ORIGINAL ARTICLES The Cell Membrane is the Main Target of Resveratrol as Shown by Interdisciplinary Biomolecular/Cellular and Biophysical Approaches G. L. Milardi • A. Stringaro • M. Colone • A. Bonincontro • G. Risuleo Received: 18 April 2013 / Accepted: 30 September 2013 / Published online: 29 October 2013 Ó Springer Science+Business Media New York 2013 Abstract One of the research lines developed in our laboratory is focused on the study of the bioactivity of natural substances. Resveratrol (RV) is a polyphenol non- flavonoid compound present in a number of plant species but mainly in the berries of the red grape Vitis vinifera. The powerful antioxidant action of this molecule is well doc- umented. In this work we evaluated the effects of this substance by adopting diverse experimental strategies. In particular, we studied the effects on cell vitality and cycle by MTT and cytofluorimetric assays. In addition, we explored the action of RV on the cell membrane by a well- consolidated biophysical approach: electrorotation. This technique allows assessment of the structure/function of the cell membrane. The results presented here demonstrate that RV shows a modest effect on the biological properties of the cell in terms of cytotoxicity and cell cycle altera- tions. On the contrary, a significant effect on the membrane structure/function was observed, consisting of an enhanced intramembrane ion transport. The implications and inter- pretation of these membrane alterations are discussed. Keywords Resveratrol Á Cytotoxicity Á Cell membrane Á Cytofluorometry Á Electrorotation Introduction Resveratrol (RV) is a polyphenol nonflavonoid compound belonging to the family of natural phytoalexins which are produced by plants to combat the attack of pathogens and/or stress. This molecule is particularly abundant in the berries of the red grape (Vitis vinifera) but is also present in highly pigmented vegetables and fruit such as pumpkin (Curcuma longa) or black mulberry (Morus nigra) as well as peanuts and pine kernels. The desic- cated roots of the Japanese knotweed (Polygonum cus- pidatum) are particularly rich in RV since they contain a 400-fold higher amount of the drug compared to red grapes. The use of RV in traditional Oriental medicine dates back several centuries. The drug shows a great number of diverse biological activities, such as antitumor, antioxidant, phytoestrogen and antiviral activities, just to mention a few. Its antitumor properties were ascribed to the ability of the drug to modulate negatively cyclin-cdk-dependent cell mechanisms. Cells exposed to RV undergo an arrest in G 1 phase followed by apoptosis; this phenomenon was first reported in human epidermoid carcinoma (Ahmad et al. 2001). Its powerful antioxidant character has been dem- onstrated in several different conditions such as chronic obstructive pulmonary disease and microbial infections (Hosoda et al. 2012; Biswas et al. 2013; Li et al. 2012; Ding et al. 2012). Due to its antioxidant properties, RV decreases platelet aggregation; therefore, this drug may find a clinical role in the control of the formation of ath- erogenic plaques (Olas et al. 1999). Electronic supplementary material The online version of this article (doi:10.1007/s00232-013-9604-1) contains supplementary material, which is available to authorized users. G. L. Milardi Á G. Risuleo (&) Dipartimento di Biologia e Biotecnologie, Sapienza Universita ` di Roma, Piazzale Aldo Moro, 5, 00185 Rome, Italy e-mail: gianfranco.risuleo@uniroma1.it A. Stringaro Á M. Colone Dipartimento di Tecnologie e Salute, Istituto Superiore di Sanita `, V.le Regina Elena, 299, 00161 Rome, Italy A. Bonincontro Dipartimento di Fisica, Sapienza Universita ` di Roma, Piazzale Aldo Moro, 5, 00185 Rome, Italy 123 J Membrane Biol (2014) 247:1–8 DOI 10.1007/s00232-013-9604-1