Optimized extraction, enrichment, identification and pancreatic lipase inhibition of triterpenic acids from Ziziphus jujuba Mill.

Jujube (Ziziphus jujuba Mill.) is rich in bioactive triterpenic acids, but their efficient extraction and pancreatic lipase (PL) inhibition mechanisms remain unclear. Cellulase-assisted ultrasonic extraction was optimized, and the enriched fraction was purified, identified by UPLC-MS/MS, and assessed for PL inhibition by docking and 100 ns molecular dynamics (MD). It afforded a yield of 48.52 ± 0.4 mg/g and purified-fraction purity of 75.82% ± 1.11%, with 14 triterpenic acids identified and eight monomers quantified. The fraction was a reversible mixed-type PL inhibitor, acting dose-dependently (IC₅₀ = 113.47 μg/mL); corosolic and maslinic acids were the most potent monomers, whereas 3-oxo monomers were far less active. Docking indicated stable binding within the PL hydrophobic pocket via hydrogen bonds and hydrophobic interactions, while MD simulations further revealed why: the C3 hydroxyl acts as a hydrogen-bond donor maintaining the planar A-ring trans-conformation (circular SD ∼6°, R ∼ 0.995), whereas 3-oxo oxidation induces torsional distortion (31-45°) and weakens binding in a skeleton-dependent manner. This work thus enables efficient high-purity enrichment and, for the first time, unravels the PL inhibitory mechanism at static and dynamic levels, establishing the C3 hydroxyl as the key structural determinant and supporting these compounds as natural lipid-lowering ingredients.