Antiacetylcholinesterase activity and docking studies with chlorogenic acid, cynarin and arzanol from Helichrysum stoechas (Lamiaceae)

This work was aimed at the study of the chemical composition in phenolic compounds responsible for the high antiacetylcholinesterase activity of aqueous extracts (decoctions) from Helichrysum stoechas aerial parts. Chlorogenic acid, cynarin, and arzanol were the main components of decoctions, detected by high-performance liquid chromatography with diode-array detection and liquid chromatography-mass spectrometry/mass spectrometry. Flowers and stems/leaves extracts inhibited antiacetylcholinesterase with IC 50 values of 260.7 and 654.8 μg/mL, respectively. The biological activity of these extracts was maintained after in vitro gastrointestinal digestion, indicating that the active compounds present in the extracts were not enzymatically modified by the gastrointestinal system used to simulate the digestion. Molecular docking studies with the main components were carried out in order to obtain information, at the molecular level, as to how these compounds access the enzyme’s active site. The docking study showed for the first time that chlorogenic acid, cynarin, and arzanol fit nicely in the antiacetylcholinesterase active site channel, blocking all access to the catalytic triad. This explained the high inhibitory activity determined during in vitro experiments.