On the Mechanism of Action of Anti-Inflammatory Activity of Hypericin: An In Silico Study Pointing to the Relevance of Janus Kinases Inhibition

Molecules. 2018 Nov 22;23(12):3058. doi: 10.3390/molecules23123058.

Abstract

St. John's Wort (Hypericum perforatum L.) flowers are commonly used in ethnomedical preparations with promising outcomes to treat inflammation both per os and by topical application. However, the underlying molecular mechanisms need to be described toward a rational, evidence-based, and reproducible use. For this purpose, the aptitude of the prominent Hypericum metabolite hypericin was assessed, along with that of its main congeners, to behave as an inhibitor of janus kinase 1, a relevant enzyme in inflammatory response. It was used a molecular modeling approach relying on docking simulations, pharmacophoric modeling, and molecular dynamics to estimate the capability of molecules to interact and persist within the enzyme pocket. Our results highlighted the capability of hypericin, and some of its analogues and metabolites, to behave as ATP-competitive inhibitor providing: (i) a likely mechanistic elucidation of anti-inflammatory activity of H. perforatum extracts containing hypericin and related compounds; and (ii) a rational-based prioritization of H. perforatum components to further characterize their actual effectiveness as anti-inflammatory agents.

Keywords: Hypericum perforatum; anti-inflammatory activity; hypericin; hypericin metabolites; in silico pharmacodynamics; janus kinase 1.

MeSH terms

  • Adenosine Triphosphate / metabolism
  • Animals
  • Anti-Inflammatory Agents / chemistry
  • Anti-Inflammatory Agents / pharmacology*
  • Binding, Competitive
  • Computer Simulation
  • Hypericum / chemistry
  • Janus Kinase 1 / antagonists & inhibitors*
  • Janus Kinase 1 / chemistry
  • Janus Kinase Inhibitors / chemistry
  • Janus Kinase Inhibitors / pharmacology*
  • Models, Molecular
  • Molecular Docking Simulation
  • Molecular Dynamics Simulation
  • Molecular Structure
  • Perylene / analogs & derivatives*
  • Perylene / chemistry
  • Perylene / pharmacology
  • Plant Extracts / chemistry
  • Plant Extracts / pharmacology

Substances

  • Anti-Inflammatory Agents
  • Janus Kinase Inhibitors
  • Plant Extracts
  • Perylene
  • hypericin
  • Adenosine Triphosphate
  • JAK1 protein, human
  • Janus Kinase 1