ABSTRACT
Pancreatic lipase (PL), a crucial enzyme in the digestive system of mammals, has been proven as a therapeutic target to prevent and treat obesity. The purpose of this study is to evaluate and characterize the PL inhibition activities of the major constituents from Fructus Psoraleae (FP), one of the most frequently used Chinese herbs with lipid-lowering activity. To this end, a total of eleven major constituents isolated from Fructus Psoraleae have been obtained and their inhibition potentials against PL have been assayed by a fluorescence-based assay. Among all tested compounds, isobavachalcone, bavachalcone and corylifol A displayed strong inhibition on PL (IC < 10 μmol·L). Inhibition kinetic analyses demonstrated that isobavachalcone, bavachalcone and corylifol A acted as mixed inhibitors against PL-mediated 4-methylumbelliferyl oleate (4-MUO) hydrolysis, with the K values of 1.61, 3.77 and 10.16 μmol·L, respectively. Furthermore, docking simulations indicated that two chalcones (isobavachalcone and bavachalcone) could interact with the key residues located in the catalytic cavity of PL via hydrogen binding and hydrophobic interactions. Collectively, these finding provided solid evidence to support that Fructus Psoraleae contained bioactive compounds with lipid-lowering effects via targeting PL, and also suggested that the chalcones in Fructus Psoraleae could be used as ideal leading compounds to develop novel PL inhibitors.
ABSTRACT
PURPOSE: Caffeine is the most widely consumed psychostimulant. It is often adopted as a tool to modulate brain activations in fMRI studies. However, its pharmaceutical effect on task-induced deactivation has not been fully examined in fMRI. Therefore, the purpose of this study was to examine the effect of caffeine on both activation and deactivation under sustained attention. MATERIALS AND METHODS: Task fMRI was acquired from 26 caffeine naive healthy volunteers before and after taking caffeine pill (200 mg). RESULTS: Statistical analysis showed an increase in cognition-load dependent task activation but a decrease in load dependent de-activation after caffeine ingestion. Increase of attention and memory task activation and its load-dependence suggest a beneficial effect of caffeine on the brain even though it has no overt behavior improvement. The reduction of deactivation by caffeine and its load-dependence indicate reduced facilitation from task-negative networks. CONCLUSION: Caffeine affects brain activity in a load-dependent manner accompanied by a disassociation between task-positive network and task-negative network.