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Broccoli is commonly consumed as food and as medicine. However, comprehensive metabolic profiling of two broccoli varieties, Romanesco broccoli (RB) and purple broccoli (PB), in relation to their anticholinergic activity has not been fully disclosed. A total of 110 compounds were tentatively identified using UPLC-Q-TOF-MS metabolomics. Distinctively different metabolomic profiles of the two varieties were revealed by principal component analysis (PCA). Furthermore, by volcano diagram analysis, it was found that PB had a significantly higher content of phenolic acids, flavonoids, and glucosinolates, indicating the different beneficial health potentials of PB that demonstrated higher antioxidant and anticholinergic activities. Moreover, Pearson's correlation analysis revealed 18 metabolites, mainly phenolic and sulfur compounds, as the main bioactive. The binding affinity of these biomarkers to the active sites of acetyl- and butyryl-cholinesterase enzymes was further validated using molecular docking studies. Results emphasize the broccoli significance as a functional food and nutraceutical source and highlight its beneficial effects against Alzheimer's disease., (© 2024. The Author(s).)

Alzheimer's disease poses a global health concern with unmet demand requiring creative approaches to discover new medications. In this study, we investigated the chemical composition and the anticholinesterase activity of Aspergillus niveus Fv-er401 isolated from Foeniculum vulgare (Apiaceae) roots. Fifty-eight metabolites were identified using UHPLC-MS/MS analysis of the crude extract. The fungal extract showed acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibitory effects with IC50 53.44 ± 1.57 and 48.46 ± 0.41 µg/mL, respectively. Two known metabolites were isolated, terrequinone A and citrinin, showing moderate AChE and BuChE inhibitory activity using the Ellman's method (IC50 = 11.10 ± 0.38 µg/mL and 5.06 ± 0.15 µg/mL, respectively for AChE, and IC50 15.63 ± 1.27 µg/mL and 8.02 ± 0.08 µg/mL, respectively for BuChE). As evidenced by molecular docking, the isolated compounds and other structurally related metabolites identified by molecular networking had the required structural features for AChE and BuChE inhibition. Where varioxiranol G (−9.76 and −10.36 kcal/mol), penicitrinol B (−9.50 and −8.02 kcal/mol), dicitrinol A (−8.53 and −7.98 kcal/mol) and asterriquinone CT5 (−8.02 and −8.25 kcal/mol) showed better binding scores as AChE and BuChE inhibitors than the co-crystallized inhibitor (between −7.89 and 7.82 kcal/mol) making them promising candidates for the development of new drugs to treat Alzheimer's. [ABSTRACT FROM AUTHOR]

Alzheimer's disease remains a global health challenge and an unmet need requiring innovative approaches to discover new drugs. The current study aimed to investigate the inhibitory activity of Albizia lucidior and Albizia procera leaves against acetylcholinesterase enzyme in vitro and explore their chemical compositions. Metabolic profiling of the bioactive plant, A. lucidior, via UHPLC/MS/MS-based Molecular Networking highlighted the richness of its ethanolic extract with budmunchiamine alkaloids, fourteen budmunchiamine alkaloids as well as four new putative ones were tentatively identified for the first time in A. lucidior. Pursuing these alkaloids in the fractions of A. lucidior extract via molecular networking revealed that alkaloids were mainly concentrated in the ethyl acetate fraction. In agreement, the alkaloid-rich fraction showed the most promising anticholinesterase activity (IC50 5.26 µg/mL) versus the ethanolic extract and ethyl acetate fraction of A. lucidior (IC50 24.89 and 6.90 µg/mL, respectively), compared to donepezil (IC50 3.90 µg/mL). Furthermore, deep in silico studies of tentatively identified alkaloids of A. lucidior were performed. Notably, normethyl budmunchiamine K revealed superior stability and receptor binding affinity compared to the two used references: donepezil and the co-crystallized inhibitor (MF2 700). This was concluded based on molecular docking, molecular dynamics simulations and molecular mechanics generalized born/solvent accessibility (MM–GBSA) calculations. [ABSTRACT FROM AUTHOR]