High throughput huaman pancreactic lipase screening of natural product library for lipase inhibition activity

Pancreatic lipase, the primary enzyme that is involved in converting dietary triglycerides to monoglycerides and free fatty acids in the digestive system, is considered a validated pharmaceutical target for the treatment of obesity. In order to discover natural lipase inhibitors, a high-throughput (HTP) human pancreatic lipase inhibition assay was developed by utilizing recombinant human pancreatic lipase (hPL). The assay was adapted to a 96-well plate assay format with a Z' value of 0.905. The HTP lipase assay was used to screen 13,979 plant and marine extracts generated from biomasses collected mainly from Asia, North America, and Africa. 1,343 extracts exhibited strong lipase inhibition with in vitro activity over 80%. The primary hits were further filtered by IC₅₀ values, tannin index testing, and HTP screening. The confirmed hits were further studied by following the lipase inhibition activity to isolate and identify active compounds. Active compound enriched plant extracts were prepared and evaluated in high-fat diet (HFD) induced obese animal models for weight loss effects. Two plants Punica granatum and Marchantia polymorpha will be discussed in detail in this presentation.