Investigation of Active Compounds of Brucea Javanica In Treating Hypertension Using A Network Pharmacology-Based Analysis Combined with Homology Modeling, Molecular Docking and Molecular Dynamics Simulation

Hypertension is a disease that can increase the risk of stroke, cardiovascular, and heart failure. In this letter, we investigated the potency of active compounds of Brucea javanica (BJ) in treating hypertension by using network pharmacology combined with several in silico approaches, including molecular docking, homology modeling and molecular dynamics (MD) simulations. Twenty protein targets at the intersection of BJ and hypertension were identified by using network pharmacology. We found that peroxisome proliferator-activated receptor gamma (PPARG) was the first-degree rank that might strongly connect with the disease. Therefore, the tertiary structure of PPARG, generated using homology modeling, was assigned as a receptor. In docking analysis, two ligands, i. e., Javanicin and Yadanziolide A, could be potential inhibitors for PPARG due to the higher binding energy score than the control (Hydrochlorothiazide). To confirm the stability of the ligand-receptor complex in water solvent, MD simulation was performed. We found that complexes 1 and 2 reached stable structures during the simulation indicated by no significant fluctuation in the validation parameters. Furthermore, based on the binding energies calculated by Molecular Mechanics-Generalized Born Surface Area (MM-GBSA), we confirm that the ligands of these complexes strongly bind to the catalytic site of the receptor. This points out the potency of these complexes as promising drugs against hypertension targeting PPARG.

Automated summary

This study investigated the potential of Brucea javanica in treating hypertension using network pharmacology and computational simulations. Two compounds from Brucea javanica were identified as potential inhibitors for peroxisome proliferator-activated receptor gamma (PPARG), a protein strongly associated with hypertension. Molecular dynamics simulations confirmed the stability of the ligand-receptor complex and the strong binding of the ligands to the catalytic site of PPARG. These findings suggest the potential of these compounds as promising drugs for hypertension.