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Neuroprotective potential of the oxindole alkaloids isomitraphylline and mitraphylline in human neuroblastoma SH-SY5Y cells.

ABSTRACT: The purified oxindole alkaloids, isomitraphylline and mitraphylline from Uncaria perrottetii, revealed their ability to break amyloid aggregates in vitro suggesting their therapeutic potentials in Alzheimer's disease (AD). Thioflavin-T assay for assessing amyloid-beta (Aβ) aggregation of these alkaloids exhibited inhibitions at 60.321% ± 2.61 (50 μM) for isomitraphylline and 43.17% ± 3.48 (50 μM) for mitraphylline. Neuroprotective effects were elaborated against Aβ-induced SH-SY5Y cells at 20 μM and 10 μM for isomitraphylline, and 20 μM for mitraphylline. In addition, both alkaloids attenuated and protected the H₂O₂-induced SH-SY5Y cell cytotoxicity at 20 μM. The intracellular ROS levels of SH-SY5Y cells from H₂O₂-induced oxidative stress were reduced at 20 μM and 10 μM, and the mitochondrial membrane potentials of Aβ-induced SH-SY5Y cells were protected at 20 μM. The overall results suggested the potentials of both alkaloids to target certain pathological biomarkers of AD and could be further investigated as therapeutic or preventive drug leads against AD.

SUBMITTER: Tan MA

PROVIDER: S-EPMC7652979 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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Neuroprotective potential of the oxindole alkaloids isomitraphylline and mitraphylline in human neuroblastoma SH-SY5Y cells.

Tan Mario A MA An Seong Soo A SSA

3 Biotech 20201109 12

The purified oxindole alkaloids, isomitraphylline and mitraphylline from <i>Uncaria perrottetii</i>, revealed their ability to break amyloid aggregates in vitro suggesting their therapeutic potentials in Alzheimer's disease (AD). Thioflavin-T assay for assessing amyloid-<i>beta</i> (Aβ) aggregation of these alkaloids exhibited inhibitions at 60.321% ± 2.61 (50 μM) for isomitraphylline and 43.17% ± 3.48 (50 μM) for mitraphylline. Neuroprotective effects were elaborated against Aβ-induced SH-SY5Y ...[more]

PMID: 33194521

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Project description:BackgroundMaleic acid is a multi-functional chemical widely used in the field of industrial chemistry for producing food additives and food contact materials. As maleic acid may contaminate food by the release from food packages or intentional addition, it raises the concern about the effects of excessive dietary exposure to maleic acid on human health. However, the influence of maleic acid on human health has not been thoroughly studied. In silico toxicogenomics approaches have found the association between maleic acid and nervous system disease in human. The aim of this study is to experimentally explore the effects of maleic acid on human neuronal cells.MethodsA microarray-based transcriptome profiling was performed to offer a better understanding of the effects of maleic acid on human health. Gene expression profiles of human neuroblastoma SH-SY5Y cells exposed to three concentrations of maleic acid (10, 50, and 100 μM) for 24 h were analyzed. Genes which were differentially expressed in dose-dependent manners were identified and further analyzed with an enrichment analysis. The expression profile of selected genes related to the inferred functional changes was validated using quantitative polymerase chain reaction (qPCR). Specific fluorescence probes were applied to observe the inferred functional changes in maleic acid-treated neuronal cells.ResultsA total of 316 differentially expressed genes (141 upregulated and 175 downregulated) were identified in response to the treatment of maleic acid. The enrichment analysis showed that DNA binding and metal ion binding were the significant molecular functions (MFs) of the neuronal cells affected by maleic acid. Maleic acid exposure decreased the expression of genes associated with calcium and thiol levels of the cells in a dose-dependent manner. The levels of intracellular calcium and thiol levels were also affected by maleic acid dose-dependent.DiscussionThe exposure to maleic acid is found to decrease the cellular calcium and thiol levels in human neuronal cells at both transcriptional and functional levels. This study reported the first transcriptomic profiling of human neuronal cells treated with maleic acid. It is also the first experimental validation of chemical effects predicted by in silico toxicogenomics approaches. The proposed approach may be useful in understanding the potential effects of other poorly characterized chemicals on human health.

Dataset Information

Neuroprotective potential of the oxindole alkaloids isomitraphylline and mitraphylline in human neuroblastoma SH-SY5Y cells.

Publications

Neuroprotective potential of the oxindole alkaloids isomitraphylline and mitraphylline in human neuroblastoma SH-SY5Y cells.

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