Ann. N.Y. Acad. Sci. ISSN 0077-8923 ANNALS OF THE NEW YORK ACADEMY OF SCIENCES Issue: Environmental Stressors in Biology and Medicine Rottlerin and curcumin: a comparative analysis Emanuela Maioli, 1 Claudia Torricelli, 1 and Giuseppe Valacchi 2,3 1 Department of Physiology, University of Siena, Siena, Italy. 2 Department of Biology and Evolution, University of Ferrara, Ferrara, Italy. 3 Department of Food and Nutrition, Kyung Hee University, Seoul, South Korea Address for correspondence:Emanuela Maioli, Department of Physiology, Via Aldo Moro, 7-53100 Siena, Italy. emanuela.maioli@unisi.it Rottlerin and curcumin are natural plant polyphenols with a long tradition in folk medicine. Over the past two decades, curcumin has been extensively investigated, while rottlerin has received much less attention, in part, as a consequence of its reputation as a selective PKC inhibitor. A comparative analysis of genomic, proteomic, and cell signaling studies revealed that rottlerin and curcumin share a number of targets and have overlapping effects on many biological processes. Both molecules, indeed, modulate the activity and/or expression of several enzymes (PKC, heme oxygenase, DNA methyltransferase, cyclooxygenase, lipoxygenase) and transcription factors (NF-B, STAT), and prevent aggregation of different amyloid precursors ( -synuclein, amyloid A, prion proteins, lysozyme), thereby exhibiting convergent antioxidant, anti-inflammatory, and antiamyloid actions. Like curcumin, rottlerin could be a promising candidate in the fight against a variety of human diseases. Keywords: Rottlerin; curcumin; antiamyloid; antioxidant; anti-inflammatory Introduction For centuries, many plant compounds have had an outstanding role in medicine and are still used either directly or after chemical modification. Phytochem- icals, on the basis of their structure can be grouped into different classes, the most common of which are the polyphenols, characterized by multiple hydroxy- lated aromatic rings. Polyphenols are very abundant in nature and extremely diverse. Given their great heterogeneity, it is impossible to define a structure– activity relationship, and a more appropriate ap- proach is to analyze their biological effects and the associated signal-transduction pathways. One of the most intriguing and most extensively investigated polyphenols is curcumin (Fig. 1, upper panel), which has been the subject of hundreds of published papers over the past two decades. Cur- cumin has a wide range of pharmacological activ- ities, which include antitumor, antioxidant, anti- amyloid, and anti-inflammatory properties. 1 Rottlerin (Fig. 1, lower panel) has received much less attention than curcumin. Rottlerin came to at- tention in 1994 when it was identified as a selec- tive PKC inhibitor in a publication by Gschwendt et al. 2 As a consequence of this designation, this molecule has long been neglected, despite its poten- tial, though sporadic, off-site targeting activity. 3,4 Only recently has investigation of the properties of this molecule shifted beyond PKC inhibition; sev- eral PKC-independent rottlerin effects have been described so far. 5–7 The limited availability of rottlerin has also likely hampered interest in this molecule and, in the past, discouraged research of its medicinal potential. Rot- tlerin, unlike other polyphenols, is not present in ed- ible vegetables and in common beverages; instead, it is primarily present in the gland hair covering the fruit of Mallotus philippinensis (Euphorbiaceae), an evergreen rain forest tree that is inedible and only used by indigenous populations of Southeast Asian tropical regions. Rottlerin is used as a dye for coloring textiles and as an old folk remedy against tapeworm (when taken orally) and scabies and ring- worm (when administered topically). Similarly, curcumin, a polyphenol derived from the spice turmeric, has a long tradition as a drug against a variety of diseases, including fever, doi: 10.1111/j.1749-6632.2012.06514.x Ann. N.Y. Acad. Sci. 1259 (2012) 65–76 c  2012 New York Academy of Sciences. 65