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Network pharmacology and bioinformatics approach reveals the therapeutic mechanism of action of curcumin in Alzheimer disease

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Abstract

Curcumin is a natural anti-inflammatory and antioxidant substance which plays a major role in reducing the amyloid plaques formation, which is the major cause of Alzheimer’s disease (AD). Consequently, a methodical approach was used to select the potential protein targets of curcumin in AD through network pharmacology. In this study, through integrative methods, AD targets of curcumin through SwissTargetPrediction database, STITCH database, BindingDB, PharmMapper, Therapeutic Target Database (TTD), Online Mendelian Inheritance in Man (OMIM) database were predicted followed by gene enrichment analysis, network construction, network topology, and docking studies. Gene ontology analysis facilitated identification of a list of possible AD targets of curcumin (74 targets genes). The correlation of the obtained targets with AD was analysed by using gene ontology (GO) pathway enrichment analyses and Kyoto Encyclopaedia of Genes and Genomes (KEGG). We have incorporated the applied network pharmacological approach to identify key genes. Furthermore, we have performed molecular docking for analysing the mechanism of curcumin. In order to validate the temporospatial expression of key genes in human central nervous system (CNS), we searched the Human Brain Transcriptome (HBT) dataset. We identified top five key genes namely, PPARγ, MAPK1, STAT3, KDR and APP. Further validated the expression profiling of these key genes in publicly available brain data expression profile databases. In context to a valuable addition in the treatment of AD, this study is concluded with novel insights into the therapeutic mechanisms of curcumin, will ease the treatment of AD with the clinical application of curcumin.

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Data availability

The data used in the current study available from the corresponding author on reasonable request.

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Acknowledgements

M. A. I. acknowledge University Grant Commission (UGC) for Maulana Azad National Fellowship (candidate ID: MANF-2018-19-BIH-93364).

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Author notes

  1. Deepanshi Vijh and Md. Ali Imam contributed equally to this work.

Authors and Affiliations

  1. Agriculture Plant Biotechnology Lab (ARL-316), University School of Biotechnology, Guru Gobind Singh Indraprastha University, Sector 16-C, Dwarka, New Delhi, 110078, India

    Deepanshi Vijh

  2. Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, New Delhi, 110025, India

    Md. Ali Imam & Asimul Islam

  3. Department of Computer Science, Jamia Millia Islamia, New Delhi, 110025, India

    Mohd Maksuf Ul Haque

  4. National Centre for Cell Science, Pune, Maharashtra, India, 411007

    Subhajit Das

  5. Department of Biotechnology, Jawaharlal Nehru University, New Delhi, 110067, India

    Md. Zubbair Malik

  6. Department of Genetics and Bioinformatics, Dasman Diabetes Institute, P.O. Box 1180, 15462, Dasman, Kuwait

    Md. Zubbair Malik

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  1. Deepanshi Vijh
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  2. Md. Ali Imam
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Contributions

M.Z.M. conceived the model. D.A. M.A.I. and MZ.M. prepared figures of the numerical results. D.A. M.A.I. M.M.U.H. S.D. and M.Z.M. analysed and interpreted the results, D.A. M.A.I., M.M.U.H., S.D., M.A.I. and MZ.M wrote the manuscript. M.A.I and M.Z.M. supervised the study and approved the final draft.

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Correspondence to Md. Zubbair Malik.

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Vijh, D., Imam, M.A., Haque, M.M.U. et al. Network pharmacology and bioinformatics approach reveals the therapeutic mechanism of action of curcumin in Alzheimer disease. Metab Brain Dis 38, 1205–1220 (2023). https://doi.org/10.1007/s11011-023-01160-3

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