Isorhamnetin and Quercetin Derivatives as Anti-Acetylcholinesterase Principles of Marigold (Calendula officinalis) Flowers and Preparations

Marigold (Calendula officinalis L.) is one of the most common and widespread plants used medicinally all over the world. The present study aimed to evaluate the anti-acetylcholinesterase activity of marigold flowers, detect the compounds responsible and perform chemical analysis of marigold commercial products. Analysis of 23 varieties of C. officinalis flowers introduced into Siberia allowed us to select the Greenheart Orange variety due to the superior content of flavonoids (46.87 mg/g) and the highest inhibitory activity against acetylcholinesterase (IC(50) 63.52 µg/mL). Flavonoids, isorhamnetin and quercetin derivatives were revealed as potential inhibitors with the application of high-performance liquid chromatography (HPLC) activity-based profiling. Investigation of the inhibitory activity of isorhamnetin glycosides demonstrated the maximal potency for isorhamnetin-3-O-(2′′,6′′-di-acetyl)-glucoside (IC(50) 51.26 μM) and minimal potency for typhaneoside (isorhamnetin-3-O-(2′′,6′′-di-rhamnosyl)-glucoside; IC(50) 94.92 µM). Among quercetin derivatives, the most active compound was quercetin-3-O-(2′′,6′′-di-acetyl)-glucoside (IC(50) 36.47 µM), and the least active component was manghaslin (quercetin-3-O-(2′′,6′′-di-rhamnosyl)-glucoside; IC(50) 94.92 µM). Some structure-activity relationships were discussed. Analysis of commercial marigold formulations revealed a reduced flavonoid content (from 7.18–19.85 mg/g) compared with introduced varieties. Liquid extract was the most enriched preparation, characterized by 3.10 mg/mL of total flavonoid content, and infusion was the least enriched formulation (0.41 mg/mL). The presented results suggest that isorhamnetin and quercetin and its glycosides can be considered as potential anti-acetylcholinesterase agents.