Inhibition of dipeptidyl peptidase IV (DPP IV) is one of the mechanisms explaining the hypoglycemic effect of berberine

Abstract

Berberine was investigated as an inhibitor of human dipeptidyl peptidase IV (DPP IV) in an attempt to explain its anti-hyperglycemic activities. The investigation included simulated docking experiments to fit berberine within the binding pocket of DPP IV. Berberine was found to readily fit within the binding pocket of DPP IV in a low energy orientation characterized with optimal electrostatic attractive interactions bridging the isoquinolinium positively charged nitrogen atom (berberine) and the negatively charged acidic residue of glutamic acid-205 (GLU205) of DPP IV. Experimentally, berberine was found to inhibit human recombinant DPP IV in vitro with IC₅₀ = 13.3 μM. Our findings suggest that DPP IV inhibition is, at least, one of the mechanisms that explain the anti-hyperglycemic activity of berberine. The fact that berberine was recently reported to potently inhibit the pro-diabetic target human protein tyrosine phosphatase 1B (h-PTP 1B) discloses a novel dual natural h-PTP 1B/DPP IV inhibitor.

Keywords::

• Berberine
• dipeptidyl peptidase;
• DPP IV
• diabetes
• docking simulations
• inhibition

Acknowledgements

This project was sponsored by the Deanship of Scientific Research at the University of Jordan. The authors wish to thank the Deanship of Scientific Research at the University of Jordan for providing funds. The authors would also like to thank the OpenEye Scientific Software for providing us with a free license for FRED software (FRED, version 2.1.2)

Declaration of interest: The authors report no conflicts of interest.