Potential anti-Alzheimer effects of selected Lamiaceae plants through polypharmacology on glycogen synthase kinase-3ß, ß-secretase, and casein kinase 1?

Abstract

The aerial parts of Lamiaceae plants have been used since ancient times all over the world, especially in Mediterranean cultures, for their medicinal and culinary properties. Although some of them have a historical role in the improvement of cognition and memory, the precise mechanism of these plants remains unclear. This study evaluated the potential anti-Alzheimer effects of some popular cultivated Lamiaceae plants via their inhibitory potential towards glycogen synthase kinase (GSK-3ß), ß-secretase (BACE-1), and casein kinase 1? (CK-1?), enzymes related to AD. Luminometric-based assays were used for the evaluation of GSK-3ß and CK-1? inhibitory activities in which a fluorescence resonance energy transfer (FRET) assay was used for determining BACE-1 inhibitory activity. The major compounds were identified by high pressure liquid chromatography with diode array detection coupled with electrospray ionization tandem mass spectrometry (LC-DAD-ESI-MS/MS). Among the extracts tested, Origanum onites L., O. majorana L., and Mentha piperita L. were the most active ones for GSK-3ß inhibitory activity, with IC50 values under 15 µg/mL, while O. majorana and S. officinalis L. were the most active for BACE-1 and O. onites, O. majorana, and Melissa officinalis L. for CK-1?, with half maximal inhibitory concentration (IC50) values under 250 µg/mL. On the basis of the composition of these active extracts it is apparent that flavonoids, i.e. apigenin, luteolin, and their glycoside derivatives, along with phenolic acids, i.e. rosmarinic acid and salvianolic acids, are the major principles of these active extracts. The outcomes of this study supported the traditional use of Lamiaceae plants for cognitive disorders and highlighted their underlying mechanisms, targeting GSK-3ß/BACE-1/CK-1? together for the first time