (ROS) is closely related to multistage carcinogenesis [7]
Summary
Despite the fact that the total European population comprises just one-ninth of the world’s population, the percentage of the global burden of cancer in Europe is of approximately 25% [1]. Natural polyphenols are plant secondary metabolites generated through the shikimate-derived phenylpropanoid and/or the polyketide pathway(s), with two or more phenolic rings, and being devoid of any nitrogen-based functional group in their basic structure [10]. They are produced by plants to protect themselves against stressing situations such as excessive ultraviolet (UV) irradiation, heat exposition, insects attacks, and fungus or bacterial infections [10]. Natural polyphenols have received increasing attention due to their potent antioxidant properties and their marked effects in the prevention of various oxidative stress associated diseases such as cancer [12, 13]. This review will focus on stilbenes and their potential as antioxidants and chemopreventive agents, including their molecular targets and signaling pathways; evidences from clinical trials for its toxicity, bioavailability, and benefit in humans; and biological improvements based on the development of analogs
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