Molecular networking-guided investigation of the secondary metabolome of four species and their neuroprotective potential for the mitigation of Alzheimer's disease.

Alzheimer's Disease (AD) is a fatal age-related neurodegenerative condition with a multifactorial etiology contributing to 70% of dementia globally. The search for a multi-target agent to hit different targets involved in the pathogenesis of AD is crucial. In the present study, the neuroprotective effects of four extracts were assessed in LPS-induced AD in mice. Among the studied species, exhibited a profound effect on alleviating the loss of cognitive function, improved the learning ability, restored the acetylcholine esterase (AChE) levels to normal, and significantly reduced the tumor necrosis factor alpha (TNF-α) brain content in LPS-treated mice. To investigate the secondary metabolome of the studied species, ultra-performance liquid chromatography coupled to tandem mass spectrometry (UPLC-HRMS/MS), aided with feature-based molecular networking, was employed. Among the annotated features, aryl benzofurans and prenylated flavonoids were suggested as being responsible for the observed neuroprotective effect. Furthermore, some of the detected metabolites were proposed as new natural products such as moranoline di--hexoside (1), isomers of trimethoxy-dihydrochalcone--dihexoside (59 & 76), (hydroxy-dimethoxyphenyl)butenone--hexoside (82), and -methylpreglabridin--sulphate (105). In conclusion, our findings advocate the potential usage of leaves for the management of AD, yet after considering further clinical trials.