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Effects of ?-Mangostin Derivatives on the Alzheimer's Disease Model of Rats and Their Mechanism: A Combination of Experimental Study and Computational Systems Pharmacology Analysis.

ABSTRACT: ?-Mangostin (?-M) is a natural xanthone from the pericarp of fruit Garcinia mangostana and possesses versatile biological activities. ?-M has a therapeutic potential to treat Alzheimer's disease (AD) because of its anti-inflammatory, antioxidative, and neuroprotective activities. However, the use of ?-M for AD treatment is limited due to its cytotoxic activities and relatively low potency. Modifications of its chemical structure were needed to reduce its cytotoxicity and improve its therapeutic potential against AD. For this purpose, 16 ?-M carbamate derivatives were synthesized. An animal model of AD was established, and the effects of AMG-1 on the spatial learning ability and memory ability were evaluated using behavioral tests. The effect on neuropathology was tested by histopathological evaluation, Nissl staining, and silver staining. Computational systems pharmacology analysis using the chemogenomics knowledgebase was applied for network studies. Compound-target, target-pathway, and target-disease networks were constructed, integrating both in silico analysis and reported experimental data. The results show that AMG-1 can demonstrate its therapeutic effects in a one-molecule, multiple-targets manner to remarkably ameliorate neurological changes and reverse behavioral deficits in AD model rats. The improved cognitive function and alleviated neuronal injury can be observed. The ability of AMG-1 to scavenge ?-amyloid in the hippocampus was validated in AD model rats.

SUBMITTER: Chen Y

PROVIDER: S-EPMC7203693 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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Effects of α-Mangostin Derivatives on the Alzheimer's Disease Model of Rats and Their Mechanism: A Combination of Experimental Study and Computational Systems Pharmacology Analysis.

Chen Yan Y Bian Yuemin Y Wang Jian-Wei JW Gong Ting-Ting TT Ying You-Min YM Ma Lie-Feng LF Shan Wei-Guang WG Xie Xiang-Qun XQ Zhan Zha-Jun ZJ

ACS omega 20200423 17

α-Mangostin (α-M) is a natural xanthone from the pericarp of fruit <i>Garcinia mangostana</i> and possesses versatile biological activities. α-M has a therapeutic potential to treat Alzheimer's disease (AD) because of its anti-inflammatory, antioxidative, and neuroprotective activities. However, the use of α-M for AD treatment is limited due to its cytotoxic activities and relatively low potency. Modifications of its chemical structure were needed to reduce its cytotoxicity and improve its thera ...[more]

PMID: 32391472

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Dataset Information

Effects of ?-Mangostin Derivatives on the Alzheimer's Disease Model of Rats and Their Mechanism: A Combination of Experimental Study and Computational Systems Pharmacology Analysis.

Publications

Effects of α-Mangostin Derivatives on the Alzheimer's Disease Model of Rats and Their Mechanism: A Combination of Experimental Study and Computational Systems Pharmacology Analysis.

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