The Distribution of Glucosinolates in Different Phenotypes of Lepidium peruvianum and Their Role as Acetyl- and Butyrylcholinesterase Inhibitors—In Silico and In Vitro Studies

The aim of the study was to present the fingerprint of different Lepidium peruvianum tuber extracts showing glucosinolates-containing substances possibly playing an important role in preventinting dementia and other memory disorders. Different phenotypes of Lepidium peruvianum (Brassicaceae) tubers were analysed for their glucosinolate profile using a liquid chromatograph coupled with mass spectrometer (HPLC-ESI-QTOF-MS/MS platform). Qualitative analysis in 50% ethanolic extracts confirmed the presence of ten compounds: aliphatic, indolyl, and aromatic glucosinolates, with glucotropaeolin being the leading one, detected at levels between 0–1.57% depending on phenotype, size, processing, and collection site. The PCA analysis showed important variations in glucosinolate content between the samples and different ratios of the detected compounds. Applied in vitro activity tests confirmed inhibitory properties of extracts and single glucosinolates against acetylcholinesterase (AChE) (15.3–28.9% for the extracts and 55.95–57.60% for individual compounds) and butyrylcholinesterase (BuChE) (71.3–77.2% for the extracts and 36.2–39.9% for individual compounds). The molecular basis for the activity of glucosinolates was explained through molecular docking studies showing that the tested metabolites interacted with tryptophan and histidine residues of the enzymes, most likely blocking their active catalytic side. Based on the obtained results and described mechanism of action, it could be concluded that glucosinolates exhibit inhibitory properties against two cholinesterases present in the synaptic cleft, which indicates that selected phenotypes of L. peruvianum tubers cultivated under well-defined environmental and ecological conditions may present a valuable plant material to be considered for the development of therapeutic products with memory-stimulating properties

The Influence of Palmatine Isolated from Berberis sibirica Radix on Pentylenetetrazole-Induced Seizures in Zebrafish

Palmatine (PALM) and berberine (BERB) are widely identified isoquinoline alkaloids among the representatives of the Berberidaceae botanical family. The antiseizure activity of BERB was shown previously in experimental epilepsy models. We assessed the effect of PALM in a pentylenetetrazole (PTZ)-induced seizure assay in zebrafish, with BERB as an active reference compound. Both alkaloids were isolated from the methanolic root extract of Berberis sibirica by counter-current chromatography, and their ability to cross the blood-brain barrier was determined via quantitative structure-activity relationship assay. PALM exerted antiseizure activity, as confirmed by electroencephalographic analysis, and decreased c-fos and bdnf levels in PTZ-treated larvae. In a behavioral assay, PALM dose-dependently decreased PTZ-induced hyperlocomotion. The combination of PALM and BERB in ED16 doses revealed hyperadditive activity towards PTZ-induced hyperlocomotion. Notably, we have indicated that both alkaloids may exert their anticonvulsant activity through different mechanisms of action. Additionally, the combination of both alkaloids in a 1:2.17 ratio (PALM: BERB) mimicked the activity of the pure extract, which indicates that these two active compounds are responsible for its anticonvulsive activity. In conclusion, our study reveals for the first time the anticonvulsant activity of PALM and suggests the combination of PALM and BERB may have higher therapeutic value than separate usage of these compounds