Background: Matrix metalloproteinase-9 (MMP-9) expression is elevated in neurological
diseases, and its up-regulation may exert to the pathogenesis of many neurological disorders.
Therefore, inhibition of MMP-9 can be of neuroprotective approach.
Objective: The present in silico study carried out to explore the possible neuroprotective potential of
Withania somnifera phytochemicals through inhibition of MMP-9.
Method: Twenty-seven Withania somnifera phytochemicals were selected for this study based on
their BBB penetration ability and suitability for Lipinski's rule of five. Further, molecular docking
was performed to know whether these phytochemicals inhibit the MMP-9 or not.
Results: The results suggest that 17 phytochemicals have the higher affinity for S1'-specificity pocket
of the MMP-9 catalytic domain than two inhibitors reverse hydroxamate and quercetin. Because of
they directly bound to the active site with lower binding energy and established some hydrogen bonds
and hydrophobic interactions with residues critical in mediating inhibition.
Conclusion: These phytochemicals have potential as an intrinsically useful oral drug to combat
neurological disorders mediated by MMP-9.