Juncaceae species as sources of innovative bioactive compounds for the food industry: In vitro antioxidant activity, neuroprotective properties and in silico studies Maria Jo ~ ao Rodrigues a , Katkam N. Gangadhar a, d , Gokhan Zengin b , Adriano Mollica c , Jo ~ ao Varela a , Luísa Barreira a , Luísa Cust  odio a, * a Centre of Marine Sciences, University of Algarve, Faculty of Sciences and Technology, Ed. 7, Campus of Gambelas, 8005-139 Faro, Portugal b Selcuk University, Science Faculty, Department of Biology, Campus, 42250 Konya, Turkey c Department of Pharmacy, University “G. d’Annunzio” of Chieti-Pescara, 66100 Chieti, Italy d Instituto de Tecnologia Química e Biol ogica, Universidade Nova de Lisboa, Avenida da Republica, Oeiras P-2780-157, Portugal article info Article history: Received 14 March 2017 Received in revised form 6 April 2017 Accepted 7 April 2017 Available online xxx Keywords: Alzheimer's disease Halophytes Juncunol Molecular docking Neuroprotection Oxidative stress abstract Several Juncus species are traditionally used as sedative and to treat health problems like insomnia. This work was based on the hypothesis that Juncus acutus, J. maritimus and J. inflexus may have molecules with bioactivities relevant for the improvement of cognitive functions and thus with potential use as food additives and/or nutraceuticals. Therefore leaves and roots extracts of those species were evaluated for radical scavenging (RSA) and metal chelating activities, and for in vitro inhibition of acetyl-(AChE) and butyrylcholinesterase (BuChE). The bioactive compound was isolated and identified by HPLC-DAD, and its anticholinesterase capacity was determined by different assays. Docking studies were performed to elucidate its inhibitory mechanism. The dichloromethane root extract of J. acutus had the highest RSA against DPPH and ABTS radicals, and the dichloromethane extract of J. maritimus leaves had the up- permost FRAP. The dichloromethane extract from J. acutus leaves had the strongest BuChE inhibition. Juncunol was the bioactive compound, exhibiting dual anticholinesterase capacity on enzyme-based assays and AChE inhibition in neuronal and glial cells in vitro. Molecular docking studies indicate jun- cunol as a competitive reversible inhibitor. Our results suggest that Juncus spp. can be sources of bioactive compounds with application in the food industry as cognitive-enhancer nutraceuticals. © 2017 Elsevier Ltd. All rights reserved. 1. Introduction The Juncus genus is the most represented of the Juncaceae family comprising more than 300 species distributed amongst all continents and being mainly found in salt marshes and badly- drained soils (El-Shamy et al., 2015). Several Juncus species are used in traditional medicine as sedative and to treat different health disorders, as for example insomnia (El-Shamy et al., 2015). These health benefits can be ascribed to the presence of different classes of compounds such as flavonoids, coumarins, terpenes, sterols, phenolic acids, stilbenes and phenanthrenes (El-Shamy et al., 2015), the latter being typically found in this genus (Kov acs et al., 2008). Europe is facing an aging population problem and it is estimated that a quarter of the European citizens will be over 60 years old in 2020 (WHO, 2011). As the population ages brain disorders such as dementia become an increasing burden. Dementia is characterized by the loss of memory, thinking impairment, behavioural alter- ations and loss of ability to perform daily living activities. Alz- heimer's disease (AD) is the most common type of dementia; it has no cure and is the fourth main death cause in developed countries after cancer and cardiovascular diseases (WHO, 2014). AD is a multifactor neurodegenerative disorder biochemically character- ized by decreased levels of acetylcholine (ACh), a neurotransmitter hydrolysed by acetylcholinesterase (AChE) and butyr- ylcholinesterase (BuChE). Thus, inhibition of AChE and/or BuChE results in an increase of ACh levels thereby improving cognitive functions (Greig et al., 2005). Oxidative stress is also associated with the development and progression of different forms of * Corresponding author. Centre of Marine Sciences, University of Algarve, Faculty of Sciences and Technology, Ed. 7, Campus of Gambelas, 8005-139 Faro, Portugal. E-mail address: lcustodio@ualg.pt (L. Cust odio). Contents lists available at ScienceDirect Food and Chemical Toxicology journal homepage: www.elsevier.com/locate/foodchemtox http://dx.doi.org/10.1016/j.fct.2017.04.006 0278-6915/© 2017 Elsevier Ltd. All rights reserved. Food and Chemical Toxicology xxx (2017) 1e7 Please cite this article in press as: Rodrigues, M.J., et al., Juncaceae species as sources of innovative bioactive compounds for the food industry: In vitro antioxidant activity, neuroprotective properties and in silico studies, Food and Chemical Toxicology (2017), http://dx.doi.org/10.1016/ j.fct.2017.04.006