Rapid screening natural-origin lipase inhibitors from hypolipidemic decoctions by ultrafiltration combined with liquid chromatography–mass spectrometry

• Developed a rapid approach for screening lipase inhibitors from four TCM formulae by combing LC–MS with ultrafiltration.
• Sixteen natural-origin lipase inhibitors was discovered and identified by high resolution and multistage mass spectrometry.
• Inhibitory activities of two compounds were confirmed in a functional assay of lipase.
• Molecular docking simulations were performed to investigate potential mechanism of action for these compounds.

Lipase inhibitors generate hypolipidemic effect that is helpful to control or treat some obesity diseases by inactivating catalytic activity of human pancreatic lipase, a key enzyme involved in triglyceride hydrolysis in vivo. Many traditional Chinese medicine (TCM) formulae have been effectively used to treat obesity and other fat related diseases for centuries and modern biological experiments demonstrate therapeutic effect of these formulae can be linked to their lipid-lowering capability in blood. These observations suggest that these hypolipidemic decoctions (HDs) could be a promising resource of natural-origin lipase inhibitors. This work described a rapid approach for screening lipase inhibitors from four widely used HDs, including Wu-Ling-San (WLS), Ze-Xie decoction (ZX), Xiao-Xian-Xiong decoction (XXX) and Xiao-Chai-Hu decoction (XCH), by ultrafiltration combing with high performance liquid chromatography–mass spectrometry (HPLC–MS). Our results showed sixteen natural-origin lipase inhibitors were discovered and identified by high resolution and multistage mass spectrometry. Inhibitory activities of two compounds were confirmed by a functional assay of lipase, which validated the reliability of our approach. Molecular docking simulation was then performed to investigate potential mechanism of action for these compounds. Together we present an efficient method for rapid screening lipase inhibitors from complex natural products, which can be easily accommodated to other important enzymatic system with therapeutic values.

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