Quantum Chemical and Docking Insights into Bioavailability Enhancement of Curcumin by Piperine in Pepper

We
combine quantum chemical and molecular docking techniques to
provide new insights into how piperine molecule in various forms of
pepper enhances bioavailability of a number of drugs including curcumin
in turmeric for which it increases its bioavailability by a 20-fold.
We have carried out docking studies of quantum chemically optimized
piperine structure binding to curcumin, CYP3A4 in cytochrome P450, p-Glycoprotein and UDP-glucuronosyltransferase
(UGT), the enzyme responsible for glucuronosylation, which increases
the solubility of curcumin. All of these studies establish that piperine
binds to multiple sites on the enzymes and also intercalates with
curcumin forming a hydrogen bonded complex with curcumin. The conjugated
network of double bonds and the presence of multiple charge centers
of piperine offer optimal binding sites for piperine to bind to enzymes
such as UDP-GDH, UGT, and CYP3A4. Piperine competes for curcumin’s
intermolecular hydrogen bonding and its stacking propensity by hydrogen
bonding with enolic proton of curcumin. This facilitates its metabolic
transport, thereby increasing its bioavailability both through intercalation
into curcumin layers through intermolecular hydrogen bonding, and
by inhibiting enzymes that cause glucuronosylation of curcumin.