PMID- 31384856
OWN - NLM
STAT- MEDLINE
DCOM- 20200205
LR  - 20211204
IS  - 2042-650X (Electronic)
IS  - 2042-6496 (Linking)
VI  - 10
IP  - 8
DP  - 2019 Aug 1
TI  - Transepithelial transport mechanisms of 7,8-dihydroxyflavone, a small molecular 
      TrkB receptor agonist, in human intestinal Caco-2 cells.
PG  - 5215-5227
LID - 10.1039/c9fo01007f [doi]
AB  - 7,8-Dihydroxyflavone (7,8-DHF), as a high-affinity TrkB receptor agonist, has 
      been extensively explored in many human disorders involving brain-derived 
      neurotrophic factor (BDNF) such as Alzheimer's disease, Parkinson's disease, 
      depression, and obesity. However, to date, the transepithelial transport 
      mechanisms of 7,8-DHF in the intestines remain unclear. The aim of our work was 
      to quantify and to characterize in vitro transport of naturally occurring 7,8-DHF 
      distinguished by its physicochemical and pharmacological properties. We discussed 
      the transport mechanisms of 7,8-DHF using the Caco-2 cell model to determine the 
      bi-directional permeability with different environmental factors (time, 
      concentration, pH, metabolic inhibitors etc.). The influx and efflux 
      characteristics of 7,8-DHF were also clarified. 7,8-DHF was poorly transported 
      across Caco-2 cell monolayers by mainly passive diffusion via a transcellular 
      pathway and not a paracellular pathway. The transport of 7,8-DHF was time and 
      concentration-dependent in both the apical (AP) to basolateral (BL) side and the 
      reverse direction. Interestingly, decreasing the pH from 7.4 to 6.0 markedly 
      enhanced 7,8-DHF transport. It is noteworthy that 7,8-DHF transport was strongly 
      inhibited by metabolic inhibitors and was highly dependent on temperature. The 
      efflux ratio (ER) values at different concentrations were all above 1.5, 
      indicating the existence of the efflux transporter. We found that breast cancer 
      resistance protein (BCRP) was not involved in 7,8-DHF secretion and that the 
      transport mechanism of 7,8-DHF was passive transport with an active efflux 
      mediated by P-glycoprotein (P-gp) and multidrug resistance associated proteins 
      (MRPs), particularly MRP 2. Moreover, the use of various influx transporter 
      inhibitors in Caco-2 cells showed that organic cation transporters (OCTs) and 
      organic anion-transporting polypeptides (OATPs) participated in 7,8-DHF 
      transport. Taken together, the elucidated transport characteristics of 7,8-DHF 
      provide useful information for designing novel and efficient delivery systems and 
      avoiding food-food or food-drug interactions.
FAU - Chen, Yufeng
AU  - Chen Y
AD  - Department of Food Science and Nutrition, School of Biosystems Engineering and 
      Food Science, Zhejiang Key Laboratory for Agro-Food Processing; Zhejiang 
      Engineering Center for Food Technology and Equipment; Zhejiang University, 
      Hangzhou 310058, China. yzhang@zju.edu.cn.
FAU - Xue, Fan
AU  - Xue F
FAU - Xia, Guobin
AU  - Xia G
FAU - Zhao, Zhenlei
AU  - Zhao Z
FAU - Chen, Chun
AU  - Chen C
FAU - Li, Yunhong
AU  - Li Y
FAU - Zhang, Ying
AU  - Zhang Y
LA  - eng
PT  - Journal Article
DEP - 20190806
PL  - England
TA  - Food Funct
JT  - Food & function
JID - 101549033
RN  - 0 (6,7-dihydroxyflavone)
RN  - 0 (ABCC2 protein, human)
RN  - 0 (ATP Binding Cassette Transporter, Subfamily B, Member 1)
RN  - 0 (Flavones)
RN  - 0 (Multidrug Resistance-Associated Protein 2)
RN  - 0 (Multidrug Resistance-Associated Proteins)
RN  - 0 (Organic Anion Transporters)
RN  - 0 (Organic Cation Transport Proteins)
RN  - EC 2.7.10.1 (Receptor, trkB)
SB  - IM
MH  - ATP Binding Cassette Transporter, Subfamily B, Member 1/metabolism
MH  - Biological Transport
MH  - Caco-2 Cells
MH  - Epithelial Cells/*metabolism
MH  - Flavones/*metabolism
MH  - Humans
MH  - Intestinal Mucosa/*metabolism
MH  - Multidrug Resistance-Associated Protein 2
MH  - Multidrug Resistance-Associated Proteins/metabolism
MH  - Organic Anion Transporters/metabolism
MH  - Organic Cation Transport Proteins
MH  - Receptor, trkB/*agonists/genetics/metabolism
EDAT- 2019/08/07 06:00
MHDA- 2020/02/06 06:00
CRDT- 2019/08/07 06:00
PHST- 2019/08/07 06:00 [pubmed]
PHST- 2020/02/06 06:00 [medline]
PHST- 2019/08/07 06:00 [entrez]
AID - 10.1039/c9fo01007f [doi]
PST - ppublish
SO  - Food Funct. 2019 Aug 1;10(8):5215-5227. doi: 10.1039/c9fo01007f. Epub 2019 Aug 6.