Background: Overly-activated microglia are known to be the culprit in chronic neuroinflammation in the presence of excessive lipopolysaccharide (LPS). Hence, abundance of pro-inflammatory cytokines are produced which later cause toxic and death to neurons. Tolllike receptor 4 (TLR4)/MD-2 complex found on the cell surface of microglia is responsible for the attachment of LPS and activation of nuclear factor-κB (NF-κB) downstream signalling pathway. Albeit vitexin has been shown to possess anti-inflammatory property, however, little is known on its ability to bind at the TLR4/MD-2 complex of microglia as well as to be an antagonist for LPS.
Results: The molecular docking result shows that both vitexin and donepezil are able to bind at the close proximity of LPS binding site located at the TLR4/MD-2 complex with the binding energy of -4.35 and -9.14 kcal/mol, respectively. During molecular dynamic simulations, both vitexin and donepezil formed stable complex with TLR4/MD-2 throughout the 20 ns time length with the RMSD values of 1.9Å and 2.0Å, respectively. As for the RMSF, both compounds have the RMSF values of <1.2Å.
Conclusions: Taken together, our results suggest that vitexin can be a potential antineuroinflammatory drug candidate by acting as an antagonist for LPS at the TLR4/MD-2 complex.