title: Transport of ginkgolides with different lipophilicities based on an hCMEC/D3 cell monolayer as a blood-brain barrier cell model.
abstract: OBJECTIVE
  In this report, the transport of ginkgolides with different lipophilicities was investigated using an hCMEC/D3 cell monolayer as a blood-brain barrier (BBB) cell model in vitro in an attempt to explain ginkgolide transport path mediated by lipophilicity.
  
  
  METHODS
  The log P values of ginkgolides were determined by measuring the distribution of the molecule between oil and water. Additionally, the cytotoxicity of ginkgolides on hCMEC/D3 cells was assayed with the MTT method. Ginkgolide contents were determined with an ultra performance liquid chromatograph equipped with an evaporative light scattering detector (ULPC-ELSD) method. Apparent permeability coefficients (Papp) and efflux ratios (PappBL→AP/PappAP→BL) were then calculated to describe the transport characteristics of ginkgolide.
  
  
  RESULTS
  The transport of ginkgolide A, ginkgolide B, ginkgolide C, and ginkgolide J across the hCMEC/D3 cell monolayer was non-directional. Additionally, ginkgolide C transport on the cell monolayer was time- and concentration-dependent in the paracellular pathway controlled by cytochalasin D (a tight junction modulator). The transport of ginkgolide N, ginkgolide L, and ginkgolide K across the cell monolayer displayed clear directionality at low ginkgolide concentrations. This behavior indicated that the transport of ginkgolide N, ginkgolide L, and ginkgolide K was influenced by the transcellular pathway containing an efflux protein accompanied by the paracellular pathway for passive diffusion. Additionally, the transport of ginkgolide K was increased significantly by co-culturing with a P-gp inhibitor.
  
  
  CONCLUSIONS
  These findings provide important information for elucidating ginkgolide transport pathways and may be beneficial for the design of ginkgolide molecules with high neuroprotective effects.
authors.affiliation: Pharmaceutical Engineering, Institute of Chemistry and Chemical Engineering, Qiqihar University, Qiqihar 161006, PR China. Electronic address: mashuwei_2004@163.com.
authors.forename: Shuwei
authors.initials: S
authors.lastname: Ma
authors.affiliation: Department of Complex Prescription of TCM, China Pharmaceutical University, Nanjing 210038, PR China.
authors.forename: Xingyan
authors.initials: X
authors.lastname: Liu
authors.affiliation: Institute of TCM, Heilongjiang Academy of Traditional Chinese Medicine, Harbin, 150036, PR China.
authors.forename: Qingrun
authors.initials: Q
authors.lastname: Xu
authors.affiliation: Guangdong Research Institute of Traditional Chinese Medicine, Guangzhou, 510520 PR China.
authors.forename: Xiantao
authors.initials: X
authors.lastname: Zhang
mesh_terms: D000704:Analysis of Variance; D001692:Biological Transport; D001812:Blood-Brain Barrier / Q000502:physiology*; D002460:Cell Line; D002851:Chromatography, High Pressure Liquid; D020441:Ginkgo biloba / Q000737:chemistry*; D046934:Ginkgolides / Q000737:chemistry / Q000378:metabolism* / Q000633:toxicity; D006801:Humans; D015394:Molecular Structure; D010936:Plant Extracts / Q000737:chemistry / Q000378:metabolism* / Q000633:toxicity; D013778:Tetrazolium Salts; D013844:Thiazoles
chemical_list: D046934:Ginkgolides; D010936:Plant Extracts; D013778:Tetrazolium Salts; D013844:Thiazoles; C022616:thiazolyl blue
keywords: Apparent permeability coefficients; BBB; Efflux ratio; Ginkgolide; Lipophilicity; Transport; hCMEC/D3 cell