Transport in Caco-2 cell monolayers of cucurbitane triterpenoids from Momordica charantia

Bitter melon, Momordica charantia, is a widely-used treatment for diabetes in traditional medicine systems throughout the world. The compounds responsible for this biological activity are still under investigation, but curcurbitane triterpenoids are thought to be paramount. We investigated the gastrointestinal transport of a saponin-enriched n-BuOH fraction of M. charantia using a two-compartment transwell human intestinal epithelial cell Caco-2 monolayer system, simulating the intestinal barrier. Eleven triterpenoids in this extract were transported from the apical to basolateral direction across Caco-2 cell monolayers and were identified or tentatively identified by HPLC-TOF-MS. Cucurbitane-type triterpenoids permeated to the basolateral side with apparent permeability coefficient (P_app) values for 3-β-7-β,25-trihydroxycucurbita-5,23(E)-dien-19-al, momordicines I and II at 15.8 ×10^{- 6}, 7.03 ×10^{- 6} and 4.34 ×10^{- 6} cm/s, respectively. Also, small amounts of these triterpenoids were absorbed inside the epithelial cells themselves, suggesting additional bioactivity for these compounds. To our knowledge, this is the first report of the transport of the reputed anti-diabetes cucurbitane-type triterpenoids in human intestinal epithelial cell monolayers; these results therefore point to a novel mechanism for the possible bioavailability of these bitter melon compounds in vivo.