Anti-Alzheimer potential of Solanum lycopersicum seeds: in vitro, in vivo, metabolomic, and computational investigations

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Abstract

Background

Solanum lycopersicum Linn. (Tomato, Family Solanaceae) is one of the fruits that are most consumed worldwide. The current research intends to emphasise the possibility of positive and therapeutic effects of S. lycopersicum seed extract (SLSE) on Alzheimer's disease's neurodegeneration effects being reversed in a study utilising rats exposed to aluminium chloride. Investigations were done on the cholinesterase and antioxidant in vitro activity of SLSE. Rats with Alzheimer's disease were given SLSE, and donepezil (500, and 10 mg/kg.b.wt., daily for six weeks, respectively) to test SLSE biological activity. Beam-balance and T-maze tests, as well as serum levels of AChE, norepinephrine, dopamine, serotonin, IL-6, glycated end product, BDNF, MDA, TAC, and GSH were assessed, accompanied with histological investigation. To impact the effectiveness of this extract, bioinformatics study was validated.

Results

Crude SLSE showed in vitro DPPH scavenging and AChE inhibition activities, indicating the extract might have anti-Alzheimer potential, which was validated using an aluminium-intoxicated rat model, in vivo. In Alzheimer's rats, in vivo studies showed considerable improvements, as seen by improved beam balance, and T-maze tests and decreased serum levels of AChE, norepinephrine, dopamine, serotonin, IL-6, glycated end product, BDNF, and MDA, with increasing in TAC, and GSH levels. Brain tissue histological tests revealed a largely typical pattern of collagen fibre distribution. LC–HRESIMS metabolomic profiling of crude SLSE identified 33 compounds. Furthermore, the bioinformatics study discovered 378 targets related to the major identified compounds, of which only 133 were related to Alzheimer's and memory disorders, with APP, AChE, and PSEN2 targets which were marked as the top genes. Gene enrichment analysis identified the arachidonic acid metabolism and PPAR signalling pathway as the biological pathways enriched by all the gene sets under investigation.

Conclusion

As a result, the study findings are expected to pave the way for the creation of dietary supplements for Alzheimer's disease management.

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STRING v11: protein–protein association networks with increased coverage, supporting functional discovery in genome-wide experimental datasets

Damian Szklarczyk, Annika L Gable, David Lyon … (2018)

Abstract Proteins and their functional interactions form the backbone of the cellular machinery. Their connectivity network needs to be considered for the full understanding of biological phenomena, but the available information on protein–protein associations is incomplete and exhibits varying levels of annotation granularity and reliability. The STRING database aims to collect, score and integrate all publicly available sources of protein–protein interaction information, and to complement these with computational predictions. Its goal is to achieve a comprehensive and objective global network, including direct (physical) as well as indirect (functional) interactions. The latest version of STRING (11.0) more than doubles the number of organisms it covers, to 5090. The most important new feature is an option to upload entire, genome-wide datasets as input, allowing users to visualize subsets as interaction networks and to perform gene-set enrichment analysis on the entire input. For the enrichment analysis, STRING implements well-known classification systems such as Gene Ontology and KEGG, but also offers additional, new classification systems based on high-throughput text-mining as well as on a hierarchical clustering of the association network itself. The STRING resource is available online at https://string-db.org/.

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Neuropathological stageing of Alzheimer-related changes

H Braak, E Braak (1991)

Eighty-three brains obtained at autopsy from nondemented and demented individuals were examined for extracellular amyloid deposits and intraneuronal neurofibrillary changes. The distribution pattern and packing density of amyloid deposits turned out to be of limited significance for differentiation of neuropathological stages. Neurofibrillary changes occurred in the form of neuritic plaques, neurofibrillary tangles and neuropil threads. The distribution of neuritic plaques varied widely not only within architectonic units but also from one individual to another. Neurofibrillary tangles and neuropil threads, in contrast, exhibited a characteristic distribution pattern permitting the differentiation of six stages. The first two stages were characterized by an either mild or severe alteration of the transentorhinal layer Pre-alpha (transentorhinal stages I-II). The two forms of limbic stages (stages III-IV) were marked by a conspicuous affection of layer Pre-alpha in both transentorhinal region and proper entorhinal cortex. In addition, there was mild involvement of the first Ammon's horn sector. The hallmark of the two isocortical stages (stages V-VI) was the destruction of virtually all isocortical association areas. The investigation showed that recognition of the six stages required qualitative evaluation of only a few key preparations.