Berberine potently inhibits protein tyrosine phosphatase 1B: investigation by docking simulation and experimental...

Berberine was investigated as an inhibitor of human protein tyrosine phosphatase 1B (h-PTP 1B) in an attempt to explain its anti-hyperglycemic activitiy. The investigation included simulated docking experiments to fit berberine within the binding pocket of h-PTP 1B. Berberine was found to readily fit within the binding pocket of h-PTP 1B in a low energy orientation characterized with optimal electrostatic attractive interactions bridging the isoquinolinium positively charged nitrogen atom of berberine and the negatively charged acidic residue of ASP 48 of h-PTP 1B. Experimentally, berberine was found to potently competitively inhibit recombinant h-PTP 1B in vitro (Ki value = 91.3 nM). Our findings strongly suggest that h-PTP 1B inhibition is at least one of the reasons for the reported anti-hyperglycemic activities of berberine.