Psoriasis, a chronic immune-mediated disorder of the skin, shows growing evidence of upregulated Src family tyrosine kinases (SFK). The SFK is known to be the keys to the signalling pathways triggering cell growth and differentiation in addition to the immune cascades. 

Sundarrajan S. et al studied the interactions between SFK and selective Phyto-compounds using a molecular docking approach. through their study, they identified quercetin as a potential lead compound. 

They studied the binding of quercetin with the SFK, utilizing a combined molecular dynamics and binding free energy calculations and found that the binding of quercetin disrupted the intra-molecular contacts creating the SFK compact except for Src kinase. 

The MM/PBSA free energy decomposition analysis explained the role of hydrophobic and polar residues, involved in the binding of quercetin. 

Validation was performed against the top three proteins showing a high preference for quercetin, i.e. the activated forms of Fyn, Lyn and Src kinases.

The flow cytometry analysis in HaCaT cells showed a drastic increase in expression levels of Fyn, Lyn and Src kinases, But their decreased expression on the treatment of quercetin at the concentration of 51.65 µM for 24 h.

Treatment of HaCat Cells with the kinase inhibitor Ponitinib (1.43 µM) for 24 h too yielded similar results.

Source: Sundarrajan S, Nandakumar MP, Prabhu D, Jeyaraman J, Arumugam M. Conformational insights into the inhibitory mechanism of Phyto-compounds against Src kinase family members implicated in psoriasis. J Biomol Struct Dyn. 2020 Mar;38(5):1398-1414. doi: 10.1080/07391102.2019.1605934. Epub 2019 Apr 30. PMID: 30963942.