Influence of St. John’s wort extract STW3-VI, hyperforin and hyperoside on the signaling activity, density, and internalization of 5-HT_2A receptors

Background Depressive disorders belong to the most frequent diseases. Antidepressant treatment try to normalize disturbed neurotransmitter systems. In this context activity, density, and trafficking of serotonin 2A (5-HT_2A) receptors are of high interest. Deeper insights into 5-HT_2A behavior are crucial for a better understanding of the effects of antidepressants like St. John’s wort extracts.

Methods Influences of STW3-VI, hyperoside, and hyperforin on the signaling activity, receptor density and agonist-induced internalization were investigated in HEK293 reporter cells over-expressing different luciferase-based detection systems.

Results A six days pre-treatment with STW3-VI significantly and dose-dependently decreased 5-HT_2A receptor density under non-stimulating conditions by 12% and receptor internalization after agonistic stimulation from 18.8% to 8.1%. The data suggest a decrease in 5-HT_2A receptor activity, which was confirmed by reduced intracellular calcium levels of up to 41%. Pre-treatment with 1 µM hyperforin and 1 µM hyperoside for six days showed no statistically significant effects on those parameters.

Conclusion The data presented here demonstrate that 5-HT_2A receptors are an important target for understanding the complex mode of action of STW3-VI. The activity of 5-HT_2A receptors themselves and their crosstalk with other receptor systems, e. g., the 5-HT_1A receptor, is of importance in the treatment and development of depressive disorders.

Publication History

Article published online:
13 December 2021