Inhibition of dipeptidyl peptidase IV (DPP IV) is one of the mechanisms explaining the hypoglycemic effect of berberine.
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 IC(50) = 13.3 microM. 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.
Al-masri
Ihab M
IM
Department of pharmaceutical sciences, Faculty of Pharmacy, University of Jordan, Jordan.
Mohammad
Mohammad K
MK
Tahaa
Mutasem O
MO
D001599:Berberine / Q000737:chemistry* / Q000494:pharmacology*; D001665:Binding Sites; D018360:Crystallography, X-Ray; D018819:Dipeptidyl Peptidase 4 / Q000737:chemistry; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects*; D006801:Humans; D007004:Hypoglycemic Agents / Q000737:chemistry / Q000494:pharmacology*; D008958:Models, Molecular; D015394:Molecular Structure
D054873:Dipeptidyl-Peptidase IV Inhibitors; D007004:Hypoglycemic Agents; D001599:Berberine; D018819:Dipeptidyl Peptidase 4