Leveraging Natural Compounds for Pancreatic Lipase Inhibition via Virtual Screening.

Area of Science:

• Biochemistry
• Pharmacology
• Computational Chemistry

Background:

• Pancreatic lipase (PL) is crucial for dietary fat digestion and absorption.
• Increased PL activity contributes to obesity and related metabolic disorders.
• Inhibiting PL is a recognized strategy for obesity management.

Purpose of the Study:

• To identify natural compounds that inhibit pancreatic lipase (PL).
• To explore plant-derived molecules as potential anti-obesity agents.

Main Methods:

• Structure-Based Virtual Screening (SBVS) of the PhytoHub database against PL.
• Filtering compounds using binding affinity, Lipinski's Rule of Five, and clustering.
• In vitro enzymatic assays and molecular dynamics simulations.

Main Results:

• Six lead compounds were identified from over 10,000 phytochemicals.
• Pinoresinol demonstrated the strongest pancreatic lipase inhibitory activity.
• Molecular simulations confirmed stable interactions of inhibitors with PL catalytic residues.

Conclusions:

• An integrated computational and experimental approach identified novel natural PL inhibitors.
• Pinoresinol and other identified compounds are promising candidates for developing plant-derived anti-obesity drugs.