Topical but Not Systemic Epigallocatechin Gallate Reduces the Power of Cortical Oscillations: Evidence for Limited Blood-Brain Barrier Penetration

Objective: Epigallocatechin-gallate (EGCG), a tea active ingredient widely consumed worldwide, is offered as a nutritional supplement, considered as a complementary therapeutic agent in the management of various diseases. While commercialized with an emphasis on its beneficial effects on the central nervous system, there are conflicting findings regarding EGCG's blood-brain barrier (BBB) penetration. Methods: This study investigated the functional effect of EGCG intake on brain oscillations via different routes of administration. Furthermore, the pharmacokinetic properties of EGCG are presented using SwissADME. For this purpose, two different experimental groups were formed, and EGCG was administered to each experimental group using a different method: intraperitoneally (n=6), topically (n=6). Results: In the experimental group that received intraperitoneal EGCG, no change was observed in the power spectrum and band-specific analyses in the electrocorticography recordings taken from the cortex. However, EGCG applied topically to the cerebral cortex caused a significant decrease in basal oscillations. In addition, a significant decrease was observed in delta (0.5-4 Hz), theta (4-8 Hz), and alpha (8-13 Hz) oscillations. It had a reducing effect on beta (13-30 Hz) and gamma (30-50 Hz) oscillations, but these results were not statistically significant. ADME results also supported the inability of EGCG to pass through the BBB based on properties such as molecular size and polarity. Conclusion: In conclusion, EGCG has a significant functional effect on brain oscillations when administered directly to the cerebral cortex, while intraperitoneal injection failed to show any similar effect. These comparative findings clearly show the critical role of the route of administration in achieving therapeutic efficacy. We suggest that nanoencapsulation or combination therapies with other therapeutic agents would be beneficial to allow sufficient EGCG to cross the BBB.