Blood Brain Barrier Permeability of (-)-epigallocatechin Gallate, its Proliferation-Enhancing Activity of Human Neuroblastoma SH-Sy5y Cells, and its Preventive Effect on Age-Related Cognitive Dysfunction in Mice
Open accessAbstract
The consumption of green tea catechins (GTCs) suppresses age-related cognitive dysfunction in mice. GTCs are composed of several catechins, of which epigallocatechin gallate (EGCG) is the most abundant, followed by epigallocatechin (EGC). Orally ingested EGCG is hydrolyzed by intestinal biota to EGC and gallic acid (GA). To understand the mechanism of action of GTCs on the brain, their permeability of the blood brain barrier (BBB) as well as their effects on cognitive function in mice and on nerve cell proliferation in vitro were examined. The BBB permeability of EGCG, EGC and GA was examined using a BBB model kit. SAMP10, a mouse model of brain senescence, was used to test cognitive function in vivo. Human neuroblastoma SH-SY5Y cells were used to test nerve cell proliferation and differentiation. The in vitro BBB permeability (%, in 30 min) of EGCG, EGC and GA was 2.8±0.1, 3.4±0.3 and 6.5±0.6, respectively. The permeability of EGCG into the BBB indicates that EGCG reached the brain parenchyma even at a very low concentration. The learning ability of SAMP10 mice that ingested EGCG (20 mg/kg) was significantly higher than of mice that ingested EGC or GA. However, combined ingestion of EGC and GA showed a significant improvement comparable to EGCG. SH-SY5Y cell growth was significantly enhanced by 0.05 µM EGCG, but this effect was reduced at higher concentrations. The effect of EGC and GA was lower than that of EGCG at 0.05 µM. Co-administration of EGC and GA increased neurite length more than EGC or GA alone. Cognitive dysfunction in mice is suppressed after ingesting GTCs when a low concentration of EGCG is incorporated into the brain parenchyma via the BBB. Nerve cell proliferation/differentiation was enhanced by a low concentration of EGCG. Furthermore, the additive effect of EGC and GA suggests that EGCG sustains a preventive effect after the hydrolysis to EGC and GA.
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EGCG permeates the BBB at low micromolar levels.
“EGCG displays to permeate the BBB at low micromolar levels (Pervin et al., 2017)”
From Exploring the Therapeutic Potential of Phytochemicals in Alzheimer’s Disease: Focus on Polyphenols and Monoterpenes (2022) · cites this paper as Pervin et al., 2017
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Function of Green Tea Catechins in the Brain: Epigallocatechin Gallate and its Metabolites
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- Authors
- Pervin, M., Unno, K., Nakagawa, A., Takahashi, Y., Iguchi, K., Yamamoto, H., Hoshino, M., Hara, A., Takagaki, A., Nanjo, F., Minami, A., Imai, S., & Nakamura, Y.
- Affiliations
- Shizuoka University (JP)
- Mitsui (Japan) (JP)
- Tokyo University of Technology (JP)
- Corresponding author
- Unno, Keiko
- Venue
- Biochemistry and Biophysics Reports
- Publisher
- Elsevier BV
- Published
- 2017-03
- Volume
- 9
- Pages
- 180-186
- ISSN
- 2405-5808 (ISSN-L)
- PMC
- PMC5614586
- OpenAlex
- W2569912524
- Cited by
- 137
- References
- 38
- Citations by year
- 2026: 8 · 2025: 15 · 2024: 7 · 2023: 18 · 2022: 19 · 2021: 22 · 2020: 23 · 2019: 14 · 2018: 10 · 2017: 1
- FWCI
- 10.31
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Biochemistry and Biophysics Reports (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- KAKENHI (23617014, 15K00828)
- Topics
- Health Sciences › Medicine › Pathology and Forensic Medicine › Tea Polyphenols and Effects
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Keywords
- epigallocatechin gallate, green tea catechins, blood-brain barrier permeability, epigallocatechin, gallic acid, SH-SY5Y cells, neuronal proliferation, neurite length, learning ability, brain aging, cognitive enhancement
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