Contents lists available at ScienceDirect Phytomedicine journal homepage: www.elsevier.com/locate/phymed In vitro and in silico perspectives on biological and phytochemical profile of three halophyte species—A source of innovative phytopharmaceuticals from nature Gokhan Zengin a, *, Zaahira Aumeeruddy-Elalfi b , Adriano Mollica c , Mustafa Abdullah Yilmaz d , Mohamad Fawzi Mahomoodally b a Department of Biology, Faculty of Science, Selcuk University, Campus, Konya, Turkey b Department of Health Sciences, Faculty of Science, University of Mauritius, Réduit, Mauritius c Department of Pharmacy, University “G. d'Annunzio” Chieti-Pescara, 66100 Chieti, Italy d Research and Application of Science and Technology Center (DUBTAM), University of Dicle, Diyarbakır, Turkey ARTICLE INFO Keywords: Halophytes Natural products Enzymatic inhibition Molecular dockings UHPLC-ESI-MS/MS ABSTRACT Background: Halophytes are considered as valuable sources of traditional drugs in different countries. Purpose: The present study aimed to evaluate biological and chemical fingerprints of three halophytes (Arthrocnemum macrostachyum (Moric.) C, Koch, Halimione portulacoides (L.) Aellen and Salicornia europaea L.). Materials and methods: The antioxidant and enzymatic inhibitory potential (acetylcholinesterase, butyr- ylcholinesterase, α-amylase, α-glucosidase, and tyrosinase) were assessed. The total phenolic, flavonoid con- tents, and the chemical profiles were appraised using the ultra-high performance liquid chromatography-elec- trospray ionization-tandem mass spectrometry. Molecular docking was conducted to provide additional insights of molecular interactions of the enzymes/phytochemicals. Results: Ethyl acetate extract was the most efficient extract, with A. macrostachyum being the most potent to- wards DPPH and ABTS radicals and phosphomolybdenum assay. Ethyl acetate extract of A. macrostachyum was also the best reducing agent (CUPRAC and FRAP assays). Methanol and ethyl acetate extract of A. macro- stachyum, H. portulacoides, and S. europaea showed significant enzyme inhibition potential. Ethyl acetate extract of A. macrostachyum showed the highest total phenolic (29.54 ± 0.78 mgGAEs/g extract) while the ethyl acetate extract of S. europaea was more abundant in flavonoids (18.26 ± 0.11 mgREs/g extract). Phytochemical profiling allowed the identification of several components in the methanolic extracts (16 in A. macrostachyum, 14 in H. portulacoides, and 11 in S. europaea), with quinic acid, p-coumaric acid, and rhamnetin being most abundant. Docking studies revealed that the above compounds showed scores for the enzymes tested. Conclusion: The three halophytes studies could be considered as potential sources of biologically-active com- pounds for novel phytopharmaceuticals development. Introduction Halophytic plants can be found as part of traditional medicine worldwide with more than 2500 species identified around the world possessing salinity tolerance. Among these plants, several are edible plants, while others have been used as a source of biofuel, in medicinal formulation, as biochemicals, and for ornamental purposes (Abdelly et al., 2006). Halophytes have also other commercial uses and potential, such as raw material for vegetable or fodder, a source of oilseed with high nutritional value, and can be used as secondary metabolites in pharmaceuticals, food additives, and phyto-nu- traceuticals (Buhmann and Papenbrock, 2013; Buhmann et al., 2015). For instance, the aerial part of Salicornia herbacea L. has been used traditionally for treatment of nephropathy, hepatitis and diarrhoea or constipation in Korea. Plethora of studies have shed light on the nu- tritional and phytochemical profile, including characterisation of phe- nolic content and antioxidant potential of S. herbacea L., Salicornia bi- gelovii Torr., Salicornia persica Akhani, and Sarcocornia fruticosa (L.) A.J. Scott that grows in several countries (Bertin et al., 2014; Kim et al., 2009, 2011). http://dx.doi.org/10.1016/j.phymed.2017.10.017 Received 24 May 2017; Received in revised form 10 August 2017; Accepted 25 October 2017 * Corresponding author. E-mail address: gokhanzengin@selcuk.edu.tr (G. Zengin). Abbreviations: ABTS, 2,2′-azino-bis(3-ethylbenzothiazoline)-6-sulfonic acid; AChE, acetylcholinesterase; BChE, butyrylcholinesterase; CUPRAC, cupric reducing antioxidant capacity; DPPH, 1,1-diphenyl-2-picrylhydrazyl; FRAP, ferric reducing antioxidant power; GAE, gallic acid equivalent; PNPG, 4-N-trophenyl-α-D-glucopyranoside; RE, rutin equivalents Phytomedicine 38 (2018) 35–44 0944-7113/ © 2017 Elsevier GmbH. All rights reserved. MARK