Journal of Alzheimer’s Disease 52 (2016) 65–75 DOI 10.3233/JAD-151159 IOS Press 65 Salidroside, a Bioactive Compound of Rhodiola Rosea, Ameliorates Memory and Emotional Behavior in Adult Mice Agostino Palmeri, Leonardo Mammana, Maria Rosaria Tropea, Walter Gulisano and Daniela Puzzo ∗ Department of Biomedical and Biotechnological Sciences, Section of Physiology, University of Catania, Catania, Italy Handling Associate Editor: Ottavio Arancio Accepted 15 January 2016 Abstract. Rhodiola Rosea (R. Rosea) is a plant used in traditional popular medicine to enhance cognition and physical performance. R. Rosea medicinal properties have been related to its capability to act as an adaptogen, i.e., a substance able to increase the organism’s resistance to a variety of chemical, biological, and physical stressors in a non-specific way. These adaptogen properties have been mainly attributed to the glycoside salidroside, one of the bioactive compounds present in the standardized extracts of R. Rosea. Here, we aimed to investigate whether a single dose of salidroside is able to affect memory and emotional behavior in wild type adult mice. We performed fear conditioning to assess cued and contextual memory, elevated plus maze and open field to evaluate anxiety, and tail suspension test to evaluate depression. Our results showed that a single i.p. administration of salidroside was able to enhance fear memory and exerted an anxiolytic and antidepressant effect. These data confirmed the adaptogenic effect of R. Rosea bioactive compounds in animal models and suggest that salidroside might represent an interesting pharmacological tool to ameliorate cognition and counteract mood disorders. Keywords: Adaptogen, anxiety, depression, memory, Rhodiola rosea, salidroside INTRODUCTION The term “adaptogen” indicates a compound capa- ble of increasing the organism resistance against a variety of chemical, biological, and physical stressors [1–3]. Its action is due to a combination of biological properties aimed at restoring physiological functions and cellular homeostasis so that an organism can pre-adapt to appropriately respond when the environ- ment modifies. According to the general adaptation syndrome, as defined by Selye in 1950 [4], these drugs are capable of either reducing stress reactions in ∗ Correspondence to: Daniela Puzzo, Department of Biomed- ical and Biotechnological Sciences, Section of Physiology, University of Catania; Viale A. Doria 6 (ed. 2), 95125 Catania, Italy. Tel.: +39 095 7384033/4053; Fax: +39 095 7384217; E-mail: danypuzzo@yahoo.it. the alarm phase or preventing the exhaustion phase protecting by long-term stress [5]. Thus, they have been proposed as a possible therapeutic strategy for prevention and treatment of several disorders related to stressful conditions. Among different adaptogen plants, a variety of studies have focused on Rhodiola Rosea (R. Rosea) [6–8], a popular herbal medicine used in Chinese medicine and widely distributed in Russia, Scan- dinavia, and many other countries such as North America and India. For centuries, R. Rosea root and rhizome extracts have been used in traditional medicine to increase work performance, eliminate fatigue, and improve cardiovascular function and cen- tral nervous system (CNS) activity (for a review see [9]). Studies on cellular and animal models, as well as clinical trials on humans, confirmed ISSN 1387-2877/16/$35.00 © 2016 – IOS Press and the authors. All rights reserved