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 lipase activity.

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.

背景：提出了一些副作用较小的天然胰腺脂肪酶抑制剂。作为传统中药，双丹胶囊（SDC）已被用于治疗血液中的高血脂，其主要成分为丹参和牡丹皮。

目的：这项工作旨在研究该SDC中各成分对抗代谢异常的分子机制，这些成分在活性位点的分子柔性和分子间相互作用特征。

方法：从中药数据库中药数据库中提取小分子，用中药TCMSP服务器的系统级药理数据库计算ADME的相关性质。Autodock Vina用于对所选分子进行虚拟筛选，并以几种配体构象返回能量值。使用Cytoscape中的网络分析器插件计算网络参数。

结果：活性最高的六个分子全部被氨基酸ASP79，TYR114，GLU175，PRO180，PHE215，GLY216和LUE264包围，其中疏水相互作用，氢键和排斥力起着极其重要的作用。值得注意的是，范德华表面（vdW）上大多数分子静电势的局部最小值增加，而负负最大值同时减小，这表明静电势趋于稳定。通过蛋白质-蛋白质相互作用（PPI）网络的拓扑分析，PNLIP相关基因也被证明是高脂血症的关键靶标，例如LPL，AGK，MGLL，LIPE，LIPF和PNPLA2。进一步的GO分析表明，亲脂性萜类化合物可通过参与脂质分解代谢过程来降低血脂，

结论：该研究为天然降血脂药的开发和应用提供了一些有用的信息。体内和体外仍需要进一步的药理活性研究。