Minireview Cinnamtannin B-1 as an antioxidant and platelet aggregation inhibitor José J. López 1 , Isaac Jardín 1 , Gines M. Salido, Juan A. Rosado ⁎ Department of Physiology, Cell Physiology Research Group, University of Extremadura, Apdo de Correos 643, 10071, Caceres, Spain ABSTRACT ARTICLE INFO Article history: Received 6 November 2007 Accepted 17 March 2008 Keywords: Cinnamtannin B1 Platelets Aggregation Flavonoids Cinnamtannin B-1 is a naturally occurring trimeric A-type proanthocyanidin, present in a limited number of plants, which exhibits a large number of cellular actions mostly derived from its antioxidant properties. Cinnamtannin B-1 modulates several biological processes such as changes in cytosolic free Ca 2+ concentration, endogenous reactive oxygen species generation, protein tyrosine phosphorylation and platelet aggregation. Proanthocyanidins, such as cinnamtannin B-1, have been reported to exert antitumoral activity mediated by a selective proapoptotic action in a number of tumoral cell lines associated with antiapoptotic activity in normal cells. The opposite effects of proanthocyanidins in normal and tumoral cells suggest that these compounds might be the base for therapeutic strategies directed selectively against tumoral cells. In addition, cinnamtannin B-1 shows antithrombotic actions through inhibition, in platelets, of endogenous ROS generation, Ca 2+ mobilization and, subsequently, aggregation. This has been reported to be especially relevant in platelets from diabetic patients, where cinnamtannin B-1 reverses both platelet hypersensitivity and hyperactivity. Considering the large number of cellular effects of cinnamtannin B-1 the development of therapeutic strategies for thrombotic disorders or certain types of cancer deserves further studies. This review summarizes the current knowledge on the actions and relevance of the signalling pathways modulated by cinnamtannin B-1. © 2008 Elsevier Inc. All rights reserved. Contents Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 977 Flavonoids and proanthocyanidins . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 978 Cinnamtannin B-1 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 979 General actions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 979 Overview of platelet Ca 2+ homeostasis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 979 Effect of cinnamtannin B-1 in platelet Ca 2+ signalling and aggregation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 979 Effect of cinnamtannin B-1 in apoptosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 980 Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 980 Acknowledgements . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 981 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 981 Introduction Antioxidants are chemical compounds that help defend tissues and organs against cell damage caused by a variety of free radicals, unstable oxygen or nitrogen molecules that are highly reactive due to the presence of unpaired valence shell electrons (Sheu et al., 2006). Reactive oxygen species (ROS) are generated as by-products of oxidative metabolism in all aerobic organisms. ROS at physiological concentrations act as intracellular messengers for a variety of cellular processes, including protein synthesis and turnover (Moldovan and Moldovan, 2004) or Ca 2+ homeostasis (Redondo et al., 2004a; Rosado et al., 2004a), which explains why the indiscriminate use of antioxidants did not produce the expected “beneficial” results in many medical applications. Despite this physiological role, free radicals are involved in the pathogenesis of cell and tissue injury (Redondo et al., 2005b; Flora, 2007; Valko et al., 2007). Cells are normally able to protect themselves against ROS damage through the expression of enzymes, including superoxide dismutases and catalases (Sheu et al., 2006). Naturally occurring polyphenolic compounds, a major family of secondary metabolites identified in Life Sciences 82 (2008) 977-982 ⁎ Corresponding author. Tel.: +34 927 257139; fax: +34 927 257110. E-mail address: jarosado@unex.es (J.A. Rosado). 1 Both authors contributed equally to this work. 0024-3205/$ – see front matter © 2008 Elsevier Inc. All rights reserved. doi:10.1016/j.lfs.2008.03.009 Contents lists available at ScienceDirect Life Sciences journal homepage: www.elsevier.com/locate/lifescie