In Silico ADME, Molecular Targets, Docking and Molecular Dynamics Simulation of Key Phytoconstituents of Lobelia inflata.

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 − 1 and −7.537 kcal ⋅ mol − 1 respectively, while (+)-lobinaline and lobeline have binding affinity of −6.897 kcal ⋅ mol − 1 and −6.724 kcal ⋅ mol − 1 , 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. 1. Lobelia inflata, a member of the Lobelia family, is recognized for its therapeutic versatility, showing significant potential against cancer, neurodegenerative disorders, and microbial infections. 2. This study employed advanced computational methods, including pharmacokinetic predictions and molecular docking, to explore the pharmacological potential of L. inflata phytochemicals. 3. Key human targets identified for L. inflata phytochemicals include synaptic vesicular amine transporter 2 (VMAT2) and ceramide transfer protein (CERT), both of which are critical in neurodegenerative diseases and cancer. 4. The findings reveal promising interactions of lobelanidine and other phytoconstituents with VMAT2 and CERT, suggesting their potential therapeutic roles, pending further experimental validation. [ABSTRACT FROM AUTHOR]