The multi-protein targeting potential of bioactive syringin in inflammatory diseases: using molecular modelling and in-silico analysis of regulatory elements

J Biomol Struct Dyn. 2024;42(23):12851-12862. doi: 10.1080/07391102.2023.2273440. Epub 2023 Oct 26.

Abstract

Inflammation plays a crucial role in the onset or progression of a variety of acute and chronic diseases. Non-steroidal anti-inflammatory drugs (NSAIDs) are the only available FDA-approved therapy. The therapeutic outcome of NSAIDs is still finite due to off-target effects and extreme side effects on other vital organs. Bioactive syringin has been manifested to hold anti-osteoporosis, cardiac hypertrophy, alter autophagy, anti-cancer, neuro-preventive effects, etc. However, its multi-protein targeting potential in inflammation mostly remains unexplored. In the present work, we have checked the multi-protein targeting potential of bioactive glycoside syringin in inflammatory diseases. Based on the binding score of protein-ligand complexes, glycoside syringin scored greater than -7 kcal/mol against 12 inflammatory proteins. Our molecular dynamic simulation study (200 ns) confirmed that bioactive syringin remained inside the binding cavity of inflammatory proteins (JAK1, TYK2, and COX1) in a stable conformation. Further, our co-expression analysis suggests that these genes play an essential role in multiple pathways and are regulated by multiple miRNAs. Our study demonstrates that bioactive glycoside syringin might be a multi-protein targeting potential against inflammatory diseases and could be further investigated utilizing different preclinical approaches.Communicated by Ramaswamy H. Sarma.

Keywords: GeneMANIA; MD simulation; inflammatory proteins; multi-protein targets; syringin.

MeSH terms

  • Computer Simulation
  • Gene Expression Regulation / drug effects
  • Glucosides / chemistry
  • Glucosides / pharmacology
  • Humans
  • Inflammation* / drug therapy
  • Inflammation* / metabolism
  • Ligands
  • Models, Molecular
  • Molecular Docking Simulation*
  • Molecular Dynamics Simulation*
  • Phenylpropionates / chemistry
  • Phenylpropionates / pharmacology
  • Protein Binding*

Substances

  • syringin
  • Glucosides
  • Ligands
  • Phenylpropionates