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Blood–Brain Barrier Permeability of Green Tea Catechin Metabolites and their Neuritogenic Activity in Human Neuroblastoma SH‐SY5Y Cells
Author(s) -
Unno Keiko,
Pervin Monira,
Nakagawa Aimi,
Iguchi Kazuaki,
Hara Aya,
Takagaki Akiko,
Nanjo Fumio,
Minami Akira,
Nakamura Yoriyuki
Publication year - 2017
Publication title -
molecular nutrition and food research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.495
H-Index - 131
eISSN - 1613-4133
pISSN - 1613-4125
DOI - 10.1002/mnfr.201700294
Subject(s) - chemistry , blood–brain barrier , catechin , pharmacology , biochemistry , epigallocatechin gallate , polyphenol , biology , endocrinology , central nervous system , antioxidant
Scope To understand the mechanism by which green tea lowers the risk of dementia, focus was placed on the metabolites of epigallocatechin gallate (EGCG), the most abundant catechin in green tea. Much of orally ingested EGCG is hydrolyzed to epigallocatechin (EGC) and gallic acid. In rats, EGC is then metabolized mainly to 5‐(3′,5′‐dihydroxyphenyl)‐γ‐valerolactone (EGC‐M5) and its conjugated forms, which are distributed to various tissues. Therefore, we examined the permeability of these metabolites into the blood–brain barrier (BBB) and nerve cell proliferation/differentiation in vitro. Methods and Results The permeability of EGC‐M5, glucuronide, and the sulfate of EGC‐M5, pyrogallol, as well as its glucuronide into the BBB were examined using a BBB model kit. Each brain‐ and blood‐side sample was subjected to liquid chromatography tandem‐mass spectrometry analysis. BBB permeability (%, in 0.5 h) was 1.9–3.7%. In human neuroblastoma SH‐SY5Y cells, neurite length was significantly prolonged by EGC‐M5, and the number of neurites was increased significantly by all metabolites examined. Conclusion The permeability of EGC‐M5 and its conjugated forms into the BBB suggests that they reached the brain parenchyma. In addition, the ability of EGC‐M5 to affect nerve cell proliferation and neuritogenesis suggests that EGC‐M5 may promote neurogenesis in the brain.