TITLE:
L-Theanine Protects against Methylglyoxal-Induced Oxidative Stress and Tight Junction Disruption in Human Cerebral Microvascular Endothelial Cells
AUTHORS:
Kohshi Kusumoto, Kouyoh Habuchi, Satoru Sakuma, Keiichiro Okuhira
KEYWORDS:
L-Theanine, Methylglyoxal, Oxidative Stress, Tight Junction, Blood-Brain Barrier
JOURNAL NAME:
Food and Nutrition Sciences,
Vol.15 No.12,
December
12,
2024
ABSTRACT: The brain’s blood microvessels restrict the exchange of substances between the blood and brain tissue through the blood-brain barrier (BBB). Methyl-glyoxal (MG), a byproduct of glucose metabolism, contributes to the formation of advanced glycation end products (AGEs) and disrupts the BBB, which is associated with neurodegenerative diseases. L-Theanine (TA), an amino acid found in green tea with antioxidant properties, may protect the BBB. This study aimed to determine whether MG increases reactive oxygen species (ROS) and permeability by reducing tight junction proteins in human cerebral microvascular endothelial cells (hCMEC/d3), and whether TA pretreatment can counteract these effects. Our findings demonstrated that MG treatment led to increased BBB permeability, decreased transendothelial electrical resistance (TEER) values to 39% of control levels, reduced expression of Claudin-5 to 53% and Occludin to 69% of control levels, and elevated intracellular ROS levels. TA pretreatment restored barrier integrity, preserved tight junction protein expression, and decreased ROS accumulation to levels comparable to control levels. These findings suggest that TA effectively prevents MG-induced BBB dysfunction by reducing oxidative stress and maintaining tight junction proteins, showing promise as a protective agent for the BBB in conditions associated with elevated MG and AGEs.