REVIEW ARTICLE Ferulic acid and its therapeutic potential as a hormetin for age-related diseases Eugenio Barone Æ Vittorio Calabrese Æ Cesare Mancuso Received: 6 May 2008 / Accepted: 9 July 2008 Ó Springer Science+Business Media B.V. 2008 Abstract Ferulic acid (FA) is a polyphenol very abundant in vegetables and maize bran. Several lines of evidence have shown that FA acts as a potent antioxidant in vitro, due to its ability to scavenge free radicals and induce a robust cell stress response through the up-regulation of cytoprotective enzymes such as heme oxygenase-1, heat shock protein 70, extracellular signal-regulated kinase 1/2 and Akt. Furthermore, FA inhibited the expression and/or activity of cytotoxic enzymes including inducible nitric oxide synthase, caspases and cyclooxygenase- 2. On this basis, FA has been proposed for the treatment of several age-related diseases such as neurodegener- ative disorders, cardiovascular diseases, diabetes and cancer. However, although the great abundance of in vitro data, the real efficacy of FA in humans has not been demonstrated so far. New efforts and resources should be transferred to clinical research for the complete evaluation of the therapeutic potential of FA in chronic diseases. Keywords Aging Á Ferulic acid Á Free radicals Á Heme oxygenase Á Neurodegenerative disorders Introduction Several years ago artichoke-derived polyphenols, such as 1,5-dicaffeiylquinic acid as well as the caffeic acid mono-methylester [also known as ferulic acid (FA)] and di-methylester were extensively studied by Preziosi et al. (1957), Preziosi and Loscalzo (1957a, b,1958) for their coleretic, hypolipidemic and diuretic func- tions. Recently, polyphenols have been proposed as novel agents in the prevention of free radical-related diseases such as neurodegenerative disorders, cancer, acute and chronic inflammation and aging (see below). Polyphenols are widely distributed in the plant kingdom, and are integral part of diet, with significant amounts being reported in vegetables, fruit and beverages (Clifford 1999; D’Archivio et al. 2007). FA [(E)-3-(4-hydroxy-3-methoxy-phenyl)prop-2- enoic acid)] (Fig. 1) is a common polyphenolic compound most abundant in vegetables, especially artichokes, eggplants (*90% of total polyphenols) and in maize bran (*3.1% of total polyphenol content) (D’Archivio et al. 2007; Rechner et al. 2001a, b; Saulnier et al. 1995). Moreover, FA is an effective component of Chinese medicinal herbs such as Angelica sinensis, Cimicifuga heracleifolia and Lignsticum chuangxiong (Ou and Kwok 2004). During the last decade, scientists focused their attention on FA especially for its direct antioxidant property, even if this latter is not the only interesting aspect of this molecule. E. Barone Á C. Mancuso (&) Institute of Pharmacology, Catholic University School of Medicine, Largo Francesco. Vito 1, 00168 Rome, Italy e-mail: cmancuso@rm.unicatt.it V. Calabrese Department of Chemistry, University of Catania, Via Andrea Doria, 95100 Catania, Italy 123 Biogerontology DOI 10.1007/s10522-008-9160-8