<i>In Silico</i> ADME, Molecular Targets, Docking and Molecular Dynamics Simulation of Key Phytoconstituents of <i>Lobelia inflata</i>

Lobelia inflata is a remarkable member of the Lobelia family, and it possesses diverse therapeutic properties such as anticancer, anti-neurodegenerative and antimicrobial effects. This study aimed to computationally explore the pharmacological potential of L. inflata phytochemicals. The methods used are pharmacokinetic predictions, target predictions, gene network analysis, molecular docking and molecular dynamics (MD) simulation. The findings revealed that all phytoconstituents have blood-brain barrier (BBB) permeability and high gastrointestinal absorption (GIA). Synaptic vesicular amine transporter 2 (VMAT2) and ceramide transfer protein (CERT) emerged as key human molecular targets of these phytoconstituents. The binding affinity of lobelanidine and norlobelanine for CERT was −9.027 kcal ⋅ mol[Formula: see text] and −7.537 kcal ⋅ mol[Formula: see text] respectively, while (+)-lobinaline and lobeline have binding affinity of −6.897 kcal ⋅ mol[Formula: see text] and −6.724 kcal ⋅ mol[Formula: see text],[Formula: see text] respectively for VMAT2. MD simulation and molecular mechanics/generalized Born surface area (MMGBSA) calculations highlighted the stability and energetically favorable nature of the lobelanidine-VMAT2 and Lobelanidine-CERT complexes. This study underscores the potential of L. inflata in modulating CERT and VMAT2 targets in cancer and neurodegenerative diseases, respectively. There is a need for further validation of these results through additional research endeavors.