Efficient screening of pancreatic lipase inhibitors from Rheum palmatum by affinity ultrafiltration–high‐performance liquid chromatography combined with high‐resolution inhibition profiling
Sihua Quan, Mengyi Wen, Ping Xu, Chu Chu, Hui Zhang, Kai Yang, Shengqiang Tong - Complementary and alternative medicine
- Drug Discovery
- Plant Science
- Molecular Medicine
- General Medicine
- Biochemistry
- Food Science
- Analytical Chemistry
Abstract
Introduction
Pancreatic lipase is one of the most important key targets in the treatment of obesity. Inhibition of pancreatic lipase can effectively reduce lipid absorption and treat obesity and other related metabolic disorders.
Objectives
The goal of this study is the efficient screening of pancreatic lipase inhibitors in the root and rhizome of
Methods
Potential pancreatic lipase ligands and pancreatic lipase inhibitors in ethyl acetate fraction of
Results
Five new potent pancreatic lipase inhibitors were discovered, namely procyanidin B5 3,3′‐di‐O‐gallate (IC50 = 0.06 ± 0.01 μM), 1,6‐di‐O‐galloyl‐2‐O‐cinnamoyl‐β‐D‐glucoside (IC50 = 12.83 ± 0.67 μM), 1‐O‐(1,3,5‐trihydroxy)phenyl‐2‐O‐galloyl‐6‐O‐cinnamoyl‐β‐D‐glucoside (IC50 = 17.84 ± 1.33 μM), 1,2‐di‐O‐galloyl‐6‐O‐cinnamoyl‐β‐D‐glucoside (IC50 = 18.39 ± 1.52 μM), and 4‐(4′‐hydroxyphenyl)‐2‐butanone‐4’‐O‐β‐D‐(2”‐O‐galloyl‐6”‐O‐cinnamoyl)‐glucoside (IC50 = 2.91 ± 0.40 μM). It was found that procyanidin B5 3,3′‐di‐O‐gallate showed higher pancreatic lipase inhibitory activity than the positive control orlistat (IC50 = 0.12 ± 0.02 μM).
Conclusion
The combination of affinity ultrafiltration–high‐performance liquid chromatography (AUF‐HPLC) and high‐resolution inhibition profiling (HRIP) could reduce the risk of false‐negative screening and missed screening and could achieve more efficient screening of bioactive compounds in complex natural products.