Uncovering the Pharmacological Mechanism of Stemazole in the Treatment of Neurodegenerative Diseases Based on a Network Pharmacology Approach

Zhang, Jing; Li, Huajun; Zhang, Yubo; Zhao, Chenyang; Zhu, Yizi; Han, Mei

doi:10.3390/ijms21020427

Cited by 17 publications

(14 citation statements)

References 66 publications

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“…In this study, we used network pharmacology to identify the core targets of vitamin C with therapeutic potential for CVD and performed GO BP and KEGG enrichment analyses. Bioinformatics findings can reveal the proposed pharmacological mechanism and strengthen the new ideas for CVD treatment ( Zhang et al, 2020 ).…”

Section: Discussionmentioning

confidence: 91%

Targets of Vitamin C With Therapeutic Potential for Cardiovascular Disease and Underlying Mechanisms: A Study of Network Pharmacology

2021

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Vitamin C (ascorbic acid) is a nutrient used to treat cardiovascular disease (CVD). However, the pharmacological targets of vitamin C and the mechanisms underlying the therapeutic effects of vitamin C on CVD remain to be elucidated. In this study, we used network pharmacology approach to investigate the pharmacological mechanisms of vitamin C for the treatment of CVD. The core targets, major hubs, enriched biological processes, and key signaling pathways were identified. A protein-protein interaction network and an interaction diagram of core target-related pathways were constructed. Three core targets were identified, including phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform, signal transducer and activator of transcription-3 (STAT3), and prothrombin. The GO and KEGG analyses identified top 20 enriched biological processes and signaling pathways involved in the therapeutic effects of vitamin C on CVD. The JAK-STAT, STAT, PD1, EGFR, FoxO, and chemokines signaling pathways may be highly involved in the protective effects of vitamin C against CVD. In conclusion, our bioinformatics analyses provided evidence on the possible therapeutic mechanisms of vitamin C in CVD treatment, which may contribute to the development of novel drugs for CVD.

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Section: Discussionmentioning

confidence: 91%

Targets of Vitamin C With Therapeutic Potential for Cardiovascular Disease and Underlying Mechanisms: A Study of Network Pharmacology

2021

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“…Previous pharmacological mechanistic investigations of stemazole based on a network pharmacology approach identified caspase-3, caspase-8, AKT1, MAPK8, MAPK14 as the possible direct targets of stemazole and as being enriched in MAPK signalling, which is highly relevant to the occurrence and progression of neurodegenerative diseases [16]. While in this study the possible target proteins has no significant difference between the two groups.…”

Section: Discussionmentioning

confidence: 47%

“…Research on the direct targets and the underlying mechanisms of stemazole through network pharmacology was conducted. The five critical targets were identified, including caspase-3 (CASP3), caspase-8 (CASP8), RAC-alpha serine/threonine-protein kinase (AKT1), mitogen-activated protein kinase 8 (MAPK8) and mitogen-activated protein kinase 14 (MAPK14), and the mitogen-activated protein kinase (MAPK) signalling pathway was eventually screened out [16].…”

Section: Introductionmentioning

confidence: 99%

A quantitative proteomics analysis for small molecule Stemazole’s effect on human neural stem cells

Zhang

et al. 2020

Proteome Sci

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Background Stemazole is a novel small molecule that has been suggested to have the ability to protect multiple stem cells. The proliferation-promoting activity and promising neuroprotective effects of stemazole make it a prospective drug for neurodegenerative disease treatment. Methods Since previous studies have shown that it protective effect in extreme conditions, to understand more aspects of stemazole, in this study, a systematic tandem mass tags (TMT)-labelled proteomics approach was used to address the whole proteome expression profile with or without stemazole in normal conditions instead of extreme conditions. Bioinformatics analyses, including Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment and protein-protein interaction (PPI) network analyses, were employed. Results The effect of stemazole on the expression profiles of neural stem cells was obtained. A total of 408 proteins with changes at the abundance level of two groups were identified: 178 proteins increase in abundance and 240 proteins decrease in abundance, respectively. Low abundance of some mitochondrial respiratory chain enzyme, overproduction of reactive oxygen species (ROS) and reduction of mitochondrial membrane potential may indicate stemazole has cytotoxicity. Conclusions It is the first proteomics research about stemazole, and the possible cytotoxicity of stemazole has been reported for the first time. The information about proteins that were affected by stemazole and more characteristics of stemazole will help obtain a complete picture of this small molecule drug. These findings provide a scientific basis for further stemazole treatment research.

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“…The collected traditional Chinese medicine compounds and effective targets are constructed by Cytoscape 3.7.2 software ( http://www.cytoscape.org/ ) to construct a compound-target network, The CytoNCA plugin (v2.1.6) was used to measure the topology scores of the nodes, including the betweenness, closeness, and subgraph centrality. The option “without weight” was selected ( Zhang et al, 2020 ).…”

Section: Methodsmentioning

confidence: 99%

Network Pharmacology and Molecular Docking on the Molecular Mechanism of Luo-hua-zi-zhu (LHZZ) Granule in the Prevention and Treatment of Bowel Precancerous Lesions

et al. 2021

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The Luo-hua-zi-zhu (LHZZ) granule has been widely used for the treatment of colorectal adenoma (CRA), which is a precursor of colorectal cancer (CRC). However, the active components of LUZZ and its mechanism of action against CRA have not yet been elucidated. This study was designed to investigate the effect of LHZZ on CRA and explore its pharmacological mechanisms. First, a total of 24 chemical constituents were identified in the 50% aqueous methanol extract of LHZZ granule based on the mass fragment patterns and mass spectral library using the high resolution UPLC-Q-TOF MS/MS system. Subsequently, based on a network pharmacology study, 16 bioactive compounds and 28 targets of the LHZZ associated with CRA were obtained, forming a compound-target network. Molecular docking tests showed tight docking of these compounds with predicted targeted proteins. The protein–protein interaction (PPI) network identified AKT1, CASP3, TP53 and EGFR as hub targets. The Kyoto Encyclopedia of Genes and Genomes pathway network and pathway-target-compound network revealed that the apoptosis pathway was enriched by multiple signaling pathways and multiple targets, including the hub targets. Finally, the reliability of the core targets was evaluated using molecular docking technology and in vitro studies. Our study indicated that the LHZZ particle has preventive and treatment effect on colorectal adenoma through multi-component, multi-target and multi-pathway.

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Uncovering the Pharmacological Mechanism of Stemazole in the Treatment of Neurodegenerative Diseases Based on a Network Pharmacology Approach

Cited by 17 publications

References 66 publications

Targets of Vitamin C With Therapeutic Potential for Cardiovascular Disease and Underlying Mechanisms: A Study of Network Pharmacology

Targets of Vitamin C With Therapeutic Potential for Cardiovascular Disease and Underlying Mechanisms: A Study of Network Pharmacology

A quantitative proteomics analysis for small molecule Stemazole’s effect on human neural stem cells

Network Pharmacology and Molecular Docking on the Molecular Mechanism of Luo-hua-zi-zhu (LHZZ) Granule in the Prevention and Treatment of Bowel Precancerous Lesions

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