title: Investigation of the mechanisms of improved oral bioavailability of bergenin using bergenin-phospholipid complex.
abstract: OBJECTIVE
  The purpose of this study was to investigate the detailed mechanisms of oral absorption enhancement of bergenin (BN) using BN-phospholipid complex (BPC).
  
  
  METHODS
  Multiple models such as ex vivo everted rat gut sac model and in vitro Caco-2 cell model were used. Meanwhile, the effect of chitosan on the enhancement of the permeability of BPC was evaluated.
  
  
  RESULTS
  The limited absorption of BN was significantly improved in both ex vivo everted rat gut sac model and in vitro Caco-2 cell model when combined with phospholipid. The transport of BPC was uppermost 5.19-fold higher than that of BN. The results of ex vivo everted rat gut sac model showed that small intestine was a more suitable site for the absorption of BN and BPC than colon. Passive diffusion was the only way employed in the transport of BN, while BPC could transport across enterocytes by both passive diffusion and active transport which was found to be the clathrine-dependent receptor-mediated endocytosis. The absorption of BN was barely improved by the physical mixture of BN and phospholipid due to lack of stable intermolecular interactions. Moreover, the addition of chitosan could open the tight junctions of intestinal epithelial cells, thus significantly increasing the transport of BPC via paracellular route.
  
  
  CONCLUSIONS
  Totally different mechanisms, which led to the enhanced oral bioavailability, were utilized in the uptake and transport process of BPC compared with BN. These results would be of significance for the future development of oral delivery systems of BN.
authors: Key Laboratory of Drug Targeting and Drug Delivery System, Ministry of Education, West China School of Pharmacy, Sichuan University , Chengdu , PR China.
authors: Shan
authors: S
authors: Guan
authors: Xuan
authors: X
authors: Qin
authors: Zhou
authors: Z
authors: Zhou
authors: Qiang
authors: Q
authors: Zhang
authors: Yuan
authors: Y
authors: Huang
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001578:Benzopyrans / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism*; D001682:Biological Availability; D018938:Caco-2 Cells; D006801:Humans; D007408:Intestinal Absorption / Q000187:drug effects* / Q000502:physiology; D008297:Male; D009924:Organ Culture Techniques; D010743:Phospholipids / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D001578:Benzopyrans; D010743:Phospholipids; C006741:bergenin