Computational Insights into Ludwigia L. Phytochemicals as Potential PDE4B Inhibitors: Molecular Docking and Dynamics Simulations

Abstract

Phosphodiesterase 4B (PDE4B) is an enzyme that regulates inflammatory responses and has recently gained attention as a promising therapeutic target for the treatment of inflammatory diseases. However, the discovery of selective and safe PDE4B inhibitors remains a challenge. The present study aimed to investigate phytochemicals derived from Ludwigia L. as potential PDE4B inhibitors using a combination of computational approaches. A set of compounds was initially screened based on Lipinski’s Rule to assess drug-like properties, with particular emphasis on oral bioavailability and absorption. Toxicity evaluation using LD₅₀ values was performed to categorize the compounds according to safety levels. Molecular docking analysis revealed that several phytochemicals exhibited strong binding affinities toward PDE4B, notably quercetin-3-O-α-L-rhamnoside, luteolin-8-C-glycoside, betulonic acid, (23E)-feruloylhederagenin, and (23Z)-feruloylhederagenin, with compound (23E)-feruloylhederagenin demonstrating the highest docking score (10.88 kcal/mol). Molecular dynamics simulations further confirmed the structural stability of the ligand–protein complexes, with root mean square deviation (RMSD) values consistently below 0.2 nm. Additionally, MMGBSA binding energy calculations supported the strong interaction profile of compound (23E)-feruloylhederagenin, yielding a binding free energy of -54.22 kcal/mol. Taken together, these findings provide computational evidence that Ludwigia L. phytochemicals, particularly (23E)-feruloylhederagenin, represent promising leads for PDE4B inhibition and may serve as valuable candidates for the development of novel anti-inflammatory agents.