Background: Some natural pancreatic lipase inhibitors with fewer side effects are proposed.
As a traditional Chinese medicine, Shuangdan Capsule (SDC) has been used for the treatment
of higher lipid in blood, which is mainly composed by Radix Salviae and Peony skin.
Objective: This work is aimed to investigate the molecular mechanism of the constituents from this
SDC against metabolic disorders, the molecular flexibility and intermolecular interactional characteristics
of these components in the active sites.
Methods: The small molecules were obtained from the Traditional Chinese Medicine Database
TCM database, the systems-level pharmacological database for Traditional Chinese Medicine
TCMSP server was used to calculate the ADME-related properties. Autodock Vina was used to
perform virtual screening of the selected molecules and to return energy values in several ligand
conformations. The network parameters were calculated using the network analyzer plug-in in Cytoscape.
Results: The most active six molecules are all enclosed by amino acids ASP79, TYR114,
GLU175, PRO180, PHE215, GLY216 and LUE264, among which, hydrophobic interaction, hydrogen
bond and repulsive forces play extremely important roles. It is worth noting that most of
the local minima of molecular electrostatic potentials on van der Waals (vdW) surface are increased
while the maxima negative ones are decreased simultaneously, implying that the electrostatic
potential tends to be stable. From the topological analysis of the Protein-Protein Interaction
(PPI) network, PNLIP related genes are also proved to be pivotal targets for hyperlipidemia, such
as LPL, AGK, MGLL, LIPE, LIPF and PNPLA2. Further GO analysis indicated that lipophilic
terpenoid compounds may reduce the blood lipid by taking part in the lipid catabolic process, the
extracellular space and the cellular components of the extracellular region part and the triacylglycerol
Conclusion: This study provides some useful information for the development and application of
natural hypolipidemic medcines. Further pharmacologically active studies are still needed both in
vivo and in vitro.