Evaluation of Activity of Sesquiterpene Lactones and Chicory Extracts as Acetylcholinesterase Inhibitors Assayed in Calorimetric and Docking Simulation Studies

Abstract

The aim of the study was to explain the effects of sesquiterpene lactones (SLs) from chicory (Cichorium intybus L.) root extracts as inhibitors of acetylcholinesterase (AChE) at the molecular level and to determine the inhibition of AChE activity by specific SLs (lactucin and lactucopicrin) and different chicory extracts. The obtained SLs-rich extracts were purified by the countercurrent partition chromatography (CPC) technique. AChE inhibitors were analyzed using two models: isothermal titration calorimetry (ITC) and docking simulation. The results of ITC analysis of the enzyme and the ligands’ complexation showed strong interactions of SLs as well as extracts from chicory with AChE. In a test of enzyme activity inhibition after introducing acetylcholine into the model system with SL, a stronger ability to inhibit the hydrolysis of the neurotransmitter was observed for lactucopicrin, which is one of the dominant SLs in chicory. The inhibition of enzyme activity was more efficient in the case of extracts, containing different enzyme ligands, exhibiting complementary patterns of binding the AChE active site. The study showed the high potential of using chicory to decrease the symptoms of Alzheimer’s disease.

A Three-step Process to Isolate Large Quantities of Bioactive Sesquiterpene Lactones from <em>Cichorium intybus</em> L. Roots and Semi-synthesis of Chicory STLs Standards

“…Chemical shifts (δ) are in parts per million (ppm) downfield from tetramethylsilane (TMS). The assignments were made using one-dimensional (1D) 1 H and 13 C spectra and two-dimensional (2D) HSQC-DEPT and HMBC spectra. NMR coupling constants (J) are reported in Hertz (Hz) and splitting patterns are indicated as follows: s (singlet), brs (broad singlet), d (doublet), dd (doublet of doublet), ddd (double of doublet of doublet), m (multiplet).…”

“…The mixture was stirred for 2 h at 0°C 1H, H-13), 6.04 (d, J = 1.8 Hz, 1H, H-13'), 5.53 (bs, 1H, OH-8), 5.37 (d, J = 17.1 Hz, 1H, H-15), 5.03 (d, J = 17.4 Hz, 1H, H-15'), 3.98 (d, J = 10.0 Hz, 1H, H-5), 3.85 -3.80 (m, 1H, H-6), 3.78 -3.73 (m, 1H, H-8), 3.16-3.09 (m, 1H, H-7), 2.79 (dd, J = 13.5, 10.7 Hz, 1H, H-9'), 2.36 (s, 3H, H-14), 2.33 (dd, J = 13.8, 1.8 Hz, 1H, H-9). 13…”

“…In addition, Rojas-Silva P et al reported the first findings of leishmanicidal activity of bitter STLs isolated from chicory roots [12]. Recently, lactucin and lactucopicrin were also evaluated as acetylcholinesterase inhibitors [13].…”

“…J = 13.0, 1.3 Hz, 1H), 2.16-2.09 (m, 1H), 1.25 (d, J = 6.9 Hz, 3H) 13. C NMR (75 MHz, DMSO) δ 195.01, 178.28, 170.56, 147.84, 133.50, 132.20, 103.28, 80.85, 77.29, 76.85, 74.03, 70.33, 68.39, 68.32, 61.35, 60.43, 48.80, 48.54, 40.99, 21.55, 15.72.…”

A Three-step Process to Isolate Large Quantities of Bioactive Sesquiterpene Lactones from <em>Cichorium intybus</em> L. Roots and Semi-synthesis of Chicory STLs Standards

“…1 H NMR (300 MHz, DMSO) δ 6.57 (s, 1H), 5.22 (m, 2H), 4.97-4.91 (m, 2H), 4.67-4.57 (m, 2H), 4.53-4.48 (m, 1H), 4.23 (d, J = 7.7 Hz, 1H), 3.76-3.72 (m, 2H), 3.69-3.64 (m, 1H), 3.59-3.53 (m, 1H), 3.48-3.41 (m, 1H), 3.19-2.99 (m, 4H), 2.73-2.59 (m, 2H), 2.34 (s, 3H), 2.25 (dd, J = 13.0, 1.3 Hz, 1H), 2.16-2.09 (m, 1H), 1.25 (d, J = 6.9 Hz, 3H). 13…”