Abstract

Phosphodiesterase 4B (PDE4B) inhibitors increase cAMP levels and are used commonly as a therapeutic option in various inflammatory diseases. However, their adverse effects are serious and well known. Natural inhibitors of PDE4B receptor are advantageous since they are safer and exhibit specific activity on PDE4B. Psoralea corylifolia (Bakuchi), is reported to be useful in treatment of psoriasis, leukoderma and vitiligo. The goal of this study is to predict the mechanism of action of phytoconstituents of Bakuchi and to provide scientific justification for their anti-psoriatic potential. Molecular docking studies were conducted on the phytoconstituents of bakuchi seeds and apremilast. Docking score between the PDE4B receptor and these ligands was calculated. The phytoconstituents’ Glide energy, binding free energy, hydrogen bond, and hydrophobic interactions with PDE4B were compared to those of the receptor-apremilast complex. The anti-inflammatory efficacy of the plant extract was tested using ELISA andmouse RAW 264.7 cell line. The phytoconstituents namely, neobavaisoflavone, bavachinin, and bavachalcone exhibited higher docking score, Glide energy, and binding free energy than the reference molecule, apremilast. Furthermore, the phytoconstituents’ hydrogen bond and hydrophobic interactions with active site residues of PDE4B were robust. According to the findings, phytoconstituents in bakuchi seeds block active PDE4B sites. The phytoconstituents from Psoralea corylifolia seeds bind to PDE4B and function as strong PDE4B inhibitors. Bakuchi seed extract inhibited pro-inflammatory cytokines and stimulated anti-inflammatory cytokine in dose-dependent manner. The anti-psoriatic potential of Psoralea corylifolia is attributed to inhibition of PDE4B.