Abstract
The results of in silico screening of the 50 isolated compounds from Millettia dielsiana against the target proteins PDE4 (PDE4A, PDE4B, and PDE4D) showed binding affinity ranges from -5.81 to -11.56, -5.27 to -13.01, and -5.80 to -12.12 kcal mol(-1), respectively, with median values of -8.83, -8.84, and -8.645 kcal mol(-1), respectively. Among these compounds, Millesianin F was identified as the most promising PDE4A inhibitor due to its strongest binding affinity with the target protein PDE4A. (-11.56 kcal mol(-1)). This was followed by the compound 5,7,4'-trihydroxyisoflavone 7-O-β-d-apiofuranosyl-(1→6)-β-d-glucopyranoside (D50) with the binding affinity value of -11.35 kcal mol(-1). For the target protein PDE4B, compound D50 exhibited the strongest binding affinity value of -13.01 kcal mol(-1), while showing poorer inhibition ability for PDE4D. The 100 ns MD simulation examination (radius of gyration, Solvent Accessible Surface Area (SASA), Root-Mean-Square Deviation (RMSD), Root-Mean-Square Fluctuation (RMSF), and hydrogen bonding) was carried out to examine the overall stability and binding efficiency of the protein-ligand complex between compounds (Millesianin F, Millesianin G, Claclrastin-7-O-β-d-glucopyranoside, 7-hydroxy-4',6 dimethoxyisoflavone-7-O-β-d-apiofuranosyl-(1→6)-β-d-glucopyranoside, 7-hydroxy-4',8-dimethoxyisoflavone 7-O-β-d-apiofuranosyl-(1→6)-β-d-glucopyranoside, Odoratin-7-O-β-d-glucopyranoside, and 5,7,4'-trihydroxyisoflavone 7-O-β-d-apiofuranosyl-(1→6)-β-d-glucopyranoside) and PDE4 (A, B) subtype proteins. Compound D50 has shown strong anti-inflammatory activity, as evidenced by experimental results. It effectively inhibits PDE4B and PDE4D, with IC(50) values of 6.56 ± 0.7 µM and 11.74 ± 1.3 µM, respectively. Additionally, it reduces NO production, with an IC(50) value of 5.40 ± 0.9 µM. Based on these findings, it is promising and considered a potential novel anti-inflammatory drug for future development.