Effects of Octacosanol Isolated from <i>Moringa oleifera</i> Leaves on Inhibiting the Activity of Pancreatic Lipase

<i>Moringa oleifera</i> Lam., a perennial species of the Moringaceae family, is esteemed for its multifaceted nutritional, medicinal, and economic properties. <i>M. oleifera</i> leaves are abundant in bioactive compounds with potential health benefits, yet existing structural and functional studies of these bioactives remain insufficiently comprehensive. This study aimed to isolate the active compound from <i>M. oleifera</i> leaves and investigate its mechanism of inhibiting lipid absorption and its potential as a pancreatic lipase inhibitor. In the present study, octacosanol (OCT) was isolated and purified from <i>M. oleifera</i> leaves, demonstrating notable pancreatic lipase inhibitory activity with an IC₅₀ of 7.87 ± 0.72 μg/mL, and effectively suppressing lipid uptake in HepG2 cells. Simulated digestion assays indicated that OCT retained 73.5% of its pancreatic lipase inhibitory activity, with a recorded inhibition rate of 63.62%. Molecular docking analyses revealed that OCT binds to pancreatic lipase with an affinity comparable to orlistat and stronger than that of 4-nitrophenyl palmitate. The binding of OCT to key active sites (Ser152, His263, and Asp176) likely disrupts the enzyme's conformation, decreasing its substrate affinity. Additionally, OCT significantly attenuated lipid absorption and the synthesis of total cholesterol and triglycerides. This study elucidates the lipid-lowering mechanism of OCT and provides a theoretical foundation for its potential application in food production and biomedicine.