Network Pharmacology Approach Uncovering Pathways Involved in Targeting Hsp90 Through Curcumin and Epigallocatechin to Control Inflammation

Curr Drug Discov Technol. 2021;18(1):127-138. doi: 10.2174/1570163816666191210145652.

Abstract

Aims: To fetch pathways involved in targetting Hsp90 through Curcumin and Epigallocatechin through Network pharmacological approach.

Background: Hsp90 is a molecular chaperone involved in stabilizing inflammatory protein which may lead to chronic diseases. The herbal compounds Curcumin and Epigallocatechin processing antiinflammatory properties are known to follow a common pathway and control the expression of Hsp90.

Objective: To collect the gene targets of Hsp90, Curcumin and Epigallocatechin in order to understand protein-protein interactions of gene targets by constructing the interactome to identify the hub proteins. Hub proteins docking was performed with curcumin and epigallocatechin. Finally, hub proteins involvement with various human diseases were identified.

Methods: The gene targets of Hsp90, Curcumin and Epigallocatechin were obtained from there respective databases. Protein-protein interactions of Pkcδ-Nrf2 and Tlr4 pathway gene targets were collected from String database. Protein interaction network was constructed and merged to get intercession network in cytoscape and Cluego was used to predict the disease related target genes. Docking of ligands to target proteins was carried out using Autodock vina tool.

Result: The main key regulators of Curcumin and Epigallocatechin were identified particularly from Pkcδ-Nrf2 and Tlr4 pathway.

Conclusion: The combined action of Curcumin and Epigallocatechin can reduce the expression of Hsp90 eventually controlling the inflammation.

Keywords: EGC; HO-1; Hsp90; Pkcδ-Nrf2; Tlr4; curcumin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Inflammatory Agents / pharmacology
  • Catechin / analogs & derivatives*
  • Catechin / pharmacology
  • Curcumin / pharmacology*
  • Drug Synergism
  • Flavonoids / pharmacology
  • HSP90 Heat-Shock Proteins / metabolism*
  • Humans
  • Inflammation* / drug therapy
  • Inflammation* / metabolism
  • Molecular Chaperones / metabolism
  • Molecular Docking Simulation / methods
  • NF-E2-Related Factor 2 / metabolism*
  • Network Pharmacology / methods
  • Protein Interaction Mapping / methods
  • Protein Kinase C-delta / metabolism*
  • Signal Transduction / drug effects
  • Toll-Like Receptor 4 / metabolism*

Substances

  • Anti-Inflammatory Agents
  • Flavonoids
  • HSP90 Heat-Shock Proteins
  • Molecular Chaperones
  • NF-E2-Related Factor 2
  • NFE2L2 protein, human
  • TLR4 protein, human
  • Toll-Like Receptor 4
  • Catechin
  • Protein Kinase C-delta
  • gallocatechol
  • Curcumin