Pancreatic lipase inhibition activity of trilactone terpenes of Ginkgo biloba

Abstract

The prevalence of obesity is increasing at an alarming rate, but, unfortunately, only a few drugs are currently available on the market. In the present study, the methanolic extract of Ginkgo biloba L. (Ginkgoaceae) was investigated as an inhibitor of pancreatic lipase (PL) in an attempt to explain its hypolipidaemic activity. In vitro assay of G. biloba leaves extract revealed a substantial PL inhibition activity (IC₅₀ = 16.5 µg/mL). Further investigation was performed by employing theoretical docking simulations and experimental testing to uncover the active constituents responsible for G. biloba anti-lipase activity. Virtually, terpene trilactones, including ginkgolides and bilobalide, were found to fit within the binding pocket of PL via several attractive interactions with key amino acids. Experimentally, ginkgolides A, B, and bilobalide were found to inhibit PL significantly (IC₅₀ = 22.9, 90.0, and 60.1 µg/mL, respectively). Our findings demonstrated that the hypolipidaemic effects of G. biloba extract can be attributed to the inhibition of PL by, at least in part, terpene trilactones. In conclusion, this work can be considered a new step towards the discovery of new natural safe hypolipidaemic PL inhibitors.

Keywords::

• Obesity
• pancreatic lipase
• Ginkgo biloba
• docking simulation
• hyperlipidaemia
• plant extract

Acknowledgements

This project was sponsored by the Deanship of Scientific Research at the University of Jordan, Grant No. (94/2009-2010). The authors wish to thank the Deanship of Scientific Research at the University of Jordan for their generous funds. The authors would like to thank also the OpenEye Scientific Software Corporation for providing free license of FRED software.

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.