Neuroprotective effects of silibinin: an in silico and in vitro study

Int J Neurosci. 2018 Oct;128(10):935-945. doi: 10.1080/00207454.2018.1443926. Epub 2018 Mar 15.

Abstract

Aim of the study: Astrogliosis is a key contributor for many neurological disorders involving apoptosis, neuroinflammation and subsequent neuronal death. Silibinin, a polyphenol isolated from milk thistle (Silybum marianum), has been shown to suppress the astrocyte activation in various neurodegenerative disorders and also exhibit a neuroprotective role in neuroinflammation-driven oxidative damage. The present study was designed with an aim to investigate the neuroprotective effects of Silibinin against LPS induced oxido-inflammatory cascade and astrocyte activation.

Materials and methods: We have used in-silico molecular modelling techniques to study the interaction and binding affinity of silibinin with chemokine receptors associated with neuroinflammation. We have also tested silibinin against LPS induced oxido-inflammatory cascade and astrocyte activation in C6 glia cell lines.

Results: In the present study, we found that treatment with silibinin significantly attenuates LPS-oxidative-nitrosative stress in C6 astrocytoma cells. We also observed the significant inhibition of induced astrocyte activity after treatment with silibinin. Moreover, molecular modelling studies have proposed a binding pose of silibinin with binding sites of p38 MAPK, CX3CR1 and P2X4 which is an important downstream cascade involved in glia cell activation and neuroinflammation.

Conclusions: Overall, the findings from the current study suggests that silibinin exhibits neuroprotective activity by attenuating oxidative damage and astrocytes activation.

Keywords: GFAP; Silibinin; lipid peroxidation; neuroinflammation; p38 MAPK.

MeSH terms

  • Astrocytes / drug effects*
  • Cell Line, Tumor
  • Computer Simulation
  • Glial Fibrillary Acidic Protein / drug effects
  • Humans
  • In Vitro Techniques
  • Inflammation / chemically induced
  • Inflammation / drug therapy*
  • Lipid Peroxidation / drug effects*
  • Models, Molecular*
  • Neuroprotective Agents / pharmacology*
  • Oxidative Stress / drug effects*
  • Silybin / pharmacology*
  • p38 Mitogen-Activated Protein Kinases / drug effects

Substances

  • GFAP protein, human
  • Glial Fibrillary Acidic Protein
  • Neuroprotective Agents
  • Silybin
  • p38 Mitogen-Activated Protein Kinases