International Journal of Pharmacology1811-77751812-5700Asian Network for Scientific Information10.3923/ijp.2016.272.289Gentiana lutea Extracts and their Constituents as Inhibitors of Synaptosomal Ecto-NTPDase]]>NastasijevicBranislav MilosevicMaja JanjicGoran StanicVojislav VasicVesna 42016124The extracellular nucleotides act as neurotransmitters and signaling molecules in CNS, binding to a P2X and P2Y receptors. Their concentration regulates a cascade of membrane ecto enzymes, including the ecto-nucleotide triphosphate diphosphohydrolases (E-NTPDases). In many neuropathological conditions, such as neuroinflammatory, epilepsy, depression and migraine, altering of E-NTPDase activity was observed. The objective of this study was to investigate whether Gentiana lutea (G. lutea) extracts affect E-NTPDase activity and which of their constituents (loganic acid, gentiopicroside, isovitexin, amarogentin and isogentisin) exert inhibitory activity. The constituents concentration in the extracts was determined by ultra performance liquid chromatography coupled with mass spectrometry (UPLC-MS). Extracts and constituents were tested with E-NTPDase displayed on the rat synaptosomal membrane as well as by molecular docking study. Ethanol water extract (50%, v/v) exerted significant level of inhibition (52%) at concentration of 200 g mL1. By inhibition studies with single constituents about 30% inhibition was achieved in any case, thus the model of one substrate acting on two enzymes was used to determine IC50 values. Molecular docking study revealed amarogentin, isovitexin and isogentisin dimer as the potent E-NTPDase inhibitors with the binding energies ranging from -9.4 to -10 kcal mol1 versus -8.0 kcal mol1 for ATP. Presence of isogentisin only in ethanol water extracts may explain their better inhibitory acitivities. Findings of this study are useful from the perspective of safety of products based on G. lutea extracts, while investigated constituents belong to secoiridoids and xanthones class of compounds could be considered as a source of potential E-NTPDase inhibitors.]]>Aberham, A., S. Schwaiger, H. Stuppner and M. Ganzera,2007Gentiana lutea L. roots by RP-HPLC and LC-MS.]]>45437442Aiello, N., R. Bontempo and C. Vender,2013Gentiana lutea L.) populations in North-East Italy.]]>1603341Akileshwari, C., P. Muthenna, B. Nastasijevic, G. Joksic, J.M. Petrash and G.B. Reddy,2012Gentiana lutea extracts.]]>2012Arino, A., I. Arberas, M.J. Leiton, M. de Renobales and J.B. Dominguez,1997Gentiana lutea L.).]]>205295299Ashraf, M., S.M.A. Shah, I. Ahmad, S. Ahmad, S. Arshad, K. Ahmad and F.H. Nasim,2011520902094Azman, N.A.M., F. Segovia, X. Martinez-Farre, E. Gil and M.P. Almajano,20143455471Belcher, S.M., A. Zsarnovszky, P.A. Crawford, H. Hemani, L. Spurling and T.L. 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