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

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:

• Silibinin
• p38 MAPK
• neuroinflammation
• lipid peroxidation
• GFAP

Acknowledgments

The authors want to express their thanks to the Director, NIPER-Ahmedabad for providing necessary facilities and infrastructure.

Disclosure statement

The authors have no conflict of interest to declare.

Additional information

Funding

This work is supported by Department of Pharmaceuticals, Ministry of Chemicals and Fertilizers, Government of India, National Institute of Pharmaceutical Education and Research (NIPER)-Ahmedabad, Gandhinagar, Gujarat, India and Department of Science and Technology (DST), Government of India, Early Career Research Grant [grant number ECR/2016/001846] awarded to Dr Vinod Tiwari.