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The influence and mechanism of ligustilide, senkyunolide I, and senkyunolide A on echinacoside transport through MDCK‐MDR1 cells as blood–brain barrier in vitro model
Author(s) -
Zheng Qin,
Tang Yu,
Hu PengYi,
Liu Dan,
Zhang Delin,
Yue Pengfei,
Guo Yuanyuan,
Yang Ming
Publication year - 2018
Publication title -
phytotherapy research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.019
H-Index - 129
eISSN - 1099-1573
pISSN - 0951-418X
DOI - 10.1002/ptr.5985
Subject(s) - paracellular transport , blood–brain barrier , transcytosis , pharmacology , passive transport , western blot , p glycoprotein , chemistry , transcellular , permeability (electromagnetism) , in vitro , biophysics , biochemistry , cell , central nervous system , biology , multiple drug resistance , endocytosis , endocrinology , membrane , antibiotics , gene
Efficient transcytosis across the blood–brain‐barrier is an important strategy for accessing drug targets within the central nervous system. Ligusticum chuanxiong Hort. was used as a messenger drug to increase the distribution of drugs in brain tissue in Traditional Chinese Medicine. The present study investigates the transport of echinacoside (ECH) through MDCK‐MDR1 cell and the effects of ligustilide (LIG), senkyunolide A (SENA) and senkyunolide I (SENI) in chuanxiong on its transport. The results indicated that the absorption of ECH was relatively poor in MDCK‐MDR1cells, and was concentration dependent and not saturable. The P‐glycoprotein inhibitor verapamil could significantly increase the transport of ECH. It indicated that the transport mechanism might be passive diffusion as the dominating process with the active transportation mediated mechanism involved. The increased apparent permeability of ECH in A → B direction by ethylenediaminetetraacetic acid‐Na 2 suggested that ECH was absorbed via the paracellular route. The transport of ECH in A → B direction significantly increased when co‐administrated with increasing concentrations of LIG, SENI and SENA. Western blot analysis and a decrease in transepithelial electrical resistance during the permeation experiment indicated that LIG, SENI and SENA had enhanced the transport of ECH in the BBB models attribute to down‐regulate the expressions of claudin‐5 and zonula occludens‐1 expression.